| 111. |
- Löfgren, Ragnhild
(författare)
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Phagocytic-receptor signaling in human neutrophils
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The neutrophil granulocyte is one of the most mobile cells in the body and through a number of functions represents the first line of defense against invading pathogens. Adhesion and chemotactic receptors on the cell surface work together through modulation of the cytoskeleton, thereby enabling cell movement. Engulfment is facilitated by opsonization of the microbes with C3b or C3bi complement fragments or with immunoglobulins, proteins that respectively bind to complement receptors (CR) and Fey receptors (FcyR) on the neutrophil. The aim of the present study was to investigate the signal transduction properties of CR and FcyR on human neutrophils. In particular, the investigations focused on second messengers of importance for regulating actin polymerization and NADPH-oxidase activity. This was approached by selective activation of each receptor on non-adherent human neutrophils using specific antibodies that were either cross-linked or prefixed on bacterial particles.Both stimulation with f.MetLeuPhe and engagement of CR3 caused an increase in filamentous actin (F-actin) and activation of phosphatidylinositol 3-klnase with the subsequent formation of phosphatidylinositol trisphosphate (PIP,). We found that the F-actin response mediated by fMetLenPhe and CR3 were different. The F-actin response induced by fMetLeuPhe declined rapidly whereas the response induced by engagement of CR3 was more sustained. This is hypothesized to be due to the inability of CR3 to induce a cAMP signal, since direct addition of cAMP and 1-isobutyl-methylxantine (IBMX, a phosphodiesterase inhibitor) to electropermeabilized neutrophils caused a prompt reversal of the CR3-induced F-actin elevation.Engagement of CR3 and CR1 by antibody cross-linking induced a Ca2+ signal and phospholipase D (PLD) activation. Furthermore, the PLD response was potentiated by PMA pretreatment and was dependent on the form of ligand presentation. Both FcyR (FcyRITA and FcyRIIIB) and CR3 induced activation of NADPH-oxidase, a response that was dependent on intracellular Ca2+, tyrosine kinase activation and PLD activity. However, only FcyRllA induced a strong phosphorylation of p72''\ indicating that CR3 and FcyRliA might use different pathways leading to NADPH-oxidase activation.
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| 112. |
- Lönn, Urban
(författare)
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A minimally invasive axial blood flow pump : an experimental and clinical study
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The first aim of this thesis was to evaluate a new minimally invasive axial blood flow pump for treatment of patients needing circulatory support after open heart surgery. This system, the Hemopump temporary cardiac assist device, is a very small catheter mounted intracorporeal pump, which is introduced transvalvularly into the left ventricle. The pump can be inserted either through the femoral artery or directly through a graft sutured to the ascending aorta. In an experimental model, the flow capacity of three different designs of the system was investigated. Flow capacity varied between 2.0 and 4.5 liters per minute, depending on the working conditions for the different pump models. Twenty,four patients were treated for post,cardiotomy heart failure. Fourteen patients (58 %) were weaned from the device and later discharged from the hospital. In a subgroup of these patients (54%) where early intervention was instituted, the survival rate was 85%. The pump proved to be an effective tool for unloading a failing left ventricle with preservation of multi-organ perfusion. A clinical protocol was established for postoperative management. The Hemopump was easy to adapt to the clinical setting, and device~ related complications were few.The second aim was to develop a new less invasive procedure for CABG, avoiding the need for cardio~pulmonary bypass during these procedures. First an animal trial was performed as a feasibility study. In combination with the administration of a short~acting ~~blocker, esmolol, this method enabled precise coronary bypass surgery. When results became consistent a small pilot study was done on five patients showing that this was a reproducible technique. Finally a prospective randomized trial comparing this technique with conventional bypass surgery was carried out. The Hemopump supported bypass surgery did not prolong the procedure, did not require a longer time on circulatory support and bleeding was less. Postoperative enzyme levels indicated that ischemic insult to the myocardium was less than with conventional surgery.In summary, this minimally invasive axial blood flow pump proved to be a powerful left ventricular assist system enabling a less invasive approach during conditions where circulatory support is needed.
