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Biomedical subjects

S Segal

Publications and source records attributed to S Segal.

At least 145 records · Page 8Linked to original sources
PubMed1995

In vivo oxidation of [13C]galactose in patients with galactose-1-phosphate uridyltransferase deficiency.

We developed an intravenous and oral [13C]galactose breath test for the in vivo study of galactose metabolism. Following an intravenous bolus of 7 mg/kg of [1-13C]galactose in the fasting state, normal children and adults eliminated 3-6% and 21-47% of the bolus as 13CO2 in expired air collected over 1 and 5 h, respectively. Comparable fractional elimination was seen when the dose was given orally. Patients with galactosemia who have barely detectable or absent galactose-1-phosphate uridyltransferase (GALT) activity in erythrocytes and are homoallelic for the Q188R gene mutation, when given a 7 mg/kg intravenous bolus had barely detectable 13CO2 in air samples in the first hour, but eventually eliminated as much as 3.6% of the dose in 5 h. A galactosemia/Duarte (Q188R/N314D) compound heterozygote and a homozygous Duarte subject, as well as a subject with one normal allele and one Q188R allele, showed normal in vivo oxidation. An assessment of whole body galactose metabolism can be made with this procedure. Further use of this in vivo modality in patients with different genetic backgrounds should increase our understanding of genotype-phenotype relationships in hereditary galactosemia.

Adolescent↗
PubMed1995

Uterine adenofibroma presenting as a cystic adnexal mass.

Uterine adenofibroma is a form of mixed mesodermal tumor in which both the epithelial and stromal components are benign. Almost all previously reported cases have been confined to the endometrium or endocervical mucosa. Our patient presented with a cystic adnexal mass and had a hysterectomy.

Adenofibroma↗
PubMed1995

Defective galactosylation in galactosemia: is low cell UDPgalactose an explanation?

There is circumstantial evidence that defective galactosylation of complex glycoconjugates exists in tissues from galactosemic patients. Whether this is an etiologic factor in the long-term complications of the disorder is not known. Also not evident is the basis for the impaired galactosylation. The hypothesis that abnormally low cellular uridine diphosphate galactose (UDPgal) content is responsible has not been established. There is a tendency for galactosemic red cell UDPgal to be in the low normal range with a high uridine diphosphate glucose to UDP-gal ratio. This may reflect an inability of red cell UDPgal-4'-epimerase to maintain a normal ratio and consequently higher levels of UDPgal. In the more complex white blood cells and cultured fibroblasts, the UDPgal content and the uridine diphosphate glucose to UDPgal ratio of galactosemics are normal. Therefore, defective galactosylation observed in galactosemic fibroblasts must result from a defect in the transfer of galactose from UDPgal to these moieties.

Galactose↗
PubMed1995

In utero galactose intoxication in animals.

To assess in utero effects of galactose, diets containing large amounts of the sugar have been fed to pregnant rats with examination of the fetuses and newborns. Galactose levels in fetal blood parallel those of the dam and amniotic fluid contains high concentrations of galactose and galactitol. In the offspring and in the fetuses cataracts, and a decrease in brain weight, protein content and DNA are observed. There is an elevated content of galactitol and decrease in myo-inositol in the brain of galactose-intoxicated newborns. Brain synaptosomes of young rats whose mothers were fed galactose show a reduced response in vitro to acetylcholine as evidenced by a decrease in incorporation of myo-inositol into phosphatidylinositol and an inappropriate change in phosphatidylinositol content. The data indicate that there can be significant effects in the offspring of pregnant rats fed a high galactose diet. The findings support the concept that in utero toxicity may occur in the human galactosemic fetus.

Animals↗
PubMed1995

Galactosemia unsolved.

Classic galactosemia is an enigmatic disorder that presents the challenge of unraveling the basis of the long-term complications of mental disability, speech defects, ovarian failure and neurologic syndromes which occur despite a galactose-restricted diet. A complete understanding of the pathobiochemistry and molecular genetics, and evaluation of the present theories for the poor long-term outcome, continuous intoxication, critical metabolite depletion and in utero damage is needed in order to design new therapeutic strategies. Answering this urgent question of how to treat galactosemic patients mandates enhanced clinical and basic research efforts.

