| 71. |
- Holmgren-Peterson, Kajsa, 1964-
(författare)
-
Structure and dynamics of epithelial cells : Studied with confocal microscopy and flourescence recovery after photobleaching
- 1995
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Epithelial cells of the human body form a physical barrier to harmful agents and potential invading microorganisms. In the small intestine they must also produce enzymes for digestion of food and be able to absorb nutrients.The aim of this work was to study properties of epithelial cells in model systems using cell lines and toad bladder cells, and to study the effect of gluten intolerance (celiac disease, CD), viz. a pathological condition, on human small-intestine epithelial cells, enterocytes. Fluores-cence microscopy techniques, and primarily confocallaser scanning microscopy (CLSM), have beeen used as the major methods in the investigation. Part of the work has also been to develop, and apply, tools for measurements in confocal rnicroscopy images to obtain semi-quantitative information on structures.Fluorescence recovery after photobleaching (FRAP) was used to study the effect of maturation of small intestine-like epithelial cells. Lateral diffusion of membrane components was measured to reveal alterations in membrane fluidity induced by differentiation. No general effects on the lateral mobility of membrane components was observed, rather distinct effects were noticed on protein diffusion.Vasopressin induces the fusion of vesicles containing water channels with the apical membrane of toad bladder epithelial cells. This fusion is known to result in depolymerization of fllamentous actin (F-actin) of the cell. CLSM was used to assess where in the cell the depolymerization occurs. It was demonstrated that the depolymerization is not evenly distributed, but confined only to the apical region of the cells.In children suffering from celiac disease the mucosa of the small intestine is severely damaged. The damage at the enterocyte level is, however, less investigated. In the present work, CLSM was applied to compare the distributions ofF-actin and of glycoconjugates in enterocytes from children with CD to enterocytes from children not suffering from the disease. The results show that in children with active CD the distribution of both structures was altered, but also that compliance to a gluten-free diet results in the return to normal-looking enterocytes.
|
|
| 72. |
- Holmlund, Gunilla, 1951-
(författare)
-
The polymorphism of the minisatellite system D2S44
- 1999
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The polymorphism of the minisatellite system D2S44 comprises all the polymorphisms typical for a minisatellite sequence; from variation in fragment length caused by a restriction site polymorphism or due to variation in the number of a repeated core sequence, to a core sequence polymorphism comprising four variants and variation in the order in which these variants are iterated in tandem. All these polymorphisms can be utilised in paternity investigations, and analysis of the order of variant repeats in parent-child combinations showed that the D2S44 incompatibilities found are due to a mutation in the parental allele.The length polymorphism comprise fragments between 1.4 and 12 kbp, forming two size clusters. Different internal orders of the variant core sequences with a conserved motif at one end of the alleles can be used to group the alleles into three types. Alleles belonging to these types can be considered to be of separate ancestry and are named ancestor alleles of the red, green and yellow type. The red allele type is mainly found in one of the size clusters and the green-type in the other, while the yellow-type alleles are found in both clusters. The presence of different types of ancestor alleles might be the reason for the bimodal distribution.Analysis of 30 mutations showed that short alleles gain repeats and long ones lose repeats. The three allele types also have their ·own individual mutation patterns. Mutations in the red- and the green-type alleles are found at on end of the alleles, and in the yellow-type alleles along the whole array. In five mutations with gains of repeats the gains had most probably been generated by intra-allelic duplications. In the remaining gain mutations the origin of the repeats is not known. There is thus no clear evidence for inter-allelic exchange and mutations in the D2S44 system may mainly be caused by an exchange of sequences between sister-chromatides.VNTR polymorphism was also found in the chimpanzee but with a tandem iteration of a different non-variant core sequence, positioned upstream relative to the tandem array in man. The gorilla seems not to contain tandem repeats.The D2S44 minisatellite system, with a vast number of fragment lengths comprises astonishingly little sequence polymorphism with only a few core sequence variants and only three main allele types compared to other minisatellites. In essence it is a true VNTR marker.
