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Biomedical subjects

M Inoue

Publications and source records attributed to M Inoue.

At least 37 records · Page 2Linked to original sources

Chemical stimulation of the nucleus tractus solitarii decreases spinal cord blood flow in anesthetized rats.

L-Glutamate was microinjected into the nucleus tractus solitarii (NTS) in anesthetized (chloralose and urethane), paralyzed and artificially ventilated rats, and spinal cord blood flow (SCBF) was determined using a combination of labeled microspheres. Unilateral chemical stimulation of the NTS (n = 13) significantly decreased SCBF in the cervical cord from 43 +/- 6 (mean +/- SEM) to 28 +/- 4 (P < 0.05), in the thoracic cord from 35 +/- 3 to 24 +/- 4 (P < 0.01), and in the lumbar cord from 49 +/- 3 to 40 +/- 3 ml min-1 (100 g)-1 (P < 0.05). The decrease in SCBF was not due to the decrease in arterial blood pressure (ABP) because the SCBF during the chemical stimulation of the NTS was significantly smaller (P < 0.05) than the SCBF during controlled hemorrhagic hypotension (n = 11). Chemical stimulation of the NTS did not affect the reactivity of the spinal cord vessels to hypercapnia (n = 5). Microinjection of the vehicle solution into the NTS had no effects on spinal cord circulation (n = 9). These results suggest that the cell bodies within the NTS may play a role in the control of spinal cord circulation.

Animals

Regulation of substance P release mediated via prejunctional histamine H3 receptors.

The involvement of the histamine H3 receptor in the regulation of substance P release in neurogenic inflammation was studied by using rat hindpaw skin. R-(-)-alpha-Methylhistamine, a specific histamine H3 receptor agonist, significantly inhibited the increased vascular permeability induced by antidromic electrical stimulation of the sciatic nerve in a dose-dependent manner at doses of 0.5-3 mg/kg (i.v.), and thioperamide (2 mg/kg i.p.), a specific histamine H3 receptor antagonist, prevented the inhibitory effect of R-(-)-alpha-methylhistamine. The antidromic stimulation also caused a significant increase in immunoreactive substance P release in the subcutaneous (s.c.) perfusate in the rat hindpaw. R-(-)-alpha-Methylhistamine (0.25-2 mg/kg) dose dependently inhibited the increase in release of immunoreactive substance P, and thioperamide (2 mg/mg i.p.) antagonized it. Perfusion of histamine (10(-3) M) elicited a significant increase of immunoreactive substance P release in the perfusate, which was reduced by R-(-)-alpha-methylhistamine and the antagonism of thioperamide was also observed. Histamine (in the presence of histamine H1 and H2 receptor antagonists) had an inhibitory effect on the electrically evoked release of immunoreactive substance P. These results strongly support the hypothesis that histamine regulates substance P release via prejunctional histamine H3 receptors that are located on peripheral endings of sensory nerves.

Animals

Concurrent chemotherapy (5-fluorouracil and cisplatin) and radiation therapy for inoperable squamous cell carcinoma of the esophagus potentially followed by surgery.

Twenty-four previously untreated patients with primary inoperable squamous cell carcinoma of the esophagus showing no evidence of hematogenous metastasis were treated with concurrent chemotherapy and radiation therapy (CRT) followed by surgical resection if possible. The chemotherapy regimen consisted of 5-fluorouracil 750 mg/m2 on days 1-4 and 21-24, and cisplatin 70 mg/m2 on days 1 and 21. Radiation therapy was administered over days 1-26 (200 cGy/day five times per week with an initial planned dose of 40 Gy). Five patients (8%) showed complete response (CR), 14 patients (58%) had partial response (PR), and 19 had good local control (CR 2, PR 17). Eleven cases (48%) underwent esophageal resection with no operative mortality. Curative resection was accomplished in eight cases (35%). Toxicities observed in CRT were leukopenia (grades 3 and 4) 38%, nausea and vomiting (grades 2 and 3) 67%, esophagitis 42%, and fever 42%. The median survival time (MST) for 11 neoadjuvant cases was 349 days (P < 0.05) compared to 212 days for palliative treatment (six cases) and 126 days for no treatment (six cases) after CRT. The MST of eight patients who received curative resection had not been reached after a 17-month median follow-up time. Concurrent chemotherapy with 5-fluorouracil plus cisplatin and radiation proved to be a safe regimen yielding a satisfactory response and minimal toxicity in this particular group of patients. Extensive surgery was thus determined to be feasible after CRT and to contribute to prolonging survival.

