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Biomedical subjects

B Weiss

Publications and source records attributed to B Weiss.

At least 37 records · Page 2Linked to original sources

Neuronal localization and modulation of the D2 dopamine receptor mRNA in brain of normal mice and mice lesioned with 6-hydroxydopamine.

A novel oligonucleotide probe was designed, characterized and utilized to study the distribution and modulation of the mRNA encoding the D2 dopamine receptor in the brain of the mouse. Using in situ hybridization histochemistry, the highest levels of the D2 receptor mRNA were found in regions of the brain containing the cell bodies and the terminal projection fields of the nigrostriatal, mesolimbic and mesocortical dopaminergic systems. Particularly high levels of the D2 receptor mRNA were found in substantia nigra pars compacta, ventral tegmental area, caudate-putamen and olfactory tubercle. This distribution generally paralleled that of the D2 dopamine receptor. Some areas, not usually associated with dopaminergic systems, also contained significant levels of the D2 receptor mRNA signal. These areas included the hippocampus, certain thalamic nuclei, the inferior colliculus and the spinal trigeminal nucleus of the medulla and spinal cord. Lesioning the corpus striatum with 6-hydroxydopamine had little effect on the level of the D2 receptor mRNA in the striatum but greatly reduced the hybridization signal in the substantia nigra pars compacta and ventral tegmental area. Similarly, lesioning the substantia nigra, nearly abolished the signal in the pars compacta but failed to substantially alter the D2 receptor mRNA signal in the striatum. These results suggest that the D2 receptor mRNA in the substantia nigra pars compacta was localized largely to dopaminergic cell bodies, the terminal projections of which lie in the striatum and codes for D2 autoreceptors and that the D2 receptor mRNA of the striatum is in non-dopaminergic cell bodies that are intrinsic to the striatum and probably codes for post-synaptic D2 receptors. Further, the evidence that lesions of striatum and substantia nigra induced with 6-hydroxydopamine greatly reduced the D2 receptor mRNA signal in the substantia nigra, without concomitantly increasing the D2 receptor mRNA in the striatum, suggests that the increase in dopamine receptor binding in the striatum that is ipsilateral to the lesion with 6-hydroxydopamine and the enhanced behavioral sensitivity to dopaminergic agonists, cannot be accounted for solely by an increase in D2 receptor mRNA.

Animals

Studying the "referability" of child clinical problems.

Child clinical problems may differ in their power to evoke clinic referral, and this "referability" of problems may also differ with the gender or culture of the child who manifests them. The authors propose (a) a method for the study of such differences and (b) a new statistic, the referability index (RI). RI reflects the frequency with which a child problem stimulates clinic referral, adjusted for its prevalence in the general population. RI was assessed across 118 child problems as a function of problem type (overcontrolled vs. undercontrolled), child gender, and culture (U.S. vs. Thailand). Problems of both types were more referable in girls than boys: undercontrolled problems were more referable than overcontrolled in the U.S. but, surprisingly, not in Thailand. The findings shed new light on gender and culture differences and illustrate the empirical and heuristic potential of the RI statistic.

Child

Incidence of intestinal parasitic disease in an acquired immunodeficiency syndrome day-care center.

In June, 1986, the Bronx Municipal Hospital Center opened an acquired immunodeficiency syndrome day-care center to provide a quality educational experience for children infected with the human immunodeficiency virus. A major concern was the possibility of increasing secondary infections among these immunocompromised children by placing them in a group environment. One particular worry was intestinal parasitic disease, a serious public health problem in day-care centers throughout the United States. To minimize the risk of parasitic infections, scrupulous hygienic and monitoring procedures were instituted at the acquired immunodeficiency syndrome day-care center. This study reports the incidence of intestinal parasitic disease at the acquired immunodeficiency syndrome day-care center during its first 40 months of operation, encompassing 669 child-months of enrollment, with 131 stool specimens examined for ova and parasites. There were 2 cases of parasitic infection: Entamoeba histolytica in an asymptomatic 6-year-old and Giardia intestinalis in a 7-year-old with diarrhea. In neither case was there any secondary spread. None of the 15 children in diapers had a positive specimen, and we found no Cryptosporidium. Our experience suggests that with appropriate precautions human immunodeficiency virus-infected children can participate in a group day-care program without excessive risk for parasitic disease. Strict adherence to hygienic procedures may also decrease the risk of intestinal parasitic disease among healthy children attending day-care centers.