|
|
| 73. |
- Hyllienmark, Lars
(författare)
-
Influence of metabolic disturbance on nervous function : clinical and experimental studies
- 1996
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present work consists of clinical and experimental studies and describes some effects of metabolic disturbance on nervous function. It is an electrophysiological examination of both single cells and patients exposed to metabolic insult or disease. The patch-clamp technique has been used for measurements of whole-cell currents in rat brain slices and studies of nerve conduction has been used as a clinical test on peripheral nervous function in young patients with insulin-dependent diabetes mellitus (IDDM).The objective of the clinical studies was to find out to what extent young IDDM patients with multiple insulin injection therapy (MIT) still develop peripheral nerve dysfunction and to elucidate the reason why.The objective of the experimental studies was to evaluate the effect of metabolic disturbance - induced chemically or by anoxia - on the membrane potential and the ionic conductances in hippocampal CA1 pyramidal cells.It is concluded that(1) despite MIT-treatment and good metabolic control nerve dysfunction is still common in an unselected group of children and adolescents with IDDM(2) the most important risk factors for nerve dysfunction in IDDM arc increased height and poor long-term metabolic control(3) metabolic inhibition at 22-24°C or anoxia at 33-34°C causes hyperpolarization and changes in the function of several types of K+ channels in CA1 pyramidal cells(4) a change in membrane potential by a few millivolts inhibited the spontaneous impulse firing(5) a transient opening of tolbutamide-sensitive K+ channels could explain the increase in grest and the hyperpolarization observed in most cells during metabolic inhibition(6) by this mechanism the excitablity decreases which may diminish the energy demand in cortical cells during different types of metabolic insult.
|
|
| 74. |
- Håkansson, Annika, 1962-
(författare)
-
Interferon-alpha based treatment of metastatic malignant melanoma : Effect of immune parameters of importance for monitoring immunotherapy
- 1998
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cutaneous malignant melanoma is a rapidly increasing disease. Most patients are cured by surgical excision of their primary tumour, but for patients with metastatic disease the prognosis is still very poor despite various attempts with chemotherapeutic agents, and during the last decade with immunotherapy, using several different biological agents alone or in combination. Thus, there is a great need for a better understanding of various functions of the immune system, tools for monitoring immunotherapy and predictive tests for choosing patients who are suitable for this therapy.The aims of the present investigation was therefore to study factors of possible importance for the immune control of tumours such as the occurrence and distribution of tumour-infiltrating mononuclear cells, expression ofTNFa, ICAM-1 and down-regulation of the function of tumour-infiltrating mononuclear cells. Using fine-needle aspiration of melanoma metastases we show a correlation between the occurrence of CD4+ lymphocytes in the metastases and the therapeutic benefit ofiFN-a. Thus, the degree of infiltration of these cells seems to be a useful predictive test for choosing patients suited to this therapy. We report that the expression of ICAM-1 on tumour cells is up-regulated after IFN-a treatment and describe a correlation between the expression of ICAM-1 by tumour cells and infiltration of CD4+ lymphocytes in the metastases. Thus, deternllning of ICAM:- 1 expression by tumour cells obtained by fine needle aspiration could perhaps be a valuable supplement to detennining the occurrence of tumour-infiltrating CD4+ lymphocytes tocorrelate with the response to IFN-a treatment.We demonstrate a low immune reactivity in melanoma metastases with a high expression of TNF-a by the tumour cells in untreated metastases and that IFN-a treatment could increase the immune reactivity. We also demonstrate that during the second week ofiFN-a treatment tumour-infiltrating CD4+ lymphocytes migrate from the stromal areas into the tumour nodules, close to the tumour cells, and that the extent of the tumour areas with regressive changes was significantly enhanced compared to untreated patients. Markers of the function of tumour infiltrating lymphocytes, the ~-chain and CD28, were found to be down-regulated, especially in areas of extensive tumour regression. Taken together our results are compatible with the view that the immunostimulating effect of IFNa, resulting in immune-mediated tumour cell destruction, occurs early during the treatment period and is followed within a few weeks by down-regulation of the anti-tumour immune response. Thus, in immunotherapy the possibility of inducing immunosuppression due to the lysis of tumour cells and the release of immunosuppressor factors should be considered and monitored.
