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Biomedical subjects

B Winter

Publications and source records attributed to B Winter.

At least 55 records · Page 3Linked to original sources

Alkali myosin light chains in man are encoded by a multigene family that includes the adult skeletal muscle, the embryonic or atrial, and nonsarcomeric isoforms.

A set of cDNA clones coding for alkali myosin light chains (AMLC) was isolated from fetal human skeletal muscle. Nucleotide sequence analysis and RNA expression patterns of individual clones revealed related sequences corresponding to (i) fast fiber type MLC1 and MLC3; (ii) the embryonic MLC that is also expressed in fetal ventricle and adult atrium (MLCemb); and (iii) a nonsarcomeric MLC isoform that is found in all nonmuscle cell types and smooth muscle. The AMLC gene family in man comprises unique copies for MLC1, MLC3 and MLCemb, and multiple copies for the nonsarcomeric MLC genes. The gene coding for MLC1 and MLC3 is located on human chromosome 2.

Amino Acid Sequence↗

Evidence for distinct phosphorylatable myosin light chains in avian heart and slow skeletal muscle.

In mammalian organisms the regulatory or phosphorylatable myosin light chains in heart and slow skeletal muscle have been shown to be identical and presumable constitute the product of a single gene. We analyzed the expression of the avian cardiac myosin light chain (MLC) 2-A in heart and slow skeletal muscle by a combination of experimental approaches, e.g., two-dimensional gel electrophoresis of the protein and hybridization of mRNA to specific MLC 2-A sequences cloned from chicken. The investigations have indicated that, unlike in mammals, in avian organisms the phosphorylatable myosin light chains from heart and slow skeletal muscle are distinct proteins and therefore products of different genes. The expression of MLC 2-A is restricted to the myocardium and no evidence was found that it is shared with slow skeletal muscle.

Animals↗

Bulimia: a case illustration of the superiority of behavioral over cognitive treatment.

The present study compared the relative efficacy of two major clinical procedures previously used in multicomponent cognitive-behavioral programs for treating bulimia. A single-subject experimental design was used and the results showed that the behavioral procedure of exposure plus response prevention was more effective than the cognitive procedure in reducing binge and vomit episodes as well as the urges to binge-vomit. These results suggest that the exposure plus response prevention component is more relevant for cognitive as well as behavioral changes in treating bulimia.

Adult↗

Alpha 1-antitrypsin Pi-types in 965 COPD patients.

To study further the role of intermediate alpha 1-antitrypsin (AAT) deficiency in chronic obstructive pulmonary disease (COPD), AAT Pi-types and serum-trypsin-inhibitory-capacity (STIC) were measured in 965 patients with COPD. Heterozygosity of the Z variant was the major cause of intermediate AAT deficiency (primarily the MZ phenotype), accounting for 8.0 percent of the patients compared to 2.9 percent of control subjects (p less than .0005). ZZ homozygosity was detected in 1.9 percent of the patients, compared to 0.04 percent of control studies performed by others (none was present in our own control group of 1,380 subjects). The mean age for MS or MZ patients did not differ from that of the COPD patients as a whole, whereas the ZZ homozygotes were younger (55.9 +/- 9.8 vs 65.3 +/- 7.5 years). These results resemble those of a previous study in 66 male veterans with pulmonary emphysema suggesting that the MZ phenotype, or intermediate AAT deficiency in general, probably does predispose to the development of COPD. However, the prevalence of AAT deficiency in COPD patients is small (approximately 10 percent). The number with an MS phenotype was not increased in this group of COPD patients.

Adult↗

Isolation and characterization of the chicken cardiac myosin light chain (L-2A) gene. Evidence for two additional N-terminal amino acids.

The contractile proteins of striated muscle are encoded by multigene families and constitute an excellent system to investigate differentiation and developmental control of gene expression. Different forms of myosin light chains are expressed in skeletal muscle as well as in the myocard. To study the gene structure and molecular mechanisms underlying differential gene expression, the structural cardiac myosin light chain 2 (MLC-2A) gene was isolated from a chicken genomic DNA library. Restriction enzyme mapping, electron microscopic analysis, and partial sequencing revealed that the gene coding for the MLC mRNA of 700 nucleotides in length extends over 4.2 kilobases of DNA and is interrupted by 5 introns. Sequence analysis led to the detection of two codons for additional amino acids at the N terminus which were not reported to be present in the mature protein and are presumably removed post-translationally. These two amino acids, methionine and alanine, are coded on two separate exons split by the largest intron of the entire gene. Southern blot analysis of genomic chicken DNA indicates the presence of one MLC-2A gene per haploid chicken genome.

Amino Acid Sequence↗

The cardiac myosin light chain (MLC-2A) gene in chicken is methylated in both expressing and nonexpressing tissues.

Certain specific methylation sites of the chicken cardiac myosin light chain (MLC-2A) gene in DNA from embryonic heart tissue as well as from embryonic livers and brains were studied. MLC-2A specific mRNA was present in the heart only, indicating that the gene is transcriptionally active in this tissue and inactive in liver and brain. Using the methylation-sensitive restriction enzymes Hpa II and Hha I, the gene was found to be identically methylated in DNA from all three examined tissues, irrespective of its expression. Moreover, the gene was extensively methylated throughout, including the 5' end and 3' flanking regions, with the exception of 3 Hpa II sites, one located in the middle part of the gene, one in the last intron and one in the 3' flanking sequence. These results suggest that specific genes can be actively expressed even when they are highly modified, and that changes in the methylation pattern from one tissue to another are not necessarily associated with the gene activation.

Animals↗

New daunorubicin analogs. 3-Amino-2,3,6-trideoxy-alpha- and beta-D-arabino- and 3,6-diamino-2,3,6-trideoxy- alpha-D-ribo-hexopyranosides of daunomycinone.

Glycosidation of 2,3,6-trideoxy-3-trifluoroacetamido-4-O-trifluoroacetyl-alpha-D-arabino-hexopyranosyl chloride (19) (or the corresponding 4-p-nitrobenzoate, 20) with daunomycinone under Koenigs-Knorr conditions afforded, after separation of the anomers and removal of the protecting groups, the individual target glycosides 8 (alpha anomer; major product) and 9 (beta; minor) in acceptable yields. In contrast, the title diamino sugar, suitably protected with N-trifluoroacetyl and O-acetyl (or O-p-nitrobenzoyl) groups, underwent stereospecific coupling to the anthracycline aglycon by the glycal procedure to give, after deprotection, the alpha glycoside 12. All three analogs were assayed in vivo against P388 lymphocytic leukemia. They showed little (T/C 125 for 8; T/C 115 for 9) or no (compound 12) activity, but were essentially devoid of toxicity at the dose-levels tested.

Animals↗

Effect of hypercapnia on hypoxic ventilatory drive in carotid body-resected man.

Steplike end-tidal hypoxic drives (PETCO2 = 53 Torr) lasting for 5 min were generated in a group of normal subjects and a group of carotid body-resected subjects when end-tidal CO2 was maintained constant under eucapnic (PETCO2 = 39 Torr) and hypercapnic (PETCO2 = 49 Torr) conditions. The hypoxic ventilatory response of the normal subjects was prompt and significant in eucapnia and was enhanced in the hypercapnic state, evidencing CO2-O2 interaction. In contrast, the carotid body-resected subjects did not respond to eucapnic hypoxia but did demonstrate a small but significant ventilatory response to hypoxia against the hypercapnic background. This suggests that the aortic bodies in man may contribute a small component of the hypoxic ventilatory drive under hypercapnic conditions, although the possibility of neuromalike ending regeneration cannot be excluded.

Adult↗