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Biomedical subjects

S L Wang

Publications and source records attributed to S L Wang.

At least 91 records · Page 5Linked to original sources

Histopathologic alterations of periodontium in cyclosporin-treated rats. Is the periodontium a target tissue for the drug?

Gingival dimensions and histopathologic alterations in periodontium were examined in rats continuously exposed to cyclosporin-A (CSA). 60 male Sprague-Dawley rats were divided into 2 groups. Rats in the test group daily received CSA in mineral oil by gastric feeding at a dosage of 30 mg/kg body weight for 6 weeks. Rats in the control group received mineral oil only. 10 rats from each group were sacrificed at 2-week intervals. Gingival dimensions were assessed from stone models obtained from the maxillary and mandibular incisal regions. Horizontal, sagittal and frontal tissue sections were obtained from these regions as well. Gingival dimensions in the mandibular and maxillary incisal regions were significantly increased in rats exposed to CSA. Light-microscopic observations revealed a granulation tissue formation at tooth-gingiva interface and an irregular bony surface on dental alveoli in experimental animals. Because both soft and hard tissue of periodontium in experimental rats being significantly effected by CSA compared to control animals, we hypothesized that the periodontium is a target tissue for CSA.

Alveolar Process↗

Excess mortality and its relation to hypertension and proteinuria in diabetic patients. The world health organization multinational study of vascular disease in diabetes.

OBJECTIVE: To determine the extent that mortality in IDDM and NIDDM patients is in excess of that of the general population and examine its relation to hypertension and proteinuria in diabetic patients. RESEARCH DESIGN AND METHODS: A stratified random sample of 4,714 diabetic patients aged 35-55 years participating in the World Health Organization Multinational Study of Vascular Disease in Diabetes has been followed up from 1975 to 1987. Excess mortality, compared with the background population, was assessed in terms of standardized mortality ratios (SMRs) for each of the 10 international cohorts. The relationship between excess mortality and proteinuria/hypertension was examined by diabetes type and sex. RESULTS: SMRs were in general higher in patients with IDDM (ranging from 188 to 686 for men and from 336 to 790 for women) than with NIDDM (from 138 to 370 for men and from 126 to 435 for women). For both diabetes types and in both sexes, SMRs decreased with increasing age and increased with increasing diabetes duration. Patients with both hypertension and proteinuria experienced a strikingly high mortality risk: 11-fold for men with IDDM and 18-fold for women with IDDM and 5-fold for men with NIDDM and 8-fold for women with NIDDM. Even in the absence of proteinuria and hypertension, SMRs were significantly increased in both IDDM (284 men and 360 women) and NIDDM (192 men and 236 women) patients. CONCLUSIONS: Considerable international differences were found not only in mortality rates for the two types of diabetes but also in the extent of excess mortality among centers. IDDM patients had a high excess mortality in comparison with the general population. The significant excess mortality was demonstrated even in patients without proteinuria and without hypertension for both sexes and diabetes types.

Adult↗

International variations in cardiovascular mortality associated with diabetes mellitus: the WHO Multinational Study of Vascular Disease in Diabetes.

The WHO Multinational Study of Vascular Disease in Diabetes was launched in 1975-77 to investigate international variations in the occurrence of different manifestations of vascular disease in subjects with insulin-dependent and non-insulin-dependent diabetes. A morbidity and mortality follow-up extending until January 1, 1988 was carried out in 10 centres, including five European centres (London, Switzerland, Berlin, Warsaw and Zagreb), two East Asian centres (Hong Kong and Tokyo), two Native American centres (Arizona and Oklahoma) and one Caribbean centre (Havana). Of a total of 4714 diabetic subjects (2310 men and 2404 women) aged between 35 and 55 years at baseline who were successfully followed up, 1266 were classified as having insulin-dependent diabetes and 3448 as having non-insulin-dependent diabetes. There was a large variation between the centres in ischaemic heart disease and cerebrovascular disease mortality rates for both insulin-dependent and non-insulin-dependent diabetic subjects, presumably reflecting in part differences between the background populations in mortality rates from these cardiovascular causes. The lowest ischaemic heart disease mortality rates for diabetic subjects were observed in Hong Kong and Tokyo centres, representing industrialized countries which have continued to have low ischaemic heart disease mortality rates. The importance of raised blood pressure and proteinuria as potentially modifiable cardiovascular risk factors in diabetic subjects was confirmed in this study.

