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Biomedical subjects

K Chin

Publications and source records attributed to K Chin.

At least 55 records · Page 3Linked to original sources
PubMed1999

Decreased and aberrant nuclear lamin expression in gastrointestinal tract neoplasms.

BACKGROUND: Altered expression of lamins A/C and B1, constituent proteins of the nuclear lamina, may occur during differentiation and has also been reported in primary lung cancer. AIMS: To examine the expression of these proteins in gastrointestinal neoplasms. PATIENTS: Archival human paraffin wax blocks and frozen tissue from patients undergoing surgical resection or endoscopic biopsy. METHODS: Immunohistochemistry and western blotting using polyclonal antisera against A type lamins and lamin B1. RESULTS: The expression of lamin A/C was reduced and was frequently undetectable by immunohistochemistry in all primary colon carcinomas and adenomas, and in 7/8 primary gastric cancers. Lamin B1 expression was reduced in all colon cancers, 16/18 colonic adenomas, and 6/8 gastric cancers. Aberrant, cytoplasmic labelling with both antibodies occurred in some colonic cancers and around one third of colonic adenomas. Cytoplasmic lamin A/C expression was detected in 3/8 gastric cancers. Lamin expression was reduced in gastric dysplasia, but not intestinal metaplasia, atrophy, or chronic gastritis. Lamin expression was low in carcinomas of oesophagus, prostate, breast, and uterus, but not pancreas. CONCLUSIONS: Reduced expression of nuclear lamins, sometimes together with aberrant, cytoplasmic immunoreactivity is common in gastrointestinal neoplasms. Altered lamin expression may be a biomarker of malignancy in the gastrointestinal tract.

Adenocarcinoma↗
PubMed1999

The efficacy of a custom-fabricated nasal mask on gas exchange during nasal intermittent positive pressure ventilation.

Commercially available nasal masks have a large mask volume and give rise to considerable air leaks around the mask during nasal intermittent positive pressure ventilation (NIPPV) which may reduce alveolar ventilation (VA per breath). The effects of a custom-fabricated nasal mask (F-mask) versus a commercially available mask (C-mask) on arterial blood gas measurements, dead space including both physiological and apparatus dead space (VD), air leak and VA per breath were compared in patients with restrictive thoracic disease during short-term NIPPV sessions while using a volume cycled ventilator with equivalent settings for both masks. The mask volume of the C-mask was significantly larger than that of the F-mask (p<0.003). The arterial carbon dioxide tension (Pa,CO2) during NIPPV with either the F-mask (5.56+/-1.35 kPa) (mean+/-SD) or the C-mask (6.87+/-0.96 kPa) was significantly lower than during spontaneous breathing (7.75+/-0.81 kPa; p<0.003), but the Pa,CO2 decreased more during NIPPV with the F-mask than with the C-mask (p<0.003). The VD was significantly smaller (p<0.03), the air leak was significantly less (p<0.03), and the VA per breath was significantly larger (p<0.03) during NIPPV with the F-mask than with the C-mask. In conclusion, nasal intermittent positive pressure ventilation with the F-mask was more effective than nasal intermittent positive pressure ventilation with the commercially available mask due to its smaller dead space and less air leak. Further studies are needed to extend these results to all the commercially available-masks.

Blood Gas Analysis↗
PubMed1999

Definitive chemoradiotherapy for T4 and/or M1 lymph node squamous cell carcinoma of the esophagus.

