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Biomedical subjects

M Tal

Publications and source records attributed to M Tal.

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

Dp71, the nonmuscle product of the Duchenne muscular dystrophy gene is associated with the cell membrane.

The 70.8 kDa protein, Dp71, is the major Duchenne muscular dystrophy (DMD) gene product in many nonmuscle tissues including the brain. Dp71 shares most of the C-terminal and cysteine-rich domains with the dystrophins but lacks the entire large rod shaped domain of spectrin-like repeats, and the N-terminal actin-binding domain. The function of Dp71 is unknown. Using subcellular fractionation and immunostaining we show that Dp71 is associated with the plasma membrane. Dp71 is also associated with the plasma membrane in mdx myogenic cells transfected with a vector expressing Dp71.

Animals↗
PubMed1993

Dextrorphan relieves neuropathic heat-evoked hyperalgesia in the rat.

Dextrorphan (DEX), a non-competitive NMDA receptor antagonist, was given intraperitoneally and intrathecally (i.t.) to rats with an experimental painful peripheral mononeuropathy. The neuropathy was created by placing loosely constrictive ligatures around the sciatic nerve, and the pain threshold was studied with the paw-flick method. The effects of DEX on the neuropathic heat-evoked hyperalgesia that follows this nerve injury were determined during the period of peak symptom severity. DEX given i.p. relieved heat-evoked hyperalgesia in a dose-dependent manner without producing motor impairment. The highest doses tested (12.5 and 25 mg/kg) produced a large but incomplete block (about 50%). DEX had no effect on the responsiveness of the paw on the control side. i.t. injection of 20 micrograms DEX completely blocked heat-hyperalgesia when tested 1 h later; again, the effect was achieved without motor impairment and without any change on the control side. These results suggest that DEX may be useful in the treatment of human neuropathic pain.

Animals↗
PubMed1993

Diverse firing properties of single motor units in the inner and outer portions of the guinea pig anterior digastric muscle.

Microwire recordings from the histochemically heterogeneous inner compartment of the guinea pig anterior digastric muscle (ADG) revealed tonic firing of single motor units, which were spontaneously active and could also be recruited following orofacial afferent stimulation and during rhythmic jaw movements (RJM). As units with tonic firing were not observed in the homogeneously fast-twitch outer ADG, the tonic units were classified as slow-twitch motor units. Irregular patterns of motor-unit firing at variable frequencies were observed after orofacial stimulation and during RJM in the outer and inner compartments. The irregular firing pattern of units in the fast-twitch outer compartment was characterized by shorter and less variable bursts than that of units in the heterogeneous inner compartment. A phasic, centrally driven firing pattern was observed during RJM in outer and inner ADG units. The firing frequency of some of these units was modulated during the rhythmical bursts. It is suggested that, as in limb muscles, functionally specialized ADG motor units are recruited in an orderly sequence, starting with spontaneously active, slow-twitch units in the inner compartment, continuing with fast-twitch units recruited upon enhancement of the synaptic drive (as in the case of orofacial stimulation), and ending with massive, rhythmical recruitment of slow- and fast-twitch units during RJM.

Action Potentials↗
PubMed1993

Murine insulinoma cell line with normal glucose-regulated insulin secretion.

Pancreatic beta TC lines derived from insulinomas arising in transgenic mice expressing SV40 Tag under control of the insulin promoter manifest a differentiated beta-cell phenotype and secrete insulin in response to glucose. Previously reported beta TC lines respond to subphysiological extracellular glucose levels compared with normal beta-cells. Recently, several beta TC lines were developed with normal glucose-regulated insulin secretion from insulinomas obtained by breeding of the RIP-Tag transgene from the original C57BI/6 mouse strain into the C3HeB/FeJ strain. One of these beta TC lines, beta TC7, was characterized in detail. Beta TC7 cells express GLUT2 and have levels of glucokinase and hexokinase activity similar to those of normal islets. As a result these cells exhibit a normal glucose concentration dependency for glycolysis and insulin secretion, thus representing an accurate model of beta-cell function. On continuous propagation in culture, beta TC7 cells acquired a response to lower extracellular glucose levels. This change was associated with a fourfold increase in hexokinase activity, without significant changes in glucokinase activity and glucose uptake rates. These findings suggest an important role for glucose phosphorylation rates in regulation of the beta-cell insulin secretory response to glucose.

