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Biomedical subjects

S Roth

Publications and source records attributed to S Roth.

At least 235 records · Page 13Linked to original sources
PubMed1992

Immunorecognition of different ganglioside epitopes on human normal and melanoma tissues.

There is increasing evidence that cell-surface gangliosides play a role in tumor growth, progression and metastases. In order to determine the frequency of ganglioside GD3 in patients with metastatic malignant melanoma for further therapeutic trials, GD3 ganglioside expression was determined in 119 tissue samples. Of these melanomas, 93% (111/119) were R-24-positive, which indicates the value of this diagnostic marker for melanoma. To study the structural epitopes of gangliosides, 10 ganglioside antibodies with defined specificities and affinities were tested on over 100 fresh-frozen tissue specimens of human normal and melanoma tissues. All the antibodies tested recognize the ganglioside GD3, but vary in their cross-reactivity with other gangliosides. According to their epitope specificity, they can be divided into 5 groups. For example, the antibodies Z-21 and A-4 react like the previously established MAb R-24 with gangliosides GD3 and GQlb, and one MAb (Q-4) detects all gangliosides containing 2 connected sialic acids (GD3, GD2, GDlb, GTlb, GQlb). Specificity on TLC does not always correlate with specificity to melanoma tissues and vice-versa. For example, MAb A-4, which recognizes only GD3 and GQlb on TLC, shows no specific reactivity on tissues. Furthermore, antibodies with the same ganglioside specificity do not have the same staining pattern on human tissues. For example, MAb Z-21, which is directed against the same gangliosides as MAb R-24 on TLC, does not cross-react with as many neuroectodermal tissues as MAb R-24. Because of their distinct properties, some of these antibodies may be even more useful for immunodiagnosis and immunotherapy of malignant melanoma than MAb R-24.

Antibodies, Monoclonal↗
PubMed1992

The effects of isovolumic hemodilution on ocular blood flow.

Techniques by which retinal blood flow may be increased safely are potentially important in the treatment of retinal vascular disease. It was hypothesized that hemodilution, which increases cerebral blood flow, would also increase retinal blood flow. To investigate the physiological effects of hemodilution in the eye, ocular blood flow was measured in 14 cats using the radioactively labeled microsphere method. After the animals were anesthetized with halothane and oxygen, intraocular and systemic arterial pressure were recorded; blood flows were measured before and after isovolumic hemodilution to a hematocrit of 20-22% using 6% hydroxyethyl starch (a synthetic plasma expander with a molecular weight of 450 in 0.9% saline). In hemodiluted cats, retinal blood flow increased 71% from its baseline value (36.7 +/- 6.4 ml 100 g-1 min-1 to 62.9 +/- 6.4 ml 100 g-1 min-1, mean +/- S.E.M., P < 0.0001). Calculated retinal O2 delivery remained approximately constant, as the increased blood flow countered a significant decrease in arterial O2 content. Choroidal blood flow decreased (1297 +/- 140 ml 100 g-1 min-1 to 1051 +/- 144 ml 100 g-1 min-1) but the change was not statistically significant. Blood flows in the iris and sclera were not significantly altered. Hemodilution increased retinal blood flow without causing a redistribution in ocular blood flow.

Animals↗
PubMed1992

The effects of halothane on retinal and choroidal blood flow in cats.

Although general anesthesia frequently is used for eye surgery or used in experimental studies of circulation in the eye, few data are available describing its effects on ocular blood flow. The blood supply to the retina in humans and other mammals is derived from a dual circulation; the retinal vessels supply the inner neural layers while the choroidal vessels supply the outer retina. Both circulations are required for normal retinal function. Using radioactively labeled 15-microns microspheres containing Ce141, Sn113, or Nb95, blood flow was measured in the retina and choroid in cats (whose ocular circulation is similar to that of humans) and cerebral cortex during halothane anesthesia. In ten adult cats, retinal blood flow was 37 +/- 3, 54 +/- 6, and 59 +/- 4 ml.100 g-1.min-1 (mean +/- SEM) at 0.5, 1.0, and 1.5 MAC halothane, respectively, and corresponding values for cerebral cortical blood flow were 60 +/- 5, 69 +/- 6, and 98 +/- 14 ml.100 g-1.min-1 (mean +/- SEM), respectively. For both retinal and cerebral blood flows, values obtained at 1.0 and 1.5 MAC were significantly greater than those at 0.5 MAC (P less than 0.0167). In contrast to the effects on retinal blood flow, choroidal blood flow was significantly decreased during halothane anesthesia. Choroidal blood flow was 1,801 +/- 222, 1,309 +/- 167, and 1,091 +/- 126 ml.100 g-1.min-1 (mean +/- SEM) at 0.5, 1.0, and 1.5 MAC, respectively. Values obtained at 1.0 and 1.5 MAC differed significantly from those at 0.5 MAC (P less than 0.0167).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1992

