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Biomedical subjects

M Noguchi

Publications and source records attributed to M Noguchi.

At least 235 records · Page 13Linked to original sources

AFP-producing squamous cell carcinoma of the lung in an adolescent.

We report a case of primary lung cancer in a 16-year-old boy. A histologic diagnosis of squamous cell carcinoma was made by bronchoscopic biopsy before surgery. The serum alphafetoprotein (AFP) level was markedly elevated at 193 ng/dl. Preoperative and postoperative evaluation revealed no evidence of scrotal mass. We performed right pneumonectomy with combined resection of the invaded portion of the left atrium under extracorporeal circulation. Despite the rapid improvement in the patient's general condition after surgery, the AFP level continued to increase without a transient decrease and reached 3160 ng/ml on the 23rd postoperative day. When the patient was readmitted because of dyspnea and headache on the 36th postoperative day, hypercalcemia of 13.9 mg/dl was noted, and this was resistant to subsequent treatment. The patient died on the 46th postoperative day.

Adolescent↗

A four-pulp flap technique for creating nail folds in the separation of a mid-digital mass in a patient with Apert's disease.

Apert's disease is distinguished from other acrocephalosyndactylys by bilateral and symmetrical deformities, including symphalangism of the hands, which is commonly present in the index, long, and ring fingers. In the correction of the Apert hand, simple separation and skin grafting may be used to create a five-digit hand. However, this technique may result in narrow, atrophic fingertips, and pulp pads. In this paper, a simple technique to create nail folds and pulps for each finger with four transposition flaps from the common pulp is described. During the past 3 years, four Apert hand deformities in 2 patients were treated with this procedure. At a mean follow-up of 32 months, good results were obtained.

Acrocephalosyndactylia↗

Replication of hepatitis C virus in cultured non-neoplastic human hepatocytes.

We established a replication system for hepatitis C virus (HCV) using the PH5CH non-neoplastic human hepatocyte line that had been immortalized with simian virus 40 large T antigen. In cells inoculated with sera derived from two HCV-positive blood donors, positive-stranded HCV RNA was detected up to 30 days postinoculation (p.i.). Semi-quantitative analysis of HCV RNA revealed that HCV multiplied during the period of culture. Sequence analysis of the HCV hypervariable region 1 (HVR1) in both cases indicated that HVR1 populations from the cells at 8 days p.i. were apparently different from those of the original inocula. HVR1 populations in infected cells became homogeneous or just a few species were selected over time. These results suggest that HCV is replicating in the human hepatocyte PH5CH cells. This culture system will be useful for detailed studies of the biological effects of HCV in human hepatocytes.

Amino Acid Sequence↗

E-cadherin gene mutations in signet ring cell carcinoma of the stomach.

To clarify the significance of E-cadherin gene alterations in the development of diffuse-type adenocarcinoma of the stomach, we analyzed mutations of the E-cadherin gene using the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method followed by direct sequencing. Twenty-two signet ring cell carcinomas of the stomach (10 intramucosal and 12 advanced cancers) were examined. Genomic DNA was extracted separately from cancerous and non-cancerous tissues and PCR-SSCP analysis was performed on exons 5 to 9 and the adjacent 30- to 40-base-pair intron sequences of the E-cadherin gene. Mobility shifts were found in 2 of the 10 intramucosal cancers. In 2 of the 12 advanced cancers, abnormalities of the E-cadherin gene were observed in intramucosal lesions as well as in deeply invaded areas. These results indicated that E-cadherin gene mutations are an early event in the development of signet ring cell carcinoma of the stomach. Direct sequencing revealed that the locations of mutations of the E-cadherin gene included the branch point sequence in the intron which is responsible for RNA splicing. Reverse transcriptase-PCR demonstrated aberrant RNA splicing in a case with a branch point mutation, suggesting that branch point mutations play an important role in functional modifications of E-cadherin in signet ring cell carcinoma of the stomach.

Adult↗

Late bone metastasis from an encapsulated follicular carcinoma of the thyroid without capsular and vascular invasion.

