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Biomedical subjects

T H Young

Publications and source records attributed to T H Young.

At least 19 recordsLinked to original sources

Use of a diffusion model for assessing the performance of poly(vinyl alcohol) bioartificial pancreases.

Islets of Langerhans surrounded by a semipermeable membrane to prevent an immune response by the host immunosystem is a potential way of treating type I diabetes mellitus. In this study, poly(vinyl alcohol) (PVA) tubular membranes with added polyethylene glycol to create pores in the skin layer were prepared to improve their diffusion property. In a static incubation study, islets cultured in the PVA tubular membranes still demonstrated their function of secreting insulin after 30 days. When the tubular PVA bioartificial pancreas was perifused in a small chamber with RPMI-1640 medium containing glucose at concentrations of 5.6-16.6 mmol/L, insulin release began to increase without delay. Therefore, such a membrane is an alternative potential material for a bioartificial pancreas. In addition, a mathematical mass transfer model of insulin release was developed and compared with the perifusion data. It was shown that satisfactory kinetics could be achieved with a PVA membrane. However, the model showed that the insulin output of islets cultured in the PVA tubular membrane must be increased to improve the performance significantly. These findings suggest that a bioartificial pancreas using a PVA membrane is a promising material, but the technique for seeding islets in the chamber requires further modification.

Animals

Polyethylene failure in New Jersey low-contact stress total knee arthroplasty.

From January 1985 to December 1990, 598 consecutive New Jersey low-contact stress (LCS) total knee arthroplasties (TKAs) were performed for gonarthrosis. Among these 598 operations, 322 were with rotating platform elements and 276 were with meniscal bearing elements. During 5 to 8 years of follow-up, eight knees had severe symptomatic polyethylene failure that required revision surgery; all eight cases were meniscal bearing types. The failed polyethylene inserts were retrieved and studied. It was observed that there were four probable failure mechanisms associated with the catastrophic polyethylene wear. First, insufficient thickness of the meniscal bearing was the major reason for wear. Second, the malpositioning of the metal tibial tray in the transverse plane resulted in the breaking of the meniscal bearing. Third, the inability of the patellar to rotate due to tissue ingrowth made the polyethylene break. Last, yellowing of the subsurface of the meniscal bearing was a sign of polyethylene failure. These four possible failure mechanisms are all associated with the design of the meniscal bearing type of LCS knee prostheses. Therefore, it is suggested that the design of the LCS knee prosthesis should be modified.

Aged

High frequency of cytotoxin-associated gene A in Helicobacter pylori isolated from asymptomatic subjects and peptic ulcer patients in Taiwan.

Cytotoxin-associated gene A (CagA), expressed in about 60% of H. pylori isolates in Western countries, may play a role in the pathogenesis of peptic ulcer. In this study, we determined the prevalence and significance of the H. pylori cagA gene and protein expression in Taiwan. Genomic DNA from antrum biopsies and H. pylori isolates were analyzed for cagA using polymerase chain reaction, Southern hybridization, or colony hybridization. CagA seropositivity was analyzed using Helico blots. In addition, Western blotting was performed to detect the CagA protein. About 94% of antrum tissues from both asymptomatic subjects and duodenal ulcer patients and all 76 H. pylori isolates (21 asymptomatic subjects, 39 with duodenal ulcers, 13 with gastric ulcers, 2 with gastric cancers, and 1 with mucosa-associated lymphoid tissue [MALT] lymphoma) were positive for the cagA gene. Moreover 77 out of 78 H. pylori-positive serum and all 27 H. pylori lysates had anti-CagA antibodies or CagA protein, respectively. H. pylori isolated from patients with various upper gastrointestinal diseases in Taiwan contained the cagA gene and expressed CagA protein at high frequencies.

Aged

Alcoholism and alcoholic organ damage and genetic polymorphisms of alcohol metabolizing enzymes in Chinese patients.

It is still not clear why some alcoholic patients acquire certain organ-specific complications of alcoholism whereas other alcoholic patients acquire different ones. As we know the liver alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and cytochrome P4502E1 (P4502E1) are polymorphic at the ADH2, ADH3, and ALDH2 loci and the 5'-flanking region of the P4502E1. The aim of this study was to investigate the differences between Chinese alcoholic patients with cirrhosis and acute pancreatitis by studying the genetic polymorphisms of ADH2, ADH3, ALDH2, and P4502E1. Genotyping of ADH2, ADH3, ALDH2, and P4502E1 was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods on peripheral white blood cell DNA from 75 alcoholic cirrhotic patients, 48 acute alcoholic pancreatitis patients, 19 heavy drinkers without liver disease or pancreatitis, and 235 controls. The results showed that the frequencies of the alleles ADH2*1 and ALDH2*1 in the alcoholic cirrhotic patients were significantly higher than those in the nonalcoholic controls. In acute alcoholic pancreatitis patients, only the frequency of allele ALDH2*1, not ADH2*1 was significantly higher than in the nonalcoholic controls. The allele frequency of ADH2*1 in acute pancreatitis patients was significantly lower (P < .01) than in alcoholic cirrhotic patients. The daily amount of alcohol consumption was significantly lower in patients with acute pancreatitis than in patients with cirrhosis (P < .0005). The genotype distributions of P4502E1, detected by RsaI and PstI, were not different among alcoholic cirrhotic patients, alcoholic pancreatitis patients, heavy drinker, and nonalcoholic controls. In conclusion, ALDH2*1 is the most important alcohol metabolizing gene affecting predisposition to alcoholism whereas the ADH2*2 gene may influence susceptibility to acute alcoholic pancreatitis. The patients with alcohol-induced cirrhosis and with alcohol-induced acute pancreatitis are of two different subpopulations.

