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Biomedical subjects

S Lal

Publications and source records attributed to S Lal.

At least 109 records · Page 6Linked to original sources

Elevated dopa decarboxylase activity in living brain of patients with psychosis.

The hypofrontality theory of the pathogenesis of schizophrenia predicts that cortical lesions cause psychosis. During a search for abnormalities of catecholaminergic neurotransmission in patients with complex partial seizures of the mesial temporal lobe, we discovered an increase of the rate of metabolism of an exogenous dopa tracer (6-[18F]fluoro-L-dopa) in the neostriatum of a subgroup of patients with a history of psychosis. When specifically assayed for this abnormality, patients with schizophrenia revealed the same significant increase of the rate of metabolism in the striatum. The finding is consistent with the theory that a state of psychosis arises when episodic dopamine excess is superimposed on a trait of basic dopamine deficiency in the striatum. The finding is explained by the hypothesis that cortical insufficiency, a proposed pathogenetic mechanism of both disorders, causes an up-regulation of the enzymes responsible for dopa turnover in the neostriatum as well as the receptors mediating dopaminergic neurotransmission.

Adult↗

Recent trends in rifamycin research.

Rifamycin is a clinically useful macrolide antibiotic produced by the gram positive bacterium Amycolatopsis mediterranei. This antibiotic is primarily used against Mycobacterium tuberculosis and Mycobacterium leprae, causative agents of tuberculosis and leprosy, respectively. In these bacteria, rifamycin treatment specifically inhibits the initiation of RNA synthesis by binding to beta-subunit of RNA polymerase. Apart from its activity against the bacteria, rifamycin has also been reported to inhibit reverse transcriptase (RT) of certain RNA viruses. Recently, rifamycin derivatives have been discovered that are effective against Mycobacterium avium, which is associated with the AIDS complex. Consequently, the importance of and demand for rifamycin has increased tremendously, the world over. In this article, recent trends in rifamycin research and accessibility of recombinant DNA techniques to increase rifamycin production are reviewed.

AIDS-Related Opportunistic Infections↗

Localization of amplified MYC gene sequences to double minute chromosomes in acute myelogenous leukemia.

Cytogenetic and molecular studies were performed on two dmin-bearing acute myelogenous leukemia (FAB-M2) samples. Both cases were characterized by complex karyotypes containing interstitial deletions of the long arm of chromosome 8 altering band 8q24.1, aberrations affecting the short arm of chromosome 17, and multiple double minute chromosomes (dmin). Using a 1.4 kb cDNA probe coding for the third exon of the MYC oncogene, DNA slot blots indicated MYC gene sequences were amplified in both samples. Fluorescence in situ hybridization using a 9.0 kb genomic probe for MYC was performed in one case and localized the amplified MYC gene sequences to the dmin. Neither patient achieved a complete remission using traditional induction chemotherapy. The complex karyology with amplification of MYC gene sequences appears to represent a poor prognostic subgroup of acute myelogenous leukemia.

Aged↗

Prolonged penile erections induced by hydroxyzine: possible mechanism of action.

We describe a subject who developed prolonged penile erections on hydroxyzine. Molecular modelling showed that the hydroxyzine metabolite, norchlorcyclizine, has structural and conformational similarities to the trazodone metabolite, m-chlorophenylpiperazine. This suggests that a common pharmacological mechanism may underlie the ability of trazodone and hydroxyzine to induce erections.

Adult↗

Effect of pH on the bioenergetics of perfused porcine lenses.

Extracellular and intracellular pH has been shown to be an important physiological variable in many biological systems. However, studies on the effect of pH on the metabolic status of the mammalian lens have been few. It has been shown previously that a change in perfusate pH has a significant effect on the lens weight, ion transport, opacification and membrane potential. In this study we show that the bioenergetic status of the perfused pig lens, as assessed by 31P-NMR spectroscopy, is critically dependent on the pH of the bathing medium. At pH's of 7.6 and above, these perfused lenses maintained their nucleotide triphosphates concentrations steady for up to 4 days. In contrast, lenses perfused with identical media at pH 7.0, rapidly lost their nucleotide triphosphates. Our findings suggest that the pH of the extracellular pH may be an important parameter in maintaining the functional competence of the lens.

Adenosine Triphosphate↗

AIDS-case surveillance.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗

Detection of fructose-3-phosphokinase activity in intact mammalian lenses by 31P NMR spectroscopy.

