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Biomedical subjects

J Melamed

Publications and source records attributed to J Melamed.

At least 55 records · Page 3Linked to original sources

Blood group antigens in Barrett's esophagus and associated adenocarcinomas.

A panel of monoclonal antibodies (MoAbs) against BGAg A, B, and H and Lewis a, b, X, and Y (Le a, Le b, X, Y) was used to characterize and evaluate the blood group antigens (BGAg) immunohistochemistry in Barrett's esophagus (BE) and associated adenocarcinomas (ACA). Thirteen cases of ACA arising in metaplastic columnar epithelium of the distal esophagus were reviewed (12 men; 1 woman; mean age: 59). Twelve cases had juxtaposed BE of different types with low-grade dysplasia in five and high-grade dysplasia in three. ACAs were classified as well differentiated (one case), moderately differentiated (three cases), and poorly differentiated (four cases). Five cases had mixed features. Loss of BGAg H was recorded in four ACA and in one adjacent BE. Loss of BGAg B was noted in three ACAs, but in only one case in the adjacent BE. Incompatible expression of BGAg A and B was present in one case each. Anomalous expression of Le a was seen in seven ACAs and adjacent BE. Loss of Le b was noted in six ACAs. Deletion of X was seen in four ACAs and in BE. Loss of Y was present in the only nonsecretor patient. We conclude that significant alterations of BGAg occur in BE and in associated ACAs. Recognition of these antigenic alterations warrants further investigation to define a role for BGAg immunohistochemistry in the surveillance of BE patients at risk of developing ACA.

Adenocarcinoma↗

Cytomegalovirus, angiomatosis, and Kaposi's sarcoma: new observations of a debated relationship.

Kaposi's sarcoma (KS) encompasses a broad spectrum of lesions ranging from foci of muco-cutaneous angiomatosis to tumor masses of internal organs. Its strong association with immune deficiency and the marked differences in incidence between the various populations at risk are suggestive of an infectious etiology. The agent most often suspected of being implicated in the etiology of KS is cytomegalovirus (CMV); however, despite sustained research on this subject, its role remains controversial. The present work includes six cases of KS with a broad variety of lesions in which, with the use of light and electron microscopy, immunohistochemistry, and in situ hybridization, we investigated the presence of CMV and examined its relationship with KS. CMV was present in all six cases and showed a remarkable propensity for the KS lesions where both intranuclear and intracytoplasmic forms were not only next to but frequently within KS cells. Areas of angiomatosis, hemorrhage, and KS had usually an abundance of CMV. Herpes-like virus particles inside KS nuclei were documented by light and electron microscopy and identified as CMV by immunohistochemistry and in situ hybridization. The selective morphologic presence of this virus within the tumor cells, not previously demonstrated, indicates a strong association between CMV and KS, the significance of which remains to be established.

Adult↗

Renal pathology of essential hypertension.

Microscopic analysis of over 2,000 renal biopsies taken at surgical sympathectomy operations has been correlated with blood pressures in essential hypertension. Statistically significant relationships exist between the average diastolic pressure and the degree of afferent renal arteriolar thickening and narrowing. Postoperative prognosis was favorable with all but the most severe and diffuse arteriolar sclerosis, and vascular fibrinoid necrosis did not affect survival. Juxtaglomerular cell hyperplasia and inferred renin hypersecretion were significantly involved in the kidney biopsies of essential hypertension. Diabetic juxtaglomerular cell atrophy and sclerosis reduced this component of hypertension. After age 80, kidneys at autopsy showed no evident relation between arteriolar lesions and hypertension.

Aged↗

Multicenter placebo-controlled study of nedocromil sodium 1% nasal solution in ragweed seasonal allergic rhinitis.

An 8-week double-blind study was carried out in 177 ragweed patients with seasonal allergic rhinitis to compare nedocromil sodium 1% nasal solution (Tilarin, QID, Fisons plc) and placebo. Symptoms of rhinitis were significantly reduced by nedocromil sodium during the peak 3-week pollen season (P = .001 for diary summary score) and the active treatment was rated effective by 74% of patients.

Administration, Inhalation↗

Early developmental progress of preterm twins discordant for birthweight and risk.

Studies of developmental progress in high-risk twins have disparate findings. In this study, we report the outcome of 45 twin pairs born between 26 and 37 weeks gestation, and whose birthweights ranged from 840 to 2000 g. No significant differences were found for weight, risk and birth order. However, earlier preterm infants were found to have significantly lower mental scores on the Bayley Scales of Infant Development at 24 months, and lower IQ scores on the Stanford Binet Intelligence Scale at 36 months. These findings imply that gestational age is a powerful variable in determining developmental outcome.

