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Biomedical subjects

L Herman

Publications and source records attributed to L Herman.

At least 37 records · Page 2Linked to original sources
PubMed1993

Glutathione depletion increases the cytotoxicity of melphalan to PC-3, an androgen-insensitive prostate cancer cell line.

Prostate cancer that is androgen-insensitive is unresponsive to a wide spectrum of cytotoxic agents, including all of the alkylating agents. Since a major pathway for the detoxification of the alkylating agents is conjugation with glutathione (GSH), GSH depletion has proved to be effective as a technique to restore melphalan sensitivity in melphalan-resistant cancer cell lines. However, the effect of GSH depletion has not been widely studied in tumor cell lines that have not developed resistance due to previous exposure to alkylating agents. Thus, we decided to investigate GSH depletion as a technique to increase melphalan cytotoxicity to PC-3 cells, an androgen-insensitive prostate cancer line. After 2 and 6 h incubation with 0.25-5 microM melphalan, virtually no effect was observed on either clonogenic lethality or MTT viability until 5 microM exposures. A 24-h incubation of the cells with 100 microM buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, reduced the GSH content by 70%-75%. Following GSH depletion, an increase in clonogenic lethality and a decrease in MTT viability occurred after exposure to concentrations as low as 0.25 microM. The dose modification factor ranged from 2.9 after 2 h incubation to 4.5 at 6 h. These results provide support for additional studies in prostate cancer for further investigation of GSH depletion as a technique to induce sensitivity to alkylating agents in this chemotherapy-resistant tumor.

Buthionine Sulfoximine↗
PubMed1993

Prospective comparison of T2-weighted fast spin-echo, with and without fat suppression, and conventional spin-echo pulse sequences in the upper abdomen.

PURPOSE: To evaluate use of fast spin-echo (FSE) magnetic resonance imaging with and without fat suppression in the liver and upper abdomen. MATERIALS AND METHODS: Conventional spin-echo (SE) T2-weighted, FSE T2-weighted, and fat-suppressed FSE T2-weighted images from 37 patients strongly suspected to have focal hepatic lesions were evaluated. RESULTS: Quantitative analysis demonstrated that fat-suppressed FSE imaging had the highest lesion-liver contrast-to-noise ratio; conventional SE imaging, the lowest. In a qualitative analysis, FSE imaging was preferred. In a rank order analysis, FSE imaging was preferred 83% of the time and fat-suppressed FSE imaging 17% of the time as regards overall image quality; fat-suppressed FSE imaging was preferred 64% of the time, FSE imaging 23% of the time, and conventional SE imaging 13% of the time as regards signal abnormality detection. CONCLUSION: FSE imaging with and without fat suppression is a potentially useful pulse sequence for evaluating the upper abdomen.

Abdomen↗
PubMed1992

Identification of Brucella spp. by using the polymerase chain reaction.

The application of two synthetic oligonucleotides as probes and as primers in the polymerase chain reaction is presented for a specific, sensitive, and quick identification of Brucella spp. The specific oligonucleotide sequences were chosen on the basis of a 16S rRNA sequence alignment between Brucella abortus and Agrobacterium tumefaciens.

Base Sequence↗
PubMed1990

Cloning and sequence analysis of truncated T-DNA inserts from Nicotiana tabacum.

Transgenic plants produced by Agrobacterium-mediated transformation usually have one or a few stable and intact T-DNA insertions. However, in a significant number of the transformants Southern blot analysis has revealed the occurrence of aberrant T-DNA insertions missing one or both ends. During the study of this phenomenon, we obtained KmR Nicotiana tabacum clones after cocultivation with an Agrobacterium strain containing a promoterless nptII gene located internally in the T-DNA. Expression of this nptII gene requires a break in the T-DNA region upstream from the nptII-coding sequence and insertion of the truncated T-DNA in a transcriptionally active plant DNA region. The most conspicuous result from Southern analyses on four such KmR plant clones is that they contain several T-DNAs truncated at other positions besides the upstream region of the nptII sequence. Four truncated T-DNA insertions have been cloned. Two insertions contain the nptII gene fused to plant expression signals and are missing the right part of the T-DNA. Another is missing the left T-DNA part and the last T-DNA is lacking both ends. Sequence analysis of the T-DNA::plant junctions has shown that the T-DNA breakpoints are randomly distributed and do not show obvious homologies to one another or to the border consensus sequence. S1-type mapping of the most strongly expressed plant genome::nptII fusion revealed a specific transcription start point and putative TATA and CAAT boxes in the upstream plant DNA region; the steady-state nptII mRNA in these plants is about 20 times more abundant than in transgenic Pnos-nptII plants.

