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Biomedical subjects

S Segal

Publications and source records attributed to S Segal.

At least 37 records · Page 2Linked to original sources
PubMed2001

The role of MHC class I glycoproteins in the regulation of induction of cell death in immunocytes by malignant melanoma cells.

A deranged expression of MHC class I glycoproteins, characteristic of a variety of malignancies, contributes to the ability of cancer to avoid destruction by T cell-mediated immunity. An abrogation of the metastatic capacity of B16 melanoma cells has been achieved by transfecting an MHC class I-encoding vector into class I-deficient B16 melanoma clones [Gorelik, E., Kim, M., Duty, L. & Galili, U. (1993) Clin. Exp. Metastasis 11, 439-452]. We report here that the deranged expression of class I molecules by B16 melanoma cells is more than a mere acquisition of the capacity to escape immune recognition. Namely, cells of the B16 melanoma prompted splenic lymphocytes to commit death after coculture. However, a class I-expressing and nonmetastatic CL8-2 clone was found to be less potent as an inducer of apoptosis than class I-deficient and metastatic BL9 and BL12 clones. Both Thy1.2(+) and Thy1.2(-) splenocytes underwent cell death when exposed to the class I-deficient BL9 clone. A proportion of CD4(+) and CD8(+) cells among splenocytes exposed to the BL9 clone was lower than that observed in a coculture with cells of the CL8-2 clone. Consistently, none of the melanoma clones studied produced a ligand to the FAS receptor (FAS-L). Thus, our results provide evidence that (i) the production of FAS-L may not be the sole mechanism by which malignant cells induce apoptosis in immunocytes, and (ii) absence of MHC class I glycoproteins plays an important role in preventing the elimination of potential effector immunocytes by tumor cells.

Alleles↗
PubMed2001

Proton magnetic resonance spectroscopy of brain metabolites in galactosemia.

Brain edema may occur in infants with galactosemia and has been associated with accumulation of galactitol. Proton magnetic resonance spectra were obtained from 12 patients (four newly diagnosed neonates and eight patients on galactose-restricted diets, age range 1.7-47 years) and control subjects to measure brain galactitol levels in vivo and correlate them with urinary galactitol excretion. The results demonstrate that a markedly elevated brain galactitol level may be present only in newborn infants with galactosemia who exhibit massive urinary galactitol excretion.

Adolescent↗
PubMed2001

Galactose metabolism in normal human lymphoblasts studied by (1)H, (13)C and (31)P NMR spectroscopy of extracts.

The development of tools to follow and quantitate the fate of galactose in mammalian cells is crucial to the study and understanding of the inherited disorders of galactose metabolism. In this study we incubated normal human lymphoblasts with 1- or 2-(13)C galactose for 2.5 or 5 h and prepared TCA extracts of the cells. The various galactose metabolites were identified and quantified using a combination of proton, carbon and phosphorus NMR spectra. Galactose-1-phosphate (gal-1P), uridine diphosphogalactose, uridine diphosphoglucose and galactitol were present in the extracts. Average levels for gal-1P were around 10 nmol/mg protein and for uridine diphosphoglucose, uridine diphosphogalactose and galactitol in the range of 0.5-2 nmol/mg protein. Galactonate was never found in any conditions. Percentage labeling could be estimated for gal-1P and for the ribose carbons of AMP. The labeling agrees with a conversion of galactose to glucose through the Leloir pathway.

Carbon Isotopes↗
PubMed2001

Evidence for alternate galactose oxidation in a patient with deletion of the galactose-1-phosphate uridyltransferase gene.