Animals↗
PubMed1992

Expression and function of GLUT-1 and GLUT-2 glucose transporter isoforms in cells of cultured rat pancreatic islets.

We have previously investigated glucose induction of glucokinase, glucose usage and insulin release in isolated cultured rat pancreatic islets (Liang, Y., Najafit, H., Smith, R. M., Zimmerman, E. C., Magnuson, M. A., Tal, M., and Mastchinsky, F. M. (1992) Diabetes (1992) 41, 792-806). Here we studied the expression and function of GLUT-1 and GLUT-2 glucose transporter isoforms, using the same system, i.e. isolated pancreatic rat islets immediately after isolation or cultured in the presence of 3 or 30 mM glucose for as long as 10 days. We found by immunofluorescence microscopy and Western and Northern blot analysis of islet extracts that GLUT-1 expression was induced in islet beta-cells in tissue culture both with low or high glucose present. The induction of GLUT-1 was specific to beta-cells but was not present in all beta-cells and was not detected in alpha-cells. GLUT-2 expression was also specific for beta-cells and was not observed in all beta-cells. Some beta-cells in culture coexpressed GLUT-1 and GLUT-2. The expression of the two glucose transporters was regulated in the opposite direction in response to glucose concentration in the culture medium. GLUT-1 was more effectively induced when glucose was low, and GLUT-2 expression was more pronounced when glucose was high in the culture media. Another difference between the two glucose transporters was that GLUT-2 expression was increased while GLUT-1 expression was decreased as culturing continued as long as 7 days. Thus, after 7 days of culture GLUT-2 expression in beta-cells was nearly the same at low and high glucose, whereas GLUT-1 was practically absent no matter what the glucose level was. In attempts to correlate GLUT-1 and GLUT-2 expression to beta-cell function glucose uptake and glucose-stimulated insulin release in fresh and cultured islets were measured. In freshly isolated islet glucose uptake was estimated to be 100-fold in excess of actual glucose use. Glucose uptake was reduced by 7-day culture to about one-third of that observed in freshly isolated islets no matter what the glucose concentration of the culture media. We conclude that in the present experimental system GLUT-1 and GLUT-2 expression and function are not closely associated with glucose usage rates or the secretory function of beta-cells.

Animals↗
PubMed1992

[Val12] HRAS downregulates GLUT2 in beta cells of transgenic mice without affecting glucose homeostasis.

Glucose-induced insulin release from pancreatic beta cells depends on the beta-cell metabolism of glucose, which generates intracellular signals for secretion. The beta-cell glucose transporter isotype GLUT2 and the glucose phosphorylating enzyme glucokinase have both been implicated in coupling insulin secretion to extracellular glucose levels. Here we present evidence that a pronounced decrease in beta-cell GLUT2 has no immediate effect on glucose homeostasis. Analysis of transgenic mice overexpressing human [Val12]HRAS oncoprotein under control of the insulin promoter reveals a great reduction in plasma-membrane GLUT2 levels. These mice are nonetheless able to maintain normal fed and fasting plasma glucose and insulin levels for a period of several months. Insulin secretion studied in isolated islets and the perfused pancreas is characterized by a normal incremental response to increasing glucose concentrations. Glucose metabolism, as measured by glucose phosphorylation and oxidation in isolated islets, shows a normal dose dependence on extracellular glucose concentrations. These findings suggest that normal GLUT2 expression in beta cells is not essential for glucose sensing. The transgenic mice provide an experimental system for studying the role of glucose phosphorylation in regulation of insulin release in the absence of GLUT2.

Animals↗
PubMed1992

Ectopic discharge in injured nerves: comparison of trigeminal and somatic afferents.

Using the teased fiber recording method, we have compared pathophysiological properties of afferent axons injured in the infraorbital nerve (ION) vs the sciatic nerve in rats. Both myelinated and unmyelinated axons ending in ION neuromas produced much less ongoing discharge than those ending in sciatic nerve neuromas. Similarly, mechanosensitivity and acute injury discharge in ION neuromas were minimal. These differences may be related to the different spectrum of neuropathic symptomatology associated with nerve injury in the trigeminal vs the segmental innervation fields.

