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C Jaeger

Publications and source records attributed to C Jaeger.

At least 37 records · Page 2Linked to original sources
PubMed1998

Myogenic changes of the levator ani muscle in premenopausal women: the impact of vaginal delivery and age.

The aim of this study was to evaluate the impact of parity and age on histomorphology of the pelvic floor muscles in female cadavers of reproductive age and to find out whether there is evidence of myogenic or neurogenic muscle injury. In a cross-sectional study 45 premenopausal unfixed and fresh female cadavers were studied. Four groups were defined: nulliparous and parous women under the age of 40 and over 40 years of age. The pelvic floor was biopsied at six standardized locations. For evaluation of the quantitative parameters and fiber type identification, actomyosin ATPase at pH 9.4 was used. For histomorphological evaluation, sections were stained with hematoxylin/eosin, van Gieson, and Gomori trichrome. The circumference of type I fibers is significantly larger in nulliparous women younger than 40 years compared to nulliparae older than 40 years. Comparing these groups, the form factor of type II fibers also increases significantly, presenting a more circular cell form. Compared to nulliparae, vaginal delivery led to a significant difference regarding the presence of centrally located nuclei, fibrosis, and variation in fiber diameter. In nulliparous women, these significant changes were also found with increasing age. In women with a history of vaginal delivery, no further increase in these characteristics could be detected with increasing age. Comparing the three different biopsy sites, all three changes were more pronounced in the ventral part. There was no evidence of grouped fiber atrophy, small angulated fibers, or type grouping in any of the biopsy specimens. Aging and vaginal childbirth lead to histomorphological changes of the pelvic floor muscle that are consistent with changes of myogenic origin. Evidence of neurogenic damage could not be demonstrated.

Adolescent↗
PubMed1997

Persistent GAD 65 antibodies in longstanding IDDM are not associated with residual beta-cell function, neuropathy or HLA-DR status.

Persistent humoral autoimmunity to the enzyme glutamic acid decarboxylase (GAD) has been described in a substantial proportion of patients with insulin-dependent diabetes mellitus (IDDM) of long duration. The source of the stimulus for this autoimmune reactivity is still unknown. Because the GAD 65 isoform is mainly expressed in pancreatic beta-cells and in the nervous system we investigated in the present study of the largest number of well characterized patients with longstanding IDDM (n = 105; median duration: 21 years; range: 10-46 years) the presence of autoantibodies to GAD 65 and their relationship to a residual C-peptide response or peripheral and autonomic neuropathy. Additionally we studied the HLA-DR status relative to GAD 65 antibodies in 86 out of the 105 individuals. One hundred healthy control subjects and 100 recent onset IDDM patients were also studied for GAD 65 antibodies. GAD 65 antibodies were detected in a radioligand-binding-assay with recombinant human GAD 65 and were present in 32% of the long-term diabetic patients, 82% of the recent onset IDDM patients and in 3% of the healthy control subjects. A preserved C-peptide response to i.v. glucagon (Hendriksen criteria) was observed in 23% of the long-term IDDM patients. Autonomic neuropathy and peripheral neuropathy was identified using criteria based on both symptoms and formal testing giving a frequency of 67% vs 79%. The HLA specific DR 4/X was observed in 47% and HLA-DR 3/X in 22% of the long-term IDDM patients. Patients who were heterozygous for DR3/DR4 were found in 23% of the cases. GAD 65 antibodies were significantly less frequent in the long-term IDDM patients compared to recent onset IDDM (p < 0.001), and diabetes duration showed a significant negative correlation with GAD 65 antibody index levels (r = 0.22, p < 0.01). Interestingly, GAD 65 antibodies were not significantly correlated either with residual beta-cell function or neuropathy and no particular HLA-DR status was associated with persistent GAD 65 antibodies. In conclusion neither residual beta-cell function nor diabetic neuropathy or a certain HLA-DR specificity are exclusively associated with persistent autoimmunity directed to GAD 65 in longstanding IDDM. The stimulus for the persistent humoral immune response and its significance for the disease process and its complications remain to be established.

