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Biomedical subjects

J Koh

Publications and source records attributed to J Koh.

At least 37 records · Page 2Linked to original sources
PubMed1996

Prevalence of germ-line mutations in p16, p19ARF, and CDK4 in familial melanoma: analysis of a clinic-based population.

Five to ten percent of individuals with melanoma have another affected family member, suggesting familial predisposition. Germ-line mutations in the cyclin-dependent kinase (CDK) inhibitor p16 have been reported in a subset of melanoma pedigrees, but their prevalence is unknown in more common cases of familial melanoma that do not involve large families with multiple affected members. We screened for germ-line mutations in p16 and in two other candidate melanoma genes, p19ARF and CDK4, in 33 consecutive patients treated for melanoma; these patients had at least one affected first or second degree relative (28 independent families). Five independent, definitive p16 mutations were detected (18%, 95% confidence interval: 6%, 37%), including one nonsense, one disease-associated missense, and three small deletions. No mutations were detected in CDK4. Disease-associated mutations in p19ARF, whose transcript is derived in part from an alternative codon reading frame of p16, were only detected in patients who also had mutations inactivating p16. We conclude that germ-line p16 mutations are present in a significant fraction of individuals who have melanoma and a positive family history.

Base Sequence↗
PubMed1996

p16 inhibition of transformed and primary squamous epithelial cells.

We and others have recently shown that p16 can potently and specifically inhibit progression through the G1 phase of the replicative cycle in cells that express the retinoblastoma protein (pRB). However, none of these studies examined cell types in which p16 has been firmly implicated in tumorigenesis. We predicted that such cells would show sensitivity to p16 inhibition, perhaps conferred by proteins in addition to or other than pRB. Intragenic, inactivating mutations of p16 have been found at significant frequency in primary tumors derived from squamous epithelial cells of the esophagus (ESCC). We therefore examined p16 function in ESCC lines and in primary squamous epithelial cells cultured from mouse skin. We find that seven of eight ESCC lines tested are inhibited by p16 and fail to express the protein endogenously. The lone p16-resistant line expresses endogenous p16 but lacks functional pRB. Primary squamous epithelial cells are also inhibited by p16. These data suggest that squamous epithelial cells are generally sensitive to inhibition by a regulatory pathway that involves p16 and pRB, and that, by the time of establishment in culture, there is nearly universal inactivation of this pathway in ESCCs.

3T3 Cells↗
PubMed1996

Positive association between a DNA sequence variant in the serotonin 2A receptor gene and schizophrenia.

Sixty-two patients with schizophrenia and 96 normal controls were investigated for genetic association with restriction fragment length polymorphisms (RFLPs) in the serotonin receptor genes. A positive association between the serotonin 2A receptor gene (HTR2A) and schizophrenia was found, but not between schizophrenia and the serotonin 1A receptor gene. The positive association we report here would suggest that the DNA region with susceptibility to schizophrenia lies in the HTR2A on the long arm of chromosomes 13.

Adult↗
PubMed1996

Laparoscopic hernia repair in Singapore--views from a cross-section of surgeons.

Laparoscopic cholecystectomy was introduced into Singapore in 1990, and has since replaced conventional cholecystectomy as the treatment of choice for gallstone disease in most situations. In contrast, laparoscopic hernia repair introduced two years later in the same wave of enthusiasm, was received with scepticism and much less acceptance. A survey of 27 general surgeons in three large institutions in Singapore was performed to analyse this observation. The majority of surgeons felt that laparoscopic hernia repair (i) had limited applications, mainly for bilateral and recurrent hernias, (ii) was not completely established as a technique, requiring refinement in the procedure, (iii) was costly, and (iv) did not have objective evidence of long-term benefits over conventional hernia repair.

Cross-Sectional Studies↗
PubMed1995

Tumour-derived p16 alleles encoding proteins defective in cell-cycle inhibition.

