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Biomedical subjects

M Franklin

Publications and source records attributed to M Franklin.

At least 19 recordsLinked to original sources
PubMed1992

Cloning and expression of a human ATP-citrate lyase cDNA.

A full-length cDNA clone of 4.3 kb encoding the human ATP-citrate lyase enzyme has been isolated by screening a human cDNA library with the recently isolated rat ATP-citrate lyase cDNA clone [Elshourbagy et al. (1990) J. Biol. Chem. 265, 1430]. Nucleic-acid sequence data indicate that the cDNA contains the complete coding region for the enzyme, which is 1105 amino acids in length with a calculated molecular mass of 121,419 Da. Comparison of the human and rat ATP-citrate lyase cDNA sequences reveals 96.3% amino acid identity throughout the entire sequence. Further sequence analysis identified the His765 catalytic phosphorylation site, the ATP-binding site, as well as the CoA binding site. The human ATP-citrate lyase cDNA clone was subcloned into a mammalian expression vector for expression in African green monkey kidney cells (COS) and Chinese hamster ovary cells (CHO) cells. Transfected COS cells expressed detectable levels of an enzymatically active recombinant ATP-citrate lyase enzyme. Stable, amplified expression of ATP-citrate lyase in CHO cells as achieved by using coamplification with dihydrofolate reductase. Resistant cells expressed high levels of enzymatically active ATP-citrate lyase (3 pg/cell/d). Site-specific mutagenesis of His765----Ala diminishes the catalytic activity of the expressed ATP-citrate lyase protein. Since catalysis of ATP-citrate lyase is postulated to involve the formation of phosphohistidine, these results are consistent with the pattern of earlier observations of the significance of the histidine residue in catalysis of the human ATP-citrate lyase.

ATP Citrate (pro-S)-Lyase↗
PubMed1992

Laparoscopic colectomy.

Fifty-one laparoscopic colectomies were attempted at two institutions. The clinical results and methods are presented. Seven cases (14%) were converted to facilitated procedures, and four cases (8%) were converted to "open." Cases of cancer, diverticulitis, endometriosis, regional enteritis, villous adenomas, and sessile polyps were operated. Right, transverse, left, low anterior, and abdominoperineal colectomies were performed. Colotomies and wedge resections were also performed. Laparoscopic suturing was required in five cases of incomplete anastomosis by circular stapler (18%). Suturing was required in all right, transverse colectomies and colotomies. Operative time averaged 2.3 hours. Hospitalization averaged 4.6 days. Four patients had complications (8%), and one 95-year-old died of pneumonia (2%). Laparoscopic colectomies can be performed safely, but require two-handed laparoscopic coordination, as well as suturing and knot-tying skills.

Adult↗
PubMed1992

Human papillomavirus identified by nucleic acid hybridization in concomitant nasal and genital papillomas.

Presence of human papillomavirus (HPV) as the etiologic agent in nearly all upper respiratory tract recurrent papillomas is well-established. The technique of nucleic acid hybridization now allows specific typing of HPV with a high degree of accuracy. This article reports a series of nine consecutive patients treated for nasal papillomas over the past 9 years. Eight of these patients had a personal history of genital papillomas (seven patients) or exposure (one patient). With the use of in situ hybridization and autoradiographic technique on paraffin-embedded tissue sections, HPV RNA type 6/11 was expressed in eight of nine nasal papillomas, and corresponding HPV types were also found in the two cases with which concurrent anogenital papilloma tissue was also available for analysis. Human papillomavirus RNA types 16 and 18 were not detected in any of the specimens. Signals of HPV messenger RNA type 6/11 were stronger in the fungiform areas than in the inverted areas of papillomas.

Adult↗
PubMed1992

A simplified approach of assessing adult chronic energy deficiency.