Adolescent↗
PubMed1997

Progressive islet graft failure occurs significantly earlier in autoantibody-positive than in autoantibody-negative IDDM recipients of intrahepatic islet allografts.

Alloimmunity has been uncovered to be a cause of graft loss representing a major barrier for clinical islet transplantation, and several studies are designed to evaluate new strategies for immunosuppression to prevent alloimmunity. In contrast, the significance for autoimmune destruction of transplanted beta-cells has remained somewhat controversial. Recently, two case reports based on histological findings have suggested recurrent autoimmune insulitis despite immunosuppressive therapy both in clinical pancreas and in islet transplantation. In the present study, in 23 islet-grafted patients with IDDM receiving standard immunosuppressive therapy, we demonstrate that progressive impairment of islet graft function occurs significantly earlier in those individuals positive for autoantibodies as a typical stigma of diabetes-associated autoimmunity that is well established in the prediabetic periods of IDDM. Intraportal infusion of allogeneic islets was performed in 23 C-peptide-negative IDDM patients, according to the clinical transplantation categories defined as islet after kidney (IAK) or simultaneous islet and kidney (SIK). Complete islet graft failure was defined as the 1st day of permanent C-peptide negativity in the serum (<0.2 ng/ml) and C-peptide negativity in the urine (<2 microg/dl). The median observation period following islet transplantation was 12 months (range 1-50) with a cumulative follow-up of 336 months. Islet cell antibodies (ICAs) and GAD65 antibodies were monitored before and regularly after islet transplantation. Kaplan-Meier survival analysis and log-rank statistics revealed a significant (P < 0.05) difference in cumulative islet graft survival depending on the presence of islet cell and/or GAD65 antibodies. These results strongly suggest that recurrent autoimmunity directed to transplanted beta-cells contributes to islet graft failure despite sustained immunosuppression. For successful clinical islet transplantation in the future, new immunosuppressive therapies are needed to prevent both alloimmunity and autoimmunity.

Adult↗
PubMed1996

Islet cell antibodies and glutamic acid decarboxylase antibodies in patients with insulin-dependent diabetes mellitus undergoing kidney and islet-after-kidney transplantation.

The humoral immune response to islet autoantigens, here defined by the presence of islet cell antibodies (ICA) and glutamic acid decarboxylase (GAD 65) antibodies, was studied in patients with long-term insulin-dependent diabetes mellitus (IDDM) receiving immunosuppressive therapy following kidney and islet-after-kidney transplantation. In a cross-sectional study of 30 kidney-grafted, long-term IDDM patients and 30 matched, nontransplanted IDDM controls, we observed a significant (P<0.05) decrease in ICA positivity by standard immunosuppressive therapy, but not in frequency or index levels of GAD 65 antibodies. Because of this intriguing finding, we investigated, in a pilot study on seven islet-after-kidney transplant recipients, the time course of frequency and levels of ICAs and GAD 65 antibodies relative to islet graft function. Stable islet graft function was seen in the patients with low GAD 65 antibody index levels, whereas rapid islet graft failure occurred in a patient with high GAD 65 antibody index levels prior to transplantation. In addition, GAD 65 autoimmunity reoccurred in one pretransplant antibody-negative patient 2 months after graft failure was noted. In conclusion, these observations suggest that beta-cell autoimmunity directed to GAD 65 can persist despite immunosuppressive therapy and may adversely affect islet graft function, possibly indicating disease recurrence as a major threat to successful clinical islet transplantation.

Adult↗
PubMed1996

GAD 65 antibody but not ICA positivity in adult-onset diabetic patients is associated with early progression to clinical insulin dependency.