Galactosemias↗
PubMed1995

Comparison of erythrocyte uridine sugar nucleotide levels in normals, classic galactosemics, and patients with other metabolic disorders.

By limiting galactosylation mechanisms, a cellular deficiency of the uridine sugar nucleotide, UDPgalactose, has been implicated as a cause of the long-term complications seen in patients with classic galactosemia despite dietary treatment. As a result, great interest has been generated in the accurate assessment of UDPgalactose, as well as UDPglucose, from which UDPgalactose may be derived by the function of a ubiquitous, active UDPgalactose-4-epimerase. Since several series of values for the concentration of these compounds in red blood cells (RBCs) of galactosemics have been flawed by the use of methods subsequently shown to be unsuitable, we have quantified erythrocyte UDPgalactose and UDPglucose levels by an accurate high-performance liquid chromatography (HPLC) assay in 116 normals, 76 galactosemics, and 39 patients with other metabolic disorders. These large groups have permitted the evaluation of age, diet, and genotype as influential factors in the steady-state RBC levels of the sugar nucleotides. The data show that age is an important determinant of RBC levels, with children younger than 10 years having higher values than individuals older than 10 years. Mean UDPgalactose levels in galactosemic children younger than 10 years and those older than 10 years were 30% and 18% lower, respectively, than levels in comparable normals. Although the mean differences were highly significant, there was considerable overlap of individual values. There was no difference in UDPglucose levels between galactosemics and normals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Bridging the professions: an integrated and interdisciplinary approach to teaching health care ethics.

In 1993, the authors introduced an interdisciplinary course in health care ethics at the University of British Columbia. They were motivated by two convictions: (1) an interdisciplinary approach to health care decision making is best; and (2) every significant health care decision has an ethical component. They wanted to encourage students from the various health care disciplines to participate in interdisciplinary decision making in their future practices by giving them an opportunity to study health care ethics together during their training. The authors give detailed descriptions of the objectives, format, curriculum, and evaluation of this innovative course in the hope that other educators who may want to develop similar courses can learn from their experience.

British Columbia↗
PubMed1995

Expression of c-myc and c-ras oncogenes in the neoplastic and non-neoplastic cells of Hodgkin's disease.

The oncogenes c-myc and c-ras are known to elicit a cooperative tumorigenicity. In this study we investigated their role in the pathogenesis of Hodgkin's disease. The expression of these oncogenes was determined in Hodgkin's disease patients by avidin-biotin peroxidase complex immunohistochemical staining and was compared to their expression in patients with non-Hodgkin's lymphomas and inflammatory reactive lymph nodes. Of 29 examined patients with different histological types of Hodgkin's disease, 21 (72.4%) showed an elevated expression of c-myc and 28 (96.5%) of c-ras. Although this expression was marked especially in the neoplastic Reed-Sternberg cells, it was also noted in the numerous reactive cells present in the involved lymph nodes. By contrast, a much lower frequency of increased expression of these oncogenes was recorded in 19 patients with different grades of non-Hodgkin's lymphoma and in 29 patients with inflammatory reactive lymph nodes. The elevated expression of c-myc and c-ras in the neoplastic Reed-Sternberg cells may reflect an oncogenic event that directly activates these genes. However, their increased expression in the surrounding non-neoplastic cells probably results from signal transduction induced by certain growth-promoting factors possibly released by the Reed-Sternberg cells and that act paracrinally to stimulate the proliferation of the neighboring cells. Furthermore, the continuous c-ras elevation may impair the normal cell cycle control and thereby promote mutagenesis and overt malignancy.

Gene Expression↗
PubMed1995

Thymidylate synthase binds to c-myc RNA in human colon cancer cells and in vitro.

Using an immunoprecipitation-reverse transcription-PCR technique, we characterized a thymidylate synthase (TS) ribonucleoprotein complex in cultured human colon cancer cells that consists of TS protein and the mRNA of the nuclear oncogene c-myc. TS protein is complexed in intact cells with the C-terminal coding region of c-myc mRNA that includes nucleotide positions 1625 to 1790. RNA electrophoretic gel mobility shift assays confirm a specific interaction between TS protein and c-myc mRNA and provide additional evidence that the C-terminal coding region represents an important cis-acting regulatory element. Further evidence demonstrates that the in vitro translational efficiency of c-myc mRNA is inhibited as a result of its direct interaction with TS protein. In addition, the presence of exogenous c-myc mRNA specifically relieves the inhibitory effects of TS protein on TS mRNA translation.