Cardiovascular Diseases↗

Major causes of diabetic death at one hospital.

Death certificates filed between 1987 and 1990 at the Kaohsiung Medical College Hospital (KMCH) were reviewed to investigate causes of diabetic death. During this period, 1,383 patients expired at KMCH, of which 151 had diabetes mellitus. The major causes of death in these 151 diabetic patients were infection in 25.8%, cardiovascular disease in 18.5%, cerebrovascular disease in 11.3%, uremia in 8.6% and diabetic ketoacidosis in 1.3%, while diabetes was reported as the contributory or underlying cause of death. Malignancy in 12.0%, liver disease in 5.3%, trauma in 1.3% and upper gastroenteral bleeding in 0.7%, likewise, were among the leading causes of death irrespective of underlying diabetes. However, cause of death in 15.2% of these diabetic patients was undetermined. Our analysis revealed that infection and cardiocerebrovascular disease were the leading problems contributing to diabetic death. Therefore, reducing the risk of infection by strict glycemic control, intensive medical intervention in infection and the proper prevention of diabetic angiopathy-related risk factors and complications are imperative for the reduction of diabetic mortality in our patients.

Cardiovascular Diseases↗

[Study on the subclinical infection of the recipients of measles vaccine].

Through observation to subclinical infection of the 71 children who had been inoculated against measles 12 years ago and then exposed to natural measles from three classes at a primary school, we have noticed: (1) Subclinical infection did exist among the crowd who were inoculation against measles; The rate of subclinical infection of the three classes was between 18.5%-75.0%, with an average of 45.1%. (2) The level of the HI Ab titer was between 1:2-1:16. The peak level was between 1:2 and/or 1:4. So the rate of subclinical infection who had been inoculation against measles but later exposed to natural measles would depend on the proportion of those whose titer of HI Ab was 1:2-1:4 in the crowd. (3) The epidemiological significance of subclinical measles infection lies in that it can actively keep and consolidate the level of immunity to certain extent in a crowd who had been inoculation against measles.

Antibodies, Viral↗

Translocation of apolipoprotein B across the endoplasmic reticulum is blocked in abetalipoproteinemia.

Abetalipoproteinemia (ABL) is an autosomal recessive disease characterized by the inability of the liver and intestine to secrete apolipoprotein B (apoB). Mutations in the microsomal triglyceride transfer protein (MTP) gene, but not the apoB gene, are responsible for the ABL phenotype. It is not clear how loss of MTP in ABL patients leads to a complete, but specific, block in the secretion of apoB. It is to this question that our work is directed. In cultured cells lacking MTP, translocation of apoB is completely arrested, leading to the hypothesis that apoB requires MTP in order to completely enter the lumen of the endoplasmic reticulum, the site of lipoprotein assembly. We examined this hypothesis by determining the presence in plasma of distinct N-terminal apoB peptides, produced exclusively from translocation arrested apoB, in the plasma of six ABL patients and six normal subjects. The data show that N-terminal apoB peptides are present in the plasma of six ABL patients, whereas intact apoB-100 was barely detectable. Moreover, the plasma of all six ABL patients displayed a 2000-fold increase in the amount of an 85 kDa N-terminal apoB peptide relative to apoB-100. These data provide the first in vivo data supporting the essential role that MTP plays in apoB translocation. In normal humans, varied expression of MTP may be responsible for the post-transcriptional regulation of apoB secretion.

Abetalipoproteinemia↗

Cyclosporin A-induced gingival overgrowth in rats: macroscopic and microscopic observations.

