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Biomedical subjects

N Harada

Publications and source records attributed to N Harada.

At least 235 records · Page 13Linked to original sources

Benign tumour of the ampulla of Vater: surgical treatment and prognosis.

OBJECTIVE: To find out whether wide local resection is adequate treatment for patients with benign tumours of the papilla of Vater. DESIGN: Retrospective study. SETTING: University hospital, Germany. SUBJECTS: 31 patients with benign tumours out of a total of 129 with lesions of the ampulla of Vater treated between May 1978 and February 1995. INTERVENTIONS: Histological examination of specimens before, during, and after the operation. MAIN OUTCOME MEASURES: Sensitivity and positive predictive value of histological examination, and outcome of treatment. RESULTS: Histological examination before and during the operation had a sensitivity of 89% and 97%, respectively. 28 patients were treated by wide excision of the ampulla and 3 by pylorus-preserving partial pancreaticoduodenectomy. At a median follow up of 43 months (range 6-156) there was no evidence of recurrent disease. CONCLUSION: Wide excision of the ampulla with reconstruction and reimplantation of the duct is adequate treatment for benign lesions. If the histological picture is uncertain, partial pancreaticoduodenectomy is justified in patients at low risk.

Adolescent↗

Adrenocortical and gonadal expression of the mammalian Ftz-F1 gene encoding Ad4BP/SF-1 is independent of pituitary control.

Ad4BP/SF-1 is a transcription factor essential for the development of the adrenal gland and the gonads as well as for the maintenance of their functions through regulating tissue-specific gene transcription. In the whole body, hypothalamo-pituitary-gonadal and -adrenal axes are known to play prominent roles in mediating the function of the gonads and adrenal. In this study, the effects of the tropic peptide hormones secreted by the pituitary on the regulation of the rat Ftz-F1 (rFtz-F1) gene encoding Ad4BP/SF-1 were investigated. Immunochemical studies revealed that Ad4BP/SF-1 was expressed even in the adrenal cortex of hypophysectomized rats. Such persistent expression of Ad4BP/SF-1 was also observed in the testes and ovaries of the hypophysectomized animals. In contrast to Ad4BP/SF-1, the expressions of steroidogenic P450s were reduced significantly. The transcriptional activities of the endogenous and transfected rFtz-F1 genes were examined with Y-1 and I-10 cells derived from mouse adrenocortical and testicular Leydig cell tumors, respectively. Neither gene appeared to be activated significantly by cAMP, whereas both endogenous and exogenous CYP11A genes encoding P450(SCC) were activated. Taken together, these observations indicate that the expression of the rFtz-F1 gene is mainly regulated by a mechanism independent of the neuroendocrine axes.

Adrenal Cortex↗

CD44H participates in the intrahepatic growth of murine colon 26 adenocarcinoma cells.

The purpose of this study was to determine if CD44, a metastasis-associated cell adhesion molecule, is involved in the hepatic colonization by murine colon 26 adenocarcinoma cells. Indirect membrane immunofluorescence and FACS analysis showed strong expressions of CD44 and integrin beta 1 on colon 26 cells. Injection of 1 x 10(5) colon 26 cells into the superior mesenteric vein of syngeneic BALB/c mice produced macroscopic hepatic nodules in 92% (22/24) of the mice 14 days after inoculation. When colon 26 cells were pretreated with an anti-CD44 monoclonal antibody (mAb), IM7, only 30% (3/10) of the mice produced minute nodules in the liver on day 14 (P < 0.001), though IM7 did not inhibit growth of the cells in vitro. Pretreatment of colon 26 cells with an anti-integrin beta 1 mAb did not significantly block the hepatic metastasis. Histologically, microcolonies of tumor cells were detected in all of the livers on day 14 including the IM7-pretreatment mice that were free of gross nodules. However, percentages of tumor-occupied areas in the liver were consistently lower in IM7-pretreatment mice than in control mice (0.82% vs. 5.0% on day 14; P < 0.005). Reverse transcription-polymerase chain reaction (RT-PCR) amplification of mRNA revealed that colon 26 cells and splenocytes only expressed the hematopoietic isoform of CD44 (CD44H), which had no insertion of variant exons, while normal colonocytes expressed possible variant isoforms. These data suggest that malignant transformation of murine colonic epithelium altered the expression pattern of CD44 isoforms and that CD44H participates in the intrahepatic growth of colon 26 cells.

Adenocarcinoma↗

A new approach to Pneumatosis cystoides intestinalis by target air-enema CT.