Aged

Subsite-specific risk factors for colorectal cancer: a hospital-based case-control study in Japan.

To investigate the subsite-specific risk factors for colorectal cancer, we conducted a case-control study, using a common questionnaire which inquired about general lifestyles over the past five years (1988-92), at the Aichi Cancer Center Hospital, Nagoya, Japan. This study compared 432 patients with histopathologically diagnosed colorectal cancer (94 proximal colon [cecum, ascending colon, transverse colon]; 137 distal colon [descending colon, sigmoid colon]; 201 rectum [rectosigmoid, rectum]); and 31,782 first-visit outpatient controls who were free from cancer. In both genders, habitual smoking selectively increased the risk for rectum cancer. Soft or loose feces increased the risk for all subsites of colorectal cancer, particularly in female rectum cancer (odds ratio [OR] = 4.5). Among female dietary habits, Japanese-style foods decreased the risk for distal colon cancer, but increased the risk for proximal colon cancer. These results suggested that the risk factors for colorectal cancer differ by subsite among such a low-risk population as the Japanese. It is suggested also that 'irritable bowel' (soft or loose feces) might be associated with distal subsites of colorectal cancer, independently or combined with habitual smoking.

Adult

Laparoscopic extramucosal myectomy with anterior fundoplication (Dor) for esophageal achalasia using intraoperative manometry.

Laparoscopic extramucosal myectomy with anterior fundoplication according to the Dor technique was performed on a 24-year-old-woman. Intraoperative inflation of a pneumatic balloon made the operative procedures such as extended submucosal dissection quite easy. Intraoperative gastrofiberscopy was useful for confirming that the remaining mucosal layer was not injured after completion of myectomy. Intraoperative manometry confirmed a complete decompression of the high-pressure zone in the lower esophageal sphincter. Complete relief of the symptoms has been recognized for 6 months after operation without any medication. It is considered that these laparoscopic procedures including intraoperative inflation of a pneumatic balloon, gastrofiberscopy, and intraoperative manometry can be used as a standard operation for esophageal achalasia.

Adult

Expression of the T antigen on a T-lymphoid cell line, supT1.

We have measured glycosyltransferase activities of SupT1 cells, a T-lymphoid cell line shown to react with autoantibodies in the sera of many HIV patients. Since considerable alpha-N-acetylgalactosaminyl-transferase and beta 1, 3 galactosyltransferase activities were found in SupT1 cells, at least the O-glycan core 1 structure can probably be synthesized. FACS analysis using an anti-T monoclonal antibody showed expression of the T antigen (Gal beta 1-3 GalNAc). Glycoproteins with the T antigen were isolated by immunoprecipitation with the anti-T antibody from a SupT1 cell lysate labelled metabolically with 3H-glucosamine and then analysed by SDS-PAGE. It was revealed that the precipitate contained a glycoprotein with a molecular weight corresponding to that of leukosialin. O-glycans were prepared from the immunoprecipitate by alkaline-borohydride treatment and then fractionated on Bio-Gel P-2, GalNAcOH and Gal-GalNAcOH being identified inter alia. These results suggest that an anti-T antibody may be included in the autoantibodies found in HIV-1 infected individuals.

Antigens, CD

Intrapleural perfusion hyperthermo-chemotherapy for malignant pleural dissemination and effusion.

Taking advantage of the antitumor effect of hyperthermia, we administered intrapleural perfusion hyperthermo-chemotherapy for the treatment of malignant pleural seeding or pleural effusion. This consists of irrigating the pleural space for 2 hours with 43 degrees C saline solution containing cis-platinum using specially devised extracorporeal circuits. From January 1988 through December 1993, we performed this technique in 12 patients with malignant disseminated lesions stemming from lung cancer who also underwent surgical resection of the primary lesions and in 7 patients with malignant pleural effusions who did not undergo thoracotomy or surgical resection. There were no serious clinical complications associated with this procedure. The pharmacokinetics showed that a high concentration of cis-platinum (more than 17.6 micrograms/mL in the free form) was retained in the pleural cavity during perfusion. After this therapy, the cancer cells showed marked degeneration with fibrosis in the pleural wall. The pleural effusion was well controlled in 100% of the patients. The median survival time in the 12 patients with pleural disseminated lesions who were treated with intrapleural perfusion hyperthermo-chemotherapy was 20 months. On the other hand, the median survival time in 7 patients with similar lesions who did not receive IPHC was only 6 months. Intrapleural perfusion hyperthermo-chemotherapy seems to have considerable value as an adjuvant therapy for patients with pleural dissemination who have had their primary lesions removed.