The persistent, dietary-independent elevation of galactose metabolites in patients with galactose-1-phosphate uridyltransferase (GALT) deficiency is probably secondary to de novo synthesis of galactose. Relatively constant steady-state levels of galactose metabolites in patients also suggest that non-GALT metabolic pathways must function to dispose of the galactose synthesized each day. The discovery of a patient with a rare deletion of the GALT gene provided a unique opportunity to examine the availability of any alternate galactose oxidative capacity both in vivo and in vitro. Utilizing genomic DNA from the patient, Southern blot data demonstrated that 10 of the 11 GALT exons were homozygously deleted. By measurement of 13CO2 in expired air for up to 24 h after an oral bolus of [1-13C]galactose, it was demonstrated that 17% of the galactose was metabolized, a value comparable to the 3-h elimination rate in a control subject. Furthermore, lymphoblasts prepared from the patient could also convert [1-14C]galactose to 14CO2. This unique study provides the first unambiguous evidence that another pathway exists in man that can be responsible for galactose disposal. Further knowledge of this alternate galactose oxidative route and its regulation may aid in formulating new strategies for the treatment of galactosemia.

Blotting, Southern↗
PubMed2001

Galactose metabolism in mice with galactose-1-phosphate uridyltransferase deficiency: sucklings and 7-week-old animals fed a high-galactose diet.

Mice deficient in galactose-1-phosphate uridyltransferase (GALT) demonstrate abnormal galactose metabolism but no obvious clinical phenotype. To further dissect the pathways of galactose metabolism in these animals, galactose oxidation and metabolite levels were studied in 16-day-old sucklings and the effect of a 4 week prior exposure to a 40% glucose or 40% galactose diet was determined in 7-week-old mice. Suckling GALT-deficient (G/G) mice slowly oxidized [1-14C]galactose to 14CO2, 4.0% of the dose when fed and 7.9% when fasted compared to normal animals 38.3 and 36.4% in 4 h, respectively. Plasma of G/G sucklings contained 11.1 mM galactose and erythrocyte galactose 1-phosphate levels were 28.2 and 31.9 mg/dl packed cells. Galactose, galactitol, galactonate, and galactose 1-phosphate were found in G/G suckling mouse tissues. The tissue galactose concentrations were 10% or less of that in plasma, suggesting that there was limited cellular entry of galactose. In 7-week-old fasted mice with 4 weeks prior exposure to glucose or galactose-containing diet, 4-h oxidation was 12.9 and 15.0% of the administered radiolabeled galactose, respectively. Normal animals oxidized 33.9 and 37.9% of the dose when fed the same diets, respectively. The ability of G/G mice to oxidize galactose in the absence of GALT activity suggests the presence of alternate metabolic pathways for galactose disposition. G/G mice fed the galactose-free 40% glucose diet had erythrocyte galactose 1-phosphate levels ranging from 6.4 to 17.7 mg/dl packed cells and detectable galactose and galactose metabolites in tissues, suggesting that these animals endogenously produced galactose. The plasma of 40% galactose-fed G/G mice contained 9.1 mM galactose with red blood cell galactose 1-phosphate averaging 43.6 mg/dl. Tissues of these animals also contained high levels of galactose and galactose 1-phosphate. Liver contained over 4 micromol/g galactonate but little galactitol. Despite the elevated galactose and galactose 1-phosphate, the animals tolerated the high-galactose diet and were indistinguishable from normal animals, exhibiting no manifestations of galactose toxicity seen in human GALT-deficient galactosemia. The data suggest that high galactose 1-phosphate levels do not cause galactose toxicity and that high galactitol in combination with galactose 1-phosphate may be a prerequisite. Absence of GALT appears necessary but insufficient to produce human galactosemic phenotype.

Animals↗
PubMed2001

Survey of the use of intracranial pressure monitoring in children in the United Kingdom.

