Frequency and Functional Characterization of Specific T-Helper Cells Infiltrating Rat Kidney Allografts during Acute Rejection

T-helper cells (ThC) play an important role in the induction of both cytotoxic T-cell responses and B-cell responses against the grafted organ. Furthermore, ThC alone are capable of causing graft rejection in T cell-deprived mice and rats. In view of these observations we found it important to analyse the frequency and functions of donor-specific ThC in the allograft and in the recipient lymphoid system during the course of acute renal allograft rejection. A limiting dilution assay was developed which, due to the absence of exogenous interleukin 2 (IL-2) and the low numbers of stimulator cells used, appears to be highly selective for the proliferation of specific ThC. Kidney transplants were performed from LBN (RT1n) to congenic Lewis (RT1l) strain differing in major histocompatibility complex (MHC) only. The inflammatory (white) cells were recovered from the graft, and blood and recipient spleen and the frequency of RT1n-responding ThC were determined at different times after transplantation. In the kidney graft itself, the frequency of ThC responding to RT1n MHC antigens was 1:3000 on day 2 and increased to 1:670-1320 at the peak of inflammation. In the spleen, the frequency increased from 1:1000 on day 0 to 1:200 on day 8, and remained high even after the graft was rejected. In the blood, the frequency stayed at the 1:400-1:800 level, and increased to 1:200 only after the graft had been completely destroyed. Individual ThC clones deriving from limited dilution assays of kidney and spleen cells were recovered and expanded with irradiated donor cells without IL-2 and finally with exogenous IL-2 only. All clones showed the T-helper (W3/25) phenotype, seven out of eight tested clones showed a specific anamnestic response to RT1n alloantigens and no response to RT1l or RT1a in a secondary MLC, 12 out of 12 clones produced IL-2 and 11 out of 11 clones produced gamma interferon upon re-stimulation with relevant allogeneic cells, and eight out of ten clones collaborated with syngeneic B cells for Ig synthesis, indicating that they were indeed derived from specific ThC and/or from their precursors. Taken together, the results demonstrate that specific ThC and/or their precursors represent only a very small minority in the graft-infiltrating inflammatory population. This makes it most unlikely that the ThC themselves are responsible for graft destruction; the results indicate rather that a major role of ThC in situ may be instruction of immunologically specific and nonspecific components of inflammation.     

Defective Calcium-Dependent Signal Transduction in T Lymphocytes of Ataxia-Telangiectasia

T-cell functions of two patients with ataxia-telangiectasia were investigated. Patients with ataxia-telangiectasia had reduced percentages of circulating CD3⁺ cells and CD4⁺ cells, although neither patient had a reduced percentage of circulating CD8⁺ cells. The proliferative responses and interleukin-2 production of peripheral blood mononuclear cells to T-cell mitogens were reduced in the patients. The intracellular calcium concentration in T cells or CD4⁺ cells from both patients was only slightly increased after phytohaemagglutinin stimulation. Moreover, the concentration after OKT3 stimulation was not or only slightly increased in T cells or CD4⁺ cells from both patients. Our results suggest that the functional defect of T cells is caused by defective Ca²⁺-dependent signal transduction through the CD3 complex of the surface in T cells of ataxia-telangiectasia.     

Real-Time Arrhythmia Identification from Automated Analysis of Intraatrial and Intraventricular Electrograms

Implantable cardioverter defibrillators have dramatically improved survival rates for patients at risk of sudden cardiac death, but the occurrence of inappropriate shocks remains an unresolved problem. Various means for better tachycardia detection, chiefly morphological analysis, have been proposed to address this problem. A new computerized scheme entitled Two-Channel Rate-Morphology (2CRM) was introduced. It is a real-time arrhythmia detection algorithm that combines timing and morphology information from intraatrial and intraventricular electrograms for arrhythmia diagnosis. The program 2CRM applies an initial cycle-by-cycle coding scheme followed by contextual diagnosis of underlying rhythm. The program was tested on 36 distinct passages of two-channel intracardiac signals from 30 patients. The distribution of the arrhythmias are as follows: 4 atrial fibrillation, 6 atrial flutter, 6 supraventricular tachycardia, 10 ventricular tachycardia, and 10 ventricular flutter-fibrillation. Of the analyzed 3,417 individual cardiac cycles 3,135 (91.7%) were correctly identified. Contextual diagnosis reversed 123 single-cycle errors to obtain a performance of 3,258 correct out of 3,417 (95.3%). Utilizing an uninterrupted continuous correct contextual diagnosis as indicator of successful arrhythmia detection, 2CRM obtained an accuracy of 34 out of 36 passages (94.4%).     