Because the existence of cyclosporin A-induced gingival overgrowth in animals has not been well established, a pilot study was undertaken to determine whether such gingival overgrowth could be observed in Sprague-Dawley rats. Thirty-six male rats, age 6 weeks, were randomly divided into two groups. The test group was given 30 mg/kg of body weight of cyclosporin A daily by gastric feeding. The control group was given mineral oil instead. Stone casts of the gingiva in the mandibular incisor region were made biweekly for 6 weeks. The three-dimensional growth pattern-the buccolingual width, the mesiodistal width, and the vertical height of the gingiva-was analyzed on the casts. The animals were killed after the last impression was taken, and tissue sections were made. Stereomicroscopy revealed marked overgrowth of the gingiva in the test rats. All three-dimensional measurements on the stone casts were greater in the test group, beginning 2 weeks after cyclosporin A was given. Histologically the overgrowth of the epithelia and connective tissue was easily confirmed in the buccal and lingual gingiva of the test rats.

Animals↗

[Medullary mechanism of the inhibition on renal sympathetic efferent activities by stimulation of the cervical vagal afferent nerve in rabbits].

Experiments were performed on 63 rabbits anesthetized with pentobarbital, paralyzed with gallamine triethiodide and ventiled artifically. Ipsilateral renal sympathetic nerve discharge (RSND), unit discharges of rostral ventrolateral medulla (RVL), caudal ventrolateral medulla (CVL) and blood pressure (BP) were recorded. The sympatho-inhibitory response were evoked by stimulation of the central end of vagal nerve (CVN) (731/788 exp.). The inhibitory duration is 3.6 +/- 0.185 s. The responses vary with the functional state of the CNS. The RSND inhibitory duration could be shortened or prolonged, depending on the excitatory background of RSND or the basal sympathetic tonic activity. The results indicate that CVN-induced inhibitory of RSND may be mediated, at least partly, by excitation of NTS and CVL, which results, in turn, in depressing RVL and final reduction of sympathetic efferent activity.

Afferent Pathways↗

Isolation and molecular cloning of human sorcin a calcium-binding protein in vincristine-resistant HOB1 lymphoma cells.

A vincristine-resistant lymphoma cell line (HOB1/VCR1.0) that is resistant to 1.0 microM of vincristine has been established from a human immunoblastic B lymphoma cell line, HOB1. HOB1/VCR1.0 cells demonstrated the typical multidrug resistant phenotypes. Using two-dimensional gel electrophoresis, we discovered one protein with a molecular mass of 22 kDa and pI 5.7 that was overexpressed in HOB1/VCR1.0 cells. This protein was purified to the degree of apparent homogeneity by preparative isoelectric focusing and sodium dodecylsulfate-polyacrylamide gel electrophoresis. The identification of this protein with sorcin was revealed by comparing the internal amino acid sequence of three Lys-C digested peptides from the purified protein with the sequence previously determined for hamster sorcin. The complete primary structure of the human sorcin was deduced from nucleotide sequence analysis of its cDNA clones. It is composed of 198 amino acid residues with a calculated molecular weight of 21,676, and its sequence is highly similar to that of hamster sorcin (95%). Direct-binding assay with calcium showed that human sorcin is a calcium-binding protein with four 'E-F hand' structures typical of calcium-binding sites. Like the sorcin of hamster, two of the calcium-binding sites of human sorcin contain putative recognition sites for cAMP-dependent protein kinase. Southern and Northern blot analyses showed that the human sorcin gene was greatly amplified and overexpressed in resistant HOB1/VCR1.0 cells but not detected in the parental HOB1 cells. The overproduction of this protein in resistant cells implies that sorcin plays a role in expression of the resistant phenotype.

Amino Acid Sequence↗

Decreased levels of salivary prostaglandin E2 and epidermal growth factor in recurrent aphthous stomatitis.