Afferent Pathways↗
PubMed1992

Glucose transporter isotypes switch in T-antigen-transformed pancreatic beta cells growing in culture and in mice.

High-level expression of the low-Km glucose transporter isoform GLUT-1 is characteristic of many cultured tumor and oncogene-transformed cells. In this study, we tested whether induction of GLUT-1 occurs in tumors in vivo. Normal mouse beta islet cells express the high-Km (approximately 20 mM) glucose transporter isoform GLUT-2 but not the low-Km (1 to 3 mM) GLUT-1. In contrast, a beta cell line derived from an insulinoma arising in a transgenic mouse harboring an insulin-promoted simian virus 40 T-antigen oncogene (beta TC3) expressed very low levels of GLUT-2 but high levels of GLUT-1. GLUT-1 protein was not detectable on the plasma membrane of islets or tumors of the transgenic mice but was induced in high amounts when the tumor-derived beta TC3 cells were grown in tissue culture. GLUT-1 expression in secondary tumors formed after injection of beta TC3 cells into mice was reduced. Thus, high-level expression of GLUT-1 in these tumor cells is characteristic of culture conditions and is not induced by the oncogenic transformation; indeed, overnight culture of normal pancreatic islets causes induction of GLUT-1. We also investigated the relationship between expression of the different glucose transporter isoforms by islet and tumor cells and induction of insulin secretion by glucose. Prehyperplastic transgenic islet cells that expressed normal levels of GLUT-2 and no detectable GLUT-1 exhibited an increased sensitivity to glucose, as evidenced by maximal insulin secretion at lower glucose concentrations, compared with that exhibited by normal islets. Further, hyperplastic islets and primary and secondary tumors expressed low levels of GLUT-2 and no detectable GLUT-1 on the plasma membrane; these cells exhibited high basal insulin secretion and responded poorly to an increase in extracellular glucose. Thus, abnormal glucose-induced secretion of insulin in prehyperplastic islets in mice was independent of changes in GLUT-2 expression and did not require induction of GLUT-1 expression.

Animals↗
PubMed1992

Concordant glucose induction of glucokinase, glucose usage, and glucose-stimulated insulin release in pancreatic islets maintained in organ culture.

Using cultured islets as the experimental system, this study established dosage-response and time-dependency curves of the inductive glucose effect on glucose-stimulated insulin release, glucose usage, and glucokinase activity. Glucose-stimulated insulin release in islets cultured for 1, 2, or 7 days was increased as a function of glucose concentration in the culture medium and as a function of time. Glucose usage in the cultured islets showed a close relationship with glucose concentration in the culture medium at both 2 and 7 days of culture. Glucokinase activity increased in islets cultured for 1, 2, or 7 days as a function of increasing glucose concentrations in the culture medium and as a function of time. The V(max) of glucokinase in islets cultured for 7 days in medium containing 30 mM glucose was twice the value of freshly isolated islets and was almost fivefold higher than that in islets cultured for 7 days in 3 mM glucose. The glucose induction of glucose-stimulated insulin release, of glucose usage, and of glucokinase activity were tightly correlated. The biochemical mechanisms of glucose induction of islet glucokinase were further studied. Immunoblotting with an antibody against C-terminal peptide of glucokinase showed that densities of a 52,000-kD protein band from tissue extracts of islets cultured for 7 days in 3, 12, and 30 mM glucose were 25, 44, and 270% compared with that of extract from freshly isolated islets (100%). RNA blot analysis of glucokinase mRNA demonstrated virtually the same levels in fresh islets and islets after 7 days of culture in 3 or 30 mM glucose. The adaptive response of glucokinase to glucose appears therefore to be occurring at a translational or posttranslational site in cultured islets. These data greatly strengthen the concept that glucose is the regulator that induces the activity of glucokinase, which in turn determines the rate change of glucose usage as well as glucose-stimulated insulin release from beta-cells. Thus, the hypothesis that glucokinase is the glucose sensor of beta-cells is strengthened further.

