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Biomedical subjects

H Koike

Publications and source records attributed to H Koike.

426 records · Page 24Linked to original sources

Anti-pituitary antibody-induced multiple endocrine disorders in mice.

Circulating anti-pituitary antibodies (APAs) have been detected in patients with autoimmune diseases, although the role of autoantibodies in the pathogenesis of autoimmune diseases is still unclear. With the aim of elucidating the autoimmune mechanisms involved in patients with multiple endocrine disorders, we evaluated the pathological changes in the pituitary gland, thyroid, pancreas and adrenal gland of mice, both wild-type and using a murine model of autoimmune thyroid disease [MRL-lpr/lpr] that had been immunized with murine, rat, porcine or human pituitary glands. In four of seven mice, a 22 kD band corresponding to APA was detected by Western blotting in the serum from mice that had been immunized with human pituitary tissues but not in the serum from mice immunized with rat or pig tissue. Inflammatory changes were detected in all groups of mice, occurring in the hypophysis, pancreas and adrenal glands but not in the thyroid. In conclusion, APA-induced autoimmune endocrine disorders are likely to be important for studying the mechanisms involved in autoimmune syndromes.

Animals↗

Detection of point mutation for human growth hormone in patients with anti-pituitary antibody positive type 1 diabetes mellitus.

We investigated genetic mutations in the coding region of the human growth hormone (hGH) gene in anti-pituitary antibody (APA)-positive patients with type 1 diabetes mellitus (n = 6) or autoimmune thyroid diseases (n = 10) and in APA-negative, healthy controls (n = 10). A point mutation in the hGH gene was discovered in two patients with type 1 diabetes mellitus. No mutations were found in the hGH gene in control subjects, patients with autoimmune thyroid diseases (Hashimoto's thyroiditits, Graves' disease) or in the remaining four patients with type 1 diabetes mellitus. The mutation was located in the coding region for the second amino acid in the N-terminal region of hGH. This point mutation was identified in codon 2 in exon 2 of the hGH gene. We successfully developed an allele-specific amplification method for detecting this mutation using the polymerase chain reaction.

Adolescent↗

Long-term follow-up of the Indiana pouch: efficacy of the pouch construction using the absorbable gastrointestinal staples.

The Indiana pouch procedure was used on 34 bladder cancer patients. The Heinecke-Mikulicz reconfiguration was carried out, involving the conventional hand-sewn and the absorbable GIA stapled methods with the continence mechanism of a staple-tapered efferent limb. The tunnelled tenial anti-refluxing implantation of ureters was performed. The stapled pouch construction saved approximately 1 h of operating time and reduced by 18% the overall loss of blood. There were 3 complications (wound infection/dehiscence in two, leakage from the enteric anastomosis in one, and acute renal failure in one) within 30 days postoperatively. As a late complication, ureter implantation stricture was experienced in two and pouch stone formation in five. No significant difference in the incidence of stone formation was evident between the hand-sewn and the stapled pouches, nor was any difference of pouch volume and catheterization interval. All patients had acceptable continence. These data demonstrated that the Indiana pouch is a reliable procedure with an acceptable complication rate. The pouch construction using the stapled method, which simplified the procedure, is more convenient than the one using the hand-sewn technique.

Absorption↗

Molecular detection of disseminated cancer cells in the peripheral blood of patients with gastric cancer.

This study was designed to determine whether circulating cancer cells in patients with gastric cancer can be identified by a RT-PCR method and to assess the clinical significance of the hematogenic dissemination of cancer cell in gastric cancer patients. A total of 41 patients with gastric cancer were enrolled in this study. Peripheral blood samples from 41 patients with gastric cancer were analyzed for CEA mRNA using RT-PCR. Of the 36 patients undergoing radical gastrectomy, eight had a positive CEA mRNA signal in their peripheral blood before the gastrectomy. In four patients, the CEA mRNA signal was negative, positive and then negative again, before, during and after the surgery, respectively. Of the five inoperable patients with peritoneal metastasis, four had positive CEA mRNA signals despite no metastasis in any other organs. The RT-PCR method is a useful diagnostic modality to determine patient selection for chemotherapy after surgery.

Adenocarcinoma↗

Combined resection of the involved organs in T4 gastric cancer.

BACKGROUND/AIMS: It remains controversial whether extended surgeries for gastric cancer can improve the postoperative survival rate. This study was designed to evaluate the effectiveness of a combined resection of the involved organs for improving the survival of gastric cancer patients. METHODOLOGY: Of the 1600 patients treated at our Department, from 1969-1993, 231 patients were found to have evidence of adjacent organ spread at laparotomy. Of the 231 patients, 174 underwent a combined resection of the adjacent organs with a gastrectomy due to direct invasion of these organs by the gastric cancer. The clinicopathological characteristics of 231 patients who had adjacent organ spread were compared retrospectively with 495 patients who had no adjacent organ spread. RESULTS: Although the postoperative survival rate of those patients who underwent a gastrectomy with a combined resection of the involved organs was poor, 14 patients survived for 5 years or longer after the surgery. The clinicopathologic factors characteristic of these 14 surviving patients were a lesser extent of lymph node metastasis and high operative curability. CONCLUSIONS: A combined resection of the involved organs with a gastrectomy should be performed when lymph node metastasis is not evident.