Adult

Adenosarcomas originating from sites other than uterine endometrium.

We report three cases of adenosarcomas arising from extraendometrium of the uterus: one arising from the ovary, one from the paracolpium and one from the endocervix of the uterus. Microscopically, they consisted of an admixture of benign-appearing epithelial and mesenchymal components with hypercellularity and minimal atypia. Two of the tumors were initially misdiagnosed as endometriosis and one was diagnosed as adenofibroma. One patient had several recurrences and died 7 years after the initial laparotomy and another patient had sarcomatous overgrowth which invaded the muscular tissues of the large intestine. Thus it appears that adenosarcoma occasionally shows grave clinical behavior, despite the benign or low-grade appearance of its microscopic features. Problems of diagnosis and management of this tumor are discussed. An aggressive therapeutic approach including wide surgical excision is recommended even in questionable cases.

Adenosarcoma

Conserved delta-activity in reverse enantiomeric opioid peptide.

A reverse enantiomeric peptide has a reversed amino acid sequence with enantiomeric amino acid residues compared with its parent peptide. In most cases the random change of amino acid sequence or chirality might be expected to bring about significant changes in peptide activity. However, the reverse enantiomeric peptides of Leu-enkephalin and Tyr-D-Ala-Gly-Phe-D-Leu (DADLE) have shown affinity for the opioid delta-receptor, but not for mu- or kappa-receptors. This suggests that delta-opioid receptor recognition occurs primarily through interaction with the peptide side chains, since the native opioid peptide and its reverse enantiomer are able to have similar side-chain conformation.

Amino Acid Sequence

Effect of continuous infusion of lysine via different routes and hepatic vagotomy on dietary choice in rats.

The effect of continuous L-lysine (Lys) infusion on dietary choice between Lys deficient and protein-free diets in Sprague-Dawley rats was studied to determine the sensing site of Lys deficiency. After daily intake of each diet became constant, Lys was continuously infused for 11 days via intraperitoneal (IP), intragastric (IG) or intracerebroventricular (ICV) route, with an osmotic pump. Daily intake of each diet was measured. Intake of the Lys deficient diet compared with protein-free diet in either IP or IG Lys-infused group increased significantly (p < 0.001) vs. the intake in the baseline period. The selection of the Lys deficient diet was quite comparable between IP and IG groups. But the intake of the ICV group was unchanged. Hepatic vagotomy during IP infusion transiently delayed selection of the Lys deficient diet. These results imply the roles of postabsorptive mechanisms in sensing an amino acid deficiency, and possible involvement of the hepatic branch of the vagus in the sensing. However, sensing in the brain or indeed in the intestine was not excluded.

Aging

The human papillomavirus status of invasive cervical adenocarcinoma: a clinicopathological and outcome analysis.

Accumulating evidence highlights the human papillomavirus (HPV) as a risk factor for cervical adenocarcinoma. However, the part played by the HPV in predicting tumor outcome or the increasing frequency of cervical adenocarcinoma is incompletely studied. In a retrospective study the association between HPV status and the clinicopathological characteristics of 77 cases of cervical adenocarcinoma was investigated. The data were then analyzed for temporal differences in HPV status and to identify outcome predictors. Human papillomavirus status was determined by dot blot hybridization using probes for HPV 6, 11, 16, 18, 31, 33, and 35, followed by polymerase chain reaction amplification of the dot blot negative cases. Seven type-specific and consensus HPV primers were used. Human papillomavirus type 16, 18, or 33 was present in 53 (70%) cases. Human papillomavirus status did not correlate with disease outcome or any clinicopathological variable, except that tumors presenting in and after 1981 were more frequently HPV positive than those presenting before 1981 (P = .014). In a multivariate analysis only clinical stage at presentation was predictive of disease outcome. Because temporal differences in clinicopathological characteristics were not identified, the increasing frequency of cervical adenocarcinoma may relate to a more important oncogenic role for the HPV in tumors presenting after 1980.

Adenocarcinoma

Association of human papillomavirus with malignant and premalignant lesions of the uterine endometrium.