A unique case of encapsulated follicular carcinoma of the thyroid, which lacked histologic evidence of capsular and vascular invasion but developed a late bone metastasis, is described. The thyroid tumor was found in a 42-year-old man. It was relatively small (2.5 cm) and totally encapsulated. Histologically, the thyroid tumor showed a microfollicular growth pattern of follicular cells and revealed no histologic evidence of nuclear atypia, mitotic figures or capsular and vascular invasion. The diagnosis of microfollicular adenoma was made and partial thyroidectomy was performed. Bone (rlb) metastasis of the thyroid tumor developed 22 years after the thyroidectomy. The present case suggested that capsular and/or vascular invasion is not always sufficient for the diagnosis of encapsulated follicular carcinoma of the thyroid.

Adenocarcinoma, Follicular↗

Nuclear p53 accumulation by small-sized adenocarcinomas of the lung.

In order to evaluate the alterations of nuclear p53 accumulation in early stage adenocarcinomas of the lung, nuclear p53 accumulation by small-sized peripheral adenocarcinomas of the lung was examined immunohistochemically. Peripheral adenocarcinomas of the lung, 2 cm or less in diameter, have been classified into two groups; one showing replacing growth of the pulmonary alveolar structure and the other showing non-replacing growth. The former group has been subdivided into three microscopic subtypes: type A, localized bronchioloalveolar carcinoma (LBAC); B, LBAC with foci of pulmonary alveolar structural collapse; and C, LBAC with foci of active fibroblastic proliferation. Type C is thought to be advanced carcinoma, which develops progressively from types A and B. Two of 32 (6%) types A and B carcinomas, 37 of 133 (28%) type C carcinomas and 14 of 35 (40%) non-replacement-type adenocarcinomas showed positive nuclear staining for p53. The positive staining frequency was significantly higher for type C than for types A and B (P < 0.05). These results suggest that nuclear p53 accumulation occurs in the transition from the early to advanced stages of replacement-type adenocarcinoma development and it may be a clinically useful indicator of the degree of tumor malignancy.

Adenocarcinoma↗

Vitamin D receptor in endometrial carcinoma and the differentiation-inducing effect of 1,25-dihydroxyvitamin D3 on endometrial carcinoma cell lines.

In view of the potential of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] as a cell-differentiation-inducing agent in endometrial cancer, the localization of the vitamin D receptor (VDR) was examined immunohistochemically in 21 endometrial adenocarcinoma specimens, and the effect of 1,25(OH)2D3 on cell growth, as well as the phenotypic changes for cell maturation after treatment with 1,25(OH)2D3, was investigated in 2 endometrial carcinoma cell lines (AMEC-1, RL95-2). The VDR was detected in 14 of the 21 endometrial carcinoma specimens. The growth of RL95-2 cells expressing VDR was inhibited to 44% when cultured with 50 nM 1,25(OH)2D3 for 6 days. In contrast, the growth of AMEC-1 cells not expressing VDR was completely uninhibited even when cultured with 100 nM 1,25(OH)2D3 for 6 days. The RL95-2 cells exposed to 50 nM 1,25(OH)2D3 for 6 days had an increasing expression for 52.5 kD or 45 kD cytokeratin polypeptide, and they became columnar with pronounced polarity and formed gland-like structures when cultured in collagen gel. These results suggest that endometrial adenocarcinoma is a target for 1,25(OH)2D3, which appears to function as a cell-differentiation-inducing agent for the treatment of endometrial cancer.

Adenocarcinoma↗

Vasodilator effects of des(alpha-carboxy-3,4-dihydroxyphenethyl)lithospermic acid (8-epiblechnic acid), a derivative of lithospermic acids in salviae miltiorrhizae radix.

