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Biomedical subjects

S Weiss

Publications and source records attributed to S Weiss.

At least 289 records · Page 16Linked to original sources

Synthesis of 18F-labeled fluconazole and positron emission tomography studies in rabbits.

[4-18F] 2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-l-yl)-2-propanol [( 4-18F] fluconazole) was synthesized from its amino precursor. Fieldel-Crafts acylation of 3-fluoroacetanilide with chloroacetyl chloride produced 2'-fluoro-4'-acteamido-2-(1H-1,2,4-triazole-1-yl) acetophenone in 12% yield. Sequential reaction with (1) dimethylsulphoxonium methylide and (2) 1,2,4-triazole followed by in situ hydrolysis resulted in 2-(2-fluoro-4-aminophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)-2-propan ol in 19% yield. A modified Schiemann reaction on this product resulted in [4-18F]fluconazole with a radiochemical yield of 1.0-2.0% (EOS) within 2 h. [4-18F]Fluconazole was used to measure the pharmacokinetics of fluconazole in rats by measurement of radioactivity in excised tissues and in rabbits by PET. In both species, there was rapid equilibration of [4-18F]fluconazole to a relatively uniform distribution of radioactivity in most organs.

Animals↗

Phosphorylatable and epitope-tagged human erythropoietins: utility and purification of native baculovirus-derived forms.

The hematopoietic glycopeptide erythropoietin (EPO) is a prime regulator of red cell production in mammals, yet the precise nature of its interaction with specific cell surface receptors is poorly understood. Towards defining domains of EPO that are involved in receptor activation, we have developed (i) conditions for the expression of recombinant human EPO (rhEPO) at high levels in SF9 cells using modified 2- and 5-liter stirred reactors, (ii) a two-step procedure for the purification of this EPO without denaturation, and (iii) forms of EPO tagged with either a hemagglutinin influenza virus epitope or a consensus sequence for in vitro phosphorylation. Compared to EPO expressed in mammalian cells, rhEPO from SF9 cells in N-glycosylated with simple, neutral oligosaccharides of limited size, yet as purified presently using nondenaturing procedures, possesses exceptionally high in vitro activity (> or = 500,000 U/mg). Thus, this form of EPO should prove advantageous for direct physicochemical analyses. Regarding epitope-tagged and phosphorylatable EPOs, forms modified at the amino terminus (Ala1) fully retained receptor binding and in vitro biological activities. In contrast, forms modified at the carboxy terminus (Cys161) were inactive and did not compete for receptor binding, indicating that integrity of this domain is essential for receptor recognition. For active amino-terminal-modified forms, the specific binding of MAb 12CA5 to native HAI-EPO and the utility of 32P-labeled PHOS-EPO in receptor binding and internalization studies also were demonstrated. The development of these unique, highly active forms of human EPO should advance studies of essential interactions between this cytokine and its cell surface receptor.

Amino Acid Sequence↗

Sex differences in the incidence and sonographic characteristics of antipredator ultrasonic cries in the laboratory rat (Rattus norvegicus).

Long-Evans rats (Rattus norvegicus; ns = 10 males and 10 females) in a burrow system responded to a cat in the open area by retreating to a burrow and emitting ultrasounds of 18-27 kHz. Females made more frequent ultrasonic cries, with longer durations of ultrasounds. In a 2nd study (ns = 19 males and 19 females), sonographic analyses confirmed the more frequent vocalizations of females and indicated that the sound pulses of females were reliably shorter in duration and of higher base frequency than those of males. Also, females emitted more pulses per pulse train with shorter within-train interpulse intervals. Six basic pulse forms were determined, and males emitted more (70%) pulses with negatively accelerated descending frequencies than females (25%). The findings indicate that female rats show qualitatively different antipredator vocalizations than do males and add to previous findings of higher levels of female antipredator defensiveness.

Animals↗

Perception of alcoholism among Jewish, Moslem and Christian teachers in Israel.

This article describes a survey which investigated perception of alcoholism among Jewish, Moslem and Christian teachers in the north of Israel during the spring of 1991. Data were obtained from a sample of 553 teachers. The teachers were asked to agree or disagree with items associated with the disease concept or with the moral concept of alcoholism. The findings indicate differences in the perception of alcoholism among teachers of different religions, education levels, gender, and drinking practices. No differences were found among teachers of different ages or among those working in different types of schools.