The cyclin-dependent kinase inhibitor p16 is a candidate tumour-suppressor protein that maps to a genomic locus strongly associated with familial melanoma and other tumour types. Screening of primary tumours and linkage analysis of familial melanoma pedigrees have identified many potential mutations in p16, but the functional significance of these sequence variants has remained unclear. We report here that p16 can act as a potent and specific inhibitor of progression through the G1 phase of the cell cycle, and we demonstrate that several tumour-derived alleles of p16 encode functionally compromised proteins. The ability of p16 to arrest cell-cycle progression generally correlates with inhibition of cyclin D1/Cdk4 kinase activity in vitro, with two exceptions among the alleles tested. In vivo, the presence of functional retinoblastoma protein appears to be necessary but may not be sufficient to confer full sensitivity to p16-mediated growth arrest. Our results provide support for the notion that p16 is an important cell-cycle regulator whose inactivation contributes to the outgrowth of human tumours.

3T3 Cells↗
PubMed1995

3-Nitropropionic acid induces apoptosis in cultured striatal and cortical neurons.

Ingestion of 3-nitropropionic acid (3-NPA) in moldy sugar cane causes brain damage in children. The mechanism of 3-NPA toxicity is thought to be inhibition of energy production, leading to ATP depletion and excitotoxicity. We exposed cultured mouse striatal or cortical neurons to 1-2 mM 3-NPA for 48 h. This exposure produced gradual neuronal degeneration characterized by cell body shrinkage and DNA fragmentation. Addition of glutamate antagonists during 3-NPA exposure did not reduce neuronal death. However, addition of the macromolecular synthesis inhibitors cycloheximide, emetine or actinomycin D markedly reduced neuronal death. Our results do not exclude that 3-NPA can induce excitotoxicity in more intact systems, but raise the additional possibility that 3-NPA may also act to induce neuronal apoptosis.

Animals↗
PubMed1995

The use of an ileostomy connector to diminish the frequency of defecation prior to ileostomy closure in patients with a pelvic pouch.

A new method for allowing stool passage into the pelvic pouch before ileostomy closure to verify the defecation state and diminish stool frequency is reported herein. This was accomplished by fitting an ileostomy connector connecting the proximal and distal openings of the diverting loop stoma. The ileostomy connector was initially in place for 6 h a day, the length of time being gradually increased until it was able to be left in for 24 h a day over a 3-month period. The calculated daily frequency of stools decreased from 24 to 6 or 7 times, and the mean daily frequency immediately after ileostomy closure was 6.5 times. Physiological study also showed an improvement, with squeeze pressure increasing from 35 cmH2O to 116 cmH2O and the maximum tolerated volume increasing from 35 ml before, to 90 ml 3 months following the use of an ileostomy connector. Thus, we conclude that an ileostomy connector may be useful to predict postoperative functional outcome and its complications, and to diminish the frequency of defecation before ileostomy closure in patients with a covering loop stoma.

Adult↗
PubMed1995

In vivo antitumor activity of hexamethylmelamine against human breast, stomach and colon carcinoma xenografts.

We have evaluated the antitumor activity of Altretamine (hexamethylmelamine, HMM) on human carcinoma xenografts serially transplanted in nude mice. Five human breast carcinoma xenografts, MX-1, T-61, MCF-7, R-27 and Br-10, were inoculated subcutaneously into female nude mice. Two human stomach carcinoma xenografts, SC-1-NU and St-4, and three human colon carcinoma xenografts, Co-3, Co-4 and Co-6, were inoculated subcutaneously into male nude mice. One pellet of 17 beta-estradiol (0.1 mg/mouse) was inoculated subcutaneously in the mice transplanted with MCF-7 when the tumors were inoculated. HMM was administered per os daily for 4 weeks. MX-1 and T-61 tumors regressed completely after treatment with HMM at a dose of 75 mg/kg (the maximum tolerated dose: MTD) for MX-1 and 25 mg/kg for T-61. Br-10 was sensitive, whereas MCF-7 and R-27 were resistant to HMM at its MTD. HMM exerted the most potent antitumor effect against T-61. Against MX-1, it exerted an antitumor effect equivalent to that of cisplatin or cyclophosphamide. In addition, this agent was effective against all stomach and colon carcinoma xenografts, in particular St-4 (T/C% = 10.7: the mean tumor weight of treated group/the mean tumor weight of control group) and Co-3 (T/C% = 31.5%) which are insensitive to presently available agents. HMM seems worthy of further clinical investigation as a candidate agent to treat breast, stomach, colon and other carcinomas.