Base Sequence↗
PubMed1990

Plant chromosome/marker gene fusion assay for study of normal and truncated T-DNA integration events.

During Agrobacterium tumefaciens infection, the T-DNA flanked by 24 bp imperfect direct repeats is transferred and stably integrated into the plant chromosome at random positions. Here we measured the frequency with which a promoterless reporter gene is activated after insertion into the Nicotiana tabacum SR1 genome. When adjacent to the right or left T-DNA border sequences, at least 35% of the transformants express the marker gene, suggesting preferential T-DNA insertion (greater than 70%) in transcriptionally active regions of the plant genome. When the promoterless neomycin phosphotransferase II (nptII) gene is located internally in the T-DNA, the activation frequency drops to 1% since gene activation requires T-DNA truncation. These truncation events in the nptII upstream region occur independently of the nature of the upstream sequence and of the T-DNA length. Deletion of the right border region prevents the detection of activated marker genes. Therefore, T-DNA truncation probably occurs after synthesis of a normal T-DNA intermediate during the transfer and/or integration process. In the absence of border regions, expression of the nptII selectable marker directed by the nopaline synthase promoter was detected in 1 out of 10(5) regenerated calli, suggesting the possibility that any DNA sequence from the Ti plasmid can be transformed into the plant genome, albeit at a low frequency.

Base Sequence↗
PubMed1990

Morphometry and elemental analysis of rat exocrine pancreas following administration of trypsin inhibitor.

The morphological responses of the exocrine pancreas of the adult male rat to soybean trypsin inhibitor (STI) were studied by ultrastructural morphometry and electron probe X-ray microanalysis. STI administered orally in drinking water for 14 days resulted in a 72% increase in the wet weight of the pancreas. This enlargement was due, largely, to an increase in acinar cell mass. Volume increases in the acinar cell mass and extra-acinar cell compartment were 72 and 30%, respectively. The estimated total number of acinar cells in the mean exocrine pancreas was 500 million in the control and 630 million in the experimental group, representing an increase of 27%. Acinar cell volume was 1,790 microns 3 for the control and 2,457 microns 3 for the STI group. The pronounced morphometric changes of the organelles in the STI group were: the mean nucleolar volume increased by 56%; the volume of zymogen granular mass per cell increased by 93%; the volume of the Golgi complex and the condensing vacuoles per cell increased by 52 and 100%, respectively, whereas the membrane area of the Golgi complex and the condensing vacuoles increased by 98 and 47%, respectively. Spectral analysis of seven elements (Na, Mg, P, S, Cl, K and Ca) showed significant changes for nuclei, zymogen granules and mitochondria following STI: nuclei showed Na, P, K increased; zymogen granules showed Na, P, S, K increased, Cl decreased; mitochondrial particles showed Mg, P, Cl, Ca increased, and the mitochondrial matrix showed S decreased. The persistent uptake of STI probably resulted in a continual release of a trophic hormone acting on pancreatic tissue components, consequently causing hyperplasia and hypertrophy of the exocrine pancreas to accommodate a heightened demand for synthesis of exportable proteins.

Animals↗
PubMed1988

Recurrent pulmonary oedema in hypertension due to bilateral renal artery stenosis: treatment by angioplasty or surgical revascularisation.

11 patients with atheromatous renovascular hypertension had a history of multiple episodes of pulmonary oedema. 7 had stenosis of both renal arteries, 2 had stenosis of the artery to a solitary kidney, and 2 had unilateral stenosis with an intact contralateral kidney. Successful revascularisation (by angioplasty in 8, and surgery in 3) improved blood pressure and renal function, and virtually eliminated pulmonary oedema. In a second series of 55 consecutive patients with azotaemia and renovascular hypertension, pulmonary oedema occurred in 13 (23%). Blood pressure and renal function were not significant predictors of pulmonary oedema, but coronary heart disease and bilateral (vs unilateral) renal artery stenosis were. Bilateral renal artery stenosis may be a specific and treatable predisposing factor to pulmonary oedema in azotaemic hypertensive patients.

Acute Disease↗
PubMed1988

Morphometric study of the rat exocrine pancreas after diversion of bile and pancreatic juice from the intestine.