Body mass index (BMI) in conjunction with indices of energy turnover, e.g. physical activity levels (PAL), was recently proposed for classifying adult chronic energy deficiency (CED). Three deprived populations in Africa and Asia were chosen to assess the classification system. Repeated monitoring showed that the combined indicator was affected by instability in PALs and produced implausible discontinuities in the prevalence of different grades of CED. The use of BMI alone produced coherent data with changing BMI distributions, and only 5% of the population would have been wrongly classified as being malnourished, because of being thin but active. The risk of misclassification would be even smaller for populations with BMI distribution shifted towards the right. The prevalence of CED was consistently related within each country to indices of socio-economic status. Yet in Zimbabwe 18% of women and 6% of men had Grade I obesity compared with 11% and 14%, respectively, with CED. Less than 1% Indian and Ethiopian adults were obese but 61% of women and 70% of men were classified as CED in India and 57% and 50%, respectively, in Ethiopia. We propose that adult BMI alone is sufficient to provide important new insights into the problems of food availability and its control in less developed countries.

Adult↗
PubMed1991

Inhibition of myoblast differentiation by lack of zinc.

The impact of restricted zinc availability on myoblast differentiation was investigated. Lack of zinc prevented myoblast fusion and the increase in muscle-specific creatine kinase activity. The depression of activity of creatine kinase in the zinc-deficient cultures was accompanied by a similar decrease in the concentration of creatine kinase mRNA and was apparent even when fusion of the myoblasts was inhibited by cytochalasin B. Thus zinc appears to be necessary for the expression of creatine kinase during myoblast differentiation.

Animals↗
PubMed1989

Levels of soluble CD8 antigen and circulating immune complexes in intravenous drug abusers: relationships to HIV antibody serology.

A total of 36 intravenous drug abusers (IVDA) were studied for circulating immune complexes (CIC) and serum soluble CD8 antigen (sCD8). None had symptoms or signs of AIDS-related complex or AIDS. sCD8 levels were significantly higher in 18 patients who had HIV antibody (Ab) compared with 18 patients who were HIV Ab negative (1640 +/- 578 virus 804 +/- 264 U/ml, p less than 0.0001). In HIV Ab+ patients but not in HIV Ab- patients, sCD8 levels significantly correlated with percentages and absolute numbers of activated CD3+DR+ peripheral blood mononuclear cells (p = 0.0024 and 0.0183, respectively). Also in HIV Ab+ patients, CIC levels were significantly greater for both anti-C3 binding (13.1 +/- 11.1 versus 2.9 +/- 3.4 micrograms/ml, p = 0.002) and C1q binding (23.5 +/- 20.2 versus 6.3 +/- 4.3 micrograms/ml, p = 0.001) CIC. Serum C4 concentrations were lower in the HIV Ab+ patient group (33.9 +/- 10.1 versus 41.6 +/- 12.4 mg/dL, p = 0.043). In the seropositive group, IgG levels were higher (2206 +/- 859 versus 1615 +/- 645 mg/dl) and total CD4 cell counts were lower (757 +/- 344 versus 1172 +/- 402 cells per mm3), but at a less significant level (p = 0.024 and 0.005, respectively), than that seen for sCD8 and C1q CIC differences. These results suggest that elevations of both the lymphocyte activation marker sCD8 and antigen nonspecific CIC characterize earlier stages of HIV infection in IVDA.

Adult↗
PubMed1988

Thyroid hormone control of preganglionic innervation of the adrenal medulla and chromaffin cell development in the rat. An ultrastructural, morphometric and biochemical evaluation.