OBJECTIVE: To establish current practice for the monitoring and management of acute intracranial hypertension in children in United Kingdom intensive care units (ICUs). DESIGN: Postal questionnaire, targetted by prior telephone survey, to all ICUs admitting five or more children per annum with acute neurological illness. RESULTS: Of the units contacted 70 % responded, approximately one-half of which reported the use of intracranial pressure (ICP) monitoring. Only data from these units are presented. Nearly all of these units consider monitoring following serious head injury, but its use in non-traumatic brain injury is less widespread. The decision to institute ICP monitoring is based mainly upon neuroimaging appearances and Glasgow Coma Scale score. ICP and cerebral perfusion pressure targets differ markedly between centres, with only 46 % and 65 % of units, respectively, setting age-dependent parameters. Mannitol and varying degrees of hyperventilation are employed by all units to lower ICP. The majority also use barbiturates, diuretics, and fluid restriction. Controlled hypothermia is used in 52 % of units. Paediatric units are more likely to employ age-dependent cerebral perfusion pressure targets. Specific therapies employed to lower ICP are similar to those used in adult centres. CONCLUSION: Faced with a lack of both evidence and consensus, the management of acute intracranial hypertension in childhood varies widely. National or international guidelines for the management of children with raised intracranial pressure are needed. These should incorporate the physiological differences between children of different ages.

Adolescent↗
PubMed2001

Comparative pharmacokinetics of once daily intravenous and intramuscular gentamicin in patients with post partum endometritis.

In patients with post partum endometritis once daily intramuscular administration of gentamicin may be convenient in certain clinical settings. However pharmacokinetic data on once daily intramuscular gentamicin are not reported. In this study 10 women with post partum endometritis were given once daily intravenous gentamicin (4 mg/kg ideal body weight) followed at a later day by a similar intramuscular dose. Gentamicin levels coincided at 30 min. Levels at 60 and 90 min were lower with the intravenous route. Further clinical studies are needed to confirm reduced nephrotoxicity and ototxicity with the intramuscular route.

Anti-Bacterial Agents↗
PubMed2001

Adrenocortical oncocytoma in pregnancy.

BACKGROUND: Adrenal oncocytomas are uncommon, nonfunctioning tumors occurring most often in endocrine organs. CASE: A 32-year-old woman presented at 25 weeks' gestation complaining of right flank pain. Abdominal ultrasonography and computed tomography revealed a 9 x 10-cm solid right-sided adrenal mass. Endocrine evaluation was normal. At 36 weeks' gestation, she underwent cesarean followed by resection of the adrenal mass. Histopathologic and ultrastructural studies revealed a benign adrenocortical oncocytoma. CONCLUSION: Although rare, adrenocortical oncocytomas should be included in the differential diagnosis of solid, nonfunctioning, adrenal tumors in pregnancy.

Adenoma, Oxyphilic↗
PubMed2001

Transcutaneous electrical nerve stimulation does not augment epidural labor analgesia.

STUDY OBJECTIVE: To evaluate whether transcutaneous electrical nerve stimulation (TENS) can increase the quality and duration of an initiation dose of bupivacaine used for the establishment of epidural labor analgesia. DESIGN: Randomized, double-blind study. SETTING: Tertiary-care academic medical center. PATIENTS: 40 ASA physical status I and II parturients in early, active spontaneous labor with a singleton, vertex term fetus, and requesting analgesia. INTERVENTIONS: A standardized epidural technique with either an active or inactive TENS unit was performed. Before epidural placement, TENS intensity thresholds were determined with electrodes placed over the paraspinus muscles at T(10)-L(1), and S(2)-S(4); TENS settings for mode, cycle, and pulse width were standardized. MEASUREMENTS: Data were collected at timed intervals on pain as measured by visual analog scale (VAS), sensory level (pinprick), motor blockade (Bromage score), cervical dilation, and duration of analgesia. MAIN RESULTS: The duration of analgesia produced by the initial dose of epidural bupivacaine did not differ between groups (TENS turned off 82.3 +/- 26 [mean +/- SD] vs. TENS activated 80.7 +/- 40 min, p = 0.88). Kaplan-Meier survival analysis and Mantel-Cox log rank analysis showed no difference between the two treatments (p = 0.75). No difference in the quality of analgesia was observed between the two groups. CONCLUSIONS: In healthy laboring parturients, the application of a TENS unit did not alter the quality or duration of an initiation dose of bupivacaine utilized for the establishment of epidural labor analgesia.

