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Biomedical subjects

S Segal

Publications and source records attributed to S Segal.

At least 127 records · Page 7Linked to original sources
PubMed1997

Urinary galactonate in patients with galactosemia: quantitation by nuclear magnetic resonance spectroscopy.

Although numerous reports have appeared showing high levels of galactitol in the urine of patients with galactose-1-phosphate uridylyltransferase deficiency, little attention has been paid to measurement of urinary galactonate. Herein we explored the use of 1H and 13C nuclear magnetic resonance, which required only the concentration of urine without derivatization, to detect and quantitate urinary galactonate. We report that transferase deficient infants, as well as adults on galactose restricted diets excrete significant amounts of galactonate, whereas none is detected in the urine of normal subjects. Galactose-toxic infants were found to excrete large amounts of galactonate, which decreased when the lactose-free diet was instituted. We also found that normal individuals subjected to an oral galactose load also excrete high levels of galactonate for at least 4 h after galactose ingestion. Our data provide evidence that the first reaction in the oxidative pathway of galactose metabolism described in rat liver in 1966 is activated in patients with a variety of galactose-1-phosphate uridylyltransferase gene mutations even while on a lactose-restricted diet. In both patients and normal individuals, flux through the alternate galactonate pathway appears to be related to the body galactose burden.

Adolescent↗
PubMed1996

Identification of in vivo target RNA sequences bound by thymidylate synthase.

We developed an immunoprecipitation-RNA-random PCR (rPCR) method to isolate cellular RNA sequences that bind to the folate-dependent enzyme thymidylate synthase (TS). Using this approach, nine different cellular RNAs that formed a ribonucleoprotein (RNP) complex with thymidylate synthase (TS) in human colon cancer cells were identified. RNA binding experiments revealed that seven of these RNAs bound TS with relatively high affinity (IC50 values ranging from 1.5 to 6 nM). One of the RNAs was shown to encode the interferon (IFN)-induced 15 kDa protein. Western immunoblot analyses demonstrated that the level of IFN-induced 15 kDa protein was significantly decreased in human colon cancer H630-R10 cells compared with parent H630 cells. While the level of IFN-induced 15 kDa mRNA expression was the same in parent and TS-overexpressing cell lines, the level of IFN-induced 15 kDa RNA bound to TS in the form of a RNP complex was markedly higher in H630-R10 cells relative to parent H630 cells. These studies begin to define a number of cellular target RNA sequences with which TS interacts and suggest that these TS protein-cellular RNA interactions may have a biological role.

Base Sequence↗
PubMed1996

c-Myc inactivation by mutant Max alters growth and morphology of NCI-H-630 colon cancer cells.

The myc gene family has been implicated in multiple cell processes including proliferation, differentiation, tumorigenesis, and apoptosis. For its cellular growth promoting function, Myc must heterodimerize with Max. To study the effect of Myc inactivation on the growth and differentiation properties of epithelial tumor cells, we transfected the H-630 human colon cancer cell line with bm-max, a mutant Max protein in which DNA-binding activity has been abolished. Cells expressing high levels of bm-Max grow poorly, and the morphology of both colonies and single cells is altered. Moreover, increased bm-Max expression results in a prolonged G alpha/G1 phase accompanied by induced expression of p21 (WAF1/CIP1), elevated levels of alkaline phosphatase (ALP) activity, and accumulation of large fat granuli within the cells. These distinctive cell characteristics are associated with differentiation processes in numerous malignant cell lines. The results of this study support a model in which sequestering of endogenous Myc and Max proteins into "basic mutant" dimers lacking DNA-binding activity is sufficient both to inhibit proliferation and to induce changes in cell behavior consistent with differentiation.

Alkaline Phosphatase↗
PubMed1996

A mouse model of galactose-1-phosphate uridyl transferase deficiency.