The functional domains of the Drosophila morphogen dorsal: evidence from the analysis of mutants.

The dorsal (dl) protein is a member of the Rel family of transcription factors. It is distributed in a nuclear concentration gradient along the dorsoventral axis of Drosophila embryos and activates or represses a discrete set of zygotic genes in a concentration-dependent manner. The nuclear uptake of the dl protein is stimulated by products of the dorsal group genes but inhibited by the cactus (cact) product. To analyze the functional domains of the dl protein, we sequenced 11 dl alleles and studied their interaction with cact. Four of these alleles were found to result in carboxy-terminal truncations of the protein. A deletion of 80 carboxy-terminal amino acids abolishes the ability of dl protein to activate the expression of mesodermal genes. Larger deletions also affect the repressor function of dl. However, a protein consisting only of the Rel homologous region still acts as a weak repressor of zerknüllt transcription. A missense mutation in the presumptive DNA-binding domain causes a complete lack-of-function phenotype in trans to a deficiency but exerts a dominant-negative effect in trans to a wild-type copy of dl. These and genetic data with the alleles that produce truncated proteins indicate that dl oligomerizes. The proteins truncated at the carboxy-terminal end show increased levels of nuclear uptake dorsally, but they still respond to the cact-mediated inhibition of nuclear transport. Therefore, carboxy-terminal sequences influence the cytoplasmic retention, although a domain of dl-cact interaction residues in the amino-terminal portion.

Alleles↗
PubMed1992

Analysis of criteria for grading bladder cancer in urine cytological tumor diagnosis by means of an expert system.

An inductive expert system was used for the analysis of criteria for grading bladder carcinoma in urine cytological tumor diagnosis. This analysis seems necessary in order to provide a better standardization of grading and to avoid tumor grades, which are rather inhomogeneous with respect to morphology and prognosis. The analysis of the database by the inductive system shows a considerable variation of the cytomorphology of different bladder carcinomas graded as G2 tumors, whereas G1 and G3 tumors are more homogeneous groups respectively. Especially nuclear morphological criteria are important features for the detection of highly differentiated carcinomas, whereas nucleolar features might be helpful to assess the proliferative nature of the carcinoma. The future goal of avoiding a grading system with prognostically inhomogeneous tumor grades seems possible when using an inductive expert system for consultation.

Carcinoma, Transitional Cell↗
PubMed1992

Abnormal galactosylation of complex carbohydrates in cultured fibroblasts from patients with galactose-1-phosphate uridyltransferase deficiency.

An abnormality in galactosylation of complex carbohydrates may be important in the pathogenesis of the long-term complications of classic (galactose-1-phosphate uridyltransferase-deficient) galactosemia. The ability of nine galactosemic fibroblast preparations to be galactosylated with a purified galactosyltransferase was measured as an indicator of vacant sites where galactose would normally reside. The amount of galactose transferred to cell protein from galactosemic patients was significantly higher than that transferred to a group of seven controls (p less than 0.005). Galactosyltransferase activity of the galactosemic cell preparation toward N-acetylglucosamine was also significantly higher than normal (p less than 0.01), and there was a linear relationship between these two parameters in galactosemic but not normal cells. These findings suggest that there is defective galactosylation of galactosemic cell complex carbohydrates and that such cells increase their galactosyltransferase levels in an attempt to compensate for the defect. Defective galactosylation may be implicated as an etiologic factor in complications observed in galactosemic patients even when treated with galactose-restricted diets.

Carbohydrate Metabolism↗
PubMed1992

[The Bourne's test: a relevant contribution to the diagnosis of vesico-enteric fistulas].