Acquired Immunodeficiency Syndrome

Adult attitudes toward over- and undercontrolled child problems: urban and rural parents and teachers from Thailand and the United States.

In a study of adult attitudes, urban and rural parents and teachers in Thailand and the U.S. made judgments about two children, one with overcontrolled problems (e.g. shyness, fear), one with undercontrolled problems (e.g. disobedience, fighting). Consistent with previous literature, Thais (vs Americans) rated problems of both types less serious, less worrisome, less likely to reflect personality traits, and more likely to improve with time. Urban-rural differences and parent-teacher differences had negligible impact. The findings suggest that certain cultural differences in adult attitudes toward child problems may be robust across parents and teachers and across urban and rural settings.

Adult

Two divergently transcribed genes, soxR and soxS, control a superoxide response regulon of Escherichia coli.

soxR governs a superoxide response regulon that contains the genes for endonuclease IV, Mn2(+)-superoxide dismutase, and glucose 6-phosphate dehydrogenase. The soxR gene encodes a 17-kDa protein; some mutations of this gene cause constitutive overexpression of the regulon. Induction by paraquat (methyl viologen) requires both soxR and a new gene, soxS. soxS is adjacent to soxR, it encodes a 13-kDa protein, and it is required for paraquat resistance. These functions were revealed by studies in which the sequence of the 1.1-kb soxR-soxS region was determined, the 5' ends of the mRNAs were mapped, and complementation tests were performed with soxRS plasmids containing deletions of known sequence. The two genes are divergently transcribed, and the transcripts overlap. The soxS promoter is within the 85-nucleotide intergenic region, whereas the soxR promoter is within soxS. soxS mRNA increases after induction. Both protein products have possible DNA-binding (helix-turn-helix) domains. SoxR contains four cysteines (CX2CXCX5C) that might be part of a sensor region. SoxS shows 17 to 31% homology to the C-terminal portions of members of the AraC family of positive regulators.

Amino Acid Sequence

Ethanol's effects on tremor and positioning in squirrel monkeys.

Ethanol ingestion markedly reduces tremor in patients with essential tremor. This clinical observation prompted the present experiments, which were designed to investigate ethanol's reduction of tremor in squirrel monkeys trained to execute a bar-holding task. A lever was attached to the hub of a rotary variable differential transformer (RVDT) and three squirrel monkeys were trained to position this lever within a 4.5 cm band for 8 seconds for a fruit juice reward. Behavior was maintained by a random ratio 2 schedule of reinforcement. Angular position of the lever was sampled for 5.12 seconds while the monkey held the bar, differentiated twice and analyzed to obtain a spectral description of tremor in units of acceleration 2/Hz. During control and vehicle sessions a spectral peak appeared at about 6-8 Hz and the magnitude of this peak varied from 25 to 150 milli-g2/Hz (where g is the acceleration due to gravity). A second peak appeared in two animals at greater than 15 Hz. For one animal this high-frequency peak was dominant during control sessions but the 6-8 Hz peak was dominant after intubation with water or ethanol. Ethanol produced consistent and dose-related decreases in the amplitude of the spectrum describing tremor but the location of the spectral peaks did not differ from vehicle sessions. The doses that altered tremor also produced an increase in the number of short-duration holds as well as other, less consistent, alterations in the form of the response. These data confirm and quantify ethanol's potency as a tremorolytic agent.

Alcohol Drinking

Downregulation of stereotyped behavior and production of latent locomotor behaviors in mice treated continuously with quinpirole.