Animals↗
PubMed1991

Gay identity and risky sexual behavior related to the AIDS threat.

This paper explores the relationship between risky sexual behavior and issues of gay identity in homosexual men. We identify three main conceptual categories important to gay identity: sexual identity, gay social interaction, and identity development milestones. Each of these categories are analyzed as to their predictive effect on risky sexual behavior related to the threat of HIV, at six-month and eighteen-month intervals. The results suggest that successful integration into a gay network plays a role in reducing risky sexual behavior among homosexual men, regardless of the chronological timing of personal events marking a gay man's "coming out" history.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Effect of occlusal bite-raising splint on electromyogram, motor unit histochemistry and myoneuronal dimensions in rats.

Composite resin bite-raising splints were fabricated on both sides of the upper jaw in rats. EMG activity of the deep masseter muscle was monitored continuously for 24 h before and up to 4 weeks after treatment. Together with the EMG activity, measurements of the neuromuscular junction area and muscle fibre histochemistry were made. EMG activity showed great variability immediately after splint fabrication. Some of the animals showed increased EMG activity, while others exhibited less activity 48 h after splint application. Overall, the fluctuation lasted for about 4 days, and after approximately 7 days all the animals exhibited decreased EMG activity, followed by a gradual increase in activity towards baseline levels. The neuromuscular junction territory increased significantly 5-10 days after splint application. Histochemical characterization of the deep masseter muscle revealed that it contained the three main types of muscle fibre: slow oxidative (SO), fast-oxidative-glycolytic (FOG) and fast glycolytic (FG). The frequency distribution of fibre types did not change after bite-raising splint treatment. These findings indicated that splint treatment in rats is effective in reducing EMG activity, while the muscle type characteristics remain stable. The effect of lower activity on the motor end-plates suggested that the neuromuscular junctions are quite sensitive to functional changes.

Adenosine Triphosphatases↗
PubMed1991

Expression of the low Km GLUT-1 glucose transporter is turned on in perivenous hepatocytes of insulin-deficient diabetic rats.

In normal fed rats the low Km glucose transporter GLUT-1 is expressed only in one row of hepatocytes immediately surrounding a terminal hepatic venule, while the high Km GLUT-2 is expressed in every hepatocyte. Previously, we showed that additional perivenous hepatocytes express GLUT-1 in fasting animals. In diabetes, as in starvation, the liver functions to release glucose into the circulation, but unlike starvation, circulating extracellular glucose is high in diabetes. By immunofluorescence and Western blotting we studied whether glucose or insulin is the primary extracellular signal for inducing GLUT-1 expression in hepatocytes. We observed that streptozocin-induced diabetes causes induction of GLUT-1 expression in the plasma membrane of hepatocytes within four cell rows of a terminal hepatic venule; GLUT-2 expression is unaltered. Chronic insulin treatment of diabetic rats reduces the number of rows of hepatocytes expressing GLUT-1 from approximately four to approximately two. In contrast, chronic insulin infusion into nondiabetic rats does not affect the number of hepatocytes expressing GLUT-1. Thus, both fasting and diabetes induce GLUT-1 expression in specific hepatocytes that normally do not express this gene. This induction correlates with low insulin levels in the blood, and not with circulating glucose levels.

Animals↗
PubMed1991

Relapse in sexual behavior among homosexual men: a 2-year follow-up from the Chicago MACS/CCS.

Serial biannual cross-sectional assessments of HIV sexual risk indicated a consistent increase in safer sexual practices among homosexual men participating in the Chicago-Multicenter AIDS Cohort Study (MACS)/Coping and Change Study (CCS) in 1986-1988. Safer sexual practices were achieved by avoidance of anal sex and less often by consistent use of condoms. Longitudinal patterns of variability in individual behavior were also assessed. After 1 year of follow-up, 53% of the participants maintained safer practices in receptive anal sex, 6% maintained unsafe practices, while 31% relapsed at least once. After 2 years, 45% maintained safer practices, 3% maintained unsafe practices and 47% relapsed at least once. Similar trends were observed in insertive anal sex.

Chicago↗
PubMed1990

Psychological functioning in a cohort of gay men at risk for AIDS. A three-year descriptive study.