PURPOSE: To investigate the efficacy and feasibility of concurrent chemoradiotherapy for locally advanced carcinoma of the esophagus. PATIENTS AND METHODS: Fifty-four patients with clinically T4 and/or M1 lymph node (LYM) squamous cell carcinoma of the esophagus were enrolled. Patients received protracted infusion of fluorouracil 400 mg/m(2)/24 hours on days 1 to 5 and 8 to 12, 2-hour infusion of cisplatin 40 mg/m(2) on days 1 and 8, and concurrent radiation therapy at a dose of 30 Gy in 15 fractions over 3 weeks. Filgrastim was prophylactically administered to 35 patients. This schedule was repeated twice every 5 weeks, for a total radiation dose of 60 Gy, followed by two courses of fluorouracil (800 mg/m(2)/24 hours for 5 days) and cisplatin (80 mg/m(2) on day 1). RESULTS: There were 21 patients with T4M0 disease, one with T2M1 LYM, 17 with T3M1 LYM, and 15 withT4M1 LYM. Forty-nine patients (91%) completed at least the chemoradiotherapy segment. The 18 patients (33%) who achieved a complete response included nine (25%) of the 36 with T4 disease and nine (50%) of the 18 with non-T4 disease. Major toxicities were leukocytopenia and esophagitis; there were four (7%) treatment-related deaths. Prophylactic filgrastim reduced the incidence of grade 3 or worse leukopenia without improving dose-intensity or response. With a median follow-up duration of 43 months, median survival time was 9 months. The 3-year survival rate was 23%. CONCLUSION: Despite its significant toxicity, this combined modality seemed to have curative potential even in cases of locally advanced carcinoma of the esophagus.

Adult↗
PubMed1999

Respiratory impedance during positive expiratory airway pressure in patients with chronic obstructive pulmonary disease.

The effect of positive airway pressure (5.0 hPa) on airway impedance (Za) and tissue impedance (Zt) during the expiratory phase in chronic obstructive pulmonary disease (COPD) patients was evaluated using random noise oscillation and a body box method. The results were then compared with those obtained from normal subjects. In normal subjects, there was no significant difference between non-expiratory positive pressure (NPEP) and positive expiratory pressure (PEP) for the Zar (real part) and Zai (imaginary part) at 10 Hz (Zar NPEP: 2.14 +/- 0.76, PEP: 1.96 +/- 0.79; Zai NPEP: 1.42 +/- 0.66, PEP: 1.40 +/- 0.70 hPa l-1 s). However, in COPD patients, Zar decreased significantly and the Zai increased significantly during PEP as compared to the values during NPEP (Zar NPEP: 7.10 +/- 1.88, PEP: 5.97 +/- 1.67, P < 0.05; Zai NPEP: -4.10 +/- 2.27, PEP: -2.99 +/- 2.62 hPa l-1 s, P < 0.05). These results suggested that both central and peripheral airway resistance decreased during PEP in COPD patients. Tissue compliance (Ct) calculated from the Zt increased significantly during PEP as compared to during NPEP, in both normal subjects and in COPD patients (normal NPEP: 0.024 +/- 0.004, PEP: 0.021 +/- 0.003, P < 0.05; COPD NPEP: 0.024 +/- 0.004, PEP: 0.014 +/- 0.004 l hPa-1, P < 0.001). This may have been indicative of the stiffened chest wall during PEP.

Adult↗
PubMed1999

[Treatment of solid tumor by a direct electric current].

This is a case report of a 37-year-old Japanese married female with laryngeal sarcoma, treated by direct electric current so as to obtain remission for more than 4 years without signs of recurrence. Due to her hoarseness and laryngeal numb feeling she underwent a laryngeal examination including a biopsy, resulting in a diagnosis of sarcoma. She refused a total laryngectomy and was given Cobalt treatment of 40 Grey. In the following several months, no improvement was observed, objectively or subjectively. In Nagoya University Hospital the patient then received direct electric current therapy of 36 Coulombs through two platinum electrodes inserted into the tumor under a CT guide, pericutaneously. Two months later, as the hoarseness remained in spite of some improvement, she underwent another session of direct electric current therapy of 14.4 Coulombs through the platinum electrodes by bronchoscope-guided direct insertion. Her hoarseness soon disappeared thereafter and there was a regression of the tumor in 6 months. She did well thereafter without any signs of recurrence for 4 years. Clinical treatment of solid tumors with electric treatment with direct electric current has been done in more than 8,000 cases with CR in 25% of all cases and PR in 50%. Its mechanism, however, remains unclear. In our experimental animal studies, apoptosis was observed. It is considered that this electric therapy using direct electric current will be recognized as one method to treat solid tumors.

Adult↗
PubMed1998

Genetic analysis using genomic representations.