The possible association of human papillomavirus (HPV) with endometrial hyperplasia and endometrial adenocarcinoma was investigated. DNA from frozen tissues of 30 endometrioid carcinomas of Japanese patients was tested for HPV DNA by Southern blot hybridization analysis. Screening with HPV type 58 probe under low stringency conditions showed the presence of HPV DNA in two of 30 endometrioid carcinomas. High stringency hybridization identified HPV type 16 in the two positive specimens. The presence of HPV was further analyzed by polymerase chain reaction (PCR)-Southern blot analysis of DNA from archival tissue blocks of the initial 30 endometrioid carcinomas as well as an additional 17 endometrioid carcinomas and 13 atypical hyperplasias of the endometrium from Japan and 38 endometrioid carcinomas from the United States. Polymerase chain reaction amplification using type 16-specific HPV primers for a portion of the E6 open reading frame was positive in six of 47 (13%) endometrioid carcinomas from Japan, including two in which HPV 16 was not detected by Southern blot analysis and two of 38 (5%) endometrioid carcinomas from the United States. Polymerase chain reaction amplification using L1 consensus sequence primers was positive for HPV in two of 13 (15%) endometrial hyperplasias, 13 of 47 (28%) endometrioid carcinomas from Japan, and six of 38 (16%) endometrioid carcinomas from the United States. Slot blot hybridization identified HPV type 16 in seven of the L1 PCR products, including all but one specimen testing positive for HPV type, 16 using E6 type specific primers. In situ hybridization was positive for HPVs 16/18 in glandular epithelial tumor cells in six of the PCR-positive specimens. An additional specimen showed staining for HPVs 16/18 in acellular luminal debris in association with squamous metaplasia of the tumor, but staining was negative in the glandular cells of the tumor. Human papillomavirus was not detected by in situ hybridization in the remaining specimen, which was PCR positive for HPV 16. In situ hybridization was weakly positive for HPVs 31/33/35 in one specimen and was weakly positive for HPVs 6/11 in benign endometrial epithelial cells but not in tumor cells of another specimen that tested positive for HPV by L1 PCR. Two dimensional gel electrophoresis performed on two specimens showed that HPV DNAs were integrated into cellular DNA with no episomal coexistence. These findings suggest that HPV, especially HPV 16, may play an etiologic role in a fraction of endometrioid adenocarcinomas.

Adult

Effects of a single drip infusion of lipo-prostaglandin E1 on vibratory threshold in patients with diabetic neuropathy.

We evaluated acute effects of prostaglandin E1 encapsulated in lipid microspheres (lipo-PGE1), in 14 type 2 diabetic patients with neuropathy. Nerve conduction velocity (NCV), vibratory threshold (VT), skin temperature and subjective symptoms were evaluated for 24 hours after a single drip infusion of lipo-PGE1. In 6 of the 14 patients, the decrease in VT (P < 0.05) more than 50% measured by an SMV-5 vibrometer was observed at 6 hours after the infusion (responders). Subjective symptoms were improved (P < 0.05) in 5 of the 6 responders, whereas it improved in only 1 of the 8 patients who had no change in VT (nonresponders). NCV did not change (P > 0.05) either in the responders or in the nonresponders by the infusion. The responders had less impairment in VT and milder retinopathy and nephropathy than the nonresponders (P < 0.05). Our results demonstrate that vibratory sensation and subjective symptoms can be improved by a single infusion of lipo-PGE1 in type 2 diabetic patients with mild neuropathy.

Adult

Direct evidence for the occurrence of superoxide radicals in the small intestine of the burned rat.

To determine if superoxide radicals (O2-) and related metabolites are generated in extradermal tissues of burned animals, 2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazol [1,2-å]pyrazin-3-one (MCLA) was infused intravenously into rats, and change in the chemiluminescence (CL) intensity of the small intestine was determined by using a sensitive photodetector. When animals were challenged with burn stress of 40% total body surface area (TBSA), the CL intensity of the intestine gradually increased, reaching a maximum within 1 hour and remaining elevated for up to 3 hours. Pretreatment of animals with a long-acting superoxide dismutase (SOD) derivative (SM-SOD) significantly inhibited the increase in CL intensity. Administration of SM-SOD immediately after inducing burn injury also significantly inhibited the increase in CL. These results suggest that superoxide radicals are generated in extradermal tissues, such as the small intestine, in the early stage after burn injury.

Animals

Long-term follow-up of patients with familial subepithelial amyloidosis of the cornea.