|
|
| 75. |
- Højgaard, Inge
(författare)
-
Crystallisation of calcium phosphate and calcium oxalate in solutions simulating the composition at different levels of the nephron
- 1998
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Calcium oxalate (CaOx) is the most common constituent of urinary calcium stones, but in many such stones calcium phosphate (CaP) is also present and often located in the centre. From these observations it has been assumed that CaP is important in the process that leads to the development of a calcium stone and furthermore that the initial steps in this crystallisation take place in the nephron. The present investigation was undertaken to assess the risk of crystallisation of calcium salts at different nephron levels.Calculation of the ion-activity products of CaOx and different CaP salts Wlder solution conditions corresponding to those at various nephron levels, disclosed that the saturation with CaP was relatively higher than that of CaOx in the proximal tubule (PT), as well as in the proximal (DTp) and distal parts (DTd) of the distal tubule. Supersaturation concentrations necessary for the formation of CaOx crystals were recorded only in solutions with a composition corresponding to that in the collecting duct (CD).With an increased calcium concentration CaP was the crystal phase that most easily formed under solution conditions that corresponded to those at nephron levels above the CD. The relative risk of crystallisation of CaP was greatest in DTd~Urine. In CD-solutions CaOx was the preferred crystal type. Precipitation of CaOx in the lower part of CD and in final urine might be the result either of a primary nucleation of CaOx in the presence of a sufficiently high CaOx supersaturation or of a heterogeneous nucleation induced by CaP crystals formed at higher nephron levels.The nucleation of CaP and CaOx accomplished by reduction of volume of DTd- and CD- urine was apparently promoted by the urinary macromolecules in dialysed urine (dU). These macromolecules also inhibited the aggregation of CaP in solutions with a composition similar to that of urine in the distal tubule (DTd) and might counteract stone formation by inhibiting the growth and aggregation of both CaOx and CaP crystals during their passage through the CD. Furthermore, citrate had a direct inhibitory effect on the aggregation of CaP in DTd-solutions, an inhibitory effect that was additive to that of dU at concentrations of citrate above 0.5 mmol/L.The result~ obtained in these experimental studies support the hypothesis that CaP is the primary nucleus in mixed calcium stones. The process starts with the formation of CaP at a nephron level above the CD, possibly in DTd. A heterogeneous nucleation of CaOx is subsequently induced by dissolution of retained CaP crystals in the acid urine in the CD. The heterogeneous nucleation is probably accomplished by an increased local CaOx supersaturation that occurs at the CaP crystal surface as a result of this dissolution.
|
|
| 76. |
- Jacobsson, Per, 1948-
(författare)
-
Skeletal muscle metabolism in patients with severe chronic obstructive pulmonary disease : A study of carbohydrate and fat metabolism
- 1995
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In chronic obstructive pulmonary disease (COPD) deterioration of skeletal muscle metabolism is reported in both respiratory and non-respiratory muscles. This deterioration may contribute to both the development of respiratory failure and general disability often seen in severe COPD patients. The aim of this study was to obtain more information on carbohydrate and fat metabolism in advanced, stable COPD patients and to investigate the possible association between muscle glycogen and estimates of malnuttition. Furthermore, the effect of long-term oxygen therapy on the metabolic state was studied. Using the needle biopsy technique, muscle specimens were obtained from the quadriceps femoris muscle for analysis of muscle metabolites, glycolytic and oxidative enzyme activities and skeletal muscle fibre composition. Blood fuel metabolites were studied at rest, during exercise and recovery. Lipolysis was studied using a tracer technique and the response of lipolysis to insulin, as well as insulin resistance in peripheral tissues were studied using the euglycaernic, hyperinsulinaernic glucose clamp technique.Depletion of glycogen, A TP and creatine phosphate and increased concentrations of creatine and lactate were observed in the quadriceps femoris muscle. Metabolite concentrations correlated to anerial blood gas values- the lower the Pa02 and the higher the PaC02 the greater the deterioration of the metabolic state. Muscle glycogen concentration correlated to estimates of malnuttition. The correlation between glycogen concentration and prealbumin concentration was strong - the lower the glycogen concentration the lower the prealbumin concentration. After 8 months of long-term oxygen therapy (L TOT) the high energy phosphate state had improved. There was a verylow percentage "oxidative" Type I muscle fibres in the quadriceps femoris muscle. Analysis of enzyme activity also showed adaptation in the form of augmented glycolysis and decreased aerobic metabolism. No changes in enzyme activity were observed after 