Adult↗
PubMed2001

Oxidation of galactose by galactose-1-phosphate uridyltransferase-deficient lymphoblasts.

The ability of EB virus-transformed lymphoblasts with undetectable galactose-1-phosphate uridyltransferase (GALT) from 15 galactosaemic patients to oxidize [1-(14)C]galactose to 14CO2 was compared to that of cells from 7 normal subjects. The oxidation of galactose but not of glucose was markedly diminished by cells from Q188R homozygous galactosaemic patients but was not absent. After 2.5 h these cells liberated 14CO2 at nearly 3% and at 5 h up to 9% of normal. Cells from patients homozygous for the S135L mutation produced much larger amounts of 14CO2 (15-17% of normal) and were distinguishable from the Q188R homozygous cells. A cell line with a homozygous deletion of the GALT gene oxidized galactose at 7% of the normal rate, suggesting that pathways(s) other than GALT exist in these cells as well as Q188R homozygous cells for oxidation of galactose to CO2. Concentration dependence studies are consistent with the presence of a pathway that is unsaturable or has a very high Km The ability of 10(7) lymphoblasts with the S135L genotype to oxidize more than 7% of the sugar to 14CO2 in 5 h suggests the presence of residual GALT despite the inability to detect the activity by enzymatic analysis.

Adolescent↗
PubMed2001

The effects of maternal and fetal parameters on the quality of nuchal translucency measurement.

OBJECTIVE: To evaluate the influence of maternal and fetal parameters on the quality of fetal nuchal translucency measurement. DESIGN: This was a prospective study in 227 consecutive pregnant women undergoing nuchal translucency screening by transabdominal sonography. The same well-qualified sonographer performed all the scans and in each case the best-quality image was selected and scored according to an image scoring system (total maximum score, 9). The quality of the image was examined in relation to maternal age, weight, abdominal wall thickness, amniotic sac diameter, posterior uterine wall depth (distance between abdominal wall surface and posterior uterine wall surface), placental location, fetal crown-rump length and nuchal translucency thickness. Correlation coefficients were calculated and stepwise linear regression was used to adjust for confounders and to define the predictors for image score. RESULTS: The only two parameters that provided a significant independent contribution to the prediction of the image score were posterior uterine wall depth and fetal crown-rump length. Intravariable analysis of these two parameters demonstrated that the cut-off associated with a significant change in the image quality was 80 mm for posterior uterine wall depth (score difference, 1.06; P < 0.001) and 70 mm for crown-rump length (score difference, 0.77; P = 0.001). In the group of women with two values above these cut-off points, an average score decrease of 1.90 (P < 0.001) was observed. CONCLUSIONS: The quality of fetal nuchal translucency measurement is poorer when the fetal crown-rump length is > 70 mm and the posterior uterine wall depth is > 80 mm.

Crown-Rump Length↗
PubMed2001

Hyperacusis: review and clinical guidelines.

OBJECTIVE: To review the current known causes of hyperacusis and the different hypotheses concerning its etiology, and to suggest clinical guidelines. DATA SOURCE: A review of the literature with the aid of the MEDLINE database, using the following key words: hyperacusis, intolerance to sound, loudness discomfort level, and phonophobia. DATA EXTRACTION: The data collected included clinical studies, case reports and laboratory studies. CONCLUSION: Hyperacusis was shown to be caused by pathologic conditions of the peripheral auditory system, diseases of the central nervous system diseases, and hormonal and infectious diseases. In some cases there was no known cause. The pathophysiology of hyperacusis probably involves a central mechanism rather than a peripheral one. Suggested clinical guidelines and treatment are discussed.

Auditory Pathways↗
PubMed2001

Preoperative CA-125 level as a predictor of non optimal cytoreduction of advanced epithelial ovarian cancer.