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| 113. |
- Magnusson, Per, 1962-
(författare)
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Human Bone Alkaline Phosphatase Isoforms
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Determination of serum total alkaline phosphatase (ALP) is frequently requested in clinical routine, mostly to estimate skeletal and hepatobiliary status. In this respect, clarification of the various ALP isoenzymes and isoforms contributing to the total ALP activity could be valuable in daily medical decision making. The general aim of this thesis was to investigate methodological, metabolic, and clinical aspects of bone ALP (BALP) isoforms in human bone and mineral metabolism. BALP is a glycoprotein and functions as an ectoenzyme attached to the osteoblast cell membrane by a glycosyl-phosphatidylinositol (GPI) anchor. The precise function of BALP is not known, however, there is evidence that BALP is necessary for initiating bone mineralization.A weak anion-exchange high-performance liquid chromatography (HPLC) assay was developed for the determination of BALP and liver ALP (LALP) isoforms. Six peaks with ALP activity were separated and quantified in serum from healthy individuals: B/I, a minor fraction composed of bone (70%) and intestinal (30%) ALP, and two major BALP isoforms B 1 and B2, and three LALP isoforms. Reference intervals were reported for healthy children, adolescents, and adults (range 7-65 years). In healthy adults the BALP isoforms, B/I, Bl, and B2, contributed to 4, 16, and 37%, respectively, of the total ALP activity. Bone samples were prepared from human femora in order to characterize and investigate the origin of these BALP isoforms found in serum. Cortical bone had about 2-fold higher activities of Bl compared with B2, and trabecular bone had about 2-fold higher activities of B2 compared with Bl. Treatment with GPI -specific phospholipase C did not influence the activities or retention times of Bland B2. Thus, the biochemical differences between Bland B2 are likely to be due to different glycosylation patterns, rather than the presence of GPI cell membrane anchor fragments.Decreased B I activity was observed after I week of IGF-I administration, and after I month of GH therapy, followed by an increase after 3 months. B2 was not influenced by IGF-I administration, but was similarly increased after 3 months of GH therapy. It was proposed that the initial decrease of B 1 could be an effect of endocrine IGF-I action mediated by GH. Different responses of B 1 and B2 during IGF-I and during GH therapy suggest different regulations of these BALP isoforms in vivo. Differences of BALP isoforms in metastatic bone disease were found, as well as discrepant effects of clodronate on different skeletal sites indicated by the location of bone pain. Patients with skeletal metastases and healthy males had B2 activities corresponding to 75% and 35% of the total ALP activity, respectively.Taken together, the BALP isoforms B I and B2 can be used as early indicators of pharmacological efficacy and, possibly provide information relating to specific bone compartments. Future investigations have to elucidate if they also reflect different stages in osteoblast differentiation during osteogenesis where one isoform is presented before the other during extracellular matrix maturation.
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| 114. |
- Maletius, Wolfgang
(författare)
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Long term prognosis of intraarticular knee injuries
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Intraarticular knee injuries, still are a challenge for proper treatment in Sports Medicine today .The increasing life expectancy as well as the patient expectation to maintain a sufficiant physical activity up to high ages gives the topic an increasing publicity. Still, the long tenn prognosis of the most conunon intraarticular knee injuries including cartilage injuries remaines unclear. The general purpose of this work was to investigate the long- term prognosis after common intraarticular knee injuries in respect to lrnee function, sports performance, knee stability and development of radiographical osteoarthrosis.In this series, 221 patients were examined. The initial diagnosis in all cases was placed by manual examination under anesthesy and arthroscopy. The patients were reexamined at different long-term follow-up intervalls by an interview, including a subjective lmee score and an activity score, a thorough manual examination, and a radiographical examination including weight-bearing radiographs. In a part of the patients, a quality of life score was used.Patients with isolated chondral damage in one knee had a good long-term functional' prognosis but developed mild to moderate signs of radiographical osteoarthrosis in the majority of the cases.Complete ACL tears resulted in a permanent increase of sagittal knee translation no matter which initial treatment Injuries to knee joint cartilage or menisci or partial injuries to the ACL did not result in an increase of sagittal translation.Radiographical signs for osteoarthrosis were encountered in 55 to 87% after different knee injuries, and seemed to advance slowly during the years.Combined intraarticular knee injuries seemed to have a higher risk for development of radiographical osteoarthrosis than isolated injuries within the same time period.Older age at initial diagnosis and treatment of an intraarticular knee injury is associated with a higher risk to develop radiographlcal osteoarthrosis.After 12 to 20 years, patients with minor intraarticular knee injuries seem to have only a marginally better longterm prognosis for knee function and activity participation than patients with combined, major intraarticular knee injuries. However, the higher dissatisfaction with the results, the higher rate of symptoms and subsequent repeat surgery as well as the higher development of oeteoarthrosis during the years in the latter cases may point to that the risk for future lmee deterioration is greater after a combined than after a minor or/and isolated knee injury.Subjective satisfaction and quality of life was high after a partial rupture of the ACL with minor concomitant injuries, and stayed unchanged over the years. In contrast, a complete rupture of the ACL did adversely influence quality of life, and subjective satisfaction with knee performance declined with time.
