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Biomedical subjects

C C Shen

Publications and source records attributed to C C Shen.

At least 37 records · Page 2Linked to original sources

Molecular origin of the mosaic sequence arrangements of higher primate alpha-globin duplication units.

The human adult alpha-globin locus consists of three pairs of homology blocks (X, Y, and Z) interspersed with three nonhomology blocks (I, II, and III), and three Alu family repeats, Alu1, Alu2, and Alu3. It has been suggested that an ancient primate alpha-globin-containing unit was ancestral to the X, Y, and Z and the Alu1/Alu2 repeats. However, the evolutionary origin of the three nonhomologous blocks has remained obscure. We have now analyzed the sequence organization of the entire adult alpha-globin locus of gibbon (Hylobates lar). DNA segments homologous to human block I occur in both duplication units of the gibbon alpha-globin locus. Detailed interspecies sequence comparisons suggest that nonhomologous blocks I and II, as well as another sequence, IV, were all part of the ancestral alpha-globin-containing unit prior to its tandem duplication. However, sometime thereafter, block I was deleted from the human alpha1-globin-containing unit, and block II was also deleted from the alpha2-globin-containing unit in both human and gibbon. These were probably independent events both mediated by independent illegitimate recombination processes. Interestingly, the end points of these deletions coincide with potential insertion sites of Alu family repeats. These results suggest that the shaping of DNA segments in eukaryotic genomes involved the retroposition of repetitive DNA elements in conjunction with simple DNA recombination processes.

Adult↗

Vascular dementia of Binswanger's type: clinical, neuroradiological and 99mTc-HMPAO SPET study.

In 24 patients with vascular dementia of Binswanger's type (VDBT) and 14 age-matched neurologically normal volunteers, we investigated the relationship between clinical features, white matter lesions (leuco-araiosis) and cerebral atrophy on computed tomographic (CT) scan, and regional cerebral blood flow. All subjects underwent the Mini-Mental State Examination of Taiwan, version 1 (MMSE-T1), for assessing the severity of cognitive impairment. The patients were subdivided into two groups, one with mild to moderate (group I, MMSE-T1 scores: 11-24, n=11), and the other with severe dementia (group II, MMSE-T1 scores: below 10, n=13). White matter degeneration was evaluated with densitometric methods. Loss of brain parenchyma was estimated with seven linear measurements (Evan's ratio, third ventricle ratio, width of temporal horn tip, anterior-posterior length of temporal horn, anterior-posterior length of Sylvian fissure and width of frontal interhemispheric fissure) by CT scans. Regional cerebral blood flow was determined with technetium-99m hexamethylpropylene amine oxime (HMPAO) single-photon emission tomography (SPET). In neuroimaging studies, subcortical leuco-araiosis was localized at the frontal region in group I patients and scattered diffusely in group II patients. 99mTc-HMPAO SPET analysis revealed reduction of regional cerebral blood flow in the frontal lobe in group I patients and widespread reduction of regional cerebral blood flow in group II patients. A correlation between frontal leuco-araiosis and perfusion defect of the frontal pole was demonstrated in group I patients, showing findings typical of subcortical dementia. There was no difference in frontal atrophic measurements between group I patients and controls. Ratios of volumes of lost brain parenchyma and leuco-araiosis were significantly higher in group II patients than in the age-matched controls, corresponding to a diffuse cerebral perfusion defect. These results suggest that patients with VDBT have early frontal lobe involvement with posterior progression. Patients with mild VDBT are more likely to show reduction of frontal cerebral blood flow and leuco-araiosis, while those with severe VDBT are more likely to have diffuse leuco-araiosis, cerebral hypoperfusion and brain atrophy.

Aged↗

New prenylflavones from the leaves of Epimedium saggitatum.

Five new prenylflavones, yinyanghuo A (1), yinyanghuo B (2), yinyanghuo C (3), yinyanghuo D (4), and yinyanghuo E (5), along with six known flavonoids, chrysoeriol, quercetin, apigenin, apigenin 7,4'-dimethyl ether, kaempferol, and luteolin, were isolated from the leaves of Epimedium sagittatum. Their structures were determined from spectral analysis. Compounds 1 and 2 showed significant antiplatelet induced by arachidonic acid.

Arachidonic Acid↗

Brown-Séquard syndrome associated with Horner's syndrome in cervical epidural hematoma.