D1 and D2 dopamine receptors mediate different behavioral effects in animals. We have attempted to selectively modulate dopamine-mediated behaviors by continuously administering D2 agonists to mice. Acute administration of the D2 agonist quinpirole caused dose-related stereotyped effects; no locomotor or grooming behavior was apparent. Continuously infusing quinpirole with implanted Alzet minipumps initially produced stereotyped behavior, but this stereotypy decreased by 2 hours, and was completely absent from 3 hours to 6 days of infusion. Within 1 day after implanting quinpirole, there appeared a significant locomotor behavior that continued for the 6 days of infusion. Acute challenge doses of quinpirole given either 6 days after infusing quinpirole or 12 hours after removing the quinpirole implant failed to elicit any stereotyped behavior and did not alter the locomotor behavior. By contrast, acute challenge injections with the D1 agonist SKF 38393 administered 12 hours after removing the quinpirole implant produced a characteristic grooming response. In an attempt to learn the mechanism of the behavioral effects induced by the continuous administration of quinpirole, the actions of relatively selective D1 and D2 antagonists were examined. The D2 antagonist sulpiride inhibited the stereotypy but not the locomotion induced by quinpirole. By contrast, the D1 antagonist Sch 23390 blocked the locomotion but not the stereotypy induced by quinpirole. These results indicate that chronic administration of quinpirole causes two separate behavioral effects: (1) a downregulation of stereotypy, perhaps by downregulating D2 receptors; and (2) the development of locomotion, which appears to involve both the downregulation of D2 receptors and an activation of D1 dopaminergic mechanisms.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben

Cancer and the dynamics of neurodegenerative processes.

The term neurodegenerative denotes a process rather than a state. In contrast, most research on such disorders, whether clinical or experimental, represents only a slice of time. Their progressive nature is mostly confined to speculation instead of being codified in research protocols. Research on cancer, also a degenerative disease, is much more often framed in terms of process. Part of the difference is accounted for by the impact of quantitative modeling, which enjoys a long history in both basic and clinical cancer research and which originated in attempts to describe and understand tumor development. Analogous questions are posed by neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. Among the issues that modeling could help to clarify are the properties and sources of the age-specific incidence rate, which resembles that for cancer, and the pharmacokinetics governing the toxic products of neurotransmitter metabolism. Neurodegenerative disorders maintain a research advantage because functional measures, mostly inaccessible to cancer investigators, serve as the ultimate index of progression. Their exploitation, however, in longitudinal studies remains inadequate.

Animals

Growth characteristics of human laryngeal carcinoma in athymic mice.

We report the growth characteristics of seven human laryngeal carcinomas transplanted into athymic mice. Six of the tumors were harvested from surgical pathology specimens and one was from a laryngeal carcinoma cell line. Tumor tissue measuring 2-3 cubic millimeters was implanted subcutaneously into the flank of the mice. Time intervals between implantation and active growth were recorded and tumor volume was calculated weekly. Mice were sacrificed at various time intervals. For three tumors, second and third passages of the tumor were performed. Successful tumor growth was achieved in 6/7 (85.7%) tumors. Primary implantation of tumor was performed in a total of 26 mice, 17 of which grew successfully. The average time interval between tumor implantation and measurable tumor growth for the five zenografts derived directly from patients was 36 days (range 25-40 days). The mean doubling time was 16 days (range 7-30 days). The overall take rate per animal for serial passage of tumor was 36 out of 43 (83.7%). The lag phase and the mean tumor doubling time decreased with each successive passage. At autopsy most tumors were confined to the subcutaneous structures by a well-formed capsule. Lymph node metastases and disseminated metastases were not seen. We conclude that the athymic mouse model is suitable to establish primary tumor growth of human laryngeal cancer.

Animals

Regional and subcellular distribution of cytochrome P-450-dependent drug metabolism in monkey brain: the olfactory bulb and the mitochondrial fraction have high levels of activity.

In brain of female monkey (M. fascicularis) the content of cytochrome P-450 and benzo(a)pyrene hydroxylase activity in the mitochondrial fraction exceeded that of the microsomes by more than 4-fold. The mitochondrial drug metabolism activity exhibited substrate specificity and, unlike the microsomes, did not catalyze 7-ethoxyresorufin O-deethylase reaction. Moreover, the rate of benzo(a)pyrene hydroxylase activity by both the mitochondrial and the microsomal fractions displayed regional variation with the olfactory bulb displaying the highest hydroxylase activity. In contrast, the microsomal 7-ethoxyresorufin O-deethylase activity was uniformally distributed in all brain regions.

Animals

Ontogenetic development of calmodulin mRNA in rat brain using in situ hybridization histochemistry.