A 48-yr-old man was admitted to our hospital with abdominal discomfort and distension. A barium enema showed multiple radiolucent filling defects in the wall of the ascending colon. Colonic endoscopy revealed numerous round, polypoid masses covered with normal mucosa. These findings suggested Pneumatosis cystoides intestinalis. Target air-enema computed tomography was performed to make a final diagnosis, and demonstrated several gas collections covered with soft tissue in the wall of the ascending colon. This is the first reported case of Pneumatosis cystoides intestinalis in which multiple gas-filled cysts could be recognized by target air-enema computed tomography.

Abdominal Pain↗

Extended radical Whipple resection for cancer of the pancreatic head: operative procedure and results.

Pancreatoduodenectomy is now the most fundamental operation for cancer of the pancreatic head. However, with the conventional operative procedure, the resection rate is low and long-term results are extremely poor. We introduced an extended radical Whipple operation in 1978 to improve surgical curability. Systemic dissection of extended lymph nodes and plexuses and en bloc resection of the portal vein was the basic concept. The resection rate for cancer of the pancreatic head has improved from 7-20 to 50%. The curative resection rate has also improved from 10 to 40-50%. The extended procedure did not increase the risk of the Whipple operation. When curative surgery was performed, good long-term survival was expected even in cases of extensive invasion to the portal vein. As a result, 11 patients who underwent curative surgery have survived for a long period of time. At present, however, the majority of patients are in an advanced stage at diagnosis and extended radical operation plays an important role in the curative therapy for this condition.

Aged↗

Intracellular calcium changes and chemosensitivities of human epidermoid carcinoma cell lines after exposure to cisplatin.

In order to elucidate the mechanisms of cisplatin (cis-diamminedichloroplatinum; CDDP)-resistant tumor cells, we previously established a CDDP-resistant KB cell line (KBrc cells) from a parental KB cell line derived from epidermoid carcinoma (KB cells). The KBrc cells were resistant to 5 kinds of platinum (Pt) drugs. Intracellular Pt concentrations in KBrc cells were lower than in KB cells. Decrease of intracellular Pt concentrations was one of the CDDP-resistant mechanisms. When we measured changes of intracellular calcium ion concentration ([Ca2+]i) during exposure to high-dose CDDP, a sustained elevation of the [Ca2+]i level was observed in the KB cells. These results suggest that the mechanisms underlying CDDP resistance involve changes in calcium channels and an alteration of calcium homeostasis in the tumor cell line.

Antineoplastic Agents↗

Intratumoral aromatase in human breast, endometrial, and ovarian malignancies.

In human estrogen-dependent neoplasms such as breast, endometrioid endometrial, and surface epithelial-stromal ovarian carcinomas, intratumoral aromatase is considered to play important roles in converting circulating androgens derived from adrenal cortex and/or ovary to estrogens, possibly in association with 17 beta-HSD type 1 and estrogen sulfatase. Analysis of intratumoral aromatase in these estrogen-dependent neoplasms is important not only in understanding the development and biological behavior of these tumors, but also in the clinical management of these patients, because suppression of intratumoral aromatase by newly developed aromatase inhibitors may provide new potentials in endocrine therapy of these patients.

Aged↗

Localized aberrant expression of cytochrome P450 aromatase in primary and metastatic malignant tumors of human liver.

The present study was designed to demonstrate localized aberrant expression of aromatase in primary and metastatic malignant liver tumors. Immunocytochemistry revealed the presence of locally increased aromatase protein in regions around tumors in all specimens from seven primary and seven metastatic liver tumors. This observation was further confirmed by Western blotting analysis and assay of aromatase activity in tumorous, proximal, and distal regions. Western blots showed most intensely immunoreactive bands at the position corresponding to aromatase in proximal tissues where aromatase activities also were higher (2.75 +/- 1.59 pmol/mg.h) than in tumors (0.137 +/- 0.115 pmol/mg.h) and distal tissues (1.90 +/- 1.47 pmol/mg.h), in spite of a gradient decline of NADPH-cytochrome P-450 reductase activity from the distal regions to the tumors. RT-PCR analysis indicated that the aberrant increase in aromatase protein and enzyme activity in the regions proximal to tumors is caused by locally elevated aromatase messenger RNA.

Adult↗

[A new aspect of the pharmacological and physiological significance of the aromatase/estrogen system].

Aromatase (estrogen synthetase) catalyzes a key step in estrogen biosynthesis and plays an important role in reproductive processes in the ovary and placenta. In this context, aromatase is an enzyme producing estrogen as an endocrine female sex hormone. Recently, it has reported that aromatase is also present in various extra-gonadal tissues and is tissue-specifically regulated by various factors. This tissue-specific regulation of human aromatase gene is realized by alternative utilization of multiple exon 1's; exons la, 1b, 1c, 1d, 1e, and 1f that are specific for expression in the placenta, skin fibroblasts/fetal liver, ovary, ovary/prostate/testis, placenta, and brain, respectively. Each of the tissue-specific exon 1's is flanked by a unique promoter containing basic and regulatory elements. The facts that (i) aromatase is distributed in various gonadal and extra-gonadal tissues and (ii) regulated tissue-specifically by various factors, (iii) estrogen participates in specific physiological functions of various tissues, and (iv) estrogen receptor is also distributed in various tissues strongly indicate that estrogen locally produced by aromatase acts in various tissues as a multi-functional paracrine or autocrine hormone. This idea was discussed in connection with the Kd value for the estrogen receptor and serum concentration of estrogen.