Analysis of the genetic changes in human tumors is often problematical because of the presence of normal stroma and the limited availability of pure tumor DNA. However, large amounts of highly reproducible "representations" of tumor and normal genomes can be made by PCR from nanogram amounts of restriction endonuclease cleaved DNA that has been ligated to oligonucleotide adaptors. We show here that representations are useful for many types of genetic analyses, including measuring relative gene copy number, loss of heterozygosity, and comparative genomic hybridization. Representations may be prepared even from sorted nuclei from fixed and archived tumor biopsies.

Blotting, Southern↗
PubMed1998

Identification of upstream regulatory elements that repress expression of adult beta-like globin genes in a primitive erythroid environment.

Our investigations have focused on localizing cis-elements responsible for the down regulation of the adult beta-like globin genes (delta and beta) in immature, or primitive erythroid tissues. We studied their activity after transfection into K562 cells, an erythroleukemia cell line with an embryonic-fetal phenotype. Analyzed DNA sequences included delta and beta 5' flanking regions extending from approximately -500 to +50bp (promoter regions), truncated delta and beta 5' flanking regions extending from approximately -250 to +50 bp, and chimeric promoter constructions, which consisted of a distal delta or beta fragment fused to a proximal beta or delta sequence. In CAT reporter constructions no appreciable level of CAT activity was supported by the beta globin promoter, and only low level activity by the delta promoter. Truncation of the beta globin promoter led to a 2-3 fold increase in promoter activity. In contrast, deletion of the upstream portion of the delta promoter led to a 10 fold decrease in expression. Coupling of the upstream beta globin sequence from approximately -500 to -250 bp to the truncated delta promoter fragment led to complete extinction of transcription activity, consistent with a negative regulatory effect of the beta globin gene upstream element(s). Fusion of the upstream portion of the delta promoter to the truncated beta globin promoter yielded a modest increase in promoter strength relative to the truncated beta gene promoter, indicating the presence of a positive transcriptional element(s) in the upstream delta globin regulatory region. Site-directed mutagenesis of binding sites for the repressor proteins BP1 and BP2 in the upstream portion of the beta globin gene flanking region led to a 4-6 fold increase in promoter activity. DNase I footprinting of the upstream delta-globin region revealed protected sequences corresponding to consensus binding sites for GATA-1 and BP2. These results confirm that sequences in the upstream promoter region of the adult beta globin gene contribute to its factor-mediated suppression early in development and then may modulate its expression at a later stage.

Binding Sites↗
PubMed1998

The nocturnal secretion of cardiac natriuretic peptides during obstructive sleep apnoea and its response to therapy with nasal continuous positive airway pressure.

The nocturnal secretion profile of the newly identified natriuretic peptide (NP), brain natriuretic peptide (BNP), was studied in 14 patients with obstructive sleep apnoea syndrome (OSAS) (apnoea hypopnoea index: 60.5 +/- 3.4, mean +/- SE) during two separate nights before and during nasal continuous positive airway pressure (NCPAP) therapy. Plasma levels of NPs (atrial natriuretic peptides; ANP and BNP) were measured at 2-h intervals during sleep. Simultaneously, blood pressure was measured by a non-invasive method (Finapres, Ohmeda, Englewood, CO, USA) and urine was collected for determining volume and catecholamine levels. Urinary and serum sodium concentration were determined before and after the study. Eight non-snoring subjects were also studied for the investigation of normal nocturnal profiles of BNP levels. To understand the discrete secretion profiles of the two NPs during sleep, blood was sampled from an additional seven patients every 5 min over a 30-min period around 00.00 and 04.00 hours before NCPAP. In patients with OSAS, plasma BNP levels increased from the beginning of sleep (22:00 h) to the morning (06:00 h) before NCPAP therapy (P < 0.01, ANOVA). Baseline BNP levels were not significantly correlated with patient's clinical and polysomnographic parameters. However, in the latter half of the sleep period (02:00-06:00 h), increases in BNP levels during the night before NCPAP therapy were significantly correlated with blood pressure elevations (systolic: r = 0.784 P < 0.01, diastolic: r = 0.587 P < 0.01) and with apnoea duration (r = 0.582 P < 0.01). In normal subjects BP and BNP levels were not changed significantly during sleep. Plasma BNP levels were well correlated with concomitant ANP levels (P < 0.001). NCPAP therapy reduced ANP and BNP levels during sleep and in the morning (P < 0.01). Plasma levels of BNP at 5 min intervals before NCPAP therapy revealed few variations. On the other hand, ANP levels fluctuated over the 30-min period. Changes in BNP levels during sleep in the patients with OSAS may be related to blood pressure variations, but may be too small to play a significant physiological role in regulating diuresis in OSAS. Further work is required to determine the precise role of dual natriuretic system in cardiovascular load and natriuresis in OSAS.