PURPOSE: To investigate the clinical course of patients with familial subepithelial amyloidosis of the cornea (FSA). METHODS: The authors retrospectively investigated the clinical course of seven Japanese patients with FSA. Corneal specimens obtained at the time of keratoplasty were examined histopathologically. RESULTS: The mean follow-up period was 20.6 years, including four patients followed for more than 25 years. In all patients, the initial symptoms of photophobia and epiphora started in the first decade of life. All except one patient had their first keratoplasty before 30 years of age. The seven Japanese patients with FSA had a total of 35 keratoplasties, each of which was followed by a severe recurrence of disease. In each patient, subepithelial haziness developed in the graft within 1 year of keratoplasty (mean, 7.9 months). Amyloid deposition typically recurred within a few years (mean, 26.6 months) followed by a deterioration of vision. There was a high incidence of postkeratoplasty complications such as wound dehiscence, glaucoma, and cataract. Histopathologic findings demonstrated that, in the early phase of recurrence, amyloid was deposited between the basal cell of the epithelium and Bowman's layer. CONCLUSION: Patients with FSA have ocular symptoms with a deterioration in vision from an early decade of life. Conventional surgical approaches were complicated by subepithelial haziness in the first postoperative year, which was followed by a severe recurrence in each patient. New surgical approaches may be indicated in FSA.

Adult

Effect of epidermal growth factor on cadherin-mediated adhesion in a human oesophageal cancer cell line.

Epidermal growth factor (EGF) mediates many pleiotrophic biological effects, one of which is alteration of cellular morphology. In the present study, we examine the possibility that this alteration in cell morphology is caused in part by the dysfunction of cadherin-mediated cell-cell adhesion using the human oesophageal cancer cell line TE-2R, which expresses E-cadherin and EGF receptor. In the presence of EGF, TE-2R changed its shape from round to fibroblastic and its colony formation from compact to sparse. Vanadate, a tyrosine phosphatase inhibitor, further potentiated the EGF response, whereas herbimycin A, a tyrosine kinase inhibitor, interfered with it. Moreover, EGF enabled the cells to invade in organotypic raft culture. These phenomena were accompanied not by decreased expression of the E-cadherin molecule but by a change in its localisation from the lateral adhesion site to the whole cell surface. Both alpha- and beta-catenin, cadherin-binding proteins, were also expressed at the same level throughout these morphological changes. Finally, we examined tyrosine phosphorylation of E-cadherin and alpha- and beta-catenin, and observed tyrosine phosphorylation of beta-catenin induced by EGF. These results suggest that EGF counteracts E-cadherin-mediated junctional assembly through phosphorylation of beta-catenin and modulates tumour cell behaviour to a more aggressive phenotype.

Benzoquinones

Loss of expression and loss of heterozygosity in the DCC gene in neoplasms of the human female reproductive tract.

In order to identify the possible role of the DCC gene in neoplasms of the human female reproductive tract, messenger RNA expression of the DCC gene was examined by reverse transcriptase-polymerase chain reaction, and expression of the DCC gene product was detected immunohistochemically. While histologically normal endometrium, cervical epithelium and ovary expressed detectable mRNA of the DCC gene, three of eight (37%) endometrial carcinomas, one of two (50%) cervical carcinomas and 9 of 22 (41%) ovarian malignant tumours had significantly reduced or negligible DCC expression, and another endometrial carcinoma and two other ovarian tumors underexpressed DCC when compared with histologically normal endometrial or ovarian tissues. Impaired DCC mRNA expression was detected more frequently in grade 3 ovarian epithelial tumours than in grade 1 tumours (P = 0.002). Loss of expression of the DCC gene product detected by immunohistochemistry significantly correlated with the loss of mRNA expression in ovarian carcinomas (P = 0.01 by chi-square test) or in both endometrial and ovarian carcinomas combined (P = 0.001). Loss of heterozygosity of the DCC gene was also evaluated by restriction fragment polymorphism analysis of the polymerase chain reaction-amplified DNA fragment. Loss of heterozygosity of the DCC gene was detected in one of seven (14%) informative cases of endometrial carcinomas, 1 of 11 (9%) informative cases of cervical carcinomas and two of six (33%) informative cases of ovarian tumours. These results demonstrate that inactivation of the DCC gene, especially by the loss of expression, plays a significant role in the aetiology of neoplasms of the human reproductive tract.

Adenocarcinoma

Superoxide radicals play important roles in the pathogenesis of spinal cord injury.

To investigated a possible role of superoxide dismutase (SOD) in the pathogenesis of spinal cord injury (SCI), the change in the circulatory status in an experimental SCI model of rats was examined. The blood pressure (BP) of the SCI group decreased markedly by compression or head-up-tilt (60 degrees). The extent of the BP decrease was diminished by the administration of along acting SOD (SM-SOD) prior to injury. Compression, tilting and the administration of SM-SOD increased the sensitivity of resistant arteries to acetylcholine. SM-SOD treated rats had a significantly lower mortality than was found in untreated rats. These findings indicate that superoxide radicals may contribute to the pathogenesis of spinal cord injury and orthostatic hypotension caused by SCI.

Acetylcholine