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Biomedical subjects

S Teichberg

Publications and source records attributed to S Teichberg.

At least 55 records · Page 3Linked to original sources

Mitochondrial encephalomyopathy associated with a single nucleotide pair deletion in the mitochondrial tRNALeu(UUR) gene.

The investigation of pathogenic mitochondrial DNA (mtDNA) mutations has revealed a complex relation between patient genotype and phenotype. For unknown reasons, some mtDNA mutations produce specific clinical manifestations such as chronic progressive external ophthalmoplegia; myoclonic epilepsy and ragged-red fiber disease (MERRF); and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). To enhance our understanding of the association between genotype and phenotype, we investigated a patient with mitochondrial encephalomyopathy and severe cerebral calcifications for a mtDNA mutation. There was a deletion of one of three T:A nucleotide pairs in the tRNALeu(UUR) gene of the mtDNA involving positions 3271 to 3273. Pedigree analysis suggested that this mutation may have occurred spontaneously in the proband. This analysis represents the smallest mtDNA deletion observed to date and is the first deletion identified within a mitochondrial tRNA. This observation emphasizes the importance of delineating the precise mutation responsible for an oxidative phosphorylation disease for patient diagnosis as well as for genetic counseling of maternal lineage relatives.

Adult↗

Advanced glycation end products induce glomerular sclerosis and albuminuria in normal rats.

High levels of tissue advanced glycation end products (AGEs) that result from the spontaneous modification of proteins by glucose occur in diabetes and aging. To address the potential pathogenic role of AGEs in the glomerulosclerosis of diabetes or nephrosclerosis of aging, doses of AGE-modified rat albumin (25 mg per kg per day, i.v.) sufficient to elevate circulating AGE levels to the range of diabetic serum were administered daily to healthy rats alone or in combination with the AGE inhibitor aminoguanidine. After 5 months, the AGE content of renal tissues in AGE-treated rats rose to 50% above controls (P < 0.025), whereas serum contained 2.8-fold greater AGE levels (P < 0.025). Light and electron microscopy of kidneys from AGE-treated rats revealed a more than 50% increase in glomerular volume compared to controls (P < 0.001), significant periodic acid/Schiff reagent-positive deposits, basement membrane widening, and mesangial extracellular matrix increase and indicated significant glomerulosclerosis compared to untreated (P < 0.002) or albumin-treated controls (P < 0.002). These changes were associated with significant loss of protein (P < 0.005) and albumin (P < 0.002) in the urine of AGE-treated rats compared to controls. Cotreatment with aminoguanidine markedly limited both the structural and functional defects. These in vivo data demonstrate that AGEs influence glomerular structure and function in a manner leading to glomerulosclerosis. The effects are AGE-specific, as they are ameliorated by a pharmacological AGE inhibitor, aminoguanidine.

Aging↗

Splenic lymphoma with circulating villous lymphocytes: report of seven cases and review of the literature.

Splenic lymphoma with villous lymphocytes (SLVL) is a relatively new entity with only a few reports published. We report seven cases of SLVL with detailed clinicopathologic and comprehensive immunophenotypic studies to further characterize this lymphoma, which is frequently confused with hairy cell leukemia and other low-grade B-cell lymphoid neoplasms. The diagnostic criteria we used include 1) prominent splenomegaly, 2) insignificant or no lymphadenopathy, 3) lymphocytosis without leukopenia, 4) presence of circulating villous lymphocytes, 5) characteristic cytologic and histologic features, and 6) specific phenotypic and cytochemical findings. Our studies show that SLVL does not represent a pure entity but rather a morphologically heterogeneous group of low-grade lymphomas with various cytologic and histologic features. Although immunophenotyping is helpful in differential diagnosis, multiparameter studies are necessary to confirm the diagnosis. In our series, only two patients died of SLVL, who probably developed transformation to a higher-grade lymphoma.

Aged↗

Giant myofibroblastoma of the male breast.

Myofibroblastoma of the breast is a rare, benign neoplasm, seen predominantly in men. The gross appearance is that of a well-circumscribed nodule, characteristically small, seldom exceeding 3 cm. We report a case of giant myofibroblastoma measuring 10 cm and weighing 169 g in the breast of an 83-year-old man. Light microscopic, immunohistochemistry, and electron microscopic features are described. Histologically, these neoplasms may exhibit a varied cellularity that can be misinterpreted as sarcoma. However, they lack marked cellular pleomorphism, tumor necrosis, and mitosis and are characteristically composed of plump and long bipolar, spindly cells arranged in swirling fascicles with intervening broad collagen bands. As we report, immunostaining is strongly positive for vimentin, desmin, and muscle common antigen and negative for cytokeratins and S-100-associated protein. Electron microscopy shows predominantly cells suggestive of myofibroblastic differentiation. The patient has remained free of disease 2 years after mastectomy.