Acute Disease

Detection of alphafetoprotein-expressing cells in the blood of patients with hepatoma and hepatitis.

The presence of tumour cells in the blood circulation may predict disease recurrence and metastasis. We have evaluated the specificity and sensitivity of detecting hepatoma cells in blood using nested polymerase chain reaction with primers specific for the alphafetoprotein (AFP) gene. The nested polymerase chain reaction amplified a 270-base pair AFP DNA fragment from cDNA of Hep 3B hepatoma cells. In a reconstitution experiment, AFP mRNA was detected from peripheral mononuclear cells isolated from 10 ml of blood containing as few as ten Hep 3B cells. Peripheral mononuclear cells from the blood of 20 hepatoma patients were analysed, and 19 patients showed positive AFP mRNA expression. Seven of 13 samples from hepatitis patients also showed positive AFP mRNA expression. All five paired samples of peripheral blood or umbilical cord blood from pregnant mothers and their babies, respectively, showed positive AFP expression. None of 22 control samples was positive. The presence of AFP mRNA in the blood of hepatitis or hepatoma patients suggests the presence of circulating hepatoma cells or hepatocytes in the circulation. The high incidence of AFP mRNA in the blood of hepatoma patients supports the notion of early haematogenous spreading of the disease.

Feasibility Studies

Evaluation of asymmetric poly(vinyl alcohol) membranes for use in artificial islets.

Islets of Langerhans surrounded by a semipermeable membrane to prevent the host immunosystem is a potential way to treat type I diabetes mellitus. In this study, a series of poly (vinyl alcohol) membranes were formed by adding polyethylene glycols to create pores in the skin layer. The permeability study showed the skin layer structure had an influence on the diffusion of low molecular weight glucose, vitamin B12 and insulin. The mass transfer coefficient was improved from 1.04 x 10(-4) to 2.16 x 10(-4) cm/ sec for glucose, from 2.84 x 10(-5) to 8.36 x 10(-5) cm/sec for vitamin B12 and from 1.45 x 10(-6) to 4.15 x 10(-6) cm/sec for insulin, whereas the passage of immunoglobulin G was completely prevented, indicating that these membranes could be effective in protecting islets from immunorejection. Thus such a membrane is an alternative potential material for artificial islets. In addition, we examined the insulin secretory response of islets separated by a poly(vinyl alcohol) membrane. We found that the insulin-secretion rate is relatively rapid compared to the permeation rate of insulin; thus, the process of the artificial islets is insulin-diffusion-controlled.

Biocompatible Materials

Soluble CD44 isoforms in serum as potential markers of metastatic gastric carcinoma.

A splice variant of CD44 (exon V4-V7) confers metastatic behavior in a rat carcinoma model; aberrant expression of splice variants has been detected on a variety of human tumor cell lines as well as primary and metastatic human tumors, including lymphomas, carcinomas (colon, thyroid, mamma, bladder), and glioma. We used enzyme-linked immunosorbent assay to determine the concentration of soluble CD44 in the serum samples of 10 normal individuals and 41 patients with various stages of gastric cancer. Soluble CD44S and its isoforms, V5 and V6, were present in the serum of normal individuals (288.53 +/- 18.33, 25.49 +/- 1.70, and 148.32 +/- 3.15 ng/ml, respectively). The concentrations of soluble CD44 V5 and V6 were elevated in patients with advanced gastric carcinoma (69.39 +/- 6.06 and 216.62 +/- 32.98 ng/ml, respectively). Serum CD44 V5 concentrations correlated with the extent of tumor invasion (T), the status of lymph node involvement (N), and distant metastasis (M) (TNM staging) (p < 0.05), whereas CD44S did not. These results suggest that detection of abnormal regulation of CD44 splicing could be helpful in gastric cancer diagnosis and disease evaluation.

Biomarkers, Tumor

A rare case of multiple intussusceptions: intense segmentary lipomatosis of the ileum.

We report a patient who presented with intestinal obstruction; his small intestine showed intense segmentary lipomatosis associated with unusually situated multiple intussusceptions. Preoperatively, we diagnosed intussusceptions in the ileocecal region by ultrasonography and computed tomographic scan. During surgery, the ileum was dilated and contained numerous movable polypoid masses. One reducible intussusception was encountered in the ileocecal region. In addition, an ileoileal intussusception that could not be reduced was resected with an end-to-end anastomosis. At histological examination, more than 150 submucosal lipomas were found.

Adult