BACKGROUND: Suboptimal cytoreduction of advanced ovarian cancer is related to initial tumor bulk which correlates with CA125 level. METHODS: Retrospective record study of 40 patients with stage III ovarian cancer. The ability of a CA125 threshold level of 500 U/mL to predict suboptimal cytoreduction was determined. RESULTS: Twenty-four (60%) of the patients were optimally cytoreduced. At the CA125 cut off level of 500 U/mL the sensitivity for predicting suboptimal debulking was 62% and specificity was 83%. Above a CA 125 level of 1500 U/mL none of the patients were optimally cytoreduced. CONCLUSIONS: More data are needed to determine the CA125 cut off level at which the standard approach of initial laparotomy and cytoreduction may be modified.

Adult↗
PubMed2001

Thyroglossal duct cyst: is thyroid scanning necessary in the preoperative evaluation?

BACKGROUND: Evaluation of thyroglossal duct cysts before surgical excision traditionally includes hormonal evaluation, ultrasound of the neck, and thyroid scanning. OBJECTIVE: To evaluate the need for thyroid scanning in cases of thyroglossal duct cysts scheduled for operation. METHODS: A retrospective chart review of 100 cases of thyroglossal duct cyst between 1988 and 1995 was carried out. RESULTS: No cases of ectopic thyroid were detected. CONCLUSION: Our goal was to document the presence of normal thyroid tissue by non-invasive tools such as ultrasound, rather than to rule out the existence of ectopic thyroid tissue by radionuclide scanning. Radionuclide scanning is justified in cases of lingual thyroid and where a normally located thyroid gland cannot be detected.

Adolescent↗
PubMed2001

[Prenatal Down's syndrome screening at 10-14 weeks gestation using the combined nuchal translucency and maternal serum biochemistry: preliminary results of the first 358 cases].

We report our preliminary experience of prenatal screening for Down's syndrome (DS) using nuchal translucency (NT) measurement combined with the serum biochemistry analysis of Free beta-human chorionic gonadotropin (F beta hCG) and pregnancy associated plasma protein A (PAPP-A) all measurement at 10-14 weeks of gestation. Of the 358 parturient women which enrolled in the study, 9 cases were not included because of fetal anomalies or miscarriages. Thus the study group included 349 singleton pregnancies in which complete prenatal and infant follow-up was available. Forty-four pregnant women were found to be screen positive (12.6%) and in 13 cases (27%) of them fetal chromosomal aneuploidies were diagnosed. Looking into the markers profile we found that the NT was a sensitive marker which was abnormally increased in all the fetal aneuploidies. Serum F beta hCG was found to be a promising marker as well, being significantly elevated (2.26 +/- 0.86 multiple of the medians, MoM) in DS cases, and decreased (< 0.5 MoM) in two cases of Edward's syndrome. On the contrary, PAPP-A was found less sensitive, and its mean MoM values were not significantly different between DS versus euploid fetuses. Our preliminary results support the promising success of DS screening using NT and F beta hCG.

Adult↗
PubMed2001

Sweeping of membranes vs. intracervical prostaglandin E2 gel for cervical ripening. Randomized trial.

OBJECTIVE: To compare intracervical prostaglandin E2 gel and membrane sweeping for cervical ripening. STUDY DESIGN: Fifty patients were randomized to either intracervical prostaglandin E2 or membrane sweeping. A Bishop score was assigned by a blinded examiner prior to and 24 hours following the procedure. RESULTS: The Bishop scores assigned 24 hours after prostaglandin instillation and membrane sweeping were not significantly different (3.4, SE 0.42, vs. 3.3, SE 0.37, respectively; P > .05). The proportions of women entering active labor or delivering within 24 hours were similar in the prostaglandin and membrane groups (21% and 19%, respectively; P > .05). CONCLUSION: When both intracervical prostaglandin insertion and membrane sweeping are feasible, their salutary effects are comparable.

Administration, Intravaginal↗