In the rat, functional connections between the splanchnic nerve and the adrenal medulla are immature at birth and do not become fully competent until the first postnatal week. Neonatal administration of triiodothyronine (T3) accelerates this process, and the present study was undertaken to elucidate the underlying mechanisms. Rats were given T3 (0.1 mg/kg, s.c.) daily for 9 days beginning 1 day after birth. Preganglionic innervation of the adrenal medulla was examined by retrograde axonal transport of horseradish peroxidase (HRP). At 10 days of age, there was an increased number of labeled perikarya in the spinal cord of the hyperthyroid pups. Ultrastructural examination revealed a corresponding increase in synaptic density in the adrenal medulla and in the activity of choline acetyltransferase, a marker for preganglionic cholinergic nerve terminals. These effects were attenuated by 25 days of age, whereupon deficits in HRP-labeled neurons and adrenomedullary synapses were noted. Similarly, replication of chromaffin cells was enhanced transiently in the T3 group during the initial stage of hyperthyroidism, but subsequent long-lasting deficits in cell numbers were noted, along with a corresponding retardation of ontogeny of adrenal catecholamine biosynthesis and storage. Thus, neonatal hyperthyroidism accelerates synaptic development in the sympatho-adrenal axis but suppresses maturation of the target chromaffin cells, ultimately leading to impaired adrenomedullary function.

Adrenal Medulla↗
PubMed1979

Clinical significance of plasma drug and prolactin levels during acute chlorpromazine treatment: a replication study.

Nineteen patients with acute psychoses, the majority schizophrenics, were studied in the course of chlorpromazine (CPZ) treatment. Plasma levels of the drug, plasma prolactin (PRL), extrapyramidal side-effects (EPS) and changes in mental state were monitored weekly, as in our earlier study. The results confirm some of our previous findings: (a) plasma CPZ levels vary widely among patients and correlate poorly with daily doses of CPZ; (b) increased plasma PRL is associated with higher plasma CPZ levels and is more common among the patients who develop EPS; and (c) none of these three variables differ between groups of patients with good and poor treatment outcome. However we did not confirm our previous finding of a significant association between EPS and higher plasma CPZ, nor did we find that the ratio of CPZ-sulphoxide to CPZ differed between the improved patients and the rest.

Adult↗
PubMed1978

Effect of temperature on diauxic growth with glucose and organic acids in Pseudomonas fluorescens.

Growth of Pseudomonas fluorescens in batch culture with glucose and organic acids resulted in typical diauxic responses at 30 degrees C but no detectable diauxic lag at 5 degrees C. At 30 degrees C, organic acids were preferentially utilized during the first growth phase. Glucose utilization was delayed until onset of the second growth phase. Systems involved in direct uptake and catabolism of glucose responded in a manner compatible with repression by malate and/or its metabolites and induction by glucose and/or its metabolites. The oxidative non-phosphorylated pathway, through gluconate and 2-ketogluconate (2-KG) as intermediates, was not induced during either growth phase. At 5 degrees C, growth with glucose and organic acids was biphasic but without diauxic lag. Organic acids were preferentially utilized during the first growth phase. Although carbon from glucose was not fully catabolized until onset of the second growth phase, glucose was oxidized to and accumulated extracellularly as gluconate and 2-KG during the first growth phase. No significant repression of glucose-catabolizing enzymes was observed during growth with organic acids in the presence of glucose. However, uptake activities for gluconate and 2-KG did not increase significantly until onset of the second growth phase. Thus, at low temperatures, psychotrophic P. fluorescens oxidized glucose to extracellular 2-KG, while growing on preferred carbon sources. The 2-KG was then catabolized after depletion of the organic acid.

Carboxylic Acids↗
PubMed1978

Sensitive gas-chromatographic determination of fluphenazine in human plasma.

We describe a method for quantitative determination of fluphenazine in human plasma, based on gas chromatography of its trimethylsilyl derivative and the use of a structurally similar internal standard. We determined its concentrations in plasma of four patients who were receiving the drug intramuscularly as its decanoate, in doses ranging from 12.5 to 250 mg; the concentrations in the plasma of these patients ranged from 0.25 to 11.8 microgram/liter. The precision (CV) of the method over the range 2 to 17 microgram/liter was 6.8% when fluphenazine was extracted from 5 ml of plasma. Of 18 other drugs tested, only thioridazine and the cis and trans forms of flupenthixol interfere with the determination.

Chromatography, Gas↗