The effects of 6 h of diversion of bile and pancreatic juice from the intestine on the ultrastructure of rat pancreatic acinar cells were studied by morphometric procedures. After diversion the volume of zymogen granules decreased markedly, representing a reduction of 77%. The volume of autophagic vacuoles increased twofold after diversion. The volume of rough endoplasmic reticulum and Golgi apparatus was not different from that of control. It has been proved by electron microscopic morphometry that the degree of reduction of zymogen granules was similar to that after stimulation by exogenous cholecystokinin or introduction of trypsin inhibitor to the duodenum. This suggests that hypersecretion caused by diversion is due to failure of a negative feedback regulation normally induced by proteases found in pancreatic juice. An increased number of autophagic vacuoles suggests an increase of organelle turnover due to heightened secretory activity of acinar cells.

Animals↗
PubMed1987

Disease manifestations of progressive systemic sclerosis: sensitivity and specificity.

The authors conducted a study of 47 patients with a diagnosis of systemic sclerosis in order to determine the sensitivity, specificity and Youden index and consequently the diagnostic value of the generally accepted criteria and of some other common disease features. The control population consisted of 324 patients with rheumatoid arthritis and 35 patients with systemic lupus erythematosus. In addition to proximal scleroderma, the presence of which was required for inclusion in this study, other disease features score a high to moderate Youden index: sclerodactyly, Raynaud's phenomenon, appearance of perioral grooves, cinematographic evidence of esophageal hypomotility, periarticular calcifications, widening of the periodontal membrane on teeth radiographs and specific histologic changes on fingertip biopsy. Finally, a good correlation was found with most of the ARA subcommittee criteria.

Adult↗
PubMed1987

The effect of low doses of prednisolone on T-cell subsets in rheumatoid arthritis.

Prednisolone intake causes a drop in the absolute numbers of circulating T-cell populations. OKT4+ (helper-inducer) cells are more susceptible to this. Higher doses are needed to depress OKT8+ (suppressor-cytotoxic) cell numbers. Administration of up to 10 mg prednisolone affects the suppressor-cytotoxic (OKT8+) absolute cell numbers only in patients with initially low OKT4+/OKT8+ ratios and not the values of OKT8+ cells in patients with high OKT4+/OKT8+ ratios, since these patients already have low OKT8+ cell counts.

Administration, Oral↗
PubMed1986

Mammography of women with suspicious breast lumps.

We analyzed 342 women who had suspicious breast lumps to determine if preoperative mammography could improve the malignancy yield of biopsy procedures. The number of women with cancer of the breast and false-negative mammogram reports ranged from 11% to 25%, depending on how equivocal mammogram reports were interpreted. Therefore, women with clinically suspicious breast lumps should undergo biopsy regardless of mammographic findings. A significant difference in the mean (+/- SD) predictive value of a positive mammogram existed between women above and below the age of 50 years (80 +/- 8 vs 43 +/- 14) because of the age-specific relative prevalence of benign and malignant disease, and because mammography had difficulty distinguishing between benign and malignant lumps (specificity, 70). Preoperative mammography of women with suspicious breast lumps is indicated to screen for occult carcinoma, to prevent biopsy sampling errors, and to judge the adequacy of lumpectomy if the lesion is malignant.

Adult↗
PubMed1986

Aneurysmal bone cysts: MR imaging at 1.5 T.

Two patients with aneurysmal bone cysts of the pelvis were imaged using a 1.5-T magnetic resonance imaging device. Findings included multiple internal septations, cysts with fluid-fluid levels of varying intensity, and an intact rim of low-intensity signal completely surrounding the lesion. These findings allow a specific diagnosis of aneurysmal bone cyst to be made.

Adolescent↗
PubMed1984

Structural studies of glycerinated skeletal muscle. I. A-band length and cross-bridge period in ATP-contracted fibers.