Aged↗

Zinc improves postischemic recovery of isolated rat hearts through inhibition of oxidative stress.

We studied the cardiac protective qualities of zinc in the postischemic isolated rat heart. Hearts, perfused with Krebs-Henseleit buffer with or without zinc-bis-histidinate, were subjected to 20 min of "no-flow" normothermic global ischemia. Pre- and postischemic treatment with 0, 10, 20, or 30 microM zinc resulted in concentration-dependent enhancement of postischemic function as evidenced by decreased end-diastolic pressure (37 +/- 3, 25 +/- 5, 17 +/- 5, and 8 +/- 2 mmHg, respectively) and increased recovery of developed systolic pressure (41 +/- 6, 59 +/- 17, 76 +/- 18, and 87 +/- 16 mmHg, respectively) and maximum rate of rise in pressure (+dP/dtmax; 823 +/- 141, 1,413 +/- 396, 1,700 +/- 450, and 2,157 +/- 407 mmHg/s, respectively) as well as decreased lactate dehydrogenase efflux from the hearts (peak: 1,002%, 840%, 580%, and 440%, respectively). Only preischemic treatment resulted in an intermediate protective effect, whereas treatment starting at reperfusion worsened postischemic damage. In hearts perfused with zinc throughout the experiment, prolongation of the preischemic treatment interval further enhanced postischemic recovery. With the use of salicylate as a trap for .OH, it was determined that zinc virtually eliminated the early postischemic "burst" of this species normally observed in this preparation. Atomic absorption studies demonstrated that hearts treated with 30 microM zinc contained 27% less copper than control hearts by the end of the reperfusion period. In control hearts, electron microscopy revealed swollen mitochondria with marked loss of inner matrix density, whereas morphology of postischemic zinc-treated hearts was essentially normal. These studies indicate that zinc possesses cardiac cytoprotective qualities and support the concept that this metal can decrease .OH formation by affecting copper reactivity.

Animals↗

Oral rehydration solutions: increased water and sodium absorption by addition of a viscosity-enhancing agent in a rat model of chronic osmotic diarrhea.

Viscosity-enhancing agents such as carboxymethylcellulose (CMC) can alter absorption of solutes and fluid exchange in the small intestine. We investigated whether the standard World Health Organization oral rehydration solution (WHO-ORS) with the addition of CMC would improve net water and sodium absorption in rats using an in vivo intestinal perfusion technique. Four WHO-ORS, containing either 0, 2.5, 5.0, or 10.0 g/L of CMC, were perfused in rats with a well-tested model of cathartic-induced chronic osmotic diarrhea (D) and in normal controls (C). In D rats, the ORSs with CMC improved sodium absorption at the three concentrations used (p < 0.01). The same effect was shown in C rats. Net water absorption was also enhanced in D rats given ORSs with CMC, although the changes in C animals were less marked. The improvement in sodium and water absorption in both C and D rats positively correlated with the log of relative ORS viscosity. Ultrastructural examination of tissues perfused with 10 g/L of CMC showed an extended brush border glycocalyx. This study indicates that CMC added to WHO-ORS in the perfused rat jejunum improves the effectiveness of the solution by increasing sodium and water absorption.

Animals↗

Presumptive identification of common adenovirus serotypes by the development of differential cytopathic effects in the human lung carcinoma (A549) cell culture.

The neutralization test is commonly used in clinical virology laboratories for the identification by serotype of adenovirus isolates. In an effort to conserve reagents and reduce the amount of time in the performance of this assay, we evaluated the significance of differential cytopathic effects for the presumptive identification of lower-numbered adenovirus serotypes that are commonly encountered in the clinical setting. Utilizing the human lung carcinoma (A549) cell culture as our indicator system, two viral induced monolayer degenerations (i.e., cytopathic effects or CPEs) were recognized. Among our wild and the laboratory adapted (i.e., ATCC) adenovirus isolates tested in this study, serotypes 1, 2, 4, 5, 6, 8, 11, 19, 21, 27, and 31 were expectedly characterized by the typically enlarged, rounded, and refractile cells, which eventually aggregated into irregular 'grape-like' clusters. Adenovirus types 3 and 7, however, were characterized by the development of distinct intranuclear inclusions, a flattening and then a web or net-like monolayer degeneration. Differences in the intensity of intranuclear granulation were related by electron microscopy to differences in the quantity of viral crystalline aggregates within the host cell nucleus. A presumptive identification of the commonly encountered adenovirus serotypes 3 and 7 prior to the performance of the neutralization test would result in a conservation of type-specific antiserum, a decreased use of cell cultures and medium, and lastly, reduced medical technologist workload.