Galactose-1-phosphate uridyl transferase (GALT) deficiency causes classical galactosemia in humans. Mice deficient in this enzyme were created by gene targeting. GALT-deficient mice develop biochemical features similar to those seen in humans with GALT deficiency, but fail to develop the pattern of acute toxicity seen in newborns with classical galactosemia. This study suggests that alternative routes of galactose metabolism are important in the pathogenesis of galactosemia.

Animals↗
PubMed1996

Complementary organ expression of IL-1 vs. IL-6 and CSF-1 activities in normal and LPS-injected mice.

The specific expression of pro-inflammatory cytokines may affect the functioning of organs in different ways. The results of specific cytokine bioassays used in this study show a distinct pattern of tissue expression of IL-1 IL-6 and CSF-1. Cytokine activity was assessed in conditioned media (CM) and lysates (LYS), obtained from different organs of control or lipopolysaccharides (LPS)-injected mice; LPS representing a potent inflammatory stimulus. Low constitutive levels of IL-1 could be demonstrated only in CM/LYS from organs with lymphoreticular function, such as the liver, spleen, intestine and lungs. On the other hand, IL-6 and CSF-1 were mainly detected in the CM (and not in lysates) of organs, such as the heart, kidneys, muscle and brain. LPS injection basically resulted in an accentuated form of the constitutive pattern. CSF-1 displays a similar pattern of expression to that of IL-6, best detected in CM after LPS stimulation. Thus, a mirror-image relationship emerges between the patterns of IL-1 and IL-6/CSF-1 expression in two groups of organs: those with lymphoreticular function, which manifest high IL-1 and low IL-6/CSF-1 activity, as compared to organs characterized by highly specialized and potentially vulnerable functions (such as the heart, brain, muscle and kidney), which exhibit high IL-6/CSF-1 and low IL-1 activity. Due to their defensive functions, lymphoreticular organs, which are in charge of the 'gates of entry' to the body, mount extensive IL-1-mediated inflammatory responses, even at the cost of possible tissue-damage. On the other hand, the more vulnerable internal organs mount IL-6/CSF-1-mediated responses which are milder and bear less potential for tissue damage. The distinct patterns of expression of pro-inflammatory cytokines in different organs, at steady state or under inflammatory conditions, may shed light on tissue characteristic homeostatic and defence mechanisms.

Animals↗
PubMed1996

The outcome of pregnancy in an immigrant Ethiopian population in Israel.

To study the assumption that obstetric risk factors would change over time in an immigrant Ethiopian population, a retrospective study of the records of singleton births among the Ethiopian immigrants between 1981-88 was undertaken and compared to a similar study of the general population. The Ethiopian immigrants were characterized by pregnancies at age extremes, a greater incidence of preeclampsia and premature deliveries, and a lower incidence of premature rupture of membranes. There was over time an increase in maternal weight gain among the Ethiopians as well as an increase in the incidence of preeclampsia and perinatal mortality.

Adult↗
PubMed1996

Reproductive outcome after expectant management of ectopic pregnancy.

OBJECTIVE: To study fertility rates following expectant management of clinically stable ectopic pregnancies. STUDY DESIGN: Twenty of 33 patients with laparoscopically confirmed aborting tubal pregnancies managed expectantly were followed for a period of 1-5 years (mean 2.7 years). Excluded were the patients not desiring pregnancy, and patients with known impediments to fertility, such as age > 40 years and previous infertility, as well as patients lost to follow-up. RESULTS: Successful pregnancies occurred in 16 patients (80%); one patient (5%) had a repeat ectopic pregnancy. CONCLUSIONS: Expectant management is associated with a favorable reproduction outcome.

Adult↗
PubMed1996

Budd-Chiari syndrome complicating severe preeclampsia in a parturient with primary antiphospholipid syndrome.

A 27-year-old primipara with severe preeclampsia and primary antiphospholipid syndrome developed right upper quadrant pain, massive ascites, HELLP syndrome, and disseminated intravascular coagulation shortly following vaginal delivery. Computed tomography and color Doppler studies were compatible with complete thrombosis of the right hepatic veins, the Budd-Chiari syndrome. Anticoagulation was initiated, along with supportive measures, and the patient recovered completely. Imaging studies 6 months later were normal. This case demonstrates that nearly fatal forms of venous thrombosis may complicate preeclampsia in women with antiphospholipid syndrome; Doppler studies of the hepatic vein are of value in establishing the diagnosis.