Altretamine↗
PubMed1995

[Serum cardiac troponin-T in coronary artery bypass graft and mitral valve replacement].

Serum cardiac troponin-T was measured to evaluate perioperative myocardial injury in heart surgery. Twelve patients of coronary artery bypass graft (CABG) and nine of mitral valve replacement (MVR) were selected and the measurements were performed at 3 points-before, as well as after the surgery and on the first postoperative day. Elevated serum levels of troponin-T were observed in postoperative measurement in both groups (CABG 2.98 +/- 1.44, MVR 2.57 +/- 0.52 ng.ml-1), where all the preoperative values were less than 0.1 ng.ml-1. On the first postoperative day, CABG group showed a higher serum level of troponin-T than MVR group (6.05 +/- 4.16 vs. 2.57 +/- 2.12 ng.ml-1, P < 0.05 respectively). Taking another myocardial marker, such as CK-MB or myosin light chain I, into consideration, these data indicate that myocardial injury occurs during heart surgery and the grade of injury is severer in CABG than in MVR.

Aged↗
PubMed1995

[Four cases of noncardiac surgery after PTCA].

Malignant tumors were detected in four patients who had been hospitalized for acute myocardial infarction and/or postinfarction angina. All of them underwent curative operations after successful percutaneous transluminal coronary angioplasty (PTCA). Operations performed were partial colectomy on the first patient, low anterior rectal resection on the second patient, left pulmonary upper lobectomy on the third patient and partial colectomy with cholecystectomy on the fourth patient. There were no complications in the perioperative periods except the first patient in which postoperative electrocardiogram showed transient peaked T wave in leads II, III, AVf, V5 and V6. Forty six days after colectomy (55 days after PTCA), the first patient underwent emergency PTCA for restenosis. Prior PTCA, as well as CABG, is considered to have decreased cardiac complications in patients with ischemic heart disease. But when a non-cardiac operation should be done after PTCA, we should take restenosis into consideration.

Aged↗
PubMed1994

Human autonomic rhythms: vagal cardiac mechanisms in tetraplegic subjects.

1. We studied eight young men (age range: 20-37 years) with chronic, clinically complete high cervical spinal cord injuries and ten age-matched healthy men to determine how interruption of connections between the central nervous system and spinal sympathetic motoneurones affects autonomic cardiovascular control. 2. Baseline diastolic pressures and R-R intervals (heart periods) were similar in the two groups. Slopes of R-R interval responses to brief neck pressure changes were significantly lower in tetraplegic than in healthy subjects, but slopes of R-R interval responses to steady-state arterial pressure reductions and increases were comparable. Plasma noradrenaline levels did not change significantly during steady-state arterial pressure reductions in tetraplegic patients, but rose sharply in healthy subjects. The range of arterial pressure and R-R interval responses to vasoactive drugs (nitroprusside and phenylephrine) was significantly greater in tetraplegic than healthy subjects. 3. Resting R-R interval spectral power at respiratory and low frequencies was similar in the two groups. During infusions of vasoactive drugs, low-frequency R-R interval spectral power was directly proportional to arterial pressure in tetraplegic patients, but was unrelated to arterial pressure in healthy subjects. Vagolytic doses of atropine nearly abolished both low- and respiratory-frequency R-R interval spectral power in both groups. 4. Our conclusions are as follows. First, since tetraplegic patients have significant levels of low-frequency arterial pressure and R-R interval spectral power, human Mayer arterial pressure waves may result from mechanisms that do not involve stimulation of spinal sympathetic motoneurones by brainstem neurones. Second, since in tetraplegic patients, low-frequency R-R interval spectral power is proportional to arterial pressure, it is likely to be mediated by a baroreflex mechanism. Third, since low-frequency R-R interval rhythms were nearly abolished by atropine in both tetraplegic and healthy subjects, these rhythms reflect in an important way rhythmic firing of vagal cardiac motoneurones.

Adult↗
PubMed1994

[A case of fistula-cancer response to arterial chemoembolization].