A potent vasodilator substance (compound III), [alpha]D +141 degrees, was isolated from salviae miltiorrhizae radix (dan-shen). This substance was determined to be des(alpha-carboxy-3,4-dihydroxyphenethyl)lithospermic acid on the basis of spectrometric and chemical evidence, and was identified with an authentic sample of 8-epiblechnic acid. However, comp. III seemed to be formed from lithospermic acid (LSA) and LSA-B during a chemical procedure to separate active ingredients. It caused a sustained, slowly developing relaxation of rat aortic strips precontracted with norepinephrine (NE) in preparations with or without endothelium. The NE-induced concentration-dependent contraction of aortic strips was significantly attenuated by pretreatment with comp. III. Concentration-response curves for Ca(2+)-induced contracture of depolarized aortic strips with isotonic high K+ (60 nM) were not affected by comp. III. Ca(2+)-induced contraction of aortic strips, preincubated with 10(-6) M NE in the presence of 10(-6) M nicardipine and 0.01 mM EGTA in Ca(2+)-free solution, was slightly inhibited by comp. III. Pretreatment of aortic strips with comp. III slightly inhibited the phorbol ester (PMA)-induced contraction. These results suggest that comp. III inhibits NE-induced contraction of the aortic strips through reduction in Ca2+ mobilization. Since comp. III inhibits NE-induced sustained contraction, this agent may be useful in the treatment of hypertension.

Animals↗

[Effectiveness of NKH477, a novel forskolin derivative, in rat cardiac preparations with desensitized beta-adrenoceptors].

Effects of prolonged noradrenaline infusion on the density of cardiac beta-adrenoceptors, phosphodiesterase (PDE) and adenylate cyclase (AC) activities, and the ability of NKH477, 6-(3-dimethylaminopropionyl) forskolin hydrochloride, to increase tension development and heart rate were studied in rat cardiac preparations. Noradrenaline infusion (400 micrograms/kg/hr, s.c.) for 7 days significantly decreased cardiac beta-adrenoceptor density (Bmax), whereas the binding affinity (Kd) of the ligand was unchanged. The basal cardiac PDE activity was increased in treated rats, whereas there was no difference in the basal cardiac AC activity between treated and untreated rats. Significant decreases in basal developed tension and heart rate were observed in the left and right atrial muscles from treated rats, respectively. The positive inotropic and chronotropic potencies of NKH477 were unaffected by noradrenaline infusion, whereas the positive inotropic potencies of isoproterenol and 3-isobutyl-1-methylxanthine were significantly reduced. Thus, NKH477 appears to be superior to beta-adrenoceptor agnosits or PDE inhibitors as a cardiotonic drug in the treatment of heart failure accompanied by beta-adrenoceptor downregulation.

Animals↗

Anomalous systemic arterial supply to normal basal segments of the left lower lobe. A report of two cases.

Two cases of anomalous systemic arterial supply to the basal segments of the lower lobe of the left lung without sequestration are presented. In the first case, the final diagnosis was made during a surgical operation, and lobectomy of the lower lobe of the left lung was performed. In the second case, the preoperative diagnosis made by CT was confirmed by angiography. An anastomosis was performed between the anomalous artery and the pulmonary artery without resection of the basal segments. Six months after surgery, pulmonary angiography showed improved flow of the anastomosed vessel, but little improvement was evidenced in the perfusion scan.

Adult↗

Effects of phenobarbital on aniline metabolism in primary liver cell culture of rats with ethionine-induced liver disorder.

In experiment 1, the amount of aniline (AN) metabolites in the primary cell culture medium of the liver cells obtained from ethionine (ET)-treated rats was compared with that of the control (normal) rats. Although the metabolites detected in both groups were p-aminophenol (p-AP), N-acetyl-p-AP (AAP), acetoanilide (AAN), AAP-glucuronide (AAPG), phenylhydroxylamine sulfate (PHAS) and p-AP-glucuronide (p-APG), the amount of AAP was lower and that of p-APG was markedly higher in the ET-treated rats than in the control rats. In experiment 2, phenobarbital (PB) was orally administered to the ET-treated and control rats at a dose of 100 mg/kg. The time course changes in AN metabolites in the primary cell culture medium of liver cells obtained at 2 or 48 hr after PB treatment were compared with those without PB treatment. In the ET-treated rats, the amount of PHAS was slightly higher at 2 hr after PB treatment, and that of AAP was lower and that of p-APG was higher at 48 hr after PB treatment as compared with those without PB treatment. In the control rats, the amounts of AAP, AAN, p-AP and p-APG at 2 hr after PB treatment remained lower than those without PB treatment, and that of AAP was markedly lower and that of p-APG was higher at 48 hr after PB treatment as compared with those without PB treatment. These findings indicated greater detoxication in the primary liver cell culture in the ET-treated rats than in the control rats. Furthermore, detoxication was greater in the primary cell culture of liver cell obtained from the ET-treated rats after PB treatment than from those without PB treatment, because the production of acetylates (AAP) decreased and p-APG increased (induction of conjugated enzyme) in the PB treatment group.