Adult↗
PubMed1996

Sugar nucleotide concentrations in red blood cells of patients on protein- and lactose-limited diets: effect of galactose supplementation.

Uridine diphosphate (UDP) galactose, a pivotal compound in the metabolism of galactose, is the obligate donor of galactose in the formation of complex glycoconjugates. The cellular UDPgalactose concentration has been thought to be maintained by the interconversion of UDPglucose and UDPgalactose by UDPgalactose-4-epimerase. However, recent findings of lower average red blood cell (RBC) UDPgalactose concentrations in galactose-1-phosphate uridyltransferase-deficient patients suggest that other factors play a role in determining its concentration. To test the hypothesis that the amount of galactose traversing the Leloir pathway contributes to the cellular UDPgalactose pool, we determined RBC UDPgalactose in patients with maple syrup urine disease (MSUD), phenylketonuria (PKU), and other metabolic diseases who were treated with a low-protein, and consequently, low-lactose diet. Six patients with MSUD were also supplemented with 19 g galactose/d and their UDPhexose concentrations were measured at intervals. We show that young patients with MSUD or PKU have decreased average RBC UDPgalactose concentrations when compared with similarly aged healthy subjects. Galactose supplementation of MSUD patients significantly increased their UDPgalactose concentrations in both RBCs and white blood cells (WBCs) from 29.5 +/- 1.5 to 42.3 +/- 5.8 nmol/g hemoglobin and from 69.0 +/- 7.5 to 193.0 +/- 49.0 nmol/g protein, respectively. Discontinuation of supplementation was associated with a return to basal values in RBCs and a reattainment of the pretreatment ratio of UDPglucose to UDPgalactose in WBCs. These observations demonstrate that dietary galactose is a factor in establishing the steady state concentrations of the uridine sugar nucleotides and imply that galactose metabolism modulates the achievement of an epimerase-mediated equilibrium.

Adolescent↗
PubMed1996

Retroperitoneal abscess after normal delivery. A report of two cases.

BACKGROUND: Retroperitoneal abscess is a rare complication of normal labor and delivery, and no apparent etiology is evident. CASES: We report on two patient who presented with back and leg pain soon after normal deliveries. While the condition was initially clinically misdiagnosed, ultrasonography and computed tomography demonstrated retroperitoneal collections and aided in guided percutaneous drainage. After a protracted course of antibiotic treatment and daily irrigation, the collections resolved. CONCLUSION: Ultrasonography and computed tomography were invaluable in the diagnosis and guided drainage of rare psoas abscesses complicating delivery.

Abdomen↗
PubMed1996

Gestational diabetes mellitus and hypertension in pregnancy: hemodynamics and diurnal arterial pressure profile.

We characterised the 24-h arterial pressure (AP) profile and the left ventricular (LV) structures and functions in pregnant women with pregnancy-induced hypertension (PIH) or gestational diabetes mellitus (GDM). Thirty pregnant women after 20 weeks' gestation--(10 normotensive; 10 with PIH; and 10 with GDM)--were investigated haemodynamically using 24-h AP monitoring and Doppler echocardiography for determination of LV structures and functions, both systolic and diastolic. The PIH women had significantly higher AP determinations throughout the 24 h, with no change in the diurnal variation, ie, nocturnal decline and early morning peaks. The LV mass was greater in PIH and GDM than in the normotensive women, despite normal AP in GDM. The increased LV mass in GDM was mainly due to LV dilatation and not to increased thickness of its walls. In PIH, the increase in AP was due to peripheral vasoconstriction, while cardiac output was preserved. The LV systolic functions did not differ among the three groups. However, a slight reduction in the myocardial contractility was found in PIH and GDM. The LV relaxation was significantly impaired in both PIH and GDM. Thus, GDM and PIH, although differing in their 24-h AP profile, are characterised by LV hypertrophy and reduction in diastolic function.