An oligonucleotide probe complementary to the area on calmodulin coding for the calcium binding domain II on calmodulin was used to study the ontogenetic development of calmodulin mRNA in rat brain using in situ hybridization histochemistry. The hybridization signal for this probe was saturable, RNAse sensitive and was displaced by excess unlabelled calmodulin probe but was not displaced by an S-100 probe or by another calmodulin probe which was complementary to the mRNA coding for a different portion of calmodulin. At birth, high levels of calmodulin mRNA were found in hippocampus, cerebral cortex, thalamic nuclei and corpus striatum, and relatively low levels were in white matter. The rate at which calmodulin mRNA changed during development in the different brain areas varied with the brain area. At postnatal day one, the highest hybridization signals were in the cortical plate of the cerebral cortex, in thalamus and in the pyramidal cell layers of hippocampus and pyriform cortex. This distribution became more uniform with age. In contrast to most other brain areas, calmodulin mRNA in cerebellum increased markedly between one and 32 days postnatal; the hybridization signal was low at day one and was confined to the external germinal layer, but by day 16 calmodulin mRNA was largely in the granular layer. These results taken together with other findings on the effects of calmodulin on cellular growth differentiation, suggest that calmodulin may play a role in neuronal maturation.

Aging

Anatomical localization of calmodulin mRNA in the rat brain with cloned cDNA and synthetic oligonucleotide probes.

Calmodulin is a small, acidic calcium-binding protein that regulates a number of calcium-dependent enzyme activities and is thought to be involved in neurotransmission. To begin to explore further the regulation of this important protein in the brain, we have cloned a rat calmodulin cDNA and designed an oligonucleotide probe based on this sequence. Both the cDNA and oligonucleotide probes revealed a markedly heterogeneous distribution of hybridization signal for calmodulin mRNA in the rat brain. The greatest apparent abundance of mRNA for calmodulin was seen in the hippocampus and cerebral cortex, whereas many brain regions showed relatively low hybridization signal, including the striatum and portions of the hypothalamus and brainstem.

Animals

The impact of methodological factors on child psychotherapy outcome research: a meta-analysis for researchers.

Two recent meta-analyses have generated evidence for child and adolescent psychotherapy effects. However, critics note that such meta-analyses often include studies with methodological shortcomings which might invalidate their results. In the present study, we explored whether the results of the most extensive child/adolescent meta-analysis might have been influenced by such methodological variables, focusing on internal validity and external validity factors. Together, these factors accounted for two-thirds as much variance as the substantive factors (e.g., type of therapy, age) in the original meta-analysis. This suggests that relative to these therapy and child-characteristic variables, methodological factors have a substantial, though smaller, impact on meta-analysis results. In general, increased experimental rigor was related to larger effect sizes; this argues against the hypothesis that methodologically weak studies have led to an overestimate of therapy effects. No significant interactive relations were found between validity factors and predictors of outcome; this suggests that the relations noted in previous meta-analyses between outcome and various variables were not distorted by the validity factors tested here.

Adaptation, Psychological

Drug effects on an effortful operant: pentobarbital and amphetamine.

The behavioral effects of amphetamine and pentobarbital depend upon the conditions maintaining behavior. For example, amphetamine usually decreases the rate of operant behavior maintained by fixed ratio schedules while pentobarbital either increases it or leaves it unaffected. However, when considerable exertion is required, as in situations that require endurance, amphetamine tends to enhance performance while barbiturates degrade it. These differences complicate predictions of the effects of these two drugs on effortful operants. The present experiment was designed to characterize effortful responding behaviorally and pharmacologically. Cebus monkeys were trained to operate a lever by flexing their arms and extending their legs; this response exerted a force approximating their body weight. This operant was maintained by a multiple fixed ratio fixed interval (Mult FR FI) schedule. The two schedules maintained dramatically different response patterns. The FR schedule maintained vigorous, high rate responding characterized by a narrow IRT distribution centered at 0.5 sec. The FI schedule maintained very low overall rates of responding characterized by a variable IRT distribution with a median of 1.5 to 2 sec. Despite very low rates of responding during the FI component, no consistent rate increases appeared after amphetamine, and 0.3 mg/kg eliminated responding altogether. Pentobarbital increased overall rate but also shifted the interresponse time (IRT) distribution toward longer IRTs. The increase in overall rate arose from an earlier onset of responding during the FI component and occurred simultaneously with response slowing. The present studies do not support suggestions of a generalized enhancement of effortful performance by amphetamine or a generalized degradation by pentobarbital.

Animals

Vibration sensitivity recovery after a second course of acrylamide intoxication.