STUDY DESIGN: This report analyzed the likely locations of lesions that cause a combination of Horner's and Brown-Séquard syndromes. One must know the anatomic structure of spinal cord and the sympathetic nerve chain. OBJECTIVES: A hypertensive patient had Brown-Séquard and Horner's syndromes after neck trauma. The magnetic resonance imaging and surgical findings showed the correlation between the clinical symptoms and the likely lesion. METHODS: The patient underwent right hemilaminectomy from C2 to C6 with total removal of hematoma. CONCLUSION: The spinal epidural hematoma rarely is a surgical emergency. The patient presented with Brown-Séquard and Horner's syndromes. Magnetic resonance imaging made a rapid and correct diagnosis. The patient received an emergent right hemilaminectomy from C2 to C6 with removal of hematoma and subsequently made a complete recovery.

Brown-Sequard Syndrome↗

Isodicentric Y chromosome: cytogenetic, molecular and clinical studies and review of the literature.

Dicentrics are among the most common structural abnormalities of the human Y chromosome. Predicting the phenotypic consequences of different duplications and deletions of dicentric Y chromosomes is usually complicated by varying degrees of mosaicism (45,X cell lines), which may, in some cases, remain undetected. Molecular studies in patients with dicentric Y chromosomes have been few, and only two studies have attempted to determine the presence of SRY (the putative testis-determining factor gene). We report an 18-year-old female with short stature, amenorrhea, hirsutism, hypoplastic labia minora, and clitoromegaly who has a 45,X/46,X,idic(Y)(p11.32)/47,X,idic(Y)(p11.32),idic(Y) (p11.32) karyotype. Southern analysis using Y-specific probes (Y97, 2D6, 1F5, pY3.4) and polymerase chain reaction (PCR) analysis using primers for ZFY and SRY were positive for all loci tested, indicating that almost all of the Y chromosome was present. Our findings and an extensive review of the literature emphasize the importance of molecular analyses of abnormal Y chromosomes before any general conclusions can be reached concerning the relative effects of the Y-chromosome abnormality and mosaicism on sexual differentiation.

Adolescent↗

Repair of mitochondrial DNA damage induced by bleomycin in human cells.

Damage to mitochondrial DNA (mtDNA) has recently been associated with a variety of human diseases including cancer, diabetes mellitus, and aging. The mechanisms by which the mitochondria respond to DNA damage are of prime importance in understanding how damage can persist and cause disease. Here we demonstrate the repair of mitochondrial DNA damage induced by the naturally occurring, radiomimetic drug bleomycin. WI-38 cells were first permeabilized using 20 micrograms/ml lysophosphatidylcholine in order to increase the intracellular concentration of bleomycin. Dose response studies with the permeabilized cells showed that a concentration of 5 micrograms/ml bleomycin given for 30 min caused sufficient DNA damage for repair studies. Following treatment with this concentration of bleomycin, repair of mtDNA damage was found to be about 80% by 2 h. However, after 4 h no additional repair was observed. The results indicate that there is an efficient DNA repair system in human mitochondria for some types of damage caused by bleomycin. However, there is a component of damage caused by this agent that either is not repaired or is removed at a much slower rate.

Bleomycin↗

SRVX, a sex reversing locus in Xp21.2-->p22.11.

Duplication within Xp21 causes female or intersexual development in human embryos with an XY chromosome complement. We have mapped the responsible gene, SRVX (sex reversal X), in XY-sex-reversed maternal half siblings who had inherited the duplication from their mother. The limited size of the duplication in our cases, relative to its extent in other similar cases, allows assignment of the SRVX locus to Xp21.2-->p22.11. We infer that SRVX is part of a pathway of sex-determining genes that includes SRY and SRA1, the latter recently assigned to chromosome 17q. If mutation of SRA1 or SRVX can reverse the sex of the XY fetus, this would explain why mutation within SRY is found only sporadically in women with XY gonadal dysgenesis.

Adult↗

Repeat operations in failed microvascular decompression for trigeminal neuralgia.

For the study of pathogenesis and treatment of recurrent trigeminal neuralgia, we performed 31 repeat operations from among 400 patients with trigeminal neuralgia in the past 10 years. Initially, of these 400 patients, 376 underwent microvascular decompression only, and 24 underwent partial sensory rhizotomy with or without microvascular decompression. Fifty-three patients (14%) had recurrences after microvascular decompression, of which 31 patients underwent repeat operations. Among the repeat operations, there was negative exploration in 16 patients (52%), arterial loop compression in 7 (22%), venous compression in 4 (13%), and Teflon compression or adhesion in 4 (13%). Twenty-one patients had early recurrences within 1 year, and 10 patients had late recurrences. Negative exploration and arterial compression were more likely in early recurrence (P = 0.01). Continuing demyelination might occur in patients with negative exploration, even when adequate decompression had been initially performed. Seventy percent of the patients had no recurring pain by way of partial sensory rhizotomy for negative explorations, redecompression of arterial loops, division of offending veins, or lysis and reposition of Teflon. About half of the patients had positive findings that were amenable without rhizotomy in the repeat operations. A repeat operation for failed microvascular decompression is a good choice if the condition of the patient is tolerant.