7 months of LTOT. The turnover rate of free fatty acids (FFA) and plasma FFA concentration were increased in the fasting state. There was a significant positive correlation between turnover rate ofFFA and FFA concentration in arterial plasma. The results also suggest a reduction in the inhibitory effect of inulin on lipolysis. A few hours after a light breakfast FFA, glycerol and 3-hydroxybutyrate concentrations were lower in COPD patients with chronic respiratory failure (CRF) that in COPD patients without CRF at rest, during exercise and recovery, indicating decreased lipolysis in the CRF patients compared to COPD patients without CRF. In patients with severe COPD and muscle glycogen depletion no resistance to insulin in peripheral tissues was observed.In conclusion, skeletal muscle depletion exists in patients with severe, stable COPD. Skeletal muscle glycogen concentration is associated with concentrations of serum proteins. Adaptation of muscle metabolism in the form of augmented glycolysis and reduced aerobic metabolism was observed. Lipolysis is increased in the fasting state and the results suggest a reduction in the inhibitory effect of insulin on lipolysis. No resistance to insulin in peripheral tissues was found. LTOT may improve the muscle energy state of hypoxaemic COPD patients.
|
|
| 77. |
- Jacobsson, Sven-Arne, 1953-
(författare)
-
Clinical and experimental studies on total hip arthroplasty
- 1995
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In a 12-year follow-up study, a low-friction, metal-on-plastic hip prosthetic system (Charnley) was compared with a high-friction, metal-on-metal prosthetic system (McKeeFarrar) in a consecutive series of 169 patients, mean age 67 at the start. Satisfactory results were reported in 92 percent of the patients. One-third of the prostheses showed radiographic signs of loosening. The cumulative aseptic failure rate was 8 percent for the Charnley prosthesis and 15 percent for the MKF prosthesis. The difference was not statistically significant.The performance of a flexible (Bute!) and a rigid (PCA) cementless femoral component was studied in a prospective, randomized study of 28 matched pairs of patients (mean age 52 years). A high rate of stem loosening was observed for the flexible prosthesis and 4 cases of fatigue breakage occurred within the 3- to 5-year follow-up period. Proximal resorption and distal hypertrophy of the femur were frequently noted on the radiographs for the rigid stem. The scintigraphic activity around stems well fixed to bone became normalized in the calcar region. In contrast, it was about 50 percent increased around the prosthetic tip. For loose prostheses, the bony uptake was more intense and did not show the same time-related decrease. The scintimetric results did not correlate well with the signs of bone remodeling seen on the radiographs. Repeated at different time intervals, bone scintimetry may be informative in the followup of noncemented THA.In a consecutive series of THAs, the straight ITI-I stem (n=65), made of titanium alloy, was compared at a 5-year review with the Lubinus femoral component (n=77), curved and made of cobalt-chrome alloy. The ITH stem showed a high frequency of surrounding radiolucent lines. Six of the stems were considered loose as compared with none of the Lubinus stems. To date, 5 have been revised and 2 more are in need of revision operations, all in the ITH group. Although the initial costs were somewhat reduced with the use of the cheaper ITH prosthesis, the estimated accumulated costs turned out to be higher in the ITH than in the Lubinus group due to the increased need for revisions.In a study of THA performed on patients 80 years and older, good pain relief was achieved but at the cost of increased postoperative complications and hospital expenses as compared with patients around 65 years of age at operation. Functional improvement was not as evident as pain alleviation. The procedure did not result in decreased use of welfare services in the elderly group of patients.An experimental study was performed on 10 rabbits. Hydroxyapatite coated titanium plugs were implanted in both femora of each animal. Five were treated for seven days with an NSAID (diclofenac) and five were used as controls, receiving no treatment. A significantly lower force was required to pull out the implants 3 weeks after surgery in the group treated with diclofenac than in the untreated group. The results indicate that even short-term treatment with NSAIDs might interfere with the process of bony ingrowth and thereby endanger primary fixation of the implant despite the presence of a hydroxyapatite coating.A new cementless prosthesis was designed in titanium alloy in order to integrate the principles ofpressfit and flexibility. In a special test set-up the endurance properties of the stem were determined. Prototypes of the prosthesis were subjected to load cycles of 4,000 N in one ·test and to a more physiologic load pattern in another test. In both tests the prostheses broke after approximately 600,000 cycles without showing any material defects. It was concluded that considerable difftculty exists in constructing an "isoelastic" stem with reasonable safety limits to fatigue failure when using titanium alloy.