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| 115. |
- Mårtensson, Lena G. E.
(författare)
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New pharmacological aspects of melatonin
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Melatonin is a hormone that takes part in the regulation of biological rhythms. It is produced in the pineal gland and is stimulated by darkness and inhibited by exposure to light. The increased amouot of melatonin during the hours of darkness sends a chronobiological message throughout the body, and translates it into a chemical message that can be read by target cells. This process requires that a receiving protein, a receptor, is present on the cell surface, and that it can recognize melatonin and transfer the signal from outside of the cell to the inside, where it can be transformed into a cellular response. The present investigation was focused on receptor recognition, receptor activation and receptor-mediated signaling.The scales of the cuckoo wrasse (Labrus ossifagus L.), a teleost fish, bear melanophores that contain pigment granules that can be transported to the center of the cell (pigment aggregation) or distributed throughout the melanophore (pigment dispersion). Pigment aggregation is governed by sympathetic nerve endings that stimulate an α2-adrenoceptor, and also by circulating hormones, for example melatonin. To answer questions regarding receptor interactions, melatonin was used in the melanophore bioassay.The results show that melatonin did not induce pigment aggregation when administrated alone. The hormone did, however, reinforce aggregation induced by noradrenaline, which reveals a melatonin-noradrenaline synergism. Pharmacological studies were performed to elucidate this synergism. Data obtained using α2-adrenoceptor and melatonin receptor ligands, and by investigating intracellular mediators, indicate that, hypothetically, the noradrenaline-melatonin synergism may be due to the existence of an α2-adrenergic receptor with two functional sites: one site for catecholamines, such as noradrenaline, and a second "modulatory" site for melatonin.It is known that smooth muscle cells from pregnant human myometrium express adrenoceptors and that labor tends to begin during the dark hours. The effect of melatonin on myometrial contractility was examined in order to investigate if the same synergism appeares in the myometrium as in the melanophores. The contractility of biopsied myometrial samples taken from women undergoing cesarean sections was measured in vitro. The results show that melatonin alone did not increased myometrial contractility, but it did reinforce noradrenaline-induced contraction, i.e. a melatonin-noradrenaline synergism. Consequently, it is possible that the greater production of melatonin at night induces increased myometrial contractility that leads to the beginning of labor.