Adenoviruses, Human↗

Hypertension secondary to renin-secreting juxtaglomerular cell tumor: case report and review of 38 cases.

A 15-year-old girl with severe high renin hypertension caused by a juxtaglomerular cell tumor (JCT) was successfully treated with the calcium channel blocker nifedipine until surgical removal effected a permanent cure. This case was incorporated into a review of the 37 cases previously published. Comparison of the children and adolescents with the adult population showed that the features of JCT were similar in the two groups except for the average duration of symptoms prior to diagnosis (pediatric group 2.6 years vs. 6.0 years for the adult group). Analysis of all 38 cases demonstrated the following: 1. Teenagers constituted the largest single population with JCT (39%) and approximately two-thirds of the entire population were female. 2. Many patients failed to show persistent hypokalemia despite high plasma renin activity and secondary hyperaldosteronism. 3. Renal angiography was initially negative in more than half the cases. 4. Renal vein renin failed to show lateralization to the affected kidney in 52% of the cases. 5. Computerized tomography demonstrated a renal mass in all of the cases in which it was performed, even when other imaging studies were negative. 6. Calcium channel blockers may evolve as the preferred treatment for the high renin hypertension of JCT.

Adenocarcinoma↗

Aggressive natural killer cell lymphoma/leukemia. A recently recognized clinicopathologic entity.

We report a comprehensive study of a case of aggressive natural killer cell lymphoma/leukemia, which is characterized by young male predominance, rapidly progressive clinical course, and presence of lymphadenopathy, hepatosplenomegaly, and bone marrow involvement. The leukemic phase is frequently preceded by pancytopenia. The diagnostic clues are the detection of cytoplasmic granules in tumor cells on Wright-Giemsa-stained tissue imprints or smears and a selective loss of T-cell antigens. Immunophenotyping is decisive in making the final diagnosis by showing positive natural killer cell markers (CD16, CD56, and/or CD57), CD2, CD11c, and Ia, but negative CD3, T-cell receptor heterodimers, terminal deoxynucleotidyl transferase, and B-cell markers. Genotyping always shows germline configuration in both immunoglobulin and T-cell receptor genes. The unique feature in this case is its presentation as a testicular lymphoma, which has not been previously reported. Polymerase chain reaction was performed in this case but failed to detect human T-cell leukemia virus type I/II provirus. It is important to recognize this new entity as it is a highly aggressive disease with a rapidly progressive clinical course and fails to respond to any chemotherapeutic regimen available.

Adult↗

A study of lymphoma of large granular lymphocytes with modern modalities: report of two cases and review of the literature.

Two cases of lymphoma of large granular lymphocytes are reported. The first case expressed natural killer (NK) cell, some T-cell (CD 2, CD 5, CD 8), and HLA-DR antigens, but was negative for other T-cell (CD 3, CD 4, CD 7), T-cell receptor (TCR), B-cell, and myeloid antigens. Germline configuration was demonstrated for TCR, and immunoglobulin heavy and light chain genes. The second case expressed NK cell, some T-cell (CD 3, CD 7, CD 8), and TCR antigens, but was negative for other T-cell (CD 4, CD 5), B-cell, myeloid, and HLA-DR antigens. Rearrangement of TCR alpha and beta chains were detected. Thus, the findings of case 1 were consistent with true NK cell lineage and case 2 with NK-like T-cell lineage. Our report underscores the heterogeneity of this newly recognized lymphoma, which nevertheless carries a consistently poor prognosis and is probably more prevalent in the Asian population. This study also provides information concerning immunophenotypes of cellular infiltrates in internal organs and cytogenetic abnormalities in this lymphoma; neither has been reported frequently in the literature. The importance of detecting cytoplasmic granules in tissue imprints or electron micrographs for differentiating other T-cell lymphomas is emphasized, and the classification of large granular lymphoproliferative disorders is discussed.

Adolescent↗

Distinct mechanisms of zinc uptake at the apical and basolateral membranes of caco-2 cells.