Acetaminophen↗

Sleeping time after phenobarbital treatment and the brain levels of gamma-aminobutyric acid and phenobarbital at the regaining of righting response point in ethionine-induced liver-disordered mice.

The mechanism of prolongation of sleeping (anesthesia) time after phenobarbital (PB) treatment was assessed in mice with ethionine (ET)-induced liver disorders (ET-treated group). The brain gamma-aminobutyric acid (GABA), glutamic acid (GLU), lactic acid (LA), and pyruvic acid (PA) levels were significantly higher in the ET-treated group than the control group. The ET-treated group showed an abnormal neurotransmission and a decrease in energy metabolism. After administration of PB (175 mg/kg, i.p.), sleeping time and the brain GABA, GLU, LA, PA, and PB levels at the awakening point were compared between ET-treated and control groups. Sleeping time in the ET-treated group was two times longer than that in the control group. At the awakening point, the brain GABA and LA levels in the ET-treated and control groups and the PA level in the ET-treated group were significantly lower than those without PB treatment; and the GLU level in the ET-treated group was significantly higher than that without PB treatment. The brain concentrations of PB in both groups remained the same for seven hr after PB treatment. There was no difference in the brain PB concentration between the two groups at the awakening point, although the ET-treated group showed impairment of excretion of PB at 18 hr of PB treatment. In conclusion, awakening is not directly correlated with a decrease in PB in the brain, but rather to changes in the brain GABA, GLU, and other substances, and an inhibition of the neurotransmission and decreased energy metabolism in the brain are considered to be involved in the prolongation of PB-induced sleeping time in the ET-treated mice.

Anesthesia↗

Cloning and expression of cDNA for soluble form of rat heme oxygenase-1.

Heme oxygenase catalyzes the oxidation of heme to biliverdin and carbon monoxide. The gene encoding the truncated soluble rat heme oxygenase-1 (Metl-Pro267) was cloned. The enzyme protein was expressed in E. coli JM109 and purified to homogeneity. The molecular weight of the recombinant enzyme was 30 kDa as assessed by SDS-polyacrylamide gel electrophoresis. From a 3-L culture, about 90 mg of the purified enzyme was routinely obtained. The dependency of the heme oxygenase reaction catalyzed by the soluble enzyme on the NADPH-cytochrome P-450 reductase concentrations and the effect of catalase on the reaction were examined to compare with the purified membrane-bound form of heme oxygenase-1 (Yoshida and Kikuchi, 1978b). The activity of the soluble enzyme was inhibited at high concentrations of NADPH-cytochrome P-450 reductase and the inhibition was not alleviated by addition of catalase unlike the membrane-bound form. The ferric iron of the heme-heme oxygenase complex was in a typical high spin state at acidic to neutral pH (pH 6.5-7.0) but conversion to low spin state was observed at basic pH (pH 9-10). The heme bound to heme oxygenase was converted to biliverdin at a stoichiometric ratio of unity in the presence of NADPH-cytochrome P-450 reductase system. During the heme degradation of the heme-heme oxygenase complex under atmospheric oxygen, several intermediates, that is, oxygenated heme and verdoheme, were spectrally discriminated.

Animals↗

Monocyte aggregation and multinucleated giant-cell formation in vitro in Crohn's disease. The effect of cell adhesion molecules.