Arteries↗

Tandemly duplicated alpha globin genes of gibbon.

The alpha globin gene locus of the common gibbon (Hylobates lar) was isolated, and it contains two closely linked alpha globin genes that share the same arrangement as that found for the homologous genes of other catarrhine primates. The nucleotide sequences of the gibbon alpha globin genes were determined and compared with the alpha globin gene sequences from other primate species (human, chimpanzee, orangutan, baboon, and rhesus); the prosimian primate, galago, alpha A and alpha B globin genes provided the out-group for this analysis. The degree of divergence for both synonymous and nonsynonymous substitutions among the alpha globin genes are generally smaller for intraspecies than interspecies comparisons, which is indicative of concerted evolution between the paired alpha globin genes of each catarrhine species. The pattern of differences is suggestive of gene conversions. This possibility is supported by both site-by-site and branch-swapping parsimony analyses. The site-by-site parsimony analysis was also used to determine the 3' boundary of each catarrhine species-specific conversion. These alpha globin gene conversion events encompass most of the transcriptional region, including the promoter, exons, introns, and about one-half of the 3'-untranslated region. However, the paired gibbon alpha globin genes show the highest degree of divergence, differing by five nucleotides in their coding regions, three of which encode amino acid replacement substitutions. It appears that the last convergence event between the paired gibbon alpha globin genes is relatively ancient, having occurred approximately 11 million years ago. The remaining 3'-untranslated region and flanking DNAs show no evidence of involvement in any recent conversion event as the parsimony analysis of these sequences group all the alpha 1 globin genes of the different catarrhine species into one clade and all the alpha 2 globin gene of these species into a separate clade. The sequence comparison among the alpha globin genes of different primate species also provides interesting implications regarding the evolution and functional domains of the 3'-untranslated regions.

Amino Acid Sequence↗

Renal oncocytoma: report of two cases and review of literature.

Renal oncocytoma was previously reported as a benign tumor arising from proximal tubular epithelial cells, but malignant potential with local invasion and distant metastasis has been emphasized in recent literature. It is difficult to differentiate it from renal cell carcinoma, but four typical angiographical signs may give suggestive evidence of the tumor. Radical nephrectomy with lymphadenectomy may be the choice of treatment, except in solitary kidney, bilateral tumors, or contralateral renal cell carcinoma. We report two female patients who were found incidentally to have renal tumors during a survey of right upper quadrant pain. Typical angiographic signs were found incidentally to have renal tumors during a survey of right upper quadrant pain. Typical angiographic signs were found in one patient, and atypical signs in the other. Three and eight years after radical nephrectomy with para-aortic lymphadenectomy, there has been no evidence of local recurrence or distant metastasis.

Adenoma↗

Specificity and flexibility of the recognition of DNA helical structure by eukaryotic topoisomerase I.

Many studies have been carried out to map the putative binding sites of eukaryotic topoisomerase I on double-stranded DNA. As assayed by the SDS-induced cleavage reaction, results from these studies showed little sequence specificity surrounding the enzyme binding sites. In order to investigate the possible involvement of local helix variations in the recognition of double-stranded DNA by topoisomerase I, we have applied the Calladine-Dickerson rules to analyze the structural variations surrounding over 100 HeLa topoisomerase I cleavage sites on human DNA. Our data suggest that (5'-NRRYRNN-3'/3'-NYYRYNN-5') and (5'-YRRRYYN-3'/3'-RYYYRRN-5'), in which R is a purine, Y is a pyrimidine and N is any nucleotide, form the consensus recognition sequences for the enzyme. The specific structural features of these two consensus sequences recognized by HeLa topoisomerase I appear to be the local helical twist angle variations. The same consensus sequences are present in the vicinities of other eukaryotic topoisomerase I binding sites. These results have led to a model in which the eukaryotic topoisomerase I enzymes recognize sequence-dependent structural variations of DNA double helices in a specific but flexible mode.

Animals↗

Anomalous and selective DNA mutations of the Old World monkey alpha-globin genes.