Adult↗
PubMed1996

Hemophilus influenzae septic arthritis and pneumonia in an adult as the first presentation of multiple myeloma.

We describe an apparently healthy woman who presented with monoarthritis of the right knee and a history of respiratory infection. The synovial fluid cultures grew beta lactamase-negative H. influenzae. Chest roentgenogram showed patchy densities throughout the right lung. Investigations for a predisposing factor for this H. influenzae infection revealed underlying multiple myeloma. As H. influenzae pyoarthrosis is extremely rare in adults, we suggest that an underlying systemic cause be sought in all such patients.

Aged↗
PubMed1995

Endogenous synthesis of galactose in normal men and patients with hereditary galactosaemia.

Despite restricted ingestion of lactose, patients with galactose-1-phosphate uridyltransferase deficiency have raised concentrations of galactose metabolites in blood and urine. Endogenous production of galactose may underlie this phenomenon. Using isotopically labelled galactose in a continuous intravenous infusion, we employed the steady-state flux method to calculate endogenous galactose production rate in three normal men and three patients with classic galactosaemia. We found that galactosaemic patients and normal subjects synthesise gram quantities of galactose per day. The rate of synthesis ranged from 0.53-1.05 mg/kg per h. Endogenous production of galactose may be an important factor in the pathogenesis of the complications of the brain and ovary, and could explain the persistent elevation of galactose metabolites in patients despite dietary restriction of galactose.

Adult↗
PubMed1995

DNA binding properties of the zinc-bound and zinc-free HIV nucleocapsid protein: supercoiled DNA unwinding and DNA-protein cleavable complex formation.

The HIV nucleocapsid (NC) protein contains, as those of other retroviruses, two Cys-His arrays which function as zinc finger binding domains. The nucleic acid binding properties of retroviral NC have been previously demonstrated. In this study, we characterized the DNA binding ability of the zinc-bound and zinc-free forms of HIV NC. We found that in addition to binding single-stranded DNA, both forms bind and unwind supercoiled plasmid DNA. The binding ability of the zinc-bound form was higher than the zinc-free form. In addition we showed the formation of NC protein-DNA cleavable complex which is the result of a presumably covalent bond formed between the protein and the phosphate moiety of the DNA backbone. The NC unwinding activity and the protein-DNA cleavable complex formation resembles the first step of the relaxing mechanism of DNA topoisomerase. Our results shed light on the possibility of a novel physiological function for the HIV NC protein in the viral life cycle.

Capsid↗
PubMed1995

Effect of glucose and galactose loading in normal subjects on red and white blood cell uridine diphosphate sugars.

In order to test the assumption that red blood cell (RBC) uridine diphosphate galactose content is regulated in part by dietary galactose and to help comprehend factors influencing RBC and white blood cell (WBC) uridine diphosphate hexose concentrations in vivo, oral loading studies were performed with 50 g of galactose or 75 g of glucose in normal adults. While elevations of blood glucose did not influence RBC or WBC UDPhexose levels, increased blood galactose concentrations caused transient increases in both RBC and WBC UDPgalactose. In both RBC and WBC, the UDPgalactose-4-epimerase was rate limiting. In comparison to RBC, WBC had larger changes in UDPgalactose levels, synthesized additional UDPglucose through the action of UDPglucose pyrophosphorylase and began to restore the equilibrium ratio between UDPglucose and UDPgalactose concentrations while the plasma galactose level was still increasing. Thus, galactose ingestion alters the steady-state levels of UDPhexoses in circulating cells. The modulation of UDPglucose and UDPgalactose concentrations, occurring after the presentation of galactose to cells, as a result of the combined actions of GALT and UDPgalactose-4-epimerase, may be important in determining rates of synthesis of complex glycoconjugates.

Administration, Oral↗