Diagnostic verification of vesicoenteric fistulae is necessary in order to establish the indication for surgical therapy, but this is frequently difficult. This is because uroradiological and endoscopic methods are unreliable and the symptoms are often nonspecific. The Bourne test is a simple noninvasive screening method. If necessary, it can be supplemented by computer tomography. The problems are discussed with reference to a case report.

Adult↗
PubMed1992

Choroidal effusions in two patients with glomerulonephritis.

Two patients with renal disease and choroidal effusions are presented. The renal disease was mediated by humoral immunologic mechanisms as demonstrated by immunofluorescent studies of renal biopsies. Experimental and clinical studies provided evidence of simultaneous immune-complex deposition in both the renal glomerulus and the uvea of the eye. Immune-mediated vascular damage may result in glomerulonephritis and choroidal effusions.

Adult↗
PubMed1991

Misoprostol compared with sucralfate in the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcer. A randomized, controlled trial.

OBJECTIVES: To compare the efficacy and frequency of adverse experiences of misoprostol and sucralfate in the prevention of gastric ulcers in patients receiving nonsteroidal anti-inflammatory drug (NSAID) therapy. DESIGN: A prospective, randomized, single-blind, multicenter trial. PATIENTS: Patients with osteoarthritis receiving treatment with ibuprofen, piroxicam, or naproxen and experiencing abdominal pain were eligible. INTERVENTIONS: Patients who were expected to receive at least 3 months of NSAID therapy and who did not have a gastric ulcer at the time of the initial screening endoscopy were randomized to receive misoprostol, 200 micrograms four times a day, or sucralfate, 1 g four times a day. A gastric ulcer was defined as a lesion of the gastric mucosa 0.3 cm or greater in diameter. Patients were followed clinically, and repeat endoscopies were performed after 4, 8, and 12 weeks. MAIN MEASUREMENT: The development of a gastric ulcer, which was regarded as a prophylaxis failure. RESULTS: Two hundred fifty-three patients were evaluable for efficacy analysis. A gastric ulcer developed in 2 of the 122 (1.6%, 95% CI, 0.3% to 6.4%) patients on misoprostol, compared with 21 of 131 patients on sucralfate (16%, CI, 10.4% to 23.7%). The difference in ulcer rates was 14.4% (CI, 10.4% to 19.5%; P less than 0.001). CONCLUSION: In patients receiving chronic NSAID therapy for osteoarthritis, treatment with misoprostol for 3 months was associated with a significantly lower frequency of gastric ulcer formation, compared with treatment with sucralfate (P less than 0.001).

Adult↗
PubMed1991

The polarity of the dorsoventral axis in the Drosophila embryo is defined by an extracellular signal.

Twelve maternal effect loci are required for the production of Drosophila embryos with a correct dorsoventral axis. Analysis of mosaic females indicates that the expression of the genes nudel, pipe, and windbeutel is required in the somatic tissue, presumably in the follicle cells that surround the oocyte. Thus, information coming from outside the egg cell influences dorsoventral pattern formation during embryogenesis. In transplantation experiments, the perivitelline fluid from the compartment surrounding the embryo can restore dorsoventral pattern to embryos from females mutant for nudel, pipe, or windbeutel. The positioning of the transplanted pervitelline fluid also determines the polarity of the restored dorsoventral axis. We propose that the polarizing activity, normally present at the ventral side of the egg, is a ligand for the Toll receptor. Presumably, local activation of the Toll protein by the ligand initiates the formation of the nuclear concentration gradient of the dorsal protein, thereby determining dorsoventral pattern.

Alleles↗
PubMed1991

Regulation of interleukin 2 production, interleukin 2 mRNA expression and intracellular glutathione levels in ex vivo derived T lymphocytes by lactate.

The concentration of L-lactate in the blood plasma of higher vertebrates is about 1 mM but can be as high as 30 mM under certain physiological and pathological conditions or in the vicinity of glycolytically active cells including macrophages. Here we report that high but physiologically relevant concentrations of lactate increase the expression of interleukin 2 (IL 2)-specific mRNA and the production of IL 2 activity in cultures of mitogenically stimulated T cells. Lactate supports IL 2 production most effectively if added 0-8 h after T cell stimulation and only in cultures of CD4+ but not of CD8+ T cells. In contrast to the DNA synthesis activity in these cell cultures, IL 2 production is not augmented but rather inhibited by exogenous glutathione (GSH). Lactate causes a reduction of intracellular GSH levels, and lactate-containing cultures require accordingly higher extracellular cysteine concentrations than control cultures to achieve similar intracellular GSH levels. In view of the strong variations of extracellular lactate concentrations in vivo, our experiments suggest that lactate may be part of a previously unknown mechanism by which the metabolic microenvironment modulates gene expression in T cells.

