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K Kitamura

Publications and source records attributed to K Kitamura.

At least 487 records · Page 27Linked to original sources
PubMed1995

Serological response patterns of melanoma patients immunized with a GM2 ganglioside conjugate vaccine.

Gangliosides, such as GM2, GD2, GD3, and 9-O-acetyl GD3, are receiving attention as targets for antibody-based and vaccine-based therapies of melanoma. GM2 appears to be a particularly immunogenic ganglioside in humans, as indicated by the presence of naturally occurring IgM anti-GM2 antibodies in approximately 5% of humans and the fact that immunization with irradiated GM2-expressing melanoma cells or purified GM2 adherent to bacillus Calmette-Guérin elicits GM2 antibodies of low to moderate titers in a high proportion of vaccinated patients. To develop vaccines that consistently induce high titers of IgM as well as IgG anti-GM2 antibodies, vaccines containing GM2 conjugated to keyhole limpet hemocyanin as the carrier protein and QS-21 as the adjuvant have been constructed. The serological response of vaccinated patients was monitored by ELISA using purified GM2 ganglioside for IgM and IgG anti-GM2 antibodies and for GM2 cell surface-reactive antibodies by immune adherence assays and cytotoxic tests (IgM antibodies) and mixed hemadsorption assays (IgG antibodies). The majority of vaccinated patients developed IgM and IgG antibodies detectable by ELISA. In most cases, the results of IgM ELISA correlated with assays for cell surface-reactive IgM antibodies. This was not true for IgG anti-GM2 antibodies, where strong discrepancies were seen between high titers in ELISA and little or no reactivity in mixed hemadsorption tests for cell surface-reactive antibodies. These IgG antibodies (and the less frequent IgM antibodies that show similar discrepancies) may be directed against GM2 determinants that are buried, hidden, or not present on GM2-expressing target cells. With regard to a major objective of ganglioside vaccines--i.e., generation of cytotoxic antibodies--the GM2-keyhole limpet hemocyanin/QS-21 vaccine is clearly superior to the previously tested GM2/bacillus Calmette-Guérin vaccine. However, variability in patient response and lack of persistence of high-titered IgM cytotoxic antibodies in many patients are problems that remain to be solved.

Adjuvants, Immunologic↗
PubMed1995

Carcinogenesis and histogenesis of esophageal carcinoma.

Dysplasia is one of the most important subjects regarding carcinogenesis of the esophagus, because there is continuing controversy as to whether esophageal dysplasia is a cancerous lesion or a noncancerous lesion. In this study, it is histopathologically shown that dysplasia has a close correlation with cancer itself and that there is no substantial difference in the cell proliferative activity of dysplasia and intraepithelial carcinoma. These findings thus show that dysplasia has as high a potential for malignancy, thus it should be treated as an extremely early cancerous lesion of the esophagus to substantially improve the long term results of this disease. Conversely, esophageal carcinoma with glandular and/or mucus-secreting components is commonly found in addition to the ordinary component of squamous cell carcinoma, which indicates that this type of esophageal tumor originates not only from the squamous epithelium but also from the esophageal mucus gland or the ductal epithelium. These findings support the concept of field carcinogenesis in esophageal carcinoma.

Carcinoma↗
PubMed1995

Adrenomedullin stimulates two signal transduction pathways, cAMP accumulation and Ca2+ mobilization, in bovine aortic endothelial cells.

The biological action of adrenomedullin, a novel hypotensive peptide, on bovine aortic endothelial cells, was examined. The specific binding of adrenomedullin to these cells was observed, and adrenomedullin was found to induce intracellular cAMP accumulation in a dose-dependent manner. EC50 for the cAMP accumulation was about 100 times lower than the apparent IC50 for the binding assay. Adrenomedullin also induced increase of intracellular free Ca2+ in endothelial cells in a dose-dependent manner. The Ca2+ response to adrenomedullin was biphasic with an initial transient increase due to the release from thapsigargin-sensitive intracellular Ca2+ storage and a prolonged increase by influx through the ion channel on the plasma membrane. This intracellular free Ca2+ increase resulted from phospholipase C activation and inositol 1,4,5-trisphosphate formation, and seemed to cause nitric oxide synthase activation by monitoring intracellular cGMP accumulation. Both cAMP accumulation and Ca2+ increased responses to adrenomedullin were mediated by cholera toxin-sensitive G protein, but the two signal transduction pathways were independent. Thus, the results suggest that adrenomedullin elicits the hypotensive effect through at least two mechanisms, a direct action on vascular smooth muscle cells to increase intracellular cAMP and an action on endothelial cells to stimulate nitric oxide release, with both leading to vascular relaxation.

