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Biomedical subjects

J Laufer

Publications and source records attributed to J Laufer.

At least 37 records · Page 2Linked to original sources
PubMed1995

Activation of monocytes via their Fc alpha R increases procoagulant activity.

There is increasing evidence in experimental models of glomerulonephritis, including IgA nephropathy, that macrophages accumulate within the affected kidneys. Increased procoagulant activity (PCA) consequent on the influx of these cells has been associated with the progression of kidney disease. We have studied the effect of activation of the monocyte Fc alpha receptor (Fc alpha R) on PCA. Immune complexes of immunoglobulin A (IgA) isotype formed in situ or the addition of aggregated IgA resulted in a dose-dependent increase of monocyte PCA. Maximal effect was achieved after 6 hours of incubation. PCA induced by Fc alpha R was consistent but was less than that observed after addition of endotoxin to monocyte monolayers or after activation via the Fc gamma R or mannose receptor. Specificity of the interaction of the ligands with Fc alpha R was shown; galactose inhibited effects mediated via the Fc alpha R but not via the Fc gamma R. Corticosteroids inhibited Fc alpha R monocyte-induced PCA. These results are likely to be relevant in the immunopathogenesis of IgA-mediated disease, particularly IgA nephropathy.

Antigen-Antibody Complex↗
PubMed1995

HLA-B5 in the diagnosis of Behcet's disease.

Behçet's disease, a multisystem disease is, by its nature, difficult to diagnose. The first manifestation of the disease may precede the appearance of other symptoms and signs essential for diagnosis by many years. In patients of Mediterranean origin, the early manifestations of the disease, may be confused with those of familial Mediterranean fever (FMF). Determination of HLA-B5 may, however, contribute to the diagnosis in children with partial manifestations of Beh,cet syndrome.

Adolescent↗
PubMed1995

C3, C4, factor B and HLA-DR alpha mRNA expression in renal biopsy specimens from patients with IgA nephropathy.

The deposition of complement in the kidney mesangium is a constant finding associated with renal injury in IgA nephropathy, even though IgA does not bind complement. We have previously reported that complement gene expression in the kidney increases concurrently with the progression of immune complex disease in murine lupus nephritis. We have now studied the expression of C3, C4, factor B and HLA-DR alpha mRNA by in situ hybridization in renal biopsy specimens of patients with IgA nephropathy and compared these findings to those in patients with other immune-mediated diseases of the kidney, hereditary nephritis and normal kidney. In IgA nephropathy, C3 and factor B mRNA were expressed in the renal tubular epithelial cells, while no expression of either C3 or factor B mRNA was apparent in the glomerulus. Specimens from patients with other immune-mediated forms of chronic glomerulonephritis also showed a similar pattern of expression of C3 and factor B mRNA only in the tubules, but not in the glomerules. However, C3 and factor B mRNA were not found in normal kidney tissue or biopsy specimens from patients with hereditary nephritis. C4 mRNA was expressed in the tubular epithelial cells in all specimens examined, indicating that C4 mRNA is constitutively expressed in the human kidney. In IgA nephropathy HLA-DR alpha mRNA was observed in the interstitium, but not the tubules or glomerular cells. In contrast, HLA-DR alpha mRNA was present in the glomerulus and scattered in the interstitium in other immune-mediated kidney diseases. There was no expression of HLA-DR alpha mRNA in hereditary nephritis or normal kidney. Our findings, which reflect the immunopathogenic events in vivo, provide new insights as to the interpretation of the molecular immunology of this immune complex disease.

Adolescent↗
PubMed1994

Congenital bilateral absence of vas deferens in the absence of cystic fibrosis.

The high frequency of mutations in the cystic fibrosis gene in patients with congenital bilateral absence of vas deferens (CBAVD) has raised the question whether all of them have a genital form of cystic fibrosis. We investigated 47 CBAVD patients by ultrasonography, 10 (21%) had renal malformations and 37 (79%) did not. In the former group, no cystic fibrosis mutations were found and sweat chloride concentrations were normal. In the latter group, 18 patients (49%) carried at least one cystic fibrosis mutation and sweat chloride was high in 17 of 26 tested (65%). Our findings suggest that CBAVD patients with renal malformations do not necessarily have cystic fibrosis.

Cystic Fibrosis↗
PubMed1994

[Endobronchial mass caused by tuberculosis].

A 2-year-old girl who presented with cough, had been started on prednisone and bronchodilators 10 days prior to admission because of presumed hyperactive, small airway obstruction. Fluoroscopy revealed hyperinflation of the right lung and mediastinal shift to the left on expiration. Bronchoscopy disclosed an endobronchial mass. At that time the tuberculin test was negative. Since such lesions are rare in young children, thoracotomy was performed. An enlarged mediastinal lymph node was removed and the histopathological findings were suggestive of tuberculosis. The tuberculin test 1 month following prednisone therapy was positive, suggesting that previously the skin reaction to tuberculin had been altered by the prednisone. Tuberculosis should be considered in the differential diagnosis of an endobronchial mass even in an otherwise apparently healthy child.