Animals↗
PubMed1991

Regulation of intracellular glutathione levels and lymphocyte functions by lactate.

The plasma concentration of lactate varies strongly under physiological and pathological conditions in the range of 1 to 30 mM. High but physiologically relevant lactate concentrations were previously shown to exert strong immunopotentiating effects and to augment the production of interleukin 2 (IL-2). However, the lactate derivative pyruvate can form covalent complexes with cysteine, suggesting the possibility that lactate may affect indirectly intracellular glutathione (GSH) levels and GSH-dependent lymphocyte functions. The experiments in this report now showed that 20-30 mM lactate had virtually no effect on the viability and intracellular protein content of mitogenically stimulated accessory cell-depleted splenic T cells or unfractionated spleen cells but indeed caused a marked decrease of the intracellular GSH level when compared with control cultures after 40-70 hr of incubation. The DNA synthesis of mitogenically stimulated splenic T cell cultures, i.e., a strongly GSH-dependent function, was also inhibited by lactate. This effect was overcome by high extracellular concentrations of GSH or cysteine. Lactate also inhibited the IL-2 consumption in mitogenically stimulated CD8+ T cell cultures and the activation of cytotoxic T lymphocytes in the late phase of mixed lymphocyte cultures. Additional experiments showed, finally, that lactate augments the incorporation of [14C]aspartate into 18 S and 28 S RNA, while incorporation of [14C]uridine is moderately inhibited, indicating that the de novo synthesis of pyrimidine nucleosides is markedly augmented in cells that are exposed to high extracellular lactate concentrations. Taken together, these studies show that high but physiologically relevant concentrations of lactate exert strong positive and negative effects on distinct aspects of T cell-mediated immune responses.

Animals↗
PubMed1991

Effects of fenoldopam on renal blood flow and systemic hemodynamics during isoflurane anesthesia.

The authors compared the systemic hemodynamic and renal vascular effects of hypotension induced by fenoldopam with those produced by the most commonly used hypotensive agent, sodium nitroprusside, in 10 dogs. Mean arterial pressure decreased 26% +/- 3% from control following infusion with fenoldopam, and 30% +/- 2% following infusion with sodium nitroprusside (these decreases were not significantly different between the groups). Renal blood flow (RBF) was preserved during fenoldopam-induced hypotension (214 +/- 16 mL/min at baseline and 197 +/- 16 mL/min after fenoldopam-induced hypotension). In contrast, RBF decreased from 223 +/- 17 mL/min to 167 +/- 12 mL/min during sodium nitroprusside-induced hypotension (P less than 0.02). The differences in RBF between the two groups occurred in spite of the fact that cardiac output and pulmonary capillary wedge pressure were kept similar between the two groups. The authors conclude that fenoldopam, a selective dopamine1 (DA1) receptor agonist, preserves blood flow to the kidney during induced hypotension. On the other hand, sodium nitroprusside is a nonselective arteriolar and venous vasodilator that redistributes blood flow away from the kidneys during induced hypotension.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Microscopic hematuria: advances in identification of glomerular dysmorphic erythrocytes.

The high diagnostic sensitivity and specificity of microscopically visible, typically glomerular dysmorphic erythrocytes for identification of the cause of glomerular bleeding have been recognized worldwide. Although glomerular dysmorphic erythrocytes are simple to detect on phase contrast microscopy, immediate microscopic diagnosis still is indispensable, since a change in the morphology of the erythrocytes with restriction of the diagnostic relevance is anticipated because of the high autolytic potency of the urine. It may be postulated that this need for immediate diagnosis has led to the method being neglected owing to the high work load at hospitals and physician offices. Moreover, a physician who does not perform microscopic investigations or who lacks experience with the method will not be able to use this diagnostic technique, since it appeared to be impossible to transport urine samples by mail. In the context of a study comprising 30 patients, of whom 10 had histologically confirmed glomerulonephritis, we have shown that glomerular dysmorphic erythrocytes have a manifest form stability for at least 3 days. The preservative used was thimerosal. Also, the urine can be investigated independent of time even after alcoholic Papanicolaou staining without an alteration of erythrocyte morphology. The practicality of the form stability of glomerular erythrocytes can be exploited in everyday medical routine. There are well founded prospects that the rate of early diagnosis of glomerulonephritis will increase.