Five monkeys were trained to report detection of vibration or an electrical stimulus. Three of them had been dosed previously with acrylamide administered orally until toxic signs appeared, and were then allowed to recover. Approximately 30 weeks after the end of the first dosing course, they were dosed a second time with 10 mg/kg/day of acrylamide, 5 days a week, to mimic the dosage regimen of the first dosing period. Two monkeys received vehicle, as in the first dosing period. Vibration sensitivity was reduced in the exposed monkeys to an extent comparable to the first dosing period. Analysis of covariance showed that the rate of recovery from a second exposure to acrylamide was comparable to the rate of recovery from the first exposure. Vibration sensitivity appears useful as a monitoring tool to follow the time course of acrylamide-induced peripheral nerve dysfunction.

Acrylamides

Modification of lead distribution by diethyldithiocarbamate.

Many reports indicate that dithiocarbamates such as diethyldithiocarbamate (DDC), administered in conjunction with exposure to various metals, can elevate the brain levels of such metals at the same time that they promote excretion from other sites. To more clearly define the effects of DDC on lead (Pb) distribution after prolonged exposure to relatively low levels, male Long-Evans rats were provided with drinking water containing 0, 50, or 500 ppm Pb acetate. During the 12-week experimental period, DDC was administered by ip injection twice weekly in a dose of 100 mg/kg. Every 3-4 weeks, urine and blood samples were taken 24 hr before and after a scheduled DDC injection. DDC administration exerted no discernible effect on bone Pb levels and showed only an interaction with Pb dose, but not independent effects on kidney levels. Both liver and brain Pb levels attained much higher levels in the DDC-treated rats than in animals exposed to Pb alone. The sequential measures of Pb in blood and urine and of delta-aminolevulinic acid revealed complex patterns of change over time. One possible explanation, at least for the elevated levels of Pb in brain, is the lipophilic character of the Pb-DDC complex, which facilitates entry into the central nervous system; it may also explain the elevated levels in liver. This property, common to many chelators, suggests their use in model systems to study the neurotoxic properties of metals.

Aminolevulinic Acid

Modification by nickel of instrumental thermoregulatory behavior in rats.

The effects of NiCl2 on the colonic temperature and thermoregulatory behavior (TRB) of rats were examined. TRB was evaluated in an instrumental (operant) setting in which rats were required to press a level to obtain convectional heat (SEEK) or to avoid heat (ESCAPE). Orthogonal polynomial regression was used to describe the response patterns in both the SEEK and ESCAPE situations. Two milligrams per kilogram of Ni (ip) caused rapid, transient hypothermia at an ambient temperature of 21 degrees C. When given access to heat reinforcement, rats responded for heat at a lower rate immediately after 2 or 5 mg/kg of Ni (up to 5-15 min) than after saline. Subsequently, response rates rose 30 min or more after Ni injection. A converse pattern was found with the heat escape situation. These observations, confirmed by two contrasting procedures, indicate that the changes were thermoregulatory in nature and cannot be explained by nonspecific suppressive or excitatory effects of Ni. They further suggest that Ni-induced hypothermia results from an altered body temperature set point. The subsequent reversal in behavior probably arises from a direct action of Ni on autonomic effector mechanisms. The origin and biological significance of these findings require further investigation. Physical requirements and response topography are discussed as critical variables in the interpretation of experiments requiring similar responses under different ambient temperatures.

Animals

Arrests among emotionally disturbed violent and assaultive individuals following minimal versus lengthy intervention through North Carolina's Willie M Program.

Time to first arrest after termination of Willie M Program services was compared in 2 groups of former clients. All Ss had met program criteria and "aged out" after their 18th birthday, but the two groups differed in duration and extent of intervention received: (a) A short-certification group (n = 21), because they turned 18 near the 1981 program start date, had received Willie M services for a mean of only 26 days (all cases less than 3 months); (b) a long-certification group (n = 147) averaged 896 days in the program (all cases greater than 1 year). The groups did not differ significantly in gender or race; geographic region; IQ; diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. (DSM-III, American Psychiatric Association, 1980); or age at earliest antisocial acts. A survival analysis compared the short and long groups on proportion avoiding arrest as a function of time since aging out. The long group showed slightly better arrest survival, but survival curves for the 2 groups did not differ reliably. Thus the program was not found to significantly reduce the risk of young adult arrests.

Adolescent