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| 116. |
- Mølgaard, Jørgen
(författare)
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Intermittent Claudication : Prevalence and metabolic risk factors
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The prevalence of intermittent claudication (IC) in middle-aged men (45-69 years old) and metabolic risk factors for this disease was studied in a Swedish community. All 15 253 middle-aged male residents in Linköping community, were screened for symptoms of IC using a postal questionnaire, which included detailed questions about smoking habits and presence of hypertension and diabetes mellitus.The overall response rate was 86.6% (n=l3 209). The prevalence of walking-related pain was 9.3% (n=l232), and 4.2%(n=552) had symptoms consistent with peripheral atherosclerotic disease (PAD). All men with leg symptoms according to the classical Rose criteria for IC (1.2%, n=156), and a sample of subjects (0.6%, n=84) with symptoms indicating PAD, but not fully complying with the Rose c.riteria, were invited for further examination.Subjects with IC were compared with randomly selected sex- and age-matched controls from the same population. One control group was matched for smoking habits (n=157), and one control group consisted of never-smokers (n=143). Both claudicants and healthy controls underwent objective examination of the peripheral circulation with segmental blood pressure measurements and a short treadmill exercise test.IC could objectively be verified in 1.7% (n=219) of all middle-aged men. The prevalence of IC was highly age-dependent and objectively verified IC increased from 0.2% in males 45-49 years old to 3.4% in those 65-69 years old. The prevalence of Rose IC was 0.5% for 45-49 year-old males and 2.0% for 65-69 year-old males. Thus the Rose criteria underestimated the prevalence ofiC in the older age group and overestimated it in the youngest age group. The estimated true average prevalence ofiC was at least 2.8%.More than half (57%) of all claudicants had ischaemic heart disease, and 21% had experienced a TIA or stroke.The metabolic studies investigated the role of dyslipidaemia and various metabolic abnormalities as risk factors for IC. Claudicants had multiple minor and moderate lipid and lipoprotein abnormalities, the strongest association being with elevated plasma levels of low-density lipoproteins (LDL) cholesterol and low levels of high-density lipoproteins (HDL) cholesterol, after multivariate adjustment for other major risk factors, i.e. hypertension, diabetes mellitus and smoking, and other factors that influence lipid levels. Ve1y-low-density lipoproteins (VLDL) triglycerides had a high univariate association, but did not contribute to risk for IC after multivariate adjustment for the above factors.Plasma lipoprotein (a) [Lp(a)] showed a strong association with risk for IC, which in part could be explained by a significant overrepresentation of small apo(a) isoforms, genetically associated with higher Lp(a) concentrations.Plasma a- and ~-carotene, Iycopene and retinol, but not a- or y-tocophcrol (vitamin E), showed a multivariate significant association with risk for IC in men. However, when dietary data had been accounted for, only the significance of plasma retinol remained. Lower plasma levels of lipid-soluble antioxidants after adjustment for lipid concentrations may be secondary to the atherosclerotic disease. Moderately elevated levels of plasma homocyst(e)ine, a su\fbydryl-containing amino acid with a known atherogenic potential, were significantly associated with risk of IC after adjustment for other risk factors in multivariate analyses.In conclusion, the risk for IC amongst middle-aged males was significantly associated with presence of both major traditional risk factors such as smoking (96%), hypertension (49%), diabetes mellitus (18%) and additional metabol~c risk factors such as dyslipidaemia, hypcrhomocyst(e)inaemia and elevated Lp(a) levels. Plasma levels of tocophero!s (vitamin E) were not associated with risk for IC. Carotenoids do not seem to contribute, whereas the role of plasma retinol remains unclear.
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| 117. |
- Niklasson, Magnus
(författare)
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The vestibular system, a tool to study neurotoxicants in the central nervous system
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The vestibular and opto-ocular motor (VOOM) system in pigmented rats was investigated. Horizontal eye movements were recorded by the magnetic search coil technique during different kind of stimulations. The dynamics of the vestibular ocular reflex (VOR) and the optokinetic reflex (OKR) as well as the interaction of the two rel1exes were analysed. The ability to cancel nystagmus during vestibular and optokinetic stimulation was found to be comparable to "higher" animals.The experimental model was used to study the effects of toxicants and drugs on the VOOM system. Four different solvents, known to cause disturbances of the central nervous system (CNS), were tested. Acute exposure by inhalation of each solvent gave specific dose-response related effects in the VOOM system, most of which could be explained by an alteration of the cerebellar-vestibular circuit. However there were differences among the four solvents, the results indicating that different solvents should be considered as individual substances in toxicological CNS research.The effects of drugs, related to GABAB-transmission, were investigated.Baclofen, a GABAB-agonist, affected the VOR, the OKR and the interaction of these two in a dose-related way. All these effects could be blocked by CGP 35348, a GABAB-antagonist.The similarities in the effects of baclofen to the effects of toluene were striking. It was demonstrated that effects of toluene on the VOR could be blocked by CGP 35348 at a dose which did not cause any effects per se. It was concluded that some of the effects of toluene on the VOOM system were related to GABA-transmission, directly or indirectly.The VOOM system was also used in an otoneurological test battery to investigate the effects on the CNS in workers, long-term exposed to solvents. Dynamic posturography was also performed to obtain an indication of the integration of somatosensory, visual, and vestibular stimuli in the equilibrium system. Reduced ability to visual suppression, prolonged latency of saccades and pathology in the posturography tests were found in the solvent exposed group compared to results of a non-exposed healthy control group.All exposed worker had been evaluated for a possible chronic toxic encephalopathy (CTE) and were categorized in three groups non-CTE, incipient CTE, and CTE. These categories, based on psychometric test results and case histories of exposure and symptoms, were poorly correlated to the otoneurological findings. Even in the non-CTE group pathological findings were present. Lesions in the CNS revealed by an otoneurological investigation were apparently not found in the neuropsychological investigation. This indicates that an otoncurological test battery could contribute valuable information in the evaluation of long-term solvent exposed people suspected for CTE.The studies related above, demonstrate that the VOOM system is an useful tool in evaluating toxicological effects in the CNS.