BACKGROUND: Multinucleated giant-cell (MGC) formation is a common histopathologic feature of various granulomatous diseases, including Crohn's disease (CD). METHODS: We have investigated monocyte aggregation and subsequent MGC formation by in vitro culturing peripheral monocytes from 25 CD patients, 15 ulcerative colitis (UC) patients, and 10 healthy controls. The effect of cell adhesion molecules on the monocyte aggregation and MGC formation in CD patients was investigated by using anti-beta 2 integrin and anti-ICAM-1 antibodies. RESULTS: The monocyte aggregation and MGC formation were significantly higher in CD than those seen in UC and controls (p < 0.05). In CD, antibody to beta 2 integrin could inhibit not only the monocyte aggregation but also the subsequent MGC formation. In contrast, the antibody to ICAM-1 could inhibit the monocyte aggregation; however, it could not inhibit the MGC formation. CONCLUSIONS: Monocyte aggregation and MGC formation are increased in CD. beta 2 Integrin may play an important role in the monocyte aggregation and MGC formation of CD patients.

Adolescent↗

Roentgenographically occult small-cell lung cancer: case report and review of the literature.

This report describes a rare case of roentgenographically occult small-cell lung cancer in a 73-year-old man with hemoptysis. Fiberoptic bronchoscopy disclosed a 5-mm dome-shaped lesion; a biopsy established the diagnosis of small-cell lung cancer. The patient received a combination of chemotherapy and radiotherapy. More than 10 years later, he is still alive without recurrent disease. A review of the literature of roentgenographically occult small-cell lung cancer revealed the following: (1) a history of heavy smoking was common; (2) double primary bronchogenic carcinoma was noted; (3) hemoptysis or bloody sputum was an initial common symptom; (4) the sensitivity of sputum cytologic analysis was relatively low; (5) the tumor, which was shiny, smooth, and covered with bronchial epithelium, was often located at the bifurcation; and (6) lymph node metastatic involvement occurred.

Aged↗

Loss of heterozygosity of multiple tumor suppressor genes in human gastric cancers by polymerase chain reaction.

Loss of heterozygosity (LOH) occurring on various chromosomes has been described in the majority of human tumors and its targets are believed to be tumor suppressor genes. Although allelic deletion of the p53 gene (over 60%) has been frequently observed in gastric cancer, as well as in other human malignancies, LOH of other tumor suppressor genes is still discrepant in gastric cancer. To our knowledge, simultaneous analysis of LOH using PCR in adenomatous polyposis coli (APC), deleted in colon cancer (DCC), and retinoblastoma susceptibility (Rb) genes has not yet been reported in sporadic gastric cancer. We examined 21 advanced gastric cancers (12 intestinal type and 9 diffuse type) for LOH at the APC, DCC, and Rb loci using PCR. Inclusion of these tumor suppressor genes in the allelic deletions was directly ascertained by performing PCR at polymorphic sites within the genes. LOH occurred in 30% of informative cases at APC, in 27% of informative cases at DCC, and in 30% of informative cases at Rb. Thirty-three percent of tumors informative at all loci (fully informative) lost heterozygosity at all three loci. There were no significant differences among histologic types in the prevalence of LOH at any locus and no correlations between losses involving APC, DCC, and Rb genes. These data suggest that inactivation of APC, DCC, and Rb is involved in the development and progression of some human gastric cancers regardless of histologic type.

Base Sequence↗

Prognostic significance and surgical management of lymph node metastasis in gastric cancer.

Regional lymph node metastasis is a critical prognostic factor in gastric cancer, and extended lymph node dissection and routine microscopic examination of all resected nodes could potentially provide accurate information regarding lymph node status. On the other hand, the therapeutic value of extended lymph node dissection is controversial. While retrospective and prospective nonrandomized comparative studies have shown that extended lymph node dissection significantly improves the survival rate, two prospective randomized trials have failed to demonstrate the efficacy of extended dissection, although the number of patients in these studies was limited. There is a further, ongoing, trial involving a larger series of patients; the final results of this study should help to determine whether extended lymph node dissection is of therapeutic or merely prognostic value in gastric cancer.

Humans↗