Atrial Natriuretic Factor↗
PubMed1998

Improvement of factor VII clotting activity following long-term NCPAP treatment in obstructive sleep apnoea syndrome.

Obstructive sleep apnoea syndrome (OSAS) is a very common disorder. Patients with OSAS are at an increased risk for cardiovascular events. It has also been reported that a 25% rise in factor VII clotting activity (FVIIc) is associated with a 55% increase in ischaemic heart disease death during the first 5 years. We examined the effects of nasal continuous positive airway pressure (NCPAP) treatment on FVIIc in patients with OSAS. FVIIc was investigated prospectively in 15 patients with OSAS before (mean +/- SEM apnoea and hypopnoea index (AHI) 61.5 +/- 4.2 and after (AHI 3.0 +/- 0.9) NCPAP treatment for immediate relief, at 1 month after treatment and at over 6 months. FVIIc levels gradually decreased after NCPAP treatment. After 6 months of NCPAP treatment, FVIIc levels had decreased significantly (before 141.1 +/- 11.7% vs. after 6 months 110.7 +/- 6.2%; p < 0.01). Six of the seven patients whose FVIIc levels were over 140% before the NCPAP treatment had FVIIc levels below 130% after 6 months or 1 year of NCPAP treatment. This decrease in FVIIc after long-term NCPAP treatment could improve mortality in OSAS patients. If patients, especially obese ones, present with high FVIIc of unknown origin, it would be prudent to check for OSAS.

Adult↗
PubMed1998

New insights into the therapy and pathophysiology of patients with obstructive sleep apnoea syndrome.

The objective of this study was to investigate the effects of obstructive sleep apnoea on: (i) PaCO2 levels; (ii) coagulation systems (plasma fibrinogen levels and whole blood viscosity); and (iii) heat shock proteins (HSPs) levels, which are also called stress proteins, in patients with obstructive sleep apnoea syndrome (OSAS). Patients treated with or without nasal continuous positive airway pressure (NCPAP) had arterial blood gases, plasma fibrinogen, haematocrit, serum total protein and changes in PaCO2 (estimated by transcutaneous PaCO2) measured before and after polysomnography. Heat shock protein 72 levels in peripheral blood mononuclear cells were also measured during sleep with and without NCPAP. OSAS patients with hypercapnia demonstrated significant increases in PaCO2 in the morning compared with the previous night. In such OSAS patients, treatment with NCPAP resulted in a normalization of the 20 mg/dL increase in fibrinogen levels which had been seen previously in the morning after sleep. Basal HSP 72 levels (08.00 pm before sleep) were high in OSAS patients compared to normal subjects and progressively decreased during sleep in the absence of NCPAP therapy. NCPAP relieved disabling day-to-day symptoms in addition to improving cardiovascular morbidity in patients with OSAS. Therefore it is important to understand the effects of OSAS on various organ systems as the prevalence of patients with OSAS is high.

Blood Viscosity↗
PubMed1998

Deep breathing and awake apnoea in a patient who had recurrent hypoxaemia and hypercapnia without sleep apnoea.

A 21 yr old with deep breathing and awake apnoea, who had recurrent hypoxaemia and hypercapnia without sleep apnoea, was presented. Although the organic abnormality responsible for the breathing disturbance was not found, administration of acetazolamide facilitated several breaths between sighs, and the patient's hypoxaemia with hypercapnia improved. Some patients who have abnormalities in the cortical control of breathing that cannot be detected by present methods of examination may experience some improvement in breathing with the administration of chemical stimulants such as acetazolamide.

Acetazolamide↗
PubMed1998

Spigelian hernia: case report.