Birth Weight↗

The metabolism of C1 inhibitor and C1q in patients with acquired C1-inhibitor deficiency.

The metabolism of 125I-labeled C1 inhibitor (C1INH) and C1q was studied in five patients with B cell lymphoproliferative disorders, C1INH deficiency, and angioedema. C1INH catabolism was markedly accelerated in these patients. The fractional catabolic rate (FCR) was 0.053 of the plasma pool per hour compared to that of normal subjects (0.025) or patients with hereditary angioneurotic edema (HANE) (0.035). The catabolism of two dysfunctional proteins Wel and Ta was studied. Protein Wel was catabolized at an accelerated rate (0.041) compared to that in patients with HANE (0.029) or in normal subjects (0.020). In contrast, the FCR of protein Ta was 0.012, which is similar to that in normal patients and in patients with HANE. The extravascular to plasma ratio (E/P) of the normal C1INH in patients was 1.55 compared to 0.60 in normal patients. This is consistent with the rapid extravascular sequestration of the C1INH. The synthesis rate of the C1INH was 0.29 mg/kg/hr in patients that is similar to that in control subjects. The metabolism of C1q was studied in two normal control subjects and three patients. The FCR of C1q was 0.051 in patients compared to 0.023 in control subjects. The E/P was increased in patients (2.8) compared to E/P in control subjects (0.6). The acquisition of C1INH deficiency results from increased consumption of C1INH in vivo.

Adult↗

Chemical dependence and clinical depression in pregnancy.

The Short Form of the Beck Depression Inventory (BDI) was administered to 54 chemically dependent pregnant women to assess the extent and depth of depression in the population. The women were divided into three groups by age: Teenagers, young adults, and older adults. Results suggested that this population, as a whole, scored very high on this depression scale. Further, results indicated that the older chemically dependent women scored significantly higher on the depression index than did either of the two younger groups, while the teenagers obtained a mean score comparable to that of the general adolescent population.

Adolescent↗

RNA content and chromatin structure of CHO cells arrested in metaphase by colcemid.

To evaluate the stability of cells arrested in metaphase, cell viability, RNA content, and chromatin structure (the latter probed by the DNA in situ sensitivity to acid-induced denaturation) were studied in uniform-age mitotic CHO cell populations maintained either at 37 degrees C (in the presence of Colcemid) or at 0-4 degrees C for up to 6 h. No significant changes in cell viability and RNA content were seen throughout the experiment for both groups of cells. The sensitivity of DNA in situ to denaturation was significantly increased during the initial 40 min of cell arrest in mitosis. However, no further chromatin changes for up to 6 h were evident regardless of whether cells were kept at 37 degrees C with Colcemid or at 0-4 degrees C in its absence. The data indicate that neither significant deterioration of metaphase cells nor progressive chromatin changes are expected during stathmokinesis experiments in vitro or during the metaphase cell arrest in cytogenetic studies lasting up to 6 h. Also, no RNA turnover can be detected in mitotic cells during this time interval.

Animals↗

Role of human factor I and C3b receptor in the cleavage of surface-bound C3bi molecules.

Control of functions mediated by the third component of complement (C3) depends on the rate of generation and degradation of biologically active C3 fragments. To evaluate the mechanisms of degradation of active C3 fragments, the role of the control protein C3b/C4b inactivator (factor I) was investigated under conditions approximating those found in vivo, i.e. in the presence of plasma. The breakdown of human erythrocyte-bound C3bi molecules in serum or plasma was mediated only by factor I, since factor I-deficient or -depleted plasma was inactive until reconstituted with highly purified factor I. The rate of cleavage of C3bi bound to human erythrocytes by purified factor I was not affected by the presence or absence of beta 1H (factor H). The released breakdown product of C3bi has been shown to be C3c antigenically and on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Two different monospecific antibodies to the human C3b receptor totally abrogated factor I-mediated cleavage of cell-bound C3bi, suggesting that the C3b receptor (but not factor H) is required as an obligate cofactor. The rate of this C3b receptor-dependent, factor I-mediated cleavage of bound C3bi is strongly regulated by the surface to which C3bi is bound. Whereas C3bi bound to particulate nonactivators of the alternative complement pathway such as human erythrocytes is rapidly degraded by this mechanism, the rate of cleavage of C3bi bound to activators is significantly slower. These data suggest a physiologic role of C3b receptors in the degradation of biologically active C3 fragments deposited on host tissues. They also suggest that C3bi molecules on restricted surfaces are relatively stable and can thereby interact with complement C3 receptors in vivo.