Airway Obstruction↗
PubMed1993

Effect of short-term hyperthyroxinemia on vitamin D metabolism in congenital hypothyroidism.

The circulating concentrations of vitamin D metabolites were measured in nine children (four to ten years of age) with congenital hypothyroidism on L-thyroxine therapy, before and after a short term increase (33%) in dosage. The concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were not altered, but the concentration of 1,25 dihydroxyvitamin D was significantly higher in the serum of the children after three weeks of hyperthyroxinemia. This was associated with an increase in urinary calcium excretion. The increases in serum concentration of 1,25 dihydroxyvitamin D cannot be explained by differences in serum levels of calcium, phosphorus or parathyroid hormone. These findings differ from data obtained in adults.

25-Hydroxyvitamin D 2↗
PubMed1993

The human gene encoding cytokeratin 20 and its expression during fetal development and in gastrointestinal carcinomas.

The differentiation of the predominant cell types of the mucosal epithelium of the mammalian gastrointestinal tract is characterized by increasing amounts of an intermediate-sized filament (IF) protein designated cytokeratin (CK) 20 which is a major cellular protein of mature enterocytes and goblet cells. Here we report the isolation of the human gene encoding CK 20, its complete nucleotide sequence and the amino acid sequence deduced therefrom that identifies this polypeptide (mol. wt. 48553) as a member of the type I-CK subfamily. Remarkable, however, is the comparably great sequence divergence of CK 20 from all other known type I-CKs, with only 58% identical amino acids in the conserved alpha-helical 'rod' domain of CK 20 and, e.g. CK 14. Using riboprobes corresponding to exon 6 of the gene in Northern blot and ribonuclease protection assays, we show that the approximately 1.75 kb mRNA encoding CK 20 is specifically produced in cells of the intestinal and gastric mucosa, including tumors and cell lines derived therefrom. The appearance of CK 20-positive cells in human embryonic and fetal development and in adult tissues has been studied using immunohistochemistry with CK 20-specific antibodies. CK 20 synthesis has first been recognized at embryonic week 8 in individual 'converted' simple epithelial cells of the developing intestinal mucosa. In later fetal stages, CK 20 synthesis extends over most goblet cells and a variable number of villus enterocytes. The distribution of CK 20-positive cells in the developing gastric and intestinal mucosa is similar to--but not identical with--the pattern in the adult intestine in which all enterocytes and goblet cells as well as certain 'low-differentiated' columnar cells contain CK 20, whereas the neuroendocrine ('enterochromaffin') and Paneth cells are negative. In gastrointestinal carcinomas similarly examined, CK 20 has been detected in almost all cases (50/52) of colorectal adenocarcinomas, including all grades of differentiation and malignancy and also metastatic tumors, whereas CK 20 immunostaining in gastric carcinomas has been found less consistent and more heterogeneous. The possible biological meaning of the specific expression of the CK 20 gene in certain cells of the gastrointestinal tract and carcinomas derived therefrom and the regulatory mechanisms involved in the integration of the protein in the IF cytoskeleton are discussed.

Adenocarcinoma↗
PubMed1993

[Uroplakin III, a specific membrane protein of urothelial umbrella cells, as a histological markers for metastatic transitional cell carcinomas].

We have investigated, by immunohistochemical staining of various paraffin-embedded carcinoma sections, the tissue-specific expression of uroplakin III--a recently characterized constituent glycoprotein (47 kD) of the asymmetrical unit membrane which forms plaques on apical surface of urothelial umbrella cells. The apical membrane pattern of normal urothelial umbrella cells was in part maintained in papillary transitional cell carcinomas (TCCs). In addition, in both papillary and invasive TCCs, variously sized lumina exhibited positive membrane staining of uroplakin III. In some cases, basal cell membrane staining was seen. Positive reactions (which sometimes were very focal) were noted in 16/18 papillary non-invasive TCCs (89%), 21/37 invasive TCCs (57%) and 12/15 TCC metastases (80%). Non-TCC carcinomas of different origin (n = 63) were consistently negative. These results show that uroplakin III may serve as a useful marker for TCCs, revealing specific urothelial differentiation features to be expressed in such tumors even after metastasis. This marker, while of only intermediate sensitivity, is highly specific, thus opening interesting histodiagnostic possibilities in the case of unclear carcinoma metastases.

Biomarkers, Tumor↗
PubMed1993

Cross-linking of monocyte plasma membrane Fc alpha, Fc gamma or mannose receptors induces TNF production.