A spigelian hernia is an uncommon hernia of the anterior abdominal wall. We herein report a case of spigelian hernia, pre-operatively diagnosed as an incisional hernia. A 61-year-old woman had undergone an abdominal hysterectomy 14 years prior to her admission to our hospital complaining of a left lower abdominal mass with recurring pain. At the time of the operation the hernial orifice appeared not to be related to her previous surgical scar, but was located at the spigelian fascia below the level of the umbilicus. The hernial sac was dissected and the defect of the abdominal wall was closed. The diagnosis of a spigelian hernia can be difficult because of its nonspecific clinical findings and insidious nature. Diagnostic procedures and differential diagnosis are herein discussed with a review of the literature.

Diagnosis, Differential↗
PubMed1998

Effects of nasal continuous positive airway pressure therapy on respiratory parameters of upper airway patency in patients with obstructive sleep apnea syndrome.

OBJECTIVES: To assess whether an initial treatment with nasal continuous positive airway pressure (NCPAP) therapy, applied for one night, had any effect on airway patency. METHODS: In 18 patients with obstructive sleep apnea syndrome (OSAS), we measured the total resistance of the respiratory system (Rrs) and their relevant lung functions before and after polysomnography, with and without NCPAP therapy. The Rrs was measured at 3 Hz with the forced oscillation technique. The overnight changes in the specific respiratory conductance (SGrs=reciprocal of the Rrs per unit lung volume) was also calculated in the sitting position. Since many reports have suggested that obesity, through fat deposits around the pharynx, can affect the mechanical and neuromuscular properties of the upper airway, we also investigated if the degree of obesity was related to the magnitude of improvement in these parameters. RESULTS: After the first night of NCPAP therapy, the Rrs decreased (sitting: 4.8+/-0.4 vs 4.3+/-0.4 cm H20/L/s, p < 0.05; lying: 6.5+/-0.4 vs 5.6+/-0.4 cm H20/L/s, p < 0.05) and the maximal voluntary ventilation increased in the morning (sitting: 101.6+/-5.8% vs 106.4+/-4.5%, p < 0.05; lying: 91.2+/-5.4% vs 97.9+/-4.7%, p < 0.05). The overnight difference in the SGrs showed a significant improvement after the initial treatment with NCPAP therapy (p < 0.05). However, the lung volume, flow volume loop, and closing volume in the morning did not change significantly after the therapy. An overnight decrease in the Rrs following NCPAP therapy is significantly correlated with the body mass index (sitting: r=0.54, p < 0.05; lying: r=0.61, p < 0.01). CONCLUSION: The improvements in Rrs without changes in spirometry may reflect improved upper airway patency after NCPAP therapy. The degree of obesity is suggested to be associated with the treatment effect on upper airway in patients with OSAS.

Adult↗
PubMed1998

Biological markers as a predictor for response and prognosis of unresectable gastric cancer patients treated with 5-fluorouracil and cis-platinum.

We investigated the utility of examining biological markers to predict chemoresponse and survival. The subjects consisted of 39 unresectable gastric cancer patients treated with a combination of 5-fluorouracil and cis-platinum. The expression of p53, bcl-2, thymidylate synthase (TS), glutathione S-transferase pi (GST-pi), and vascular endothelial growth factor (VEGF) in the formalin-fixed biopsy samples of primary tumors before chemotherapy was examined immunohistochemically. The positive rate for VEGF, bcl-2, TS, p53, and GST-pi was 51, 10, 46, 38, and 69%, respectively. VEGF-positive cases showed a higher response rate than did negative cases (11 of 20 versus 2 of 19 cases; P = 0.0057). The cases that were negative for p53, TS, bcl-2, and GST-pi were more likely to respond to chemotherapy than the cases that were positive for these markers. The 10 cases having 4 or 5 favorable phenotypes (VEGF positive, p53 negative, bcl-2 negative, TS negative, and GST-pi negative) survived longer than the remaining 29 cases (P = 0.0069). Multivariate analysis revealed that the number of favorable phenotypes (> or = 4 versus < or = 3) had a greater impact on survival than performance status (0 versus 1 or 2), age (> 60 years versus < or = 60 years), macroscopic type (scirrhous versus nonscirrhous), histological type (intestinal versus diffuse), or tumor extent (locally advanced versus metastatic). Immunohistochemical examination of biological markers in biopsy samples may be useful in predicting the clinical outcome of unresectable gastric cancer patients treated with 5-fluorouracil and cis-platinum.

