Identification of mimicry peptides based on sequential motifs of epitopes derived from 65-kDa glutamic acid decarboxylase.

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease with a predominantly non-hereditary etiology that results in a destruction of pancreatic beta cells by autoaggressive T lymphocytes. Neither the mechanism of initial stimulation of these T cells nor the nature of the environmental factors implicated in the disease have so far been identified. However, both issues are taken into account by the hypothesis of initial T cell activation by viral or bacterial mimicry peptides with sequence similarities to pancreatic self antigens.

Carcinoid tumor of the middle ear in a 28-year-old patient.

Carcinoid tumor of the middle ear is an extremely rare condition. The origin of the tumor cells is still speculative and the closeness of relationship to adenomas of the middle ear has been a matter of discussion since the first description of this tumor entity in 1980. In this study we report a case of a 28-year-old male patient with a carcinoid tumor of the middle ear.

Somatostatin receptor scintigraphy in small-cell lung cancer: results of a multicenter study.

Unlabelled: The aims of this study were to determine the accuracy of somatostatin receptor scintigraphy in the detection of the primary tumor and its metastases in small-cell lung cancer (SCLC) in a large patient population, and to investigate the course of somatostatin uptake in primary tumors during therapy.

Methods: In a total of 100 patients, 134 examinations were performed. Twenty-seven of the patients were examined before and after chemotherapy.

Structural changes are associated with soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor complex formation.

SNAP-25, syntaxin, and synaptobrevin play a key role in the regulated exocytosis of synaptic vesicles, but their mechanism of action is not understood. In vitro, the proteins spontaneously assemble into a ternary complex that can be dissociated by the ATPase N-ethylmaleimide-sensitive fusion protein and the cofactors alpha-, beta-, and gamma-SNAP. Since the structural changes associated with these reactions probably form the basis of membrane fusion, we have embarked on biophysical studies aimed at elucidating such changes in vitro using recombinant proteins.

Podocytes are the major source of IL-1 alpha and IL-1 beta in human glomerulonephritides.

To address the question of in situ production of IL-1 alpha and IL-1 beta in proliferative and non-proliferative forms of human glomerulonephritis (GN), we performed immunocytochemical and in situ hybridization studies on renal biopsies from patients with mesangial IgA-GN (N = 38), idiopathic membranous GN (MGN; N = 12), minimal change disease (MCD; N = 9), focal segmental glomerulosclerosis (FSGS; N = 5) and acute endocapillary GN (AGN; N = 3). Normal kidneys (N = 10) served as controls. Concomitantly, the expression of IL-1 receptor type I (IL-1 RI), IL-1 receptor type II (IL-1 RII) and of IL-1 receptor antagonist (IL-1 RA) was analyzed.

High affinity presentation of an autoantigenic peptide in type I diabetes by an HLA class II protein encoded in a haplotype protecting from disease.

Polymorphism of the genes coding for the human histocompatibility leukocyte antigen class II DR and DQ molecules makes the single largest genetic contribution to the risk of developing insulin-dependent diabetes mellitus (IDDM) and can be associated with highly elevated as well as decreased disease frequency. The mechanism of IDDM risk modification by HLA polymorphism is likely to involve differential presentation of autoantigenic peptides by HLA class II proteins. We have generated T cell lines (TCL) with specificity for the IDDM autoantigen 65 kDa glutamic acid decarboxylase (GAD65) from lymphocytes of two patients carrying HLA class II alleles associated with distinct risk of IDDM (DRB1*0101/0401 and 1302/1501).

Assembly and disassembly of a ternary complex of synaptobrevin, syntaxin, and SNAP-25 in the membrane of synaptic vesicles.