Correct classification of diabetic patients in adulthood at the time of diagnosis is often difficult. Some may be initially diagnosed as having non-insulin-dependent diabetes mellitus and be treated with diet and/or oral hypoglycaemic agents (OHA) but later require insulin treatment. Islet cell antibodies and antibodies to GAD 65 have been associated with the development of insulin deficiency in this group of patients. In the present study, 150 patients with the initial diagnosis of type 2 diabetes mellitus in adulthood (30-60 years) were seen regularly over a period of 5 years in our diabetes outpatient clinic. Though treatment was started with diet or diet plus OHA, insulin therapy had to be introduced in a subset of patients. In all cases, serum obtained at the time of the initial diagnosis was analysed for islet cell antibodies and GAD 65 antibodies, as well as for thyroid and adrenal autoantibodies as possible markers for polyendocrine involvement. Islet cell antibody status, body mass index and the presence of thyroid and adrenal autoantibodies showed no significant correlation to subsequent insulin requirement (< 2 years after diagnosis). In contrast, GAD 65 antibodies were significantly associated with the occurrence of clinical insulin dependency less than 2 years after the initial diagnosis (P < 0.01), thus identifying a substantial proportion of patients requiring insulin therapy within the first 2 years after the diagnosis of type 2 diabetes. Determination of GAD 65 antibodies in patients with late-onset diabetes may contribute to their correct classification and adequate treatment.

Adult↗
PubMed1996

Plasminogen activation in bullous pemphigoid immunohistology reveals urokinase type plasminogen activator, its receptor and plasminogen activator inhibitor type-2 in lesional epidermis.

Keratinocytes synthesize urokinase-type plasminogen activator (uPA) and a specific cell surface receptor for uPA (uPA-R, CD 87). Plasminogen is present in plasma and interstitial fluids from where it is bound to cell surfaces via plasmin(ogen) binding sites. uPA binds to the uPA-R in an autocrine manner and activates cell-bound plasminogen: a mechanism, which provides plasmin for pericellular proteolysis. Cell-bound uPA is regulated by plasminogen activator inhibitor type-1 (PAI-1) or type-2 (PAI-2). Bullous pemphigoid is an autoimmune inflammatory skin disease characterized by subepidermal blisters. Although circumstantial evidence suggested plasminogen activation in lesional epidermis of bullous pemphigoid, immunohistological data on the type of plasminogen activators, on the uPA-receptor or the type of plasminogen activator inhibitors in the lesions of bullous pemphigoid are lacking so far. To obtain this information we have performed the present immunohistological study. The presence of uPA and its receptor as well as PAI-2 was disclosed in epidermal keratinocytes in the roof of the subepidermal blisters. Moreover, keratinocytes at the bottom of the blister, which most likely represent keratinocytes during reepithelialization were stained. Co-localization was found for uPA and its receptor, uPA and plasmin(ogen) as well as for uPA and PAI-2. In non-lesional epidermis of bullous pemphigoid only PAI-2 was found. We propose that the expression of uPA and uPA-R, as well as the upregulation of PAI-2 in keratinocytes of lesional epidermis is part of the repair and reepithelialization process following lesion formation, i.e. epidermo-dermal dyshesion, in bullous pemphigoid.

Aged↗
PubMed1995

Pancreatic islet xenografts at two different transplantation sites (renal subcapsular versus intraportal): comparison of graft survival and morphology.

Our primary objective in this study was to determine the effect of two different transplantation sites (renal capsule vs. portal vein) on islet xenograft survival and graft morphology. 59 chemically induced diabetic C57BL/6J mice were transplanted either intraportally (n = 30) or under the left renal capsule (n = 29) receiving 300-350 either freshly isolated or culture pretreated (37 degrees C or 22 degrees C) Lewis rat islets without any immunosuppressive therapy. Histology was performed by immunohistochemical staining to examine the morphologic pattern after rejection or after post-transplant normoglycemia for more than 120 days. Life table analysis revealed a significant (p < 0.001) prolongation of xenograft survival using the renal capsule as transplantation site. 75% graft rejection occurred 56 days after transplantation when the renal capsule was used, compared to 19.5 days intraportal. The intriguing finding was that graft morphology was different depending on the transplantation site. After transplantation under the renal capsule we observed predominantly a more periinsular infiltration with focal aggregates of mononuclear cells at the periphery of the graft. This pattern was more consistent with a non-destructive type of insulitis. In contrast, we found direct infiltration of the transplanted islets following intraportal transplantation reflecting a more destructive type of insulitis. In summary, we could demonstrate a significant prolongation of islet xenograft survival by using the renal capsule as transplantation site in contrast to intraportal transplantation. The morphological pattern possibly indicates two different mechanisms of rejection depending on the transplantation site.