|
|
| 78. |
- Jansson, Kjell, 1956-
(författare)
-
Treatment in Dilated Cardiomyopathy : with special emphasis on beta-adrenergic receptor blockade and angiotensin-converting enzyme inhibition
- 1999
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dilated cardiomyopathy (DCM) is a heart muscle disease of unknown origin, characterised by ventricular dilatation and impairment of systolic function. The basic treattnent is medical, according to different pharmacological principles. Evaluation of the severity of the disease and the effects of medication are important for optimal management.Fifty-four patients (42 male and 12 female) with DCM were randomized to receive treatment with either a beta-adrenergic receptor blocker (metoprolol) or an angiotensin-converting enzyme (ACE) inhibitor (captopril). Almost all patients had a history of congestive heart failure and were therefore treated with furosemide. Baseline characteristics and the effects of therapy were studied by invasive haemodynamics, echocardiography, neurohormonal function, heart rate variability and quality of life evaluation.There were favourable effects on left ventricular (LV) function with both drugs but metoprolol seemed to be superior to captopril in improving LV stroke volume and reducing LV filling pressure. There was a reduction in both systolic and diastolic dimensions and the non-invasive findings were in accordance with invasive results. Neurohormonal activation was less than expected and the levels of plasma renin activity and angiotensin II were within the normal range while the levels of atrial natriuretic peptide were increased. Urinary excretion of Aldosterone was reduced with both metoprolol and captopril therapy, but treatment with petoprolol reduced the level of ANP during exercise.Both drugs increased heart rate variability but petoprolol was superior to captopril in increasing totaol power and power in the low and very low frequency.Quality of life was assessed by a disease-specific questionnaire and wsa improved in the dimension "emotion" in both groups during treatment. In the captopril group there were also improvements in total score and in the dimension "physical activity". Improvements in quality of life dimensions, however, did not correlate to improvement in LV function.In conclusion both metoprolol and captopril were well tolerated. There were effects of beta-adrenergic receptor blockade on LV performance that were not obtained, at least not equally, during therapy with ACE inhibitor. Itreatment of patients with DCM should therefore include a beta-receptor blocker. Carefully performed, non-invasive methods can be used to evaluate the effects of therapy.
|
|
| 79. |
- Jendle, Johan H.
(författare)
-
Intrapulmonary insulin : Experimental and clinical studies
- 1996
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- After intrapulmonary insulin administration was first reported in 1925, the development of highly efficient nebulisers has once again made this area interesting. Therefore, the distribution and retention of aerosol produced by a new jet nebuliser was evaluated in an animal model. Anaesthetized and mechanically ventilated pigs were given radiolabelled aerosol, insulin or the combination of insulin and a surface active agent. After sacrifice the lungs were histologically examined or scintigrafted using a gamma camera. The distribution of aerosol was even and reached the peripheral parts of the lung parenchyma. The retention of insulin was estimated to be 36%. No morfological changes were observed. The biological effects of intrapulmonary insulin administration were evaluated in 14 pigs in a double-blind placebo controlled randomized intervention trial. Insulin at a dose of 10 and 40 U as well as 0.9% saline solution was given as aerosol. The blood glucose and serum insulin concentrations were assessed at certain intervals during 90 min. The mean blood glucose concentration fell from 4.6 ± 0.1 to 2.8 ± 0.2 mmol/L reaching a nadir 40 min after the start of nebulisation. Serum insulin rose from 5.2 ± 0.1 to 25 ± 9 mUlL. Eight healthy volunteers received insulin aerosol in three different doses (40, 80 and 160 U) in a double-blind randomized intervention study. As a control saline solution was given. Blood glucose, serum insulin and serum C-peptide were assessed during 120 min. A reduction of the mean