Base Sequence↗
PubMed1995

Evaluation of breast stimulation for induction of labor in women with a prior cesarean section and in grandmultiparas.

BACKGROUND: Information on the efficacy of breast stimulation for inducing labor in grandmultiparas and in women with a previous cesarean section with or without premature rupture of membranes is limited. METHODS: Retrospective study of labor data from 135 women of grand multiparity or those with a previous section with or without premature rupture of the membranes in whom labor was induced by breast stimulation. RESULTS: The success rate in achieving vaginal delivery was 84%. The duration of breast stimulation, length of labor, vaginal delivery rate, and Apgar score did not differ significantly among the four groups studied. CONCLUSION: Breast stimulation in grandmultiparas and in women with a previous cesarean section is efficacious and safe.

Adult↗
PubMed1994

Inhibition of topoisomerase I activity by tyrphostin derivatives, protein tyrosine kinase blockers: mechanism of action.

DNA topoisomerase I (topo I) is a member of a group of essential nuclear enzymes which control and modify the topological state of DNA and is recognized as the target for anticancer drugs. During the course of the catalytic activity of topo I, a covalent bond is formed between a tyrosine group at the active site of the enzyme and a 3' phosphate group along the DNA backbone. This chemical reaction resembles the protein kinase-mediated tyrosine phosphorylation process. We assumed, therefore, that tyrphostins, potent and selective blockers of protein tyrosine kinases, might affect topo I activity. We found that of three derivatives of tyrphostins (AG-555, AG-18, and AG-213) that inhibited topo I activity in an in vitro assay, AG-555 was the most active. Examination of the mechanism by which these compounds act as topo I inhibitors revealed that AG-555 blocked the binding of this enzyme to the DNA due to its interaction with the topo I enzyme. We showed that its mode of action differed from that observed for camptothecin, a known topo I inhibitor. However, AG-555 did not affect the activity of other major DNA binding enzymes (i.e., DNA ligase, DNA polymerase I, and reverse transcriptase). This study suggests that tyrphostins may serve as a new class of topo I inhibitors, and these results also present additional explanations for their antiproliferative effect.

3T3 Cells↗
PubMed1994

Oral sustained-release ritodrine as a substitute for prolonged intravenous tocolysis.

Prolonged administration of intravenous ritodrine is necessary in some pregnant women with recurrent preterm labor as serum levels achieved by oral administration of ritodrine are insufficient to prevent recurrent contractions. New oral sustained-release ritodrine at 320 mg/day was given to 38 women with recurrent preterm labor. Serum levels of the drug at this dosage are considered comparable with levels achieved by i.v. treatment. The average duration of treatment was 8 days (range, 1-22). Patient tolerance was acceptable, and major maternal complications did not occur. We conclude that in selected cases, it may be possible to substitute oral sustained-release ritodrine at 320 mg/day for prolonged i.v. treatment.

Administration, Oral↗
PubMed1994

Invasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation.

The met protooncogene product, Met, is the tyrosine kinase growth factor receptor for hepatocyte growth factor/scatter factor (HGF/SF). NIH 3T3 cells express HGF/SF endogenously and become tumorigenic in nude mice via an autocrine mechanism when murine Met is expressed ectopically (Metmu cells) or when human Met and human HGF/SF are coexpressed (HMH cells). Here, we show that Metmu and HMH cells are invasive in vitro and display enhanced protease activity necessary for the invasive phenotype. In experimental and spontaneous metastasis assays, Metmu or HMH cells metastasize to the lung, but lower numbers of subcutaneously injected Metmu and HMH cells produced invasive tumors in the heart, diaphragm, salivary gland, and retroperitoneum. It has been reported elsewhere that Met expression increased with tumor passage in athymic nude mice, and these tumor explants show enhanced activity in the metastasis assays. Autocrine-mediated Met-HGF/SF signal transduction in NIH 3T3 mesenchymal cells may provide an important system for understanding the biological process of metastasis.

3T3 Cells↗