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Biomedical subjects

A Arnold

Publications and source records attributed to A Arnold.

At least 199 records · Page 11Linked to original sources

Immunoglobulin gene rearrangement and cell surface antigen expression in acute lymphocytic leukemias of T cell and B cell precursor origins.

We have explored the relationship among immunoglobulin gene rearrangement, cytoplasmic immunoglobulin production, and cell surface antigen expression within 37 cases of acute lymphocytic leukemia. All 12 cases of the T cell type had germ-line kappa and lambda genes and 11 of 12 had germ-line heavy chain genes. In contrast, all 25 cases of the "non-T, non-B" classification, which lacked both definitive T cell markers and surface immunoglobulin, had rearranged immunoglobulin genes, indicating that they represent precursor cells already committed to the B cell lineage at the gene level. 14 had rearranged heavy chain genes, yet retained germ-line light chain genes, whereas 11 cases had both heavy and light chain gene reorganizations. All patterns of immunoglobulin gene rearrangement predicted by a model that proceeds from heavy chain gene recombination to light chain genes were observed. Despite the uniform presence of rearranged immunoglobulin genes, only five cases produced cytoplasmic mu-chain, one exceptional case produced gamma-chain, and another produced only lambda-chain. The cases of B cell precursor type that do not produce immunoglobulin may represent cells that frequently possess ineffectively rearranged immunoglobulin genes. Included in this group may be a set of cells trapped within the B cell precursor series because their ineffective rearrangements have eliminated certain gene subsegments necessary for the assemblage of an effective heavy chain gene. All seven cases of the non-T, non-B subgroup that bore HLA-DR but lacked CALLA (the common acute lymphocytic leukemia-associated antigen) represented the earliest recognizable stage of B cell precursors with rearranged heavy chain genes but germ-line light chain genes. Correlations here suggest that cells entering B cell development express HLA-DR and rearrange heavy chain genes before the expression of a B cell-associated antigen recognized by the antibody BA-1, the antigen CALLA, and any subsequent light chain gene rearrangements.

B-Lymphocytes↗

Chemotherapy of advanced ovarian carcinoma: initial experience using a platinum-based combination.

Thirty-five previously untreated patients with FIGO Stage III or IV ovarian carcinoma were treated with cis-diamminedichloroplatinum (II), Adriamycin and cyclophosphamide (PACe). Following four or five cycles of PACe, patients were assessed clinically for response. Twenty-one (60%) of the patients attained a clinical complete remission (CCR), seven (20%) a partial remission, and seven (20%) did not respond. The median survival of all patients was 19 months, 6.4 months for partial and nonresponders, and 26.5 months for clinical complete responders. Six patients remain relapse-free for more than two years. Patients entering into the study during the second year underwent a second-look procedure if they attained a CCR. Ten patients in CCR were assessed for second look; two refused, and eight underwent a laparotomy. Three of eight were in complete remission after second look, and a fourth patient who had microscopic disease in one ovary was rendered free of disease by surgery. Subjective toxicity was marked due to severe nausea and vomiting. Renal toxicity was not troublesome and myelosuppression was moderate. Ototoxicity and peripheral neuropathies were seen in seven patients. PACe is a highly effective induction regime but randomized studies are required to show that improved survival will result from it's use.

Adenocarcinoma, Mucinous↗

Detection of HLA antigens on progeria syndrome fibroblasts.

It has been suggested that cultured skin fibroblasts derived from patients with progeria, a premature aging syndrome, have absent or markedly reduced HLA antigen expression, thus implicating a possible immunological role in the pathogenesis of this disease. An analysis of HLA expression in nine progeric fibroblast strains and related familial strains is reported. Normal HLA expression and inheritance were found. No significant association between HLA type and progeria was detected. Therefore, we conclude an abnormality of HLA expression is unlikely to be an underlying defect in progeria.

Cells, Cultured↗

Metabolic effects of a new hypolipidemic agent, ciprofibrate.

Ciprofibrate, a new orally effective hypolipidemic agent like clofibrate, suppressed tyloxapol-induced hypercholesterolemia in rats. Ciprofibrate at 10 mg/kg was effective. Clofibrate required a dosage of 180 mg/kg to suppress the tyloxapol effect. Norepinephrine-induced free fatty acid release was inhibited by clofibrate in rats in accordance with earlier findings. Ciprofibrate and lifibrate differed from clofibrate in that, at hypocholesterolemically effective doses, neither inhibited the hormone sensitive lipase in vivo.

Animals↗

The results of animal studies with ciprofibrate, a new orally effective hypolipidemic drug.