Alcohol Drinking↗

Israeli Christian, Druze, and Moslem adolescents' attitudes toward magazine alcohol advertisements.

This article summarizes the Christian, Druze, and Moslem part of an Israeli study which was carried out in 1988 in the framework of an international comparative project conducted simultaneously also in Australia and in the USA in order to compare the perception of a set of 64 magazine alcohol advertisements by youth from three nations and various cultural and religious groups within those nations. This study is a breakthrough in the Christian, Druze, and Moslem sectors, since it is the first project in the "alcohol domain" among high school students from those sectors. The article presents the results concerning Christian, Druze, and Moslem adolescents' attitudes toward magazine alcohol advertisements. The results have implications for prevention efforts among adolescents from those three religions.

Adolescent↗

A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes.

The mitogenic actions of epidermal growth factor (EGF) were examined in low-density, dissociated cultures of embryonic day 14 mouse striatal primordia, under serum-free defined conditions. EGF induced the proliferation of single progenitor cells that began to divide between 5 and 7 d in vitro, and after 13 d in vitro had formed a cluster of undifferentiated cells that expressed nestin, an intermediate filament present in neuroepithelial stem cells. In the continued presence of EGF, cells migrated from the proliferating core and differentiated into neurons and astrocytes. The actions of EGF were mimicked by the homolog transforming growth factor alpha (TGF alpha), but not by NGF, basic fibroblast growth factor, platelet-derived growth factor, or TGF beta. In EGF-generated cultures, cells with neuronal morphology contained immunoreactivity for GABA, substance P, and methionine-enkephalin, three neurotransmitters of the adult striatum. Amplification of embryonic day 14 striatal mRNA by using reverse transcription/PCR revealed mRNAs for EGF, TGF alpha, and the EGF receptor. These findings suggest that EGF and/or TGF alpha may act on a multipotent progenitor cell in the striatum to generate both neurons and astrocytes.

Animals↗

MHC class II-restricted presentation of intracellular antigen.

An endogenously produced immunoglobulin light chain (lambda 2(315] is processed and presented to T cells in association with major histocompatibility complex (MHC) class II molecules. Using transfectants producing variant forms of lambda 2(315) that are neither expressed on the cell surface nor secreted, we demonstrate that intracellular lambda 2(315), which has never been exported outside of the cell, is the source of processed lambda 2(315) idiotype. This challenges the currently accepted paradigm that endogenous antigens are only presented by MHC class I molecules. Variants of lambda 2(315) protein that are retained in the endoplasmic recticulum (ER) are also presented. Variants that are expressed in the cytosol as well as those that are transported into the nucleus rather than the ER are not presented. Thus, the ER is likely to be the processing compartment.

Animals↗

A rearranged lambda 2 light gene chain retards but does not exclude kappa and lambda 1 expression.

Mice transgenic for the lambda 2 light chain of MOPC315 were established. In newborn transgenics (TG), lambda 2 was the only light chain found on B cells. However, by day 21, lambda 2 high kappa low as well as lambda 2 low kappa high double expresser populations were emerging. lambda 2 was found on an increased fraction of serum immunoglobulins (Ig), this fraction declined with age. Correspondingly, kappa and lambda 1 expression was suppressed in young mice but increased with age. In adult mice kappa or lambda 1 were often co-expressed with lambda 2 in single serum Ig molecules. Most B cell hybridomas from and adult TG secreted lambda 2,kappa mixed molecules and had rearranged their kappa chain genes. One lambda 2,lambda 1 hybridoma and even a lambda 2,kappa,lambda 1 hybridoma were also found. In conclusion, isotypic exclusion in lambda 2 TG is complete in newborns but becomes increasingly leaky with age. Antigen probably expands the lambda 2 low kappa high B cell population; this population is most likely the major source of serum Ig in adult lambda 2 TG mice. In contrast, the lambda 2 high kappa low population, a major fraction of which is CD5+ Mu low delta low, appears only infrequently to develop into antibody-secreting plasma cells.

Animals↗

Modulation of intracellular Ca++ in cultured astrocytes by influx through voltage-activated Ca++ channels.