It has been a widely accepted hypothesis that the molecular clock slows down during evolution of higher primates. By molecular cloning and nucleotide sequence comparison of a rhesus macaque alpha-globin gene to its homologs in man, orangutan, olive baboon, and other mammals, we demonstrate a burst of evolution of the baboon alpha-globin gene since its separation from the rhesus macaque. This mutation burst has occurred only at the nonsynonymous sites but not the synonymous sites. Its magnitude is at least 10-fold higher than the synonymous substitution rates in higher primates and as high as the synonymous substitution rates of the rodent lineage. On the contrary, the rate of synonymous site substitutions in the alpha-globin genes of either the rhesus macaque or the olive baboon is several times slower than that of human. Our data demonstrate an anomalous exception to the slow rates of molecular evolution in higher primates and provide strong evidence for a recently accelerated evolution of a primate globin gene under an as yet unknown selective force(s).

Amino Acid Sequence↗

Enrichment and depletion of Hela topoisomerase I recognition sites among specific types of DNA elements.

The SDS-induced nicking of DNA helix by Hela topoisomerase I in vitro has been studied by using 2.9 kb of cloned human DNA as the substrate. The frequency of nicking is increased from 1/23 (nick/nt) to 1/19 (nick/nt) when camptothecin is present in the nicking reaction. The cytotoxic drug also induces DNA nicks without the addition of SDS. Although the consensus built from DNA sequences from -20 to +20 of more than one hundred of the nicking sites only shows a preference for T at position -1, the distributions of the topoisomerae I-cleavable sites among different categories of specific DNA sequences are apparently non- random. Long stretches of tandem (CA), A, or T residues, and the GC-rich promoter region of alpha 1 globin gene are all refractory to the nicking reaction. However, the nicking frequencies of short direct repeats flanking different Alu type sequences are as high as 1/6 (nick/nt). Finally, several tandemly arranged minirepeats of the form (TxAy)z, that are usually found at the 3' ends of the primate Alu family or Kpnl family repeats, can be cleaved efficiently in a regular pattern by the enzyme. These data are discussed in terms of the mode of recognition of DNA sequences/structures by topoisomerase I, and its possible roles in the nonhomologous insertion of repetitive DNA sequences.

Adult↗

Structure and expression of the human theta 1 globin gene.

The recently identified theta-globin gene subfamily consists of the theta 1-globin gene located downstream from the alpha 1-globin gene, and several other members including at least one truncated, processed pseudogene psi theta 2 (refs 1,6). Unlike the theta 1-globin genes of the rabbit and galago, the structure of these genes in the orangutan and baboon and their flanking regions show no apparent defects that would prevent their expression. Both theta 1-globin genes are split into three exons with the potential to code for a polypeptide of length 141 amino acids. Besides differing by 26% in replacement-site substitutions, the theta 1 and alpha 1-globin genes of the orangutan and baboon also differ in their promoter structures, in the use of TGA versus TAA as the termination codon, and in the use of AGTAAA versus AATAAA as the polyadenylation signal. In contrast, the two theta 1-globin genes from primates only differ by 1.7% in the replacement-site substitutions. Here we present the complete DNA sequence of a cloned theta 1-globin gene of humans, and show that it contains no apparent defects that would abolish its expression. Furthermore, by primer extension of single-stranded oligonucleotide probes, we show that the theta 1-globin gene of humans is transcribed in an erythroleukemia cell line K562. Three messenger RNA species were detected, with 5'-ends mapping to approximately 70 base pairs (bp) downstream from a TATA promoter sequence, at 8 bp downstream from a GGGCGG promoter sequence and at 40 bp upstream from the ATG inititrion codon, respectively. Haemin treatment of the K562 cells slightly enhances the level of the longest theta 1-transcript. Our results provide strong evidence that the theta 1-globin gene of humans is transcriptionally active in cells of erythroid origin, and suggests the presence of a functional theta 1-polypeptide in specific cells, possibly those of early erythroid tissue.

Amino Acid Sequence↗

Free vascularised bone graft using microvascular technique.

The authors investigated 212 dried human fibulae to find out the length, the circumference and the entry points of nutrient artery to the fibula. Angiography of six freshly amputated limbs was studied to show the relationship of the posterior tibial artery and peroneal artery. Seven clinical cases of free vascularised fibula graft are reported. The length of the fibula graft varies from 10 cm to 20 cm. A postoperative 113M-In EDTMP examination revealed the blood supply to the grafted fibula was adequate. The bony healing and functional restoration of the extremities proved to be satisfactory.

Adolescent↗