bloodglucose concentration was seen, falling from 4.3 ± 0.2 to 2.8 ± 0.2 mmol/L after 160 U. Serum insulin rose from 9.5 ± 1.5 mUlL to 26.1 ± 2.5 mUlL. Serum C-peptide was suppressed in a dosedependent fashion. Twelve patients with NIDDM treated with anti-diabetic drugs were given intrapulmonary insulin in a double-blind randomized intervention trial. Insulin was given at a dose of 2.5 U/kg BW. As a control saline solution was given. Blood glucose, serum insulin and serum C-peptide were assessed during 180 min. Blood glucose fell from 10.2 ± 0.5 to 6.1 ± 0.5 mmol/L. Serum insulin rose from 11.2 ± 1.8 to 28.0 ± 2.6 mUlL. Likewise serum C-peptide was suppressed after inhaling the insulin aerosol. A flow cytometric assay was developed to assess the changes of the F-actin content and DNA synthesis in adherent cells after short-time and long-term stimulation with insulin and PDGF. No stimulatory effect on the DNA synthesis was seen on lung fibroblasts after repetitive insulin treatment. Thus, intrapulmonary insulin administration has been evaluated in experimental and clinical studies. Significant lowering of the blood glucose concentrations and clinically relevant serum insulin concentrations were achieved. No subjective adverse effects were reported. No changes in lung function could be observed experimentally.
|
|
| 80. |
- Jenmalm, Maria C., 1971-
(författare)
-
Development of IgG subclass antibodies to allergens in early childhood
- 1999
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Immune responses to allergens in young children include both Thl and Th2 like immunity, which may regulate the secretion of IgG subclass antibodies differently. The time, route and level of exposure to an allergen, as well as maternally transferred immunity, may be decisive whether sensitisation or tolerance will ensue. To study this, we established sensitive methods and investigated the development of IgG subclass antibodies to food and inhalant allergens during childhood.Material and Methods: The study group comprised a cohort of 96 children participating in a prospective study. IgG subclass antibodies to ß-lactoglobulin, ovalbumin, Bet v 1 and cat dander were analysed at birth, 6 and 18 months and 8 years by ELISA. At 8 years of age, PBMC from 55 of the children were stimulated with birch and ß-lactoglobulin. Production of IL-5, IL-6, IL-10, IL-13 and IFN-y was analysed by ELISA and expression of IL-4 and IL-9 mRNA by semiquantitative RTPCR.Results: High cord blood levels of IgG antibodies to inhalant, but not to food, allergens were associated with less development of atopy in the children during the first eight years of life. IgG subclass antibody responses to allergens were commonly detected during childhood and were largely restricted to the IgG1 subclass. The production of this opsonising and complement activating subclass was associated with Thllike immunity at 8 years of age. IgG subclass antibodies to food allergens peaked in infancy, whereas antibodies to the inhalant perennial allergen cat, but not the inhalant seasonal allergen birch, increased with age. Exposure to cow's milk during the first three months of life was associated with high IgG subclass antibodies to ß-lactoglobulin up to eight years. Exposure to cat and birch tended to be associated with high antibody levels to those allergens, whereas antibody levels to ovalbumin were not related to the introduction of egg in the diet. Atopic symptoms and the presence of positive skin prick tests and circulating IgE antibodies to allergens were associated with high levels of IgG subclass, especially Th2 associated IgG4, antibody responses to allergens. For the food allergens, the differences were mostly marked early in life. Birch induced IL-4 expression may be the major factor determining IgE antibody formation to that allergen, while allergen induced IL-5, IL-6 and IL-10 secretion in PBMC was associated with atopic symptoms.Conclusions: Maternally derived antibodies may modulate immune responses. The tolerance-inducing mechanisms in the intestinal mucosa may be less effective during the first months of life. Responses to food and inhalant allergens show different kinetics. Thl like associated IgG1 antibodies to allergens are commonly observed in both atopic and non-atopic children, whereas Th2 like associated IgG4 responses are more atopy dependent.
|
|