This study describes the mental health of a large cohort of gay men participating in the Chicago Multicenter AIDS Cohort Study/Coping and Change Study. Six biannual questionnaires were self-administered between 1984 and 1988. General mental health was determined by the Hopkins Symptom Checklist (HSCL). An abbreviated version of the Center for Epidemiologic Study Depression Scale (CESD-5) and an adapted Diagnostic Interview Schedule (DIS) question also measured depression. Suicidal ideation was assessed by one question in the HSCL. AIDS-specific distress was determined by three subscales specifically developed for this study. While mean HSCL and CESD-5 scores were stable during the observational period, AIDS-specific distress increased over time. The HSCL scores for the cohort were somewhat elevated above general population norms but considerably below psychiatric outpatient norms. Fewer than 12% of the men reported elevated HSCL or CESD-5 scores three or more times. A self-reported episode of depression of two weeks or more, measured by the DIS screening question, was experienced by 40.1% of the sample. Suicidal ideation was reported on three or more visits by 18.8% of the men. The younger members of this cohort exhibit greater general and AIDS-specific distress. Income was inversely associated with general distress. HIV-seropositive participants had generally higher AIDS-specific distress scores than those who were seronegative, but their scores were equivalent on the HSCL and CESD-5.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Restricted expression of the erythroid/brain glucose transporter isoform to perivenous hepatocytes in rats. Modulation by glucose.

The "erythroid/brain" glucose transporter (GT) isoform is expressed only in a subset of hepatocytes, those forming the first row around the terminal hepatic venules, while the "liver" GT is expressed in all hepatocytes. After 3 d of starvation, a three- to fourfold elevation of expression of the erythroid/brain GT mRNA and protein is detected in the liver as a whole; this correlates with the expression of this GT in more hepatocytes, those forming the first three to four rows around the hepatic venules. Starvation-dependent expression of the erythroid/brain GT on the plasma membrane of these additional hepatocytes is lost within 3 h of glucose refeeding; however, by immunoblotting we show that the protein is still present. Its loss from the surface is possibly explained by internalization.

Animals↗
PubMed1989

Masseter inhibitory periods and sensations upon electrical tooth-pulp stimulation in children and adults.

Sensations and masseter inhibitory periods (MIP) evoked by electrical tooth-pulp stimulation were recorded in 5 adults and 10 children. In the adult group there was always a sensation and it was usually associated with a two-phase MIP, with an early and a late component. Sensory detection in teeth with partially formed roots in the younger children (7-9 years old) was markedly reduced, and the MIP was mostly monophasic with a predominantly early component. In the older children with fully formed roots (10-12 years old) sensations did not differ from those in the adults, but the late MIP component occurred in significantly fewer trials (P less than 0.01). It is concluded that response to electrical tooth-pulp stimulation develops in the following stages: (1) early, oligosynaptic MIP, (2) sensation, and (3) the late, polysynaptic component of the MIP.

Adult↗
PubMed1989

Masseter inhibitory periods and sensations evoked by electrical tooth-pulp stimulation in subjects under hypnotic anesthesia.

Sensation and masseter inhibitory periods (MIP) to electrical tooth-pulp stimulation were recorded under hypnotic anesthesia and placebo to local anesthesia. In the first experiment, 8 subjects were tested for the effect of hypnotic anesthesia on sensory detection and MIP at non-painful stimulus levels (mean = 42.1 microA) and painful levels (mean = 86.5 microA). The percentage of detection for non-painful stimuli changed from 94.3% to 14.1% and for painful stimuli from 100% to 28%; both changes were significant (P less than 0.001). Hypnotic anesthesia blocked sensation without interrupting the initiation of the early component of the MIP, but did suppress its late component. In the second experiment, 8 subjects were tested for the perceived intensity of 5 levels of electrical tooth-pulp stimulation under hypnotic anesthesia and placebo. Sensory intensity was measured by the visual analog scale (VAS). Hypnotic anesthesia was significantly more effective than placebo (P less than 0.001) in reducing sensation. The differential effect of hypnotic anesthesia on the early and late component of the MIP lends further support to the hypothesis that hypnotic anesthesia operates primarily at suprasegmental, higher levels in the brain.

Adolescent↗