Zinc uptake mechanisms at the apical and basolateral membrane borders of caco-2 cells were examined. This human-derived cell line possesses many morphological and functional characteristics of absorptive small intestinal cells. By day 14, confluent and well-differentiated monolayers were formed when the cells were grown on porous polycarbonate filters. Labelled zinc was placed on the apical or basal side of the monolayer and its uptake by the cells, as well as its transport across the monolayer, were measured. Zinc uptake by the cells from the apical side was found to be a saturable process (Kt = 41 microM; Vmax = 0.3 nmols/cm2/10 min) with a diffusional term at higher concentrations (1.0 sec/cm). Apical uptake was not affected by metabolic inhibitors or potential zinc ligands. Zinc uptake from the basolateral side was concentration dependent (Kd = 1.3 sec/cm) and was partially inhibited (30%) by ouabain and vanadate, suggesting that the (Na-K)-ATPase on the basolateral membrane is involved in the serosal uptake of zinc by the cell. Transport of zinc across the monolayers from the apical or basolateral compartment was concentration dependent and was not affected by metabolic inhibitors. Zinc transport from the basolateral side was greater than 2-fold greater than apical transport. Hence, separate mechanisms can be distinguished with respect to zinc uptake at the apical and basolateral membranes of caco-2 cells.

Biological Transport↗

Mediatory role of copper in reactive oxygen intermediate-induced cardiac injury.

In this report the mediatory role of copper in cardiac injury produced by reactive oxygen intermediates was examined. Isolated rat hearts were perfused with Krebs-Henseleit buffer containing 0.25 mM ascorbate plus varying concentrations of copper-bis-histidial for up to 60 min. Using salicylate as a probe, OH generation by this system was demonstrated. Copper or ascorbate alone had minimal effect on cardiac function as determined by heart rate, coronary flow, left ventricular systolic pressure development, end diastolic pressure and +/- dP/dtmax. Copper, from 0.5 microM to 20 microM, and ascorbate, 0.25 mM, resulted in concentration-dependent decreases in all of the experimental variables. Treatment with 5 or 20 microM copper resulted in complete loss of cardiac function within 40 and 30 min, respectively. By 30 min, 5 microM copper had resulted in increased end diastolic pressure to greater than 40 mmHg. By 60 min, perfusion with 1 microM copper resulted in almost 100% loss of function and end diastolic pressure greater than 25 mmHg. Copper, 0.5 microM, also decreased cardiac function, but to a lesser degree. Catalase, 100 units/ml, was effective in preventing the copper-ascorbate induced cardiac damage while superoxide dismutase, 25 units/ml, was ineffective. Observations by light and electron microscopy demonstrated patchy regions with vacuolization corresponding to swollen mitochondria. These results clearly demonstrate that copper-catalyzed redox reactions can induce cardiac injury via a mechanism which appears to be related to the production of OH.

Animals↗

Development of the neonatal rat small intestinal barrier to nonspecific macromolecular absorption. II. Role of dietary corticosterone.

The role of oral corticosterone (C) in the maturation of the neonatal rat jejunal barrier to the absorption of nonspecific macromolecules was evaluated. This was done by adding C to the diet of rat pups weaned at an early age, 17 d, from maternal milk (MM) to either a protein hydrolysate (PH) or soy (S) artificial formula. Both PH and S are known to cause a delay in small intestinal closure to the absorption of a 40-kD glycoprotein tracer, horseradish peroxidase (HRP), on d 21 of age. C was added to PH and S formulas from d 17 to 21 at 0.26 mumol/L (10 micrograms/dL), a level found in the MM of lactating rat dams, or at 10.29 mumol/L (400 micrograms/dL) (PH + 10C, PH + 400C) (S + 10C, S + 400C). Controls consisted of rat pups fed PH or S without C and animals remaining with the dam on MM. The delay in jejunal closure to HRP on d 21 in both PH- and S-fed pups was prevented by C supplementation at both the higher and lower concentrations. Geometric mean (95% confidence intervals) jejunal HRP absorption in PH + 10C pups was 74 (32,167) IU HRP/mL x cm x min, less than in pups fed PH without C [353 (200,615); p less than 0.05] and indistinguishable from HRP absorption in MM-fed animals [111 (79,154)]. HRP absorption in PH + 400C pups [52 (23,115)] was also less than that in animals fed PH without C (p less than 0.01) and indistinguishable from those fed MM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Alanine stimulation of water and sodium absorption in a model of secretory diarrhea.