Adult↗

Gene expression profiles in human BPH: utilization of laser-capture microdissection and quantitative real-time PCR.

Human benign prostatic hyperplasia (BPH) nodules consist of epithelium and stroma that have different properties functionally as well as morphologically. To investigate the molecular profiles of the prostate gland, separate examination of these components are necessary. Laser-capture microdissection (LCM) is a newly-developed device which enables one to dissect interesting parts of tissues under the microscope. In the current work we studied the gene expression profiles of prostatic epithelium and stroma using LCM. Androgen receptor (AR), estrogen receptor alpha and beta (ER alpha and ER beta), progesterone receptor (PR) and 5-alpha reductase type I and type II (5alphaR I and 5alphaR II) gene expressions were studied by RT-PCR. All of these genes were expressed both in the epithelium and stroma. Furthermore, AR transcript was quantified by quantitative real-time PCR. AR transcript ranged from 302 to 1440 copies per 10(5) GAPDH copies and from 257 to 3223 copies per 10(5) GAPDH copies in the epithelium and stroma, respectively. Thus, LCM and quantitative real-time PCR are powerful tools for molecular analysis of heterogeneous tissues including prostate gland.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Distribution of water, fat, and metals in normal liver and in liver metastases influencing attenuation on computed tomography.

The quantity of water, lipid and some metals was measured in autopsy specimens of 8 normal livers, 9 livers with fatty change, and in 12 livers with metastases of various origins. These parameters contribute to the CT number measured in the liver. Water played a major role in demonstration of liver metastases as a low-density area on CT. Other contributory factors include iron, magnesium and zinc. Lipid and calcium had no influence in this respect. Heavy accumulation of calcium in a metastatic lesion gives a high-density area on CT. However, even when a metastatic lesion was perceived on CT as a low-density area, the calcium content of the lesion was not always lower than that of the non-tumour region.

Body Water↗

Fallopian tube prostaglandin production with and without endometriosis.

OBJECTIVE: To investigate the potential role of prostaglandins (PGs) in tubal function in endometriosis. SUBJECTS: Fallopian tubes were obtained from 36 women undergoing abdominal total hysterectomy. METHODS: PG production of the human fallopian tube was measured by radioimmunoassay. RESULTS: In normal controls, ampulla and fimbriae in the proliferative and secretory phases produced more PGE and PGF than isthmus. PGE production in ampulla and fimbriae increased in proliferative and secretory phases. PGF production was predominant in the proliferative phase in all parts. There was no significant cyclic or regional variation in 6-keto-PGF1 alpha and thromboxane B2 production. CONCLUSIONS: In patients with endometriosis, isthmus and ampulla produced much more PGE and PGF in the proliferative phase than normal controls. The variation of PGF/PGE ratio in endometriosis was different from that of normal controls. It was apparent that tubal PG production is altered in endometriosis.

6-Ketoprostaglandin F1 alpha↗

Cytokinetic and morphologic differences in ovarian cancer cells treated with ET-18-OCH3 and the DNA-interacting agent, etoposide.

New antineoplastic agents with different cytotoxic mechanisms are of interest for their ability to overcome resistance to conventional DNA-interacting agents. Ether lipids are known to be active against ovarian carcinoma both in vitro and in vivo, and the cell membrane is believed to be the target of their antitumor activity. In this study we have investigated the different cytokinetic and morphologic responses of human ovarian carcinoma cells (BG-1) to one of the ether lipids (ET-18-OCH3) and to etoposide. Etoposide induced a significantly greater G2/M block. However, the proportion of the cycling cell fraction decreased significantly in cells treated by ET-18-OCH3 and induction of the hypodiploid traction was strongly correlated with reduction of the cycling cell fraction. On the other hand, the hyperdiploid fraction was found to correlate with reduction of the cycling cell fraction in etoposide treated cells. Despite the significant appearance of the hypodiploid fraction, apoptosis was not observed by DNA-gel assay. Microscopic study showed that the hyperdiploid fraction represented cells with multiple nuclei. These observations support the unique lethal effect of ET-18-OCH3 on ovarian carcinoma cells, distinguishing it from the action of a typical DNA-interacting agent. The membrane-targeted ether lipids deserve consideration for the future chemotherapy of ovarian carcinoma, perhaps in combination with the appropriate DNA-interacting agent. New antineoplastic agents with different cytotoxic mechanisms are of interest not only for their unique inhibitory properties but also for their potential of overcoming resistance to conventional DNA-interacting agents. Ether lipids are known to be active against ovarian carcinoma both in vitro (1, 2, 3) and in vivo (4, 5), and the cell membrane is believed to be the target of their antitumor activity. Etoposide, a DNA-interacting agent, is also active against human ovarian cancer cells in vitro (6) or in clinical trials either as a single agent (7) or in combination with cisplatin (8). We have reported that a cytotoxic dose of one of the ether lipids, ET-18-OCH3, induces a G2/M block in BG-1 human ovarian cancer cells, and also a hypodiploid fraction as shown on DNA analysis by flow cytometry (FCM) (9). The G2/M block was also observed in BG-1 cells following etoposide treatment (6). In the present study, we have investigated the differences in the cytokinetic and morphologic responses of BG-1 cells to ET-18-OCH3 and to etoposide.

Antineoplastic Agents↗