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Biomedical subjects

M Meltzer

Publications and source records attributed to M Meltzer.

7 recordsLinked to original sources
PubMed1992

Phorbol ester reduces constitutive nuclear NF kappa B and inhibits HIV-1 production in mature human monocytic cells.

NF kappa B is a potent mediator of specific gene expression in human monocytes and has been shown to play a role in transcription of the HIV-1 genome in promonocytic leukemias. There is little information available on the response of NF kappa B to cytokines in normal human monocytes. We have used a 32P-labeled oligonucleotide derived from human immunodeficiency virus (HIV-1) long terminal repeat, which contains a tandem repeat of the NF kappa B binding sequence, as a probe in a gel retardation assay to study this transcription factor. Using this assay, we have detected NF kappa B in extracts of nuclei from normal human monocytes. Treatment of normal monocytes with 12-0-tetradecanoyl phorbol-13-acetate (TPA) for 4-24 h caused the complete disappearance of NF kappa B from nuclear extracts of monocytes. A similar result was obtained with the mature monocytic leukemia cell line THP-1. The constitutive transcription factor SP1 was unaffected by addition of TPA. The disappearance of NF kappa B from the nucleus was concentration dependent between 10 and 50 ng/ml of phorbol ester. In THP-1 cells, TPA also induced a new, faster-migrating NF kappa B species not induced in monocytes. Protein kinase C inhibitor staurosporine, but not cyclic nucleotide-dependent protein kinase inhibitor HA-1004, also dramatically reduced constitutive levels of nuclear NF kappa B. Finally, TPA addition to monocytes infected with HIV-1 inhibited HIV-1 replication, as determined by reverse transcriptase assays, in a concentration-dependent manner. These results are in striking contrast to the increase in nuclear NF kappa B and HIV-1 replication induced by phorbol esters in promonocytic leukemia cells U937 and HL-60, and emphasize the importance of studying cytokine regulation of HIV-1 in normal monocytes.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Rabies control in the Republic of the Philippines: benefits and costs of elimination.

We compared the benefits and costs of eliminating animal and human rabies in the Philippines. If rabies had been eliminated in 1988, economic benefits would total P52.8 (US$2.5) million in 1989. These benefits would largely arise from the abolition of expenses associated with rabies prevention: P29.7 (US$1.4) million for animal vaccination, P21.6 (US$1.0) million for human postexposure prophylaxis, and P0.3 (US$0.02) million for animal rabies examinations. Benefits also included P1.2 (US$0.06) million in additional earnings of humans whose death due to rabies would be prevented. Nationwide elimination was estimated to cost between P88.1 (US$4.2) million and P317.2 (US$15.0) million, assuming a canine-to-human ratio of 1:10, vaccine coverage of 60%, and a cost per vaccination of no less than P25 (US$1.19) and no more than P90 (US$4.27). These costs would be recouped 4.1-11.0 years after the initiation of a one-year elimination campaign. A sensitivity analysis showed that an elimination programme would be economically beneficial in all but the most extreme cases.

Animals↗
PubMed1991

Determination of Ro 14-4767 (Loceryl) by LC using automated column switching with ultraviolet and electrochemical detection.

Ro 14-4767, Loceryl is a member of a new class of antimycotics, and a number of dosage forms are being developed for its topical application. The active, impurities and its major oxidation products are amenable to ultraviolet detection at wavelengths of approximately 220 nm. As new delivery systems and lower strengths have been developed, it was recognized that a more sensitive detection method may be necessary to support product development. Ro 14-4767, Ro 14-3168 (impurity) and diastereomers are readily oxidized at potentials of 0.8 V (vs Ag/AgCl) at a glassy carbon electrode. Electrochemical detection substantially improved the sensitivity relative to UV detection. However, detection of impurities and oxidation products by either UV or electrochemical detection exhibited interference problems from the cream matrix. Employing column switching eliminated the interference problem from the cream matrix and adding tetrahydrofuran to the mobile phase (acetonitrile and pH 7.0 phosphate buffer) significantly increased the selectivity and sensitivity for both UV and electrochemical detection. The method requires the use of two pumps to continually deliver the mobile phase through both detectors before and after valve switching, preventing the baseline from shifting during a stop in the flow to the electrochemical detector. Quantitative recovery of the active, the potential degradation products, and Ro 14-3168 from a placebo cream using column switching and UV detection has been demonstrated. Utilizing this methodology it is possible to quantitate 0.1% of the formulation label claim for the potential degradation products and Ro 14-3168. Electrochemical detection provides greater selectivity in that only Ro 14-3168, Ro 14-4767 and its diastereomers are detected. However, the sensitivity of detection relative to UV is enhanced. The method is linear in the range of 50 to 150% of the working standard solution for 0.01% and 0.001% active concentration of the cream. The column switching technique can be automated for reproducible assay of a large number of samples.

Antifungal Agents↗
PubMed1977

Haemolytic anaemia due to erythrocyte pyrimidine 5'-nucleotidase deficiency. Report of the first South African family.

The first South African case of haemolytic anaemia due to erythrocyte pyrimidine 5'-nucleotidase deficiency is reported. The anaemia is characterized by the presence of high erythrocyte pyrimidine nucleotide levels and marked basophilic stippling. The enzyme levels in 20 family members confirm an autosomal recessive mode of inheritance and illustrate the difficulty of diagnosing the carrier state.

Anemia, Hemolytic↗
PubMed1976

Leucocyte migration test in patients after corneal transplantation.

Twenty-four patients with corneal homografts were repeatedly evaluated by the leucocyte migration test using pooled human corneal extract 0.2 mg/ml as antigen. All patients were treated with small doses of local or systemic steroids. If cloudiness of the graft developed, the doses were increased up to 40 mg methylprednisolone or 48 mg triamcinolone daily. Before transplantation, two patients showed inhibition of leucocyte migration. During the third postoperative week seventeen responded with migration inhibition. The grafts remained clear in all but one patient during this period of time. After the second postoperative month, leucocyte migration inhibition was found in none of sixteen patients whose grafts remained clear. Three of seven patients with late graft rejection exhibited migration inhibition and in two of them this response was demonstrated repeatedly several months prior to the clinical reaction. These findings suggest that the test may predict graft failure in some patients.

Adolescent↗
PubMedDate not supplied

Cerebral arteritis in scleroderma.

Central nervous system (CNS) involvement is rare in scleroderma unless there are concomitant abnormalities in renal or lung function or malignant hypertension. A 43-year-old woman with typical scleroderma developed subacute encephalopathy despite absence of the above abnormalities. Cerebral angiography demonstrated a focal arteritis. The patient improved while being given corticosteroids. We believe this case indicates that cerebral arteritis can occur in scleroderma.

Adult↗