Adult↗
PubMed1997

Evidence of a dominant transcriptional pathway which regulates an undifferentiated and complete metastatic phenotype.

The highly metastatic amelanotic C8161 human melanoma line was found to exhibit complete dominance of its undifferentiated and metastatic phenotype in multiple somatic cell hybridization studies designed to bypass the presence of potential tumor suppressor genes. In a three armed approach involving somatic cell fusions of C8161 with recipient lines of greater differentiation, different lineage, and different tumorigenicity status, the metastatic and undifferentiated phenotype of C8161 was promiscuously dominant. In somatic cell hybrids produced between the C8161 and a group of non-metastatic human melanoma lines which exhibited melanocyte differentiation markers including S100, HMB-45, NKI/C3, and melanin, the fusions were uniformly metastatic and undifferentiated. In somatic cell hybrids of C8161 and MCF-7 the fusions exhibited an estrogen independent and unresponsive, estrogen receptor (ER) negative, and highly metastatic phenotype. In fusions between C8161 and HMS-1, an immortalized 'benign' human myoepithelial line which produced an abundant extracellular matrix (ECM) and high levels of protease and angiogenic inhibitors including maspin, tissue inhibitor of metalloproteinase-1 (TIMP-1), alpha1-antitrypsin (alpha1-AT), protease nexin II (PN-II), thrombospondin-1 and soluble basic fibroblast growth factor (bFGF) receptors, the hybrids showed complete absence of matrix, absent maspin expression, markedly decreased protease inhibitor and angiogenic inhibitor production, high levels of proteases and angiogenic factors, and a highly metastatic phenotype. In our somatic cell fusions, the human-human hybrids represented true and complete fusions and not hybrid clones selected for by loss of dominant-acting growth suppressor genes. This finding was supported by detailed comparative genomic hybridization (CGH) studies, Q-banding karyotype analysis, and autofusions of representative clones. The purposeful creation of inherently unstable human-murine fusions between C8161 and B16-F1 where loss of putative suppressor loci would be expected, resulted in fusions exhibiting decreased growth and non-metastatic behavior with progressive chromosomal loss. Neither p53, nm23, DNA methyltransferase, activated ras, fibroblast growth factor-4 (FGF-4), or epidermal growth factor receptor (EGFR) mediated the acquisition of the metastatic or undifferentiated phenotype within the C8161-human fusions. These studies are the first studies ever to successfully transfer the complete metastatic phenotype by somatic cell fusion and support the presence of a new high level regulatory pathway(s) involving dominant trans-acting factors which act pleiotropically to regulate an undifferentiated and highly metastatic phenotype.

Animals↗
PubMed1997

Induction of vascular endothelial growth factor by nitric oxide in human glioblastoma and hepatocellular carcinoma cells.

We evaluated the effect of nitric oxide (NO) on vascular endothelial growth factor (VEGF) gene expression in human A-172 glioblastoma cells and human HepG2 hepatocellular carcinoma cells. The mRNA level of VEGF increased in response to S-Nitroso-N-acetyl-D,L-penicillamine (SNAP) in both cell lines, and increased in mRNA level well coincided with VEGF protein production in A-172 cells. SNAP at 0.5 mM induced maximal stimulation of 4.4 and 3.7 kb VEGF mRNA expression after 6 h about 11 and 8 fold increase, respectively above control level. Similar VEGF mRNA accumulation was observed also with NOR3, another chemical NO generator. To evaluate the effect of SNAP on VEGF mRNA stability, half-lives of VEGF mRNA were measured in A-172 cells cultured with or without 0.5 mM SNAP and treated with actinomycin D (25 microg/ml). Half-life for VEGF mRNA was found to be prolonged about 2.4 fold by SNAP. VEGF expression induced by SNAP was inhibited by guanylate cyclase inhibitors, methylene blue (10 microM) and LY-83583 (1 microM), and by the protein synthesis inhibitor, cycloheximide (25 microg/ml). These results suggest that induction of VEGF gene expression by NO is mediated through guanylate cyclase activity and requires on-going protein synthesis.

Carcinoma, Hepatocellular↗