Aromatase↗

Chemical structure of antithrombin-active Rhamnan sulfate from Monostrom nitidum.

Rhamnan sulfate was extracted with boiling water from the cell wall of Monostroma nitridum, and the resulting extract was purified by ion-exchange and size-exclusion chromatography. The polysaccharide, which is regarded as a homopolysaccharide, was 6-fold more antithrombin-active than the heparin standard. The antithrombin activity was decreased, by desulfation, although the non-active product still retained 8% of the sulfate ester. A comparative structural study of the intact rhamnan sulfate and rhamnan, its desulfated product, by periodate oxidation, Smith degradation and methylation analysis revealed the rhamnan sulfate to consist of alpha-1,3-linked L-rhamnose residues, some of which were substituted with sulfate groups mainly at position O-2. Minor amounts of internal 1,2-linked rhamnose and branched rhamnose linkages were also detected.

Carbohydrate Sequence↗

Effects of room temperature, seasonal condition and food intake on finger skin temperature during cold exposure test for diagnosing hand-arm vibration syndrome.

For diagnosing the hand-arm vibration syndrome, peripheral circulation and sensory tests immersing one hand in cold water at 10 degrees C for 10 min have been performed widely in Japan. The authors investigated the effects of room temperature, seasonal condition and food intake on the test results, especially finger skin temperature. Six healthy males were examined repeatedly under six different room temperatures at 10 degrees C, 15 degrees C, 20 degrees C, 22.5 degrees C, 25 degrees C and 30 degrees C. Eight healthy males were examined under room temperatures at 10 degrees C, 20 degrees C and 30 degrees C, repeatedly in winter, spring, summer and autumn. Six healthy males were examined in summer under room temperature at 22.5 degrees C repeatedly 1 hr after, 3 hr after meal and after fasting for 13 hr. The finger skin temperature was strongly affected by room temperature. The finger skin temperature was also affected by seasonal condition. No remarkable effect of food intake was observed. For estimating circulatory function of the upper extremities using the finger skin temperature, the room temperature should be strictly controlled and the effect of seasonal condition must be taken into consideration.

Adult↗

Tensile bond strengths and adhesive interfaces of ten dentin bonding systems.

Tensile bond strength measurements and scanning electron microscopic observations have been performed to evaluate the adhesive properties of new dentin bonding systems. To date, however, it was impossible to compare previously reported data among researchers, because there was no standardization of in vitro test methods. There have also been few reports about the correlation among tensile bond strengths (TBS) and morphological features of the adhesive interfaces of recent systems. Therefore, the purpose of this study was to investigate the relationship between TBS to bovine dentin, following the guidelines documented by the International Organization for Standardization (ISO), and the morphology of resin/dentin interfaces of nine commercially available and one experimental bonding systems. The nine recent bonding systems used in this study showed significantly higher mean TBS (ranging from 25.0 to 14.8 MPa) than did a system (PhB) marketed ten years ago (9.3 MPa). However, morphological features of the resin/dentin interface varied among the systems, and no statistically significant correlation was found between TBS and width of the hybrid layer (p = 0.62). In order to evaluate the quality of the resin/dentin interface, quantitative analyses are needed to clarify the saturation and polymerization of resin in the hybrid layer.

Adhesiveness↗

[Identification of aneuploids in uncultured amniotic fluid cells by interphase fluorescence in situ hybridization].

We report the diagnosis of aneuploids in uncultured amniotic fluid cells by the use of interphase fluorescence in situ hybridization (FISH). About a dozen of cases was studied to detect chromosome aneuploids (trisomies 13, 18 and 21, and monosomy X), especially those in the perinatal period. Results of FISH experiments in each specimen were compared with those of conventional chromosome analysis, and showed no discrepancy between them in most cases. FISH analysis revealed that four 18-trisomies had two different cells, one of which showed two fluorescence signals and the other three signals, the result indicating a maternal cell contamination. Thus, special attention should be paid when FISH analysis is adopted to the diagnosis in uncultured amniotic fluid cells in order to avoid misdiagnosis that may originate in maternal cell contamination.

Amniotic Fluid↗

[A report of two siblings with both maternal dentato-rubro-pallido-luysian atrophy and paternal Ehlers-Danlos syndrome type III].

