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Biomedical subjects

T C Cheng

Publications and source records attributed to T C Cheng.

At least 73 records · Page 4Linked to original sources

A lectin on the hemocyte membrane of the oyster (Crassostrea virginica).

Using antisera produced against a serum lectin we have shown by employing immunocytofluorescence that hemocytes from the oyster, Crassostrea virginica, possess a lectin which is situated on the external surface of the cell membrane. The antisera block the binding of hemocyte microsomes to protease-treated vertebrate erythrocytes, thus confirming that the hemocyte membrane lectin is serologically related to the serum lectin. The major serum lectin has an apparent mass of 34,000. Flow cytometry has revealed that the distribution of the surface lectin on hemocytes represents a heterogeneous expression on a population basis, but no discrete cell subpopulations can be identified.

Animals↗

beta-Thalassemia in American Blacks: novel mutations in the "TATA" box and an acceptor splice site.

beta-Thalassemia genes, although often mild in their effects, are common among American Blacks. We have begun a systematic molecular analysis of beta-thalassemia mutations in this group. DNA polymorphisms in the beta-globin gene cluster were examined among 22 beta-thalassemia chromosomes. Six different haplotypes were observed. beta-globin genes of two of these were cloned, and their phenotypes were examined both in heterologous cells upon transient expression and in vivo. The gene found in the most common haplotype (9 of 22 chromosomes) contained a single base substitution (A----G) at position -29 within the highly conserved proximal promoter element (the "TATA" box). This mutant gene directed beta-globin RNA at 25% of normal levels both in heterologous cells and in vivo. It was associated with a mild beta +-thalassemia phenotype. A different gene, isolated from an apparently rare haplotype (1 of 22 chromosomes), had a single base substitution (A----G) within the acceptor splice site of the second intervening sequence. This mutation abolished normal RNA splicing so that the only RNA made from the gene in vitro was an alternatively spliced RNA, which could not encode beta-globin. The mild deficit in beta-globin production attributable to the -29 A----G mutant allele most likely accounts for the frequently mild nature of beta-thalassemia among American Blacks.

Adolescent↗

beta-Thalassemia in Chinese: use of in vivo RNA analysis and oligonucleotide hybridization in systematic characterization of molecular defects.

To perform a systematic analysis of beta-thalassemia genes among Chinese, we have determined the DNA haplotype in the beta-globin gene region of 37 Chinese beta-thalassemia chromosomes. Only four haplotypes were found. Blot hybridization analysis of erythroid RNA from patients homozygous for haplotypes 1, 2, and 3 demonstrated different patterns, suggesting that a different mutation was associated with each haplotype. The mutation associated with haplotype 1 was a C----T substitution at IVS-2, position 654. This mutation produces a new donor splice site and leads to formation of a beta-globin RNA with an insertion of 73 nucleotides. The mutation associated with haplotype 2 was a nucleotide insertion of A between codons 71 and 72, which results in a frameshift and premature termination of beta-globin synthesis. Haplotype analysis suggests that these two mutations may account for up to 85% of beta-thalassemia genes in this ethnic group. The haplotype 3 gene contained a transcriptional "TATA" box mutation that has been previously reported. Oligonucleotide hybridization demonstrated that the mutation associated with haplotype 4 was the same IVS-1 position 5 substitution commonly observed among beta-thalassemia genes in Asian Indians. Since haplotype 4 of Chinese differs at polymorphic sites on either side of the IVS-1 position 5 mutation from the haplotype associated with this mutation in Indians, the mutation presumably arose independently in these two populations.

China↗

Genetic selection for tolerance to niclosamide and copper in Biomphalara glabrata (Mollusca: Pulmonata).

Successive generations of the PR-79 and M-line laboratory stocks of Biomphalaria glabrata were exposed in the LC90 of niclosamide or copper sulfate. Survivors from each generation produced the succeeding generation by self fertilization. The PR-79 stock showed no evidence of tolerance to either molluscicide following five generations of selection. On the other hand, M-line F5 snails demonstrated approximately two-fold higher tolerance to both molluscicides than did non-selected M-line snails.

Animals↗

ATA box transcription mutation in beta-thalassemia.

DNA sequence analysis of a cloned beta-globin gene from a Chinese patient with beta-thalassemia revealed a single nucleotide substitution (A leads to G) within the ATA box homology and 28 base pairs upstream from the cap site. The patient was homozygous for this particular allele based on restriction mapping at nine different polymorphic sites in the beta-globin gene cluster. Upon transient expression in HeLa cells this gene directed the production of 3-5-fold less beta-globin mRNA than the normal beta-gene. In RNA isolated from the patient's erythroid cells beta-RNA was 10-fold less abundant relative to alpha-RNA than normal, indicating close approximation of the heterologous cell expression results and the in vivo state. These findings support the validity of such transient expression assays for analysis of phenotypes associated with naturally occurring mutant genes and establish the functional significance of nucleotide substitutions at position -28 for human beta-globin gene transcription.

Base Composition↗

Electrical alternans. An association with coronary artery spasm.

A patient's condition was unique for having both QRS- and ST-segment alternans. The close association between ST-segment alternans and ischemic episodes is reproducible in an animal experimental study. Although such phenomena are usually associated with extensive myocardial disease, the postulated mechanism is far from perfected. It is more than likely that no single hypothesis will explain all types of phasic cardiac electrical phenomena.

Angina Pectoris, Variant↗

Missed large left ventricular thrombus. Failure of two-dimensional echocardiography in one case.

In the case reported, two-dimensional echocardiographic study of a man six weeks after he sustained an extensive transmural anterolateral infarct failed to show evidence of an intraventricular thrombus. Ten days later the patient suddenly died. Autopsy findings included a large fibrin clot, weighing 50 gm, in the left ventricle. Two-dimensional echocardiography is a very sensitive method of defining aneurysm in the apex of the heart and identifying and locating ventricular thrombi usually associated with aneurysm. I consider the false-negative finding in this case to be a rare exception.

Aged↗

Severe chest pain due to infectious mononucleosis.

Infectious mononucleosis complicated by acute myopericarditis was finally diagnosed in a 17-year-old boy who presented with sore throat and severe left-sided chest pain. A mononucleosis spot test and heterophil agglutination test turned strongly positive only on the sixth hospital day. The natural course of infectious mononucleosis complicated by myopericarditis appears to be benign.

Adolescent↗

Etiology of growth hormone deficiency in little, Ames, and Snell dwarf mice.

There are three recessive genes (little, Snell, and Ames) which cause dwarfism and GH deficiency in mice. These genes are nonallelic, and in the case of little mice, GH deficiency is isolated, while Snell and Ames dwarfs have deficiencies of GH as well as other anterior pituitary hormones. Previous reports in which restriction endonuclease analyses were used suggested that the GH genes are grossly intact in each of these types of dwarfs. In this report, ultrastructural studies of the anterior pituitary glands of little mice showed a deficiency or absence of secretory granules within somatotropes, while Snell and Ames dwarf pituitaries lacked identifiable somatotropes. Furthermore, there were deficiencies of GH precursor RNA and mRNA in total RNA from little pituitaries, while GH transcripts appeared to be absent in total RNA from Snell or Ames dwarf pituitaries. Thus, the primary defect in little mice may be in the production of GH transcripts, while GH deficiency in Snell and Ames dwarfs is probably due to defects other than alterations of the GH genes.

Animals↗