Findings are given to show that ciprofibrate, a new orally active phenoxyisobutyrate, is significantly more hypolipidemic than is the reference clofibrate. In hyperlipidemic rats ciprofibrate suppresses the increase in blood lipids 33% at a daily dosage of 0.6--3 mg/kg. The corresponding dosage for clofibrate is 125--460 mg/kg. Based on studies with cholesterol pools pre-labeled with [14C]mevalonate or with cholesterol-labeled pools in ciprofibrate-treated normolipidemic rats, ciprofibrate was shown to inhibit cholesterol biosynthesis. No evidence of the presence of 7- or 24-dehydrocholesterol was obtained in the sera of ciprofibrate-treated rats as shown by gas chromatography examination. The order of hypolipidemic effectiveness of ciprofibrate in hyperlipidemic rats provides a basis for anticipating that ciprofibrate will be hypolipidemic in hyperlipoproteinemic subjects who are considered at high risk of acquiring coronary artery disease.

Administration, Oral↗

Blood levels, tissue distribution and the duration of action in rats of ciprofibrate, a new hypolipidemic agent.

The blood levels, distribution and duration of action of ciprofibrate, an orally active hypolipidemic agent, was investigated in rats. Serum concentrations of 30 micrograms of ciprofibrate/ml are associated with significant reductions in both serum cholesterol and triglycerides in rats on a hyperlipidemic diet. Increasing the plasma concentrations of ciprofibrate to 69 micrograms/ml resulted in only a modest incremental reduction in serum lipids. The distribution of radioactivity from [14C]ciprofibrate within rat tissues was not affected by prior treatment for 14 days with ciprofibrate at either 1.5 or 3.0 mg/kg/day. Varying the dosage regimen of ciprofibrate at 30 mg/kg, with medication at intervals of one, 2 or 3 days resulted in similar peak plasma levels of about 300 micrograms/ml, 4 h after medication. The half-life of ciprofibrate, during the terminal disposition phase, was about 82 h. Levels of serum cholesterol remained suppressed up to 3 days after medication with ciprofibrate was discontinued; triglyceride levels returned to control values more slowly.

Animals↗

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Germany↗

Spinal branching of rubrospinal axons in the cat.

The branching patterns of rubrospinal (RS) axons projecting to the cervical spinal cord between C3 and C8 were studied in the cat. RS neurons were identified by their antidromic responses to microstimulation of local axon branches within the cervical gray matter. Twenty-six of 58 RS neurons projecting to the cervical gray matter also sent axon branches to the thoracic spinal cord. Two out of 40 of these RS neurons also sent axon branches to the lumbar spinal cord. Using a collision technique, it was demonstrated that stem axons of rubrospinal neurons commonly sent multiple collaterals to different cervical segments. Neurons projecting to the cervical spinal cord alone were located in the dorsal quadrants of the red nucleus. Those projecting to cervical, as well as to more caudal segments, were intermingled with the former, and in slightly more ventral portions of the red nucleus. The presence of RS neurons projecting to widely separate levels of the spinal cord suggests that individual RS neurons may be capable of ultimately influencing two or more different motoneuron pools.

Animals↗

[Influence of internal fluoride uptake on the eruption of deciduous teeth].

The possibility of influencing the eruptive behavior of deciduous teeth through the intake of fluorine is analyzed by comparing the average dates of eruption determined for several thousand subjects living in regions in which the drinking water has low and optimum contents of fluorine.

Child, Preschool↗

Further study on the excitation of pyramidal tract cells by intracortical microstimulation.

The effective spread of stimulating current for pyramidal tract (PT) cells and fibers was studied using a method of cancelling the shock artifacts and the following results were obtained: 1. The excitability of PT axon collaterals was as high as that of PT cells. 2. These axon collaterals extended as far as 1.0 mm horizontally from the PT cells. 3. The low threshold area for activation of a given PT cell was as wide as 3--4 mm2 on the surface of the cortex. 4. Intracortical microstimulation (ICMS) delivered to the PT cell layer produced direct (D) and indirect (I) descending volleys in the pyramidal tract, but ICMS to the superficial layer (III) produced only I-waves. 5. These I-waves grew significantly larger after 15--20 msec from the start of the train of stimuli. 6. It is concluded that either surface stimulation, or short train of ICMS is inadequate for delineating fine localization of motor function within the cortex. Longer train (30--40 msec) with high frequency pulses (300--400 cy/sec) can produce muscle contraction with much smaller currents, increasing the accuracy of measuring the localization of motor function.

Animals↗