Fura-2 and indo-1 fluorescence measurements were used to examine intracellular Ca++ concentration ([Ca++]i) and its modulation by voltage-activated influx in murine cortical astrocytes in primary cell culture. Extracellular K+ was increased from 5 to 50 mM to depolarize cells to determine if Ca++ influx through voltage activated Ca++ channels could alter [Ca++]i. In confluent 4 to 6 weeks in vitro astrocyte cultures 50 mM K+ increased [Ca++]i 3-4-fold (from 150 nM up to 550 nM); this increase was blocked by nifedipine and enhanced by BayK 8644 indicating that influx was through L-type channels. However, in 1 to 2 weeks in vitro astrocyte cultures, high K+ reduced [Ca++]i. L-type channels were apparently present in these cells because high K+ in combination with BayK 8644 increased [Ca++]i. Following pretreatment of 1 to 2 weeks in vitro astrocytes with dibutyryl cAMP (dbcAMP) high K+ increased [Ca++]i in the absence of BayK 8644 indicating enhanced activity of Ca++ channels in agreement with previous voltage-clamp studies. Ca++ influx through voltage-activated channels in cultured cortical astrocytes can substantially increase [Ca++]i and these channels can be dynamically modulated by dihydropyridines. Immature astrocytes may express 'silent' or inactive Ca++ channels or have a much lower number of channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Quisqualate agonists occlude kainate-induced current in cultured striatal neurons.

We employed the whole cell patch-clamp technique to examine the ionic currents induced via activation of kainate/quisqualate receptors on striatal neurons in primary culture when N-methyl-D-aspartate receptors were blocked by selective antagonists. Bath perfusion of 10 microM-1 mM each of quisqualate, glutamate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (a selective quisqualate agonist) or kainate, induced only a sustained current, but more rapid application by pressure ejection of each of the first three agonists (but not kainate) also activated a rapidly desensitizing current. The current induced by a near-saturating concentration of kainate (1 mM) was, on average, 16-fold larger than the maximum sustained current induced by quisqualate (10 microM), or 7.5-fold larger than that induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (100 microM) or glutamate (100 microM). When kainate (100 microM-10 mM) was co-applied with each of the agonists (1 microM-1 mM), the sustained current was not the algebraic sum of the currents activated by kainate or the other agonist alone; rather, the kainate-induced current was increasingly occluded by co-application with increasing concentrations of another agonist. The potency to occlude kainate-induced current had a rank order of quisqualate greater than alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate approximately glutamate; although at sufficiently high concentrations all three agonists could occlude the kainate-induced current completely. When kainate and quisqualate were co-applied during the continued presence of quisqualate, the onset of the kainate-induced sustained current was dramatically slowed. However, the steady-state occlusion by quisqualate could be abolished when the ratio kainate to quisqualate was raised to 100:1; therefore, the occlusion appears to involve a competition between kainate and quisqualate at some shared receptor binding sites which have a higher affinity for quisqualate than kainate.

Amino Acids↗

N-methyl-D-aspartate evokes the release of somatostatin from striatal interneurons in primary culture.

Indirect immunocytochemistry of striatal neurons in primary culture, generated from the embryonic mouse brain, suggested that 2-4% of the neurons contained somatostatin-like immunoreactivity; the majority of these cells also contained neuropeptide Y immunoreactivity, characteristic of a subset of striatal interneurons. Although 10-15% of cultured striatal neurons showed moderate or intense immunoreactivity for calbindin-D28k, the majority of neurons with somatostatin-like immunoreactivity did not contain calbindin-D28k-like immunoreactivity; parvalbumin immunoreactivity was absent from the culture preparation. A highly sensitive radioimmunoassay was used to examine the actions of depolarizing agents and excitatory amino acids on the release of endogenous somatostatin-like immunoreactivity from striatal interneurons. During a 15 min incubation period, 47 +/- 10 fmol of somatostatin-like immunoreactivity were released from 14 days in vitro striatal neurons, cultured in 35 mm dishes. Depolarization with 56 mM KCl or 10 micrograms/ml veratrine resulted in an additional 105 +/- 9 and 56 +/- 5 fmol, respectively, of somatostatin-like immunoreactivity released; the release evoked by veratrine was blocked by 1 microM tetrodotoxin. In the presence of 100 microM N-methyl-D-aspartate, 112 +/- 21 fmol of somatostatin-like immunoreactivity (above basal) were released (+238%); the N-methyl-D-aspartate-evoked release was dose-dependent (EC50, 20 microM), attenuated in the absence of added Ca2+, potentiated in the absence of added Mg2+ and unaffected by the presence of 1 microM tetrodotoxin. The selective antagonists 2-amino-5-phosphonovalerate (100 microM) and MK-801 (1 microM) blocked the N-methyl-D-aspartate-evoked release of somatostatin-like immunoreactivity; KCl-evoked release was unaffected. Kainate was slightly more effective, yet five-fold less potent (EC50, 100 microM), than N-methyl-D-aspartate in evoking somatostatin-like immunoreactivity release; quisqualate was marginally effective. The results of this study suggest that N-methyl-D-aspartate and kainate receptors are present on striatal somatostatinergic interneurons in primary culture.