Prostaglandin E2 and epidermal growth factor are two important cytoprotective compounds in saliva. This study investigated their salivary levels in controls and individuals with minor recurrent aphthous stomatitis. The development of recurrent aphthous stomatitis was divided into three stages: (1) early active stage (mucosal redness); (2) active stage (mucosal ulceration); (3) convalescent stage. Unstimulated mixed saliva was collected from each volunteer. Salivary prostaglandin E2 and epidermal growth factor concentrations were determined by radioimmunoassay. Their levels (mean +/- SEM) were significantly lower during the active stage of ulceration as compared to the control: (a) for prostaglandin E2, 200 +/- 55 versus 73 +/- 11 pg/mg salivary protein (p < 0.01), 447 +/- 123 versus 112 +/- 19 pg/ml saliva (p < 0.01), 215 +/- 30 versus 63 +/- 12 pg/min salivary flow (p < 0.01), control (n = 12) versus active stage (n = 15); (b) for epidermal growth factor, 1.09 +/- 0.17 versus 0.67 +/- 0.17 ng/mg salivary protein (p < 0.05); 2.51 +/- 0.53 versus 0.84 +/- 0.19 pg/ml saliva (p < 0.05), 1.24 +/- 0.26 versus 0.41 +/- 0.09 pg/min salivary flow (p < 0.05), control (n = 12) versus active stage (n = 12). Salivary prostaglandin E2 and epidermal growth factor showed stage-dependent alterations during the development of the stomatitis. The prostaglandin E2 concentration decreased significantly during the active stage of ulceration, and then increased significantly during the convalescent stage. However, the recovery of salivary epidermal growth factor after the ulceration was slower than that of the prostaglandin E2. It is suggested that the diminution of prostaglandin E2 and epidermal growth factor in the saliva may be associated with the ulcer development.

Adult↗

Propranolol disposition in Chinese subjects of different CYP2D6 genotypes.

Propranolol pharmacokinetics among different genotypes of CYP2D6 was compared in this study. The Chinese (Han) population consisted of 44 healthy unrelated individuals living in southern Taiwan. Endonuclease tests based on polymerase chain reaction were used to determine C/T188 genotypes of CYP2D6 in leukocyte deoxyribonucleic acid. Based on codon 188 genotypes, subjects were categorized into three groups: homozygous C/C188 (n = 13), heterozygous C/T188 (n = 14); and homozygous T/T188 (n = 17). Each subject was given a 40 mg propranolol tablet. Blood samples were drawn before and 12 hours after propranolol administration to measure propranolol and 4-hydroxypropranolol. Three genotypes showed distinct time profiles of plasma propranolol and 4-hydroxypropranolol. The area under plasma concentration curve values (mean +/- SEM), were 322.0 +/- 40.8, 481.6 +/- 77.5, and 766.1 +/- 92.8 nmol.hr/L, respectively, for C/C188, C/T188, and T/T188 subjects (p < 0.05). The 48-hour excreted amount of 4-hydroxy-S-propranolol-O-glucuronide, but not 4-hydroxy-R-propranolol-O-glucuronide, was significantly higher for C/C188 than for T/T188 subjects (p < 0.05). This study shows a different propranolol disposition in Chinese subjects of different CYP2D6 genotypes.

Adrenergic beta-Antagonists↗

A sensitive lacZ-based expression vector for analyzing transcriptional control elements in eukaryotic cells.

We have developed a eukaryotic expression vector that provides a rapid and sensitive measure of transcriptional activity modulated by general and tissue-specific regulatory motifs. The lacZ structural gene has been linked to the minimal promoter of the human liver/bone/kidney alkaline phosphatase gene. In addition, a trimerized cassette of the SV40 polyadenylation region has been placed 5' of this promoter to reduce plasmid-initiated transcripts extending through the lacZ gene that would contribute to background beta-galactosidase (beta-Gal) activity. By combining the weak promoter and the poly(A) cassette, only a very low level of lacZ activity is detected in the absence of additional regulatory sequences. Regulatory domains can be inserted into this vector via a unique Bam HI restriction site and their activity can be rapidly monitored in situ via a colorimetric 5-bromo-4-chloro-3-indolyl-beta-D-galactoside (X-Ga) staining protocol. Also, the activity of linked regulatory domains can be measured quantitatively by assaying beta-Gal levels in cell extracts. We show that derivatives of this vector can be used to monitor the activity of general and tissue-specific control elements and can be transactivated by a single transcription factor in cotransfection experiments.