The report deals with the first description of two siblings, a 43-year-old woman and 39-year-old man, who have developed cerebellar ataxia, choreoathetosis, dementia, epilepsy, hyperelasticity of the skin, and hypermobility and dislocation of joints. The frequent dislocations of joints sometimes could not be corrected surgically. Their mother and maternal uncle have the same neurological signs and symptoms as the siblings do. However, they do not present with the signs of skin and joints. Gene analysis of peripheral blood lymphocytes from these 4 patients revealed that the CAG repeat length of the dentato-rubro-pallido-luysian atrophy (DRPLA) gene is increased in all four. On the contrary, their father has displayed only hyperelasticity of the skin. From the clinical signs, family history and skin biopsy, we consider that the siblings and their father have Ehlers-Danlos syndrome (EDS) type III. In conclusion, the previously unreported coincidental development of maternal DRPLA and paternal EDS observed in two siblings deserves to be described.

Adult↗

Rebamipide prevents indomethacin-induced gastric mucosal lesion formation by inhibiting activation of neutrophils in rats.

Since granulocyte elastase has been shown to be involved in the pathogenesis of gastric mucosal lesion formation induced by nonsteroidal antiinflammatory drugs, inhibition of granulocyte elastase release from neutrophils may be useful in the prevention of these lesions. The objective of this study was to determine whether rebamipide inhibits neutrophil activation in vivo and in vitro. Rebamipide and ONO-5046, a specific granulocyte elastase inhibitor, markedly inhibited indomethacin-induced mucosal injury in rats. Gastric myeloperoxidase activity was significantly increased 3 h after indomethacin administration. This increase was significantly inhibited by rebamipide and ONO-5046. Although cimetidine markedly prevented the indomethacin-induced mucosal lesion formation, it did not reduce the gastric myeloperoxidase activity. Rebamipide inhibited granulocyte elastase release from neutrophils in vitro by inhibiting the increase in intracellular Ca2+ level. Cimetidine did not inhibit granulocyte elastase release from neutrophils. Furthermore, the elevation of intracellular Ca2+ level was not inhibited by cimetidine. Therefore, unlike cimetidine, rebamipide may prevent indomethacin-induced mucosal injury by inhibiting neutrophil activation.

Alanine↗

[Analysis of Mycobacterium tuberculosis-derived substance which induces interleukin-12 production from macrophages].

Protection of hosts against tuberculosis depends on expression of cellular immunity. To express cellular immunity, interleukin 12 (IL-12) has been shown to play an important role. Although Mycobacterium tuberculosis is known to induce IL-12 from macrophages (M phi s), the mechanism for the induction is still unclear. To understand the mechanisms of IL-12 induction from M phi s by M. tuberculosis, the IL -12-inducing ability of substances derived from M. tuberculosis was investigated in vitro. Production of IL-12 in culture medium of M phi s was measured by ELISA system using specific antibodies. Live M. tuberculosis H37Rv induced slightly higher IL-12 production than live M. tuberculosis H37Ra upon stimulation of human or mouse alveolar macrophages (hAM phi s or mAM phi s). Heat-killed M. tuberculosis failed to induce IL-12 production of alveolar macrophages (AM phi). The responses of hAM phi s and mAM phi s to M. tuberculosis were remarkably different. mAM phi s produced five times larger amount of IL-12, compared with that from hAM phi s. Human peripheral blood mononuclear cells (PBMC) obtained by the density gradient centrifugation were also used for induction of IL-12 production. Although production levels of IL-12 from PBMC stimulated with M. tuberculosis were below the detectable level, addition of interferon-gamma (IFN-gamma) or neutralizing antibody against IL-10 augmented the production of IL-12 from PBMC, suggesting that IFN-gamma and IL-10 regulate the production of IL-12 from M phi positively and negatively, respectively. To characterize the physicochemical properties of IL-12-inducing molecules, M. tuberculosis H37Rv was disrupted by pressing with 1,000 bar and centrifuged and separated into cytosol and cell wall fraction. The culture filtrate was also examined on IL-12-inducing activity. Among the three subjects examined, cytosol was found to induce the highest production of IL-12 from mAM phi s 1 day after the stimulation. Addition of IFN-gamma to the cytosol fraction markedly increased the production of IL-12 from mAM phi s. The molecular weight of IL-12-inducing substance was shown to be more than 30kDa by fractionating with molecular filters. Treatment of 30kDa-fraction with IL-12-inducing activity by proteinase K completely abolished the activity. Furthermore, approximately 90% of IL-12-inducing activity of 30kDa-fraction was lost by proteinase K treatment even in the presence of IFN-gamma. These results indicate that the major component of IL-12-inducing activity is a protein. The identification of this IL-12-inducing active substance may provide a new therapeutic tool for tuberculosis.

Animals↗