The synaptic membrane proteins synaptobrevin, syntaxin, and SNAP-25 form a ternary complex that can be disassembled by the ATPase N-ethylmaleimide-sensitive factor (NSF) in the presence of soluble cofactors (SNAP proteins). These steps are thought to represent molecular events involved in docking and subsequent exocytosis of synaptic vesicles. Using two independent and complementary approaches, we now report that such ternary complexes form in the membrane of highly purified and monodisperse synaptic vesicles in the absence of the plasma membrane.

Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double-blind study.

One hundred twenty-six patients with cirrhosis, hyperammonemia (>50 micromol/L), and chronic (persistent) hepatic encephalopathy (HE), which developed spontaneously without the existence of known precipitating factors, were enrolled in a randomized, double-blind, placebo-controlled clinical trial of intravenously administered L-ornithine-L-aspartate (OA). Patients with subclinical (grade 0, West-Haven criteria) hepatic encephalopathy (SHE), characterized by a prolonged number connection test A (NCT-A) time, and manifest HE (grades I and II, West-Haven criteria) were included in the investigation. The trial was planned as a confirmatory clinical trial OA administered in a dose of 20 g/d, as well as placebo, were dissolved in 250 mL of 5% fructose and infused intravenously for a period of 4 hours during 7 consecutive days with a superimposed protein load at the end of the daily treatment period.

Identification of naturally processed T cell epitopes from glutamic acid decarboxylase presented in the context of HLA-DR alleles by T lymphocytes of recent onset IDDM patients.

Glutamic acid decarboxylase (GAD) has been defined as a major target antigen in insulin-dependent diabetes mellitus (IDDM). To identify the molecular ligands triggering a T cell response to GAD, a panel of human GAD65-specific T lymphocyte lines was generated from peripheral blood of three recent onset IDDM patients. All lines derived from a patient expressing the high-risk-conferring HLA-DR*0301/ *0401 haplotypes recognized a single epitope localized between amino acid positions 270 and 283 of GAD65, a stretch that is located in close proximity to the homology region shared with Coxsackie virus P2-C protein.

Transferral of extrathoracic donor neoplasm by the cardiac allograft.

The transference of neoplasm from the donor to the recipient is a rare but recognized complication of organ transplantation. It has been reported after kidney transplantation from cadaver donors. We report a case in which an extrathoracic tumor was transmitted by the donor heart.

A 19-week-old fetus with craniosynostosis, renal agenesis and gastroschisis: case report and differential diagnosis.

A case of a fetus affected with craniosynostosis, unilateral renal agenesis and gastroschisis is reported. The propositus was delivered on the 19th week of gestation for premature rupture of the membranes. Macroscopy showed turricephaly, shallow orbits, exophthalmos, hypertelorism, hypoplastic maxilla with relative mandibular prognathism and gastroschisis.

[Subtyping and prognostic assessment of invasive lobular breast carcinoma].

Invasive lobular carcinoma (ILC) is recognized in its classical form and as variants with tubulo-lobular, solid, pleomorphic, alveolar or signet ring cell differentiation. The most common classical form differs from invasive ductal carcinoma (IDC) by its slower tumor proliferation and less common axillary metastases. When compared stage by stage, long term prognosis is similar to IDC, however.

[DNA cytometry in breast carcinoma. Review of method and value in assessing prognosis].

DNA flow cytometry (FCM) has become a routine method in breast cancer diagnosis for evaluation of ploidy and proliferation kinetics (cell cycle analysis). Image cytometry is less practicable and provides less information than flow cytometry. An optimized technique with a low coefficient of variation is required for optimal results in flow cytometry.

Epidemiology of Whipple's disease in Germany. Analysis of 110 patients diagnosed in 1965-95.

Background: The epidemiology of Whipple's disease (WD) is obscure. To obtain basic data, we performed an evaluation of WD patients in Germany.

Methods: Information was collected from 110 WD patients diagnosed during 1965-95 at 5 institutions in different regions of Germany.

Histology of intestinal Whipple's disease revisited. A study of 48 patients.