Animals↗

Alcohol drinking among Moslem and Druze adolescents in Israel in 1990.

This article describes the Moslem and Druze parts of a survey conducted in the north of Israel during spring 1990 in order to investigate alcohol drinking habits of Moslem, Druze and Jewish high school students and to draw implications for prevention efforts. Of a general sample of 2763 students, 932 Moslem and 215 Druze adolescents were drawn from junior and senior high schools in a Druze village, several Moslem villages, an Arab town, and a mixed Arab-Jewish town. This is the first epidemiological study among students from those sectors in Israel. Involvement with alcohol was greatest among Druze males, lower by Moslem males from an Arab town and Moslem villages, and lowest by Moslem students in a mixed Arab-Jewish town. Druze students reported a higher rate of father's drinking than Moslem students did. Prevention efforts among these populations are discussed.

Adolescent↗

Adult women's drinking in Israel: a review of the literature.

This article presents a review and critique of research on Israeli Jewish women's drinking. It has been prepared in an attempt to bring together the results of all Israeli studies dealing with Jewish women's drinking. It summarizes, on the basis of a review of all Israeli alcohol research in the professional literature in Hebrew and English, women's drinking practices over the last 42 years (May 1948-May 1990) with emphasis on the last decade. Three main areas of interest (alcohol-dependent women in treatment, drinking habits of women in special populations, and drinking habits and attitudes of women in the general population) have been elucidated by looking at three periods: the late 40s-60s, the 70s, and the 80s. The 60s and 70s are characterized by studies concerning pathological drinking patterns among women in clinical and treatment settings, and the 80s are characterized by research in the general population. The review concludes with a call for more investigation and topics for further study are discussed.

Adult↗

Nonritual alcohol drinking practices among high school students from the Kibbutz movement in Israel: implications for prevention.

This article describes the Kibbutzim part of a survey conducted in the north of Israel during spring 1990, in order to investigate alcohol drinking habits of Jewish students from Kibbutzim and urban areas, as well as those of Moslem and Druze students, and to draw conclusions for designing alcohol abuse prevention activities. Of the general sample of 2763 students, 572 subjects were drawn from eleven schools which belong to sixty-two Kibbutzim. Exactly 435 students were Kibbutzim-born and 137 were outsiders living and being educated in the Kibbutzim. Kibbutzim-born youth showed the highest rate of involvement with alcohol in Israel, and a striking difference concerning the rates of alcohol consumption was revealed between the above mentioned two groups. This article explains this gap, as well as the high prevalence of alcohol use among Kibbutzim-born youth, and discusses implications for prevention.

Adolescent↗

Elevated 18-hydroxy-corticosterone in inbred salt-sensitive rats.

Rats susceptible to the hypertensive effect of dietary salt (SS/Jr) have excess 18-hydroxydeoxycorticosterone (18-OH-DOC) and 19-nor-DOC compared to control rats (SR/Jr). This may be caused by an abnormal adrenal 11 beta-hydroxylase, which catalyzes the 11 beta, 18, and 19-hydroxylations of DOC. A comparison of the urinary products of this enzyme including 18-OH-DOC, 19-nor-DOC, corticosterone (B), and 18-OH-B have not been described in the SS/Jr. Therefore, these steroid products were measured at 7 and 12 weeks of age in 36 weanling male and female, SS/Jr and SR/Jr (n = 9 in each group), on a low-salt diet. In both the male and female SS/Jr urinary free levels of 18-OH-DOC, 19-nor-DOC, and 18-OH-B were elevated, while B was not different at 6 and 10 weeks of age. The largest increases were in 18-OH-B levels, and these levels correlated with 18-OH-DOC and B but not 19-nor-DOC. The high degree of correlation between these steroids probably reflects their closely related dependence on adrenal 11 beta-hydroxylase biosynthesis.

18-Hydroxycorticosterone↗