We investigated the effectiveness of L-alanine (Ala) addition to oral hydration solutions (OHSs) during secretory conditions induced by ileal instillation of 10 mM theophylline in anesthetized rats using a perfusion procedure, and monitoring water and sodium transport. Ala was added to two hypotonic OHSs in which the sodium:glucose ratio was 2:1, and compared with the OHS recommended by the World Health Organization (WHO), which has a sodium:glucose ratio of 0.81:1. Theophylline had the expected secretory effect on water and sodium absorption in the WHO-recommended OHS, and on sodium transport in a formula containing 60 mM sodium and 30 mM glucose. However, an OHS with 90 mM sodium and 45 mM glucose canceled the secretory effect of theophylline and yielded a greater rate of net water absorption than the WHO formula. Addition to this solution of either 15 or 30 mM Ala enhanced water and sodium absorption of both control and theophylline-treated rats. In the hypotonic OHS with 60 mM sodium and 30 mM glucose, Ala had little effect on both sodium and water transport. Therefore, the data support the view that Ala added to solutions with 90 mM sodium, containing sufficient glucose to maintain a sodium:glucose ratio of not less than 2:1, is most effective at compensating fluid and sodium losses under secretory conditions. Ala presumably exerts its sodium-sparing effect because of its cotransport with sodium and the consequent water influx into the intestinal cells.

Absorption↗

Development of the neonatal rat small intestinal barrier to nonspecific macromolecular absorption: effect of early weaning to artificial diets.

We studied the effect of early weaning from maternal breast milk to artificial diets on rat jejunal absorption of an exogenous 40-kD glycoprotein, horseradish peroxidase (HRP). Rat pups, fed maternal milk (MM) from birth, received one of three diets for the last 4 d before weaning (d 17-21): MM, protein hydrolysate formula (PH), or soy formula (S). Some rats were pretreated on d 14 with intraperitoneal hydrocortisone (5 mg/rat). In MM-fed rat pups, jejunal HRP absorption was markedly higher on d 17 than on d 21. [Geometric means (95% confidence interval) were: d 17, 626.4 (461.3, 850.6) versus d 21, 90.6 (48.2, 170.5) IU HRP/mL x cm x min, p less than 0.01.] By contrast, 21-d-old PH- and S-fed pups maintained elevated absorption of the tracer [PH, 292.3 (177.5, 480.6), p less than 0.05 versus MM pups, S, 340.8 (164.4, 704.8), p less than 0.01 versus MM pups]. Wt-matched control studies indicate that the difference in HRP absorption was not due to the smaller body wt of formula-fed pups. The increased absorption in formula-fed animals was suppressed by hydrocortisone. In S-fed pups, the increased macromolecular absorption appeared, in part, to be the result of diffusion across altered villus absorptive cells. In PH-fed pups, there was no evidence of damage and HRP absorption appeared to occur by vesicle-mediated transport. Delay in the normal maturation of small intestinal "closure" appears to be associated with early weaning to artificial diets. This may lead to increased nonspecific macromolecular permeability that could result in immune-mediated sensitization and food intolerance.

Age Factors↗

Stereologic analysis of monocytes and their subcellular organelles in patients with acute monocytic and myelomonocytic leukemia.

The stereologic characteristics of monocytes from patients with acute nonlymphocytic leukemia containing a monocytic component (FAB M4 and M5), and the monocytes from normal individuals were determined by morphometric analysis. The cells studied were monocytic cells beyond the promonocyte stage of development, as defined by ultrastructural criteria. Parameters evaluated included cell and nuclear volumes and surface areas, mitochondrial and myeloperoxidase (MPO)-positive secretory granule volume and numerical density as well as volume and number of the organelles/cell. Peripheral blood and bone marrow monocytes of leukemic patients could not be distinguished by their cell or organelle stereologic characteristics. Monocytes from patients with both M4 and M5 acute leukemia had relatively large cell and nuclear volumes. Mitochondrial volume density and volume/cell were also high in monocytes from leukemic patients (M4; 21 microns 3/cell, M5 20 microns 3/cell) as compared with monocytes from normal individuals (8.5 microns 3/cell). On the other hand, MPO-positive secretory granule stereologic parameters in monocytes from leukemic patients were indistinguishable from those of normal individuals. A small number (3 of 18) patients showed very low monocyte MPO-positive granule volume densities. There was a slight positive correlation between MPO-positive granule volume density and patient survival time. No relationship between mitochondrial characteristics and survival was noted.

Adult↗