Whipple's disease is an infectious disorder with intestinal and extra-intestinal manifestations. We reinvestigated the intestinal histology in a series of 48 patients (10 females, 38 males; mean age 56.5 years, standard deviation of the mean +/- 11.

3-Methylidene-beta-lactams as potential inhibitors of beta-lactamases. Part 1: Synthesis of alpha-substituted derivatives from imines by Reformatzky reaction with chlorotrimethylsilane, silylation and Peterson olefination.

A new variation of the Reformatzy reaction with use of I2/zinc and chlorotrimethylsilane in THF and a shortened work-up is described allowing the synthesis of a wide variety of substituted beta-lactams 3 in fairly good yield. These lactams are silylated according to the Peterson reaction yielding by reactions with appropriate carbonyl compounds E/Z-mixturs of the substituted 3-methylidene beta-lactams 7, 8 and 10. The isomers are separated by CC and completely characterized by spectroscopic methods, mainly 1H NMR spectroscopy.

Aspergillus endocarditis, myocarditis and pericarditis complicating necrotizing fasciitis. Case report and subject review.

A patient with Aspergillus endocarditis, myocarditis and pericarditis is described. A 55-year-old man developed necrotizing fasciitis of the lower abdominal wall, pelvis and right thigh. Despite aggressive surgical débridement and antibiotic coverage, the patient died of multisystem organ failure.

Sulfogriseofulvin derivatives. synthesis by [4 + 2]cycloaddition, structure, properties, crystal structure analysis, and antifungal activity of spiro[1,3-benzoxathiole-2,1'-cyclohex-2'-en]-4'-one 3,3-dioxides.

Syntheses of substituted, especially of fluoro substituted benzoxathiole 1,1-dioxides, are described. These derivatives were transformed via the Peterson olefination into substituted 2-alkylidene derivatives 27. Diels-Alder reactions of 27 with 1,1-dimethoxy- and 1-methoxy-3-trimethylsiloxy-1,3-butadiene (30, 32) gave sulfone analogues 31 of griseofulvin (named sulfogriseofulvins).

A rapid and highly specific technique to detect hepatitis C RNA in frozen sections of liver.

Aims: To develop a polymerase chain reaction (PCR) based technique that would permit the rapid and highly specific detection of hepatitis C virus (HCV) RNA extracted from frozen liver tissue.

Methods: Samples of liver tissue from 18 patients undergoing orthotopic liver transplantation were studied. Nine patients were HCV positive.

Bone marrow-derived macrophage lines and immortalized cloned macrophage and dendritic cells support priming of Borrelia burgdorferi--specific T cell responses in vitro and/or in vivo.

In vitro propagated bone marrow-derived macrophage populations (BMMO) as well as cloned immortalized macrophage (MT2/1) and dendritic (D2SC/1) cell lines were analyzed for their capacity to promote activation and/or proliferation of naïve T cells to Borrelia burgdorferi antigens in vitro and in vivo. All three cell types constitutively express high levels of MHC class I structures as well as the co-stimulatory molecules B7/BB1 and heat-stable antigen (HSA); MHC class II molecules (I-A) are upregulated following incubation with either intact spirochetes or the purified lipoprotein OspA (Lip-OspA) but not with its delipidated from (MDP-OspA). Only BMMO were able to induce proliferation of naïve T cells or T cells derived from infected mice to intact spirochetes in vitro.

Proton transport by a bacteriorhodopsin mutant, aspartic acid-85-->asparagine, initiated in the unprotonated Schiff base state.

At alkaline pH the bacteriorhodopsin mutant D85N, with aspartic acid-85 replaced by asparagine, is in a yellow form (lambda max approximately 405 nm) with a deprotonated Schiff base. This state resembles the M intermediate of the wild-type photocycle. We used time-resolved methods to show that this yellow form of D85N, which has an initially unprotonated Schiff base and which lacks the proton acceptor Asp-85, transports protons in the same direction as wild type when excited by 400-nm flashes.