An electron microscope study is reported of structural changes during ATP-induced contraction of glycerinated rabbit psoas. In the absence of ATP, A-band length is constant at sarcomere lengths above 1.9 micron, with average length of 1.54 mu. In ATP-treated fibers, A-band length is also constant at sarcomere lengths above 2.0 microns, but the apparent length of A-band decreases to approximately 1.3 micron, as sarcomere length decreases from 1.9 micron to 1.5 mu. The occurrence of short A-bands cannot be attributed to crumpling of thick filaments against Z-lines, since I-bands remain patent; nor to the presence of heterogeneous filaments, since resting muscle does not show comparable heterogeneity, nor to compressive artifacts, which are minor when knife edge is oriented parallel with fiber axis during microtomy . The decrease of A-band length appears related, at least in part, to disarray of terminal cross-bridges as the thick filaments encroach upon the N-line, a structure which becomes evident within the I-band during contraction of glycerinated fibers. In preliminary studies, optical transforms of A-bands from individual sarcomeres reveal a characteristic myosin layer-line pattern as low as 1.5 micron sarcomere length. A cross-bridge repeat of 143 A is obtained for sarcomeres above 1.6 micron length; however, an appreciable proportion of sarcomeres in the range from 1.5 micron to 1.9 mu length generate meridional reflections less than 143 A, and as low as 130 A.

Adenosine Triphosphate↗
PubMed1981

Stereological analysis of normal rabbit pancreatic islets.

Stereological methods were applied to obtain morphometric data related to pancreatic islets of Langerhans in the normal rabbit. By light microscopy, it was found that 1 mm3 of pancreatic parenchyma contained 47.7 islets, constituting 2.2% of its volume. Approximately 69% of the islets had diameters less than 80 micrometer; 31% were greater than 80 micrometer. The former group of islets, however, composed only 13% of the volume of the endocrine pancreas and the latter group, 87%. Using electron microscopy, a unit volume of islet tissue was observed to consist of 86% beta cells, 7.7% alpha cells, and 2.2% delta cells. The average beta-cell volume was 1260 micrometer 3 and its cytoplasm consisted of 52.6% matrix, 12.7% rough endoplasmic reticulum, 10.2% secretory granules, 7.8% mitochondria, and 3.3% Golgi apparatus. A typical beta cell contained 662 mitochondria, intermediate (10-nm) filaments whose length totalled 50 mm, and 9,200 secretory granules with a ratio of four mature granules to each immature or "pale" granule. Within alpha and beta cells, three parameters were used for the quantitation of organelles or their component parts: 1) volume; 2) surface; and 3) numerical densities. In the beta cell, the surface densities of rough endoplasmic reticulum and Golgi membranes exceeded, by two- or threefold, their counterparts in alpha cells. Similarly, the number of beta-cell mitochondria exceeded by 30% that of alpha cells; but beta-cell mitochondrial volume was twice that of the alpha cell, as were surface densities of both inner and outer mitochondrial membranes. Volume and surface densities of secretory granules within beta cells were half the values obtained for alpha cells. An alpha cell contained three times the number of granules present in a beta cell.

Animals↗
PubMed1978

Ultrastructural localization of calcium in unfertilized sea-urchin eggs.

The pyroantimonate technique was employed to identify the binding sites for calcium in unfertilized Arbacia punctulata and Strongylocentrotus purpuratus eggs. Since antimony is non-specific and binds with a variety of cations, the indentification of calcium was established by specific chelation with ethyleneglycol tetra-acetic acid (EGTA) and X-ray microprobe analysis. Antimony deposits were observed on the egg's membranes, i.e. plasma, cortical (secretory) granule, pigment granule, smooth-surfaced vesicle, and yolk platelet. Deposits were also observed in the mitochondria, rod-containing vesicles, and the vitelline layer. Two types of yolk platelets were observed: a more numerous electron-opaque platelet which had precipitate along its limiting membrane as well as within the stored-matrix substance, and a less-frequently seen platelet with lower electron opacity which contained precipitate only along its limiting membrane. Deposits were reduced at all sites following exposure of eggs to EGTA either prior to or after osmium-antimonate fixation. Initial fixation in glutaraldehyde followed by postfixation in osmium-antimonate solutions provided better preservation of structure but less precipitation than direct fixation in osmium-antimonate. The organelle sites of calcium binding identified within unfertilized sea-urchin eggs may participate in stimulus-secretion coupling (exocytosis of the cortical granules) and the activation of embryogenesis at fertilization.

Animals↗
PubMed1975

Localization of a thrombin-sensitive calcium pool in platelets.

Electron microscopic x-ray microprobe analysis of pyroantimonate precipitates in platelets fixed in osmium tetroxide-pyroantimonate revealed calcium localization in the nucleoids of alpha-granules. This pool of calcium had largely disappeared within 10 sec after stimulation of platelets by thrombin. Such a rapid change suggests that this calcium pool may have a regulatory role in stimulus-response coupling.

Animals↗