Animals↗
PubMed1994

Effect of transplantation site and culture pretreatment on islet xenograft survival (rat to mouse) in experimental diabetes without immunosuppression of the host.

Recently, we reported on indefinite islet graft survival in allotransplantation (rat to rat). This was achievable without the use of any immunosuppression by performing transplantation of culture-pretreated (22 degrees C) islets of Langerhans under the renal capsule (r.c.) of chemically induced diabetic recipients. The aim of this study was to test this successful islet modulation technique in a xenogeneic animal model. Six groups of chemically induced diabetic, inbred, C57BL/6J mice received by transplantation either into the liver via the portal vein (i.po.) or under the renal capsule (r.c.) 300-350 either freshly or culture-pretreated (37 degrees C and 22 degrees C) Lewis rat islets without any immunosuppressive therapy. Histology was performed after rejection or post-transplant normoglycaemia (> 120 days) for evaluation of the graft. Transplantation of freshly isolated islets resulted in 75% graft rejection 17 days after transplantation. Using culture pretreatment at 37 degrees C, we noted 75% graft rejection 31 days after transplantation. In contrast, culture pretreatment at 22 degrees C resulted in a marked prolongation of xenograft survival, 75% graft rejection occurring 58 days after transplantation, and in two cases there was indefinite graft survival (> 120 days). Statistical analysis showed a significant prolongation of xenograft survival after culture pretreatment, with the most beneficial effect appearing after low-temperature culture at 22 degrees C (P < 0.05). Interestingly, xenograft survival was markedly prolonged only using the r.c. approach. Statistical comparison revealed a highly significant prolongation using the r.c. as transplantation site compared with i.po. (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Pronounced differences in the frequency of TaqI beta A-inhibin alleles between sheep breeds with different reproductive performance.

A total of 419 individuals of four breeds with differing fecundity (Rhoenschaf, Merinolandschaf, East Friesian Milksheep, Romanov) and several wild sheep of the Ovis musimon, O. orientalis, O. vignei and O. ammon groups were screened for genetic variation at the beta A-inhibin (INHBA) locus with up to 11 enzymes. The four breeds differed significantly (P < 0.001) in TaqI allele frequencies. The frequency of the TaqI A allele coincided with the average litter size in each breed.

Alleles↗
PubMed1991

Organizational debate.

Explore the source record for details and available documents.

American Nurses' Association↗
PubMed1989

Organotypic slice cultures of dopaminergic neurons of substantia nigra.

Morphological methods were used to study the plasticity of target-deprived mammalian dopaminergic (DA) neurons. Slices of substantia nigra (SN) were taken from the midbrain of rats aged one to twelve days, and cultured for one to two weeks. Localization of tyrosine hydroxylase (TH) was used to examine the distribution and shapes of DA neurons. Histochemical staining for acetylcholinesterase (AChE) was carried out to estimate both survival and biosynthesis of SN neurons. We found that some DA neurons can survive in vitro without their usual target neurons. This was demonstrated by injecting rhodamine-conjugated microspheres (RD) into the caudate putamen, a SN target area, at 6 to 8 days prior to culturing. RD-labeled cells survived in SN cultures and some of them were doubly labeled with AChE. TH neurons had different shapes and their axon terminals formed close contacts with adjacent nondopaminergic neurons. These findings suggest that a subset of DA neurons may switch targets, but the majority of them require target interactions with the caudate putamen for survival in vitro.

Acetylcholinesterase↗