Analysis of the Action of Corticosteroid Treatment in Immunologic Infertility: A Preliminary Report and an Alternative Hypothesis

ABSTRACT: The presence of sperm antibodies can be demonstrated in 8–10% of the male partners of infertile couples. The therapeutic schedule with which the highest pregnancy rate has been obtained in these cases is that proposed by Shulman, which uses methylprednisolone (MP). If treatment with corticosteroids (CS) is effective, the way in which it acts is not entirely clear. In this study we report the results of 16 treatment cycles with CS administered to eight male patients having sperm antibodies in their serum, in which several parameters of humoral immunity were evaluated. The results are conflicting: several parameters (such as IgG concentration) underwent only slight variations after 7 days of therapy, whereas in 12 cycles out of 16, the Tray agglutination test (TAT) indicated that a reduction or disappearance of the antibodies had been obtained. This confirms the usefulness of CS in immunological infertility, and allows us to hypothesize that the beneficial effect may be found in a reduction of inflammation rather than in a suppression of the immunological response, since CS are well known to have these two kinds of effect.     

VLA protein expression on epidermal cells (keratinocytes, Langerhans cells, melanocytes): a light and electron microscopic immunohistochemical study

The very late antigens, or VLA proteins, are a family of cell surface heterodimers (alpha 1-b beta 1) that mediate cell adhesion to specific components of the extracellular matrix (collagens, fibronectin, laminin). In normal human epidermis, the common VLA beta 1 subunit is expressed on basal keratinocytes (BK). Langerhans cells (LC) and melanocytes. By means of light and electron microscopic immunostaining procedures, we have investigated the distribution of VLA alpha 1,2,3,4,6 subunits on normal human adult and foetal epidermal cells. alpha 1 antigen expression was not observed on any epidermal cell type. Both during foetal development and in adult epidermis, alpha 2 and alpha 3 were strongly expressed on the cell membrane BK, while alpha 6 was mainly expressed at their dermal pole. These different patterns of distribution suggest that the alpha 6 subunit may mediate BK anchorage to the basement membrane zone, while the alpha 2 and alpha 3 subunits may also be involved in intracellular adhesion. Moreover, with immunoelectron microscopy, LC were seen to be weakly alpha 5 and alpha 6 positive and melanocytes were alpha 3 and alpha 6 positive. Thus, VLA proteins are expressed by epidermal cells in a cell-type-specific pattern that could be related to particular functional roles of these proteins.     

CLINICAL AND HISTOPATHOLOGIC SPECTRUM OF PILOMATRICOMAS IN ADULTS

Background. Pilomatricomas are benign cutaneous neoplasms with differentiation toward hair matrix. Although previously reported to occur mostly in children and young adults, Taaffe et al. recently observed a second onset peak in adults and the elderly. Methods. To study the clinical and histopathologic features of pilomatricomas in adults we analyzed files and histologic sections of all cases of pilomatricomas seen at the Department of Dermatology, University of Graz, Graz, Austria, between January 1980 and December 1990. Results. A total of 118 patients were identified, 58 of whom were >45 years of age. The clinical features of patients >45 years of age were generally similar to those of patients <45 years of age. Differential diagnoses in both groups were also comparable except in some cases of the older study-group where differential diagnoses included basal cell carcinoma, keratoacanthoma, and metastasis. Recurrence of the lesions after simple excision was observed in one patient >45 years of age. Histopathologically, lesions in both age groups showed similar features except in four lesions of the older patients where “atypical” features were present. The histopathologic differential diagnosis of the lesions with “atypical” features included pilomatrical carcinoma, basal cell carcinoma with matrical differentiation, and matricoma. Conclusions. Our study reveals the relatively frequent occurrence of pilomatricomas in adults and the elderly. Pilomatricoma should be considered along with other benign and malignant conditions in the clinical differential diagnosis of solitary, firm skin nodules presenting in adults and the elderly, especially on the head and neck.     

NAD-and NADP-dependent 11β-hydroxysteroid dehydrogenase isoforms in guinea pig kidney with gossypol inhibition

探讨棉酚诱发低钾血症机制．方法：从豚鼠肾脏皮质制备１１βＯＨＳＤ，反相高效液相测定该酶活性．结果：依赖辅酶Ｉ的１１βＯＨＳＤ的Ｖｍａｘ＝０６４ｍｍｏｌ·ｈ－１／ｇｐｒｏｔｅｉｎ，Ｋｍ＝００７μｍｏｌ；依赖辅酶ＩＩ的１１βＯＨＳＤ的Ｖｍａｘ＝１７５ｍｍｏｌ·ｈ－１／ｇｐｒｏｔｅｉｎ，Ｋｍ＝０２１μｍｏｌ．棉酚对它们的抑制有显著差异，ＩＣ５０（９５％可信限）前者为５０２（４８３－５２０）μｍｏｌ，后者为１１４３（１０９８－１１８８）μｍｏｌ，抑制常数Ｋｉ分别为９６ｍｍｏｌ·Ｌ－１和３４０ｍｍｏｌ·Ｌ－１．结论：抑制依赖辅酶Ｉ的１１βＯＨＳＤ是棉酚诱发低钾血症的更主要的生理因素．