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| 118. |
- Nilsson, Lennart, 1954-
(författare)
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Risk factors for atopic disease in childhood
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: It is important to assess risk factors for the development of allergic diseases, primarily because these diseases are so common and affect one third of all children in the western world, sometimes with serious manifestations, and also because these diseases have continued to increase over the last few decades.Aims: To study the difference between the cumulative incidence of allergic diseases in 7-ycarold children in 1974 and 1994. To ascertain whether a/ urban as opposed to rural living, b/ maternal allergy, cl season of birth, and particularly, dl pertussis vaccination influence the development of allergic diseases.Material & methods: Two cross-sectional and two prospective studies were evaluated in regard to allergic diseases and their relation to various risk factors. Diagnoses of allergic diseases were obtained from questionnaires and intensive prospective clinical evaluations. Skin prick tests and analyses of IgE to common allergens and pertussis toxin were performed.Results: Allergic diseases increased from 15.1% to 26.1% with a relative risk of 1.7 (95% C.!. 1.4-2.1). The increase was attributed to the children having a heredity of allergic disease. Today, it is more common to have a family member with an allergic disease than not to have allergy in the immediate family. Bronchial asthma and allergic rhinoconjunctivitis in 7-year-old girls increased more than fourfold between 1974 and 1994 but the increase in 7-year-old boys was only 50%.Urban as opposed to rural living during the first two years of life was a moderate risk factor for allergic disease up to 13-14 years of age. The risk was particularly high for bronchial asthma with a relative risk of 2.1 (95% C.!. 1.2-3.7) associated with urban living during the first year of life and 2.1 (1.2-3.6) with urban living the second year. The increase in risk remained after adjustment for family history of allergy, gender, environmental tobacco smoking, smoking during pregnancy, pets indoors, damp indoors and living area. Smoking during pregnancy was an independent risk factor for asthma in the child. The two crosssectional studies both showed significant increase (I 0%) in children if the mother had an allergic disease. Allergic diseases were associated with birth during the winter and negatively associated with birth during spring time. The acellular pertussis vaccines did not influence the development of allergy significantly more than the whole cell pertussis vaccines, or placebo (with diphtheria and tetanus only).Discussion/Conclusions: The increased risk of allergic disease over the last few decades cannot be explained by genetic factors. The most plausible explanation is that there is some factor or factors that influence children with a genetic pre-disposition to allergy. Differences in microbial exposure and infections are conceivable reasons for the increase and may contribute to the difference seen between urban and rural areas. Other possible causes may be exposure to different adjuvants, e.g. nitrogen dioxide and diesel exhausts.The increase in family size in families with an allergic mother, would be a survival advantage of being atopic. This could explain a long-term accumulation but not the dramatic increase during the second half of the 20th century.The seasonal effect is moderate. One plausible explanation of the effect in relation to pollen allergy may be that the levels of maternal IgG to inhalants are dependent on the pollen season. However, the seasonal effects of IgE to egg in infancy may be attributable to the indoor environment.In spite of the fact that acellular vaccines induced more IgE to pertussis toxin and that the Th2-type cytokines increased more than Thl-type cytokines after acellular pertussis vaccines, these vaccines did not significantly increase the risk of allergic disease in the children. Acellular vaccines are therefore recommended owing to their documented safety as well as effectiveness. All in all, several risk factors for allergic diseases have been found but none of them is strong enough to explain the increase over the last few decades.