Recently we have identified two novel phosphorylated metabolites in the lenses of diabetic rats as sorbitol 3-phosphate (Sor-3-P) and fructose 3-phosphate (Fru-3-P). The latter compound is of particular interest since it is a potent glycating agent, which could account, at least in part, for the increased protein cross-linking and cataract formation in the lens of the diabetic rat. In order to gain insight into the mechanism of formation of these compounds, 31P NMR spectra of rat, pig, and rabbit lenses, perfused with media supplemented with glucose, fructose, or sorbitol, were acquired. Perfusion with fructose-supplemented media resulted in the production of Fru-3-P in all three species. This compound was not produced upon perfusion with fructose-deficient media. The identification of the newly synthesized material as Fru-3-P was confirmed by spiking perchloric acid extracts of the perfused lenses with synthetic Fru-3-P. Our results provide strong evidence for the existence of a fructose-3-phosphokinase in mammalian lenses. If this enzyme is present in human lenses as well, it will reinforce the hypothesis that this enzyme and its product, Fru-3-P, may play a role in diabetic cataractogenesis and that lenticular fructose-3-phosphokinase may provide another therapeutic target in the prevention and alleviation of diabetic cataracts.

Animals↗

Predictors of outcome in acute meningococcal infection in children.

OBJECTIVES: To develop a rapid and sensitive method for identification of patients at risk for organ system failure and death due to acute meningococcal infection, and to evaluate the reliability of the Pediatric Risk of Mortality score in predicting mortality rates from acute meningococcal infection. DESIGN: A prospective study which followed a retrospective analysis. SETTING: The Emergency Department and pediatric intensive care unit (ICU) of a university-affiliated children's hospital. PATIENTS: The hospital records of 86 pediatric patients with acute meningococcal infection during a 5-yr period (group 1) were reviewed. Twenty-two ICU patients (group 2) were then prospectively evaluated, and the occurrence rate of organ system failure was compared with that rate predicted by the model developed from the analysis of group 1. INTERVENTIONS: The occurrence of prognostic factors was compared with the development of organ system failure and death by Fisher's exact test and logistic regression analysis for patients in group 1. The mortality rates for groups 1 and 2 were compared with those rates that were predicted by the use of the Pediatric Risk of Mortality score. MAIN RESULTS: Eighteen of 86 patients in group 1 developed organ system failure, and seven (8.1%) patients died. Logistic regression analysis found that the combination of circulatory insufficiency, peripheral WBC counts of < 10,000 cells/mm3, and coagulopathy best predicted organ system failure. Ten of 22 patients in group 2 developed organ system failure, and two died. All patients with organ system failure exhibited > or = 1 of three identified prognostic factors. The probability of organ system failure occurring was > .5 for nine of ten patients with organ system failure. A total of nine patients in groups 1 and 2 developed multiple organ system failure, and all nine patients died. Based on Pediatric Risk of Mortality scoring, the mortality risk for nonsurvivors ranged from 27% to 94%, compared with 1% to 48% for survivors. The overall mortality rate was consistent with that rate predicted by the Pediatric Risk of Mortality scoring system. CONCLUSIONS: Patients with acute meningococcal infection who exhibit signs of circulatory insufficiency, a peripheral WBC count of < 10,000 cells/mm3, or a coagulopathy have a high probability of developing organ system failure. Death is highly probable when multiple organ system failure develops, and the overall mortality rate is accurately predicted by the Pediatric Risk of Mortality score.

Acute Disease↗

Secondary syphilis mimicking borderline (BL) leprosy.

A young woman with syphilids resembling borderline lepromatous (BL) leprosy is being described. This is yet another addition to its already well-documented manifestations. The high prevalence of leprosy and syphilis augments the epidemiological significance of the case.

Adult↗

Resolution of chlorpromazine-induced cutaneous pigmentation following substitution with levomepromazine or other neuroleptics.

Eleven chronic schizophrenic patients with abnormal skin pigmentation associated with neuroleptic treatment were withdrawn from chlorpromazine (CPZ), which was replaced by levomepromazine (n = 4), trifluoperazine (n = 1) or thioproperazine (n = 1) as the sole neuroleptic, by a combination of these phenothiazines (n = 4) or with haloperidol plus pipotiazine (n = 1). Seven patients showed complete resolution of abnormal skin pigmentation over a period of 1-5 years and 4 markedly improved over 2.0-2.6 years of follow-up. Our observations suggest that neuroleptic-induced abnormal skin pigmentation is (i) predominantly, if not exclusively, a side effect of CPZ and (ii) reversible, providing that CPZ is withdrawn and sufficient time is allowed to elapse.

Adult↗

Levomepromazine receptor binding profile in human brain--implications for treatment-resistant schizophrenia.

The receptor binding profile of levomepromazine (LMP) in human brain was compared with that of clozapine (CLOZ) and chlorpromazine (CPZ). LMP showed significantly greater binding affinity for both alpha-1 and serotonin-2 binding sites than either CLOZ or CPZ, and significantly greater binding to alpha-2 sites than CPZ. A potent pharmacological effect at these receptor sites may explain the beneficial effect of LMP on psychotic symptoms and akathisia in treatment-resistant schizophrenia recently described in 2 open studies. LMP requires further appraisal as a potentially useful neuroleptic in the management of treatment-resistant schizophrenia.

Adolescent↗