Erythrocytes, Abnormal↗
PubMed1991

Fourier analysis as a planimetric procedure--application to malignant and normal urothelial cells with reactive changes.

The shape of urothelial cell nuclei in 27 urinary cytological preparations has been quantified by means of Fourier analysis. Fourier amplitudes were calculated as parameters of the nuclear shape. The T-test and a discriminance analysis showed significant differences in nuclear shape between preparations with malignant urothelial cells and nonmalignant cells with reactive changes. Only one preparation was reclassified false-negatively. No preparation was reclassified false-positively. No significant differences were found between normal cells with and without reactive changes. Thus it can be concluded that nuclear shape is an important criterion for the diagnosis of urothelial carcinomas in urinary cytological preparations. Fourier analysis allows the complete reproduction of the convex shape of a nucleus and it seems to be useful as an additional quantitative procedure in the diagnosis of malignant tumours.

Carcinoma, Transitional Cell↗
PubMed1991

A laboratory study of glass ionomer cement as a retrograde root-filling material.

This laboratory study investigated the use of various glass ionomer cements for retrograde root filling from the point of view of sealing qualities, ion release and ease of application. The sealing qualities of the material were tested by dye penetration and microscopic and SEM examination. Fluoride and silver ion release tests showed an initial loss of these two ions from the glass ionomer cement. A modified system for mixing and application was developed. Dye penetration did not differ from that of controls using vertically condensed gutta-percha. Glass ionomer cement is possibly a clinical alternative for the sealing of retrograde cavities; however, the silver-reinforced materials may cause tissue irritation from release of silver ions and their corrosion products.

Cermet Cements↗
PubMed1991

cactus, a maternal gene required for proper formation of the dorsoventral morphogen gradient in Drosophila embryos.

The dorsoventral pattern of the Drosophila embryo is mediated by a gradient of nuclear localization of the dorsal protein which acts as a morphogen. Establishment of the nuclear concentration gradient of dorsal protein requires the activities of the 10 maternal 'dorsal group' genes whose function results in the positive regulation of the nuclear uptake of the dorsal protein. Here we show that in contrast to the dorsal group genes, the maternal gene cactus acts as a negative regulator of the nuclear localization of the dorsal protein. While loss of function mutations of any of the dorsal group genes lead to dorsalized embryos, loss of cactus function results in a ventralization of the body pattern. Progressive loss of maternal cactus activity causes progressive loss of dorsal pattern elements accompanied by the expansion of ventrolateral and ventral anlagen. However, embryos still retain dorsoventral polarity, even if derived from germline clones using the strongest available, zygotic lethal cactus alleles. In contrast to the loss-of-function alleles, gain-of-function alleles of cactus cause a dorsalization of the embryonic pattern. Genetic studies indicate that they are not overproducers of normal activity, but rather synthesize products with altered function. Epistatic relationships of cactus with dorsal group genes were investigated by double mutant analysis. The dorsalized phenotype of the dorsal mutation is unchanged upon loss of cactus activity. This result implies that cactus acts via dorsal and has no independent morphogen function. In all other dorsal group mutant backgrounds, reduction of cactus function leads to embryos that express ventrolateral pattern elements and have increased nuclear uptake of the dorsal protein at all positions along the dorsoventral axis. Thus, the cactus gene product can prevent nuclear transport of dorsal protein in the absence of function of the dorsal group genes. Genetic and cytoplasmic transplantation studies suggest that the cactus product is evenly distributed along the dorsoventral axis. Thus the inhibitory function that cactus product exerts on the nuclear transport of the dorsal protein appears to be antagonized on the ventral side. We discuss models of how the action of the dorsal group genes might counteract the cactus function ventrally.

Alleles↗