Arterial chemoembolization was performed three times preoperatively for cancer associated with fistula-in-ano for diminishing the postoperative surgical tissue defect of the perineum. Partial response of the tumor to this treatment was confirmed by computed tomography. A sixty-two-year-old male patient recognized a mass in the perineum one and a half years ago. He had suffered from fistula-in-ano for thirty years. The mass increased its size and formed a tumor in the bilateral buttocks (12 x 9 cm and 9 x 9 cm in diameter). Biopsy specimen showed a moderately differentiated adenocarcinoma. Angiography showed a hypervascular tumor stain. The main feeders to the tumor were the superior rectal artery and bilateral internal iliac artery. Arterial chemoembolization was performed three times through the right and left internal iliac artery with Gelfoam particle. Arterial infusion chemotherapy was added through inferior mesenteric artery and bilateral internal iliac artery with a total 120 mg of adriamycin and 1,500 mg of 5-FU simultaneously. The tumor decreased in size to 44% of the preoperative size by the treatment. A radical operation was performed following the preoperative treatment. Preoperative arterial chemoembolization for cancer associated fistula-in-ano was considered to be helpful for local control.

Adenocarcinoma↗
PubMed1994

[The difficulties in communication through RS-232C interface between monitor devices and a personal computer--the difference of data output format and transmit mode].

We investigated data output format and transmit mode of communication through RS-232C interface between monitor devices and a personal computer. The baud rate, start bit, data bits, parity bit and stop bits are listed with transmit mode of six companies' monitor devices which are now widely sold in Japan. Each monitor device has its own data output format and transmit mode, which are quite different from the others and make it somewhat difficult to import data from different monitor devices to a personal computer. We suggest that, because two or three different monitor devices are commonly used during anesthesia, some general standard should be established to make an easy communication between monitor devices and a personal computer for ordinary users.

Anesthesia↗
PubMed1994

[Anesthetic management of a patient with abdominal aortic aneurysm (AAA) with giant bulla].

We report a case of abdominal aortic aneurysm with giant bulla in a 58-year-old man who had an elective abdominal aortic reconstruction surgery. Preoperative chest x-ray showed a giant bulla in the right lung and small bullae in the left. General anesthesia was induced with midazolam 0.5 mg, fentanyl 0.2 mg and succinylcholine chloride 80 mg. After tracheal intubation, anesthesia was maintained under spontaneous breathing with halothane 0.5-1% in a mixture of air and oxygen (FIO2 0.4-1.0) supplemented with continuous epidural mepivacaine from the catheter inserted the day before surgery. Since satisfactory analgesia and muscle relaxation were achieved by epidural mepivacaine, no analgesics and muscle relaxants were administered during the operation. Postoperatively, no complications occurred and the patient was extubated and transferred to the intensive care unit. We emphasize that combined epidural and light general anesthesia with spontaneous respiration might be ideal for the safe anesthetic management of a patient with a giant bulla.

Anesthesia, Epidural↗
PubMed1993

Characterization of the cystic fibrosis transmembrane conductance regulator promoter region. Chromatin context and tissue-specificity.

Expression of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) is tightly regulated. Using a panel of cell lines expressing different levels of CFTR mRNA, we investigated the mechanisms mediating control of CFTR transcription. In highly expressing cells, multiple sites of transcription initiation can be identified between positions -95 and +50 of the CFTR gene, and an alternatively initiated splice variant transcript is also present. Nonepithelial cell lines expressing very low levels of CFTR utilize a start site at -32. Promoter sequence elements from -83 to +111 are at least partially responsible for dictating CFTR transcriptional tissue-specificity, while multiple elements located farther 5' augment promoter strength. Analysis of the chromatin structure and methylation status of the CFTR promoter region reveals cell line differences which correlate with expression levels, suggesting that the physical context of the CFTR gene in vivo may contribute significantly to appropriate regulation of CFTR transcription. Taken together, these findings indicate that cellular control of CFTR gene expression is likely to be a complex function of several overlapping regulatory pathways.

Base Sequence↗
PubMed1993

Lack of association between bipolar affective disorder and tyrosine hydroxylase DNA marker.

Sixty-eight patients with bipolar affective disorder and 88 controls were investigated for genetic association of tyrosine hydroxylase (TH) restriction fragment length polymorphisms (RFLPs). No significant association between bipolar affective disorder and TH was found. Thus the hypothesis that TH is involved in the pathogenesis of bipolar affective disorder was not supported.

Adult↗