Animals↗

Inhibition of phagocytosis of complement C3- or immunoglobulin G-coated particles and of C3bi binding by monoclonal antibodies to a monocyte-granulocyte membrane glycoprotein (Mol).

Events that lead to phagocytosis of complement (C3)- or IgG-coated particles after their interaction with specific cell surface receptors are poorly understood. Two mouse monoclonal antibodies (an IgM and an IgG2a) to a human granulocyte-monocyte surface membrane differentiation antigen (Mol) inhibited ingestion by granulocytes both of oil Red O particles opsonized with normal human serum or with IgG and of sheep erythrocytes sensitized with IgG. In addition, they specifically inhibited rosetting between phagocytes and sheep erythrocytes coated with C3bi, a fragment of the complement component C3, generated by cleaving C3b with C3b inactivator and beta IH protein. These monoclonal anti-Mol antibodies did not inhibit IgG Fc, C3b or C3d receptor-mediated binding of erythrocytes coated with the respective proteins. The Fab fragment of the IgG2a monoclonal antibody inhibited noncytotoxic enzyme release from granulocytes when these cells were stimulated with zymosan coated with C3bi. Electrophoretic transfer of polymorphonuclear leukocyte detergent lysates to nitrocellulose, followed by immunofixation with monoclonal antibody, showed that these antibodies were directed to a 155,000-mol wt glycoprotein. This surface membrane structure appears to be involved in Fc and C3 receptor-dependent phagocytosis and closely associated with the C3bi receptor.

Antibodies, Monoclonal↗

Induction of granulocyte histaminase release by particle-bound complement C3 cleavage products (C3b, C3bi) and IgG.

The interaction of opsonized particles with human granulocytes promotes a number of important biologic functions, including phagocytosis, superoxide generation, and release of a variety of enzymes, including histaminase. We have previously determined that histaminase release occurs via a C3-dependent process. Although fluid-phase C3b dimers can mediate release, the relative effects of particle-bound C3b and C3bi and of IgG have not been examined. In this report we demonstrate that particle-bound C3 deposited on activators of the alternative C pathway effected histaminase release in the absence of IgG. Particle-bound C3bi and C3b were both effective as mediators of histaminase release. The extent of release varied as a function of the activating surface on which C3 was deposited (zymosan C3b was considerably more potent than C3b bound to rabbit erythrocytes, which was slightly more potent than C3b bound to neuraminidase-treated sheep erythrocytes). In contrast, C3b or C3bi deposited on nonactivating surfaces (such as sheep erythrocytes) at inputs of up to 2,000,000 molecules per granulocyte failed to induce histaminase release unless IgG was also present. The ability of C3b bound to particles that serve as activators of the alternative pathway to induce histaminase release is apparently not the result of decreased susceptibility of C3b to proteolysis or to an increased binding affinity to the C3b receptor, but may relate to the interaction of other surface structures on activating particles with the PMN membrane.

Amine Oxidase (Copper-Containing)↗

[Effects of improved levels of plasma bicarbonates in terminal renal failure].

Correction of chronic renal acidosis was attempted for 6 weeks in 20 end stage renal failure patients on chronic acetate hemodialysis by means of 6-9 g of sodium bicarbonate given orally by means of gastric juice resistant capsule of 1 g. Normalisation of the inter-dialysis acid base status was obtained without major side effects.

Acetates↗

Low ionic strength or chemical cross-linking of monomeric C3b increases its binding affinity to the human complement C3b receptor.

Quantitative studies of the interaction between a fragment of the third component of complement (C3b) and its receptor on human cells have been undertaken with a recently developed radioligand binding assay. Specific binding of fluid phase monomeric C3b was direct and saturable under low (mu = 0.0513) but not physiological (mu = 0.15) ionic strength. Dimeric C3b had a greater affinity for the C3b receptor at either ionic strength. Complexing of monomeric C3b with another protein (human IgG) did not result in increase in binding to human erythrocytes when compared with monomeric C3b alone. These data suggest that ionic forces are involved in C3b receptor-ligand interactions and that the stable C3b-receptor binding site is present in monomeric C3b. Furthermore they suggest that the greater affinity of dimeric or oligomeric C3b is a result of multimeric binding to preclustered C3b receptors. These findings provide an explanation for the relatively stable interaction of particle bound C3b and C3b receptor-bearing cells in the immune adherence reaction.

Chromatography, Gel↗