Adrenomedullin↗
PubMed1995

Interleukin-1, tumor necrosis factor and lipopolysaccharide additively stimulate production of adrenomedullin in vascular smooth muscle cells.

To elucidate physiological functions of adrenomedullin (AM) secreted from vascular smooth muscle cells (VSMCs), we examined the effect of cytokines, growth factors and related substances on AM production in cultured rat VSMC. Among them, interleukin-1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor-alpha (TNF-alpha) and TNF-beta, as well as lipopolysaccharide (LPS), markedly augmented production and gene expression of AM. Although maximal stimulation levels of these substances were not greatly different, ED50 values of IL-1s (0.3 ng/ml) were about 1/10 that of TNFs and LPS. AM mRNA levels maximized at 3-6 h after stimulation with IL-1 beta and LPS, while TNF-alpha increased the AM mRNA level up to 48 h. Furthermore, IL-1 alpha, TNF-alpha and LPS additively increased AM production in VSMC. AM production was slightly augmented by fibroblast, epidermal and platelet derived growth factors. These results suggest that AM secreted from VSMC actually exerts a vasorelaxant effect under physiological conditions such as endotoxin shock, atherosclerosis and inflammation.

Adrenomedullin↗
PubMed1995

Activated carbon-oriented gastrectomy for early gastric cancer.

Twenty-two patients with early gastric cancer received injections of activated carbon particles (CH-40) to identify during surgery the location of non-palpable tumours present in the upper portion of the stomach. A few days before surgery, 0.2 ml of CH-40 was injected endoscopically into the gastric muscle adjacent to the cancer. In 20 of the 22 patients, the CH-40-stained area was recognized as a blackened patch on the serosal surface of the stomach which indicated the location of the non-palpable cancer tissue. The surgical margin for gastrectomy was defined as the proximal margin of the carbon-stained area and gastrectomies were performed on the 22 patients. CH-40 injection made it possible to choose the extent of lymph node dissection.

Aged↗
PubMed1995

Rapid and accurate method for delineating cancer lesions in laparoscopic colectomy using activated carbon injection.

The aim of our study was to evaluate the clinical efficacy of preoperative injection of activated carbon in delineation of cancer location in laparoscopic colectomy. Activated carbon particles were injected during endoscopy into the normal colonic wall surrounding cancer lesions in five cases of early colon cancer, prior to laparoscopic surgery. The carbon-stained area was clearly recognizable as a blackened patch on the serosal surface of the colon. Using the carbon-stained area as a reference point, partial colectomies were successfully performed on all five patients. The preoperative injection of activated carbon assisted in the intraoperative delineation of early colonic cancer lesions. This method is recommended for the rapid and accurate delineation of early colonic cancers in laparoscopic surgery.

Aged↗
PubMed1995

Clinicopathologic study of patients with Borrmann type IV gastric carcinoma.

Between 1979 and 1993, 665 Japanese patients with advanced gastric cancer underwent surgery at our hospital. These patients were divided into two groups, consisting of 102 patients with Borrmann type IV carcinoma, and the remaining 563 patients with all other types of gastric carcinoma, which were then compared clinicopathologically. In the patients with Borrmann type IV carcinoma, 77.4% of the lesions demonstrated poorly differentiated adenocarcinoma, and 99 patients were classified as Stage III or IV. The resection rate was 87.2% (89/102) with only 39 curative operations despite the fact that 70 total gastrectomies were performed. The incidence of peritoneal dissemination (29.4%) and serosal invasion (97.0%) was significantly higher in these patients. Microscopic lymph node metastasis was positive in 86.5%. The 5-year survival rate was 23.4% in the patients with a curative operation and 5.0% in those with a noncurative operation (p < 0.01). Peritoneal dissemination was most frequently noted in the recurrence patterns. We conclude that early detection and a curative operation are both essential to improve the prognosis of patients with Borrmann type IV gastric cancer. The addition of a potent postoperative chemotherapy regimen is also recommended.

Adenocarcinoma↗
PubMed1995

Prospective randomized study of hyperthermia combined with chemoradiotherapy for esophageal carcinoma.