We have studied and compared the effects of IgA and IgG immune complexes and concanavalin A (Con A) on human monocyte tumour necrosis factor (TNF) production. The presence of IgA-containing immune complexes in monocyte monolayers resulted in a dose-dependent increase of TNF production. Similar results were obtained with IgG-containing immune complexes and Con A. The presence of monomeric IgA or IgG did not increase TNF secretion. Both IgA and IgG immune complexes also increased monocyte interleukin-1 beta (IL-1 beta) production. Galactose inhibited the effect of IgA but not IgG immune complexes, while mannose inhibited the effect of Con A. Prednisolone abrogated TNF production, while indomethacin enhanced TNF production in all instances where cross-linking of plasma membrane receptors was achieved. These results indicate that activation of Fc alpha receptors (Fc alpha R), Fc gamma R or mannose receptors of the human monocyte plasma membrane by cross-linking results in increased TNF and IL-1 beta secretion. These findings may be of particular relevance in the pathogenesis of IgA immune complex-mediated disease.

Antigen-Antibody Complex↗
PubMed1992

Effect of low-calorie diets on the sympathetic nervous system, body weight, and plasma insulin in overweight hypertension.

When weight reduction was found to decrease blood pressure in the overweight hypertensive patient, it was hailed as the causative factor. A growing number of recent studies indicate that this association may be secondary to a correlation between diet-associated metabolic change and the sympathetic nervous system. A select group such as overweight hypertensive patients may have a genetic predisposition for such a correlation. In overweight hypertensive patients, low-calorie diet and especially very-low-calorie diet, correlate with improved glucose metabolism, a decrease in plasma insulin concentration, and altered norepinephrine concentrations and thus sympathetic nervous system activity. Several of these studies also show a lack of effect of salt intake on blood pressure. Thus, it seems that metabolic changes caused by the decrease in caloric intake are responsible for the decrease in blood pressure. These must be investigated to understand the effect of the different diets on blood pressure. Very low-calorie diets were found very useful in breaking the vicious circle of severe nonresponsive hypertension to medication.

Blood Pressure↗
PubMed1992

Cytokeratin 20 in human carcinomas. A new histodiagnostic marker detected by monoclonal antibodies.

The authors have recently identified a new cytokeratin (CK) polypeptide, CK 20, whose expression is almost entirely confined to the gastric and intestinal epithelium, urothelium, and Merkel cells. Seven monoclonal antibodies (MAbs) specific for CK 20 were raised and characterized by applying immunoblotting and immunocytochemical screening. All of them reacted on frozen tissue sections. A further MAb, IT-Ks20.8, recognized CK 20 in sections of formalin-fixed, paraffin-embedded tissue samples. A total of 711 cases of primary and metastatic cancer, mostly carcinomas, were analyzed immunohistochemically for CK-20 expression, using CK-20 specific guinea-pig antibodies and MAbs. The expression spectrum of CK 20 in carcinomas resembled that seen in the corresponding normal epithelia of origin. CK-20 positivity was seen in the vast majority of adenocarcinomas of the colon (89/93 cases), mucinous ovarian tumors, transitional-cell and Merkel-cell carcinomas and frequently also in adenocarcinomas of the stomach, bile system, and pancreas. Most squamous cell carcinomas in general and most adenocarcinomas from other sites (breast, lung, endometrium), nonmucinous tumors of the ovary, and small-cell lung carcinomas were essentially or completely negative. The authors propose to use CK 20 as a diagnostic marker valuable in distinguishing different types of carcinomas, notably when presenting as metastases.

Animals↗
PubMed1990

[Cysts and pseudocysts of the parotid].

Parotid gland are subdivided in malformative dysgenetic cysts and in acquired cysts. Among malformative cysts, lymphoepithelial cysts so-called branchial cysts are the most frequent. Histologically the cystic cavity is lined by squamous epithelium with various amounts of underlying lymphoid tissue. Other varieties of malformative cysts are exceptional: cystic teratomas with several sorts of adult tissues, polycystic parotid gland and congenital ductal ectasia. Acquired cysts are another important group: retention cysts are found in adult and old people. Microscopically these cysts are lined by a single or pseudostratified epithelium rested on a layer of connective tissue without any lymphoid tissue. Lymphoid cystic hyperplasia arising in HIV infection can be included in this group of acquired cysts. Finally these parotid cysts have to be differentiated from pseudocysts without an epithelial lining and from cystic tumors as cystadenolymphoma and cystic mucoepidermoid carcinoma.

Cysts↗
PubMed1990

[The unforeseen aspects of expertise or the proper use of ones's nose and lips].

On the basis of two expert evaluations, the author first sets out a few general principles needed to guide the expert during his mission. He then describes the peculiar features of the two examples chosen, both of which, in his opinion, justify a valuation far exceeding the standard compensation for the damage sustained by the victims, due to their occupation: one is a customs officer in a major international airport, the other is a trumpeter in a famous philharmonic orchestra. As a conclusion, the author emphasizes the necessity to thoroughly examine any wounded or ill patient prior to deciding to operate them.

Adult↗