Alkaline Phosphatase↗

Preparation of a bispecific F(ab')2 targeted to the human IL-2 receptor.

The heterodimer-forming leucine zippers Fos and Jun can efficiently mediate the formation of bispecific F(ab')2 when they are fused separately to two different Fab' fragments. This recombinant method can be used in conjunction with the humanization process to yield humanized bispecific F(ab')2. The potential immunogenicity of the leucine zippers can be eliminated by their removal using pepsin digestion. This method has been scaled up to produce hundreds of milligrams of a bispecific F(ab')2 that targets two subunits of the human IL-2 receptor.

Amino Acid Sequence↗

Detection of CYP2C9 polymorphism based on the polymerase chain reaction in Chinese.

Cytochrome P450 (CYP) 2C9 catalyses the metabolism of a wide range of drugs. Previous studies have shown the differences in the amino acid composition among CYP2C9 variants at Cys144/Arg, Tyr358/Cys, Leu359/Ile, and Gly417/Asp. PCR-endonuclease digestion methods have been developed to detect these four possible polymorphisms. The T416-->C mutation in exon 3 of CYP2C9 (Cys144-->Arg) creates an Ava II site. In the 135 subjects we tested, all leukocyte DNA samples showed a complete Ava II digestion indicating homozygous C416 (Arg144). A Tyr358-->Cys mutation will create a Nsi I site at codon 1057-1063 in exon 7. In 40 subjects tested, all samples showed negative results. DNA sequencing on a few samples showed Tyr358Ile359. A mismatched PCR primer pair was then designed to detect codon C1061-->A (Leu359-->Ile) mutation. In 115 subjects tested, 111 samples showed a complete Nsi I digestion (Ile359) and four samples showed heterozygous results. Another mismatched PCR primer pair was used to confirm the C1061 codon in heterozygous subjects. The four heterozygous subjects showed partial digestion with endonuclease Kpn I, which confirmed the heterozygous Ile/Leu at amino acid 359. The G1236-->A mutation in exon 8 of CYP2C9 (Gly417-->Asp) creates a Hph I site. In all 46 subjects, homozygous G1236 (Gly417) was found. Most Chinese subjects actually have Arg144 Tyr358 Ile359 Gly417 in CYP2C9 as previously reported human-2. Furthermore, we found an A-->T (+12 position in intron 2) mutation in our CYP2C9 sequencing process. The mutation creates a NIa III site.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

Quantitation of organ symmetry by diagnostic ultrasonic imaging: a group theoretical approach.

A method based on group theory is proposed to quantify the shape of an organ. It is proposed that a complex shape is characterized by a basic set of symmetry operations involving rotation about the center axis. Based on this concept, partial symmetry elements (PSE) were determined by stepwise rotation of the images and measurement of overlap area between the original and rotated images. These measurements were used to define a symmetry index (SI) and to "decompose" the complex shape into simpler shapes with regular geometry such as a circle, an ellipse, an equilateral triangle, a square, etc. Computer simulations and two-dimensional (2-D) ultrasonic images of the prostate were used to demonstrate the feasibility of the method. The method was also applied to a series of clinical ultrasonic cardiac images to determine the dynamic shape changes in left ventricle (LV) of a normal heart and an heart with infarction. The results of this study show that SI increased with an increase in the symmetry of the simulation models and the prostate. Cross-sectional images of prostate with triangular and ellipsoidal shapes exhibited larger proportion of three-fold and two-fold symmetries, respectively. Symmetry index of the LV changed during the cardiac cycle and exhibited a loop-like structure when plotted as a function of size. Quantitative measurements of SI indicated that the left ventricular chamber is rounder during the diastolic phase of the cardiac cycle. The loop-like structure was considerably reduced in the heart with infarction. Also, larger distortions in cardiac shape were observed over cardiac cycle in the heart with infarction, as compared to the normal heart. In conclusion, it is feasible to quantitatively characterize 2-D shapes of the organs by symmetry operations based on group theoretical analysis.

Diagnosis, Computer-Assisted↗