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| 119. |
- Nordström, Marie
(författare)
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Epidemiological aspects on hairy cell leukaemia
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Non Hodgkin's lymphoma (NHL) has an increasing incidence in many Western countries. In Sweden, about 1800 new cases were reported to the Cancer Registry in 1996 including cases of chronic lymphatic leukaemia (CLL). Hairy cell leukaemia (HCL) is a rare subgroup of malignant lymphoma. About 25 new cases are diagnosed among males in Sweden yearly. The mean age at diagnosis is 55-60 years.To further evaluate the findings in a pilot-study conducted in Uppsala, where a large proportion of patients with HCL had worked in the areas of agriculture or gardening, a case-control study was initiated. The study included 121 male cases of HCL diagnosed between 1987 and 1992, and 484 controls matched for age, sex and county. The aim of the study was to investigate potential risk factors for HCL such as occupation, and different occupational exposures such as organic solvents, pesticides, exhausts and animals. Information was also obtained on previous medical history and medications.No significantly increased risk for HCL among farmers was found. An increased risk for HCL was seen for exposure to domestic animals and different subgroups of pesticides, as well as for exposure to organic solvents and exhausts. A decreased risk for hairy cell leukaemia was correlated with smoking. A previous history of certain diseases of the cardiovascular system was associated with a moderately reduced risk for HCL.Epstein-Barr virus (EBV) has been correlated with certain subtypes of malignant lymphomas. In a subgroup of the individuals in the study, levels of certain antibodies to EBV were analysed as risk factors for HCL. These levels were related to selfreported exposure to other potential risk factors. The results suggest the possibility of an interaction between EBV and self-reported occupational exposures.Organochlorines have been suggested as risk factors for NHL. Concentrations of 36 PCB-congeners, p,p' -ODE (a metabolite of DOT), hexachlorobenzene (HCB) and 4 congeners of chlordanes in blood were measured in a subgroup of included induviduals. These concentrations were analysed as risk factors for HCL, and were also related to the levels of certain antibodies to EBV. The possibility of an interaction between EBV and these exposures is suggested.
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| 120. |
- Nybom, Pia
(författare)
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On the Regulation of the Epithelial Paracellular Permeability
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The epithelia of for instance the small intestine(s) plays a crucial role in the vectorial transport of nutrients and other solutes from the lumen to underlying body fluids, i.e. blood and lymph. However, the epithelial cells are also important in the formation and maintenance of a barrier towards harmful food components and toxic bacterial products. The research presented in this thesis aimed at further understanding theregulation of the paracellular permeability barrier in epithelia, especially in relation to structural modifications of the epithelial actin cytoskeleton and to intracellular signals. In particular, the objectives of the study were to: i) assess the associationbetween tight junctional integrity and the cytoskeleton by using cytochalasin B and dihydrocytochalasin B as modifying agents, ii) examine the involvement of phospho-inositide turnover in modulation of the paracellular barrier and the organization of the actin cytoskeleton, iii) investigate the participation of protein kinase C in the regulation of tight junctional integrity, iv) elucidate changes in the tight junction function andstructure caused by enterotoxigenic Vibrio cholerae, and v) examine the role of nitric oxide in the formation and regulation of the permeability barrier. To summarize, cytochalasin B and dihydrocytochalasin B mediate specific and dose-dependent effects on the transepithelial electrical resistance of MDCK-I epithelial cells. Furthermore, these alterations correlate well with distinct changes in the organization of filamentous actin and the tight junction-associated protein, Z0-1. Moreover, the actin-associated modulation of the epithelial barrier function appears to be dependent on phosphoinositide (PI) turnover, as elucidated by the combined effects of the PI 3-k:inase inhibitor, wortmannin, and dihydrocytochalasin B. The activation of protein kinase C with phorbol ester causes distinct changes in the transepithelial resistance and tight junction structure of MDCK-I and HT-29 cells. In addition, tight junctional function and structure also seem to be modulated by nitric oxide. A "new toxin", the hemagglutinin/protease (HNprotease) of Vibrio cho!erae was identified in the growth medium of a toxin-attenuated strain. The HA/protease causes characteristic alterations of the epithelial structure and barrier function, which were reduced in the presence of nitric oxide.
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