From January 1988 to June 1992, 66 patients with resectable squamous cell carcinoma of the thoracic esophagus underwent preoperative adjuvant therapy. These patients were prospectively divided into two treatment groups; 32 were treated with radiofrequency wave local hyperthermia combined with chemoradiotherapy (hyperthermochemoradiotherapy; HCR), while the remaining 34 patients were treated with chemoradiotherapy alone (CR). There were no procedural complications in either group and the postoperative mortality was zero. In the HCR group, no viable cancer cells were found within the entire 5 mm-width slices of the resected specimen in eight patients (25%), while only two (5.9%) in the CR group (P < 0.05) demonstrate no viable cancer cells. The cumulative 3-year survival rate was 50.4% in the HCR group and 24.2% in the CR group. The present prospective trial demonstrated that the addition of hyperthermia to chemoradiotherapy resulted in a better local control and an improved long-term survival when treating patients with advanced esophageal carcinoma.

Adult↗
PubMed1995

Total gastrectomy for early gastric cancer.

A total gastrectomy was performed in 49 patients with early gastric cancer, and the effectiveness of this procedure was evaluated by reviewing the hospital files of the patients. The reasons for this total gastrectomy were as follows: (1) lymph node dissection for 22 patients, (2) surgeon's choice in reconstruction for 10 patients, (3) modification of the surgery from subtotal to total gastrectomy for seven patients, (4) synchronous multiple cancers for seven patients, and (5) cancer in a stomach remnant for three patients. Of 49 patients, 42 had the cancerous lesions in the upper portion of their stomachs. Lymph node involvement occurred in 5 patients, but not in the supra- or infrapyloric lymph nodes. Postoperative complications such as anastomotic leakage, reflux esophagitis and pancreatic fistula occurred in five, four, and two patients, respectively. Postoperative death, including two patients who died within 30 days after the surgery, occurred in 5 patients. Our study showed that total gastrectomy resulted in excessive unnecessary surgery in 39 out of 49 patients (79.6%). We conclude that a total gastrectomy should not be performed on patients with early gastric cancer except for synchronous multiple cancers and for cancers in a stomach remnant.

Anastomosis, Roux-en-Y↗
PubMed1995

Chemo-endocrine therapy in patients with stage D2 prostate cancer.

There have only been a few studies of chemo-endocrine therapy compared with endocrine therapy alone in newly diagnosed prostate cancer patients. We assessed the effects of these two therapies by comparing long-term survival rates. One hundred and twenty-nine patients were entered in this study between November 1977 and March 1992. Seventy-seven patients were treated with endocrine therapy alone. Other 52 patients received chemo-endocrine therapy, which included orchiectomy and/or diethylstilbestrol diphosphate (DES-DP) plus Cisplatin, with or without other cytotoxic agents. All patients had bone metastasis at the beginning of the study. There was a significant difference in survival between patients who received endocrine therapy and chemo-endocrine therapy (P = 0.0078). That is, survival rate was superior for the chemoendocrine therapy patients throughout the entire follow-up period. These data suggest that early chemo-endocrine therapy containing Cisplatin, with or without maintenance chemotherapy, is a potentially effective treatment for newly diagnosed metastatic prostate cancer and is worth further investigation via a randomized trial.

Aged↗
PubMed1995

How safe are the xenogeneic hemostats?--Report of a case of severe systemic allergic reaction.

We report herein the unusual case of a 55-year-old woman who developed a severe systemic allergy to Avitene (microfibrillar collagen hydrochloride), a xenogeneic agent sometimes used for topical hemostasis in laparoscopic cholecystectomy. The patient developed fever, general fatigue, mild liver dysfunction, and prominent eosinophilia postoperatively. A skin allergy test confirmed that these abnormal findings were attributable to an allergic reaction to Avitene.

Abdominal Abscess↗
PubMed1995

Mastopathy of the accessory breast in the bilateral axillary regions occurring concurrently with advanced breast cancer.

We herein report a 41-year-old Japanese woman who demonstrated advanced cancer in the left breast occurring concurrently with mastopathy of the accessory breast tissue in the bilateral axillary regions, which appeared to be metastatic lymphadenopathy. A preoperative examination, including a mammogram, US, and CT, did not provide us with a definite diagnosis of the axillary masses: it was essential to diagnose the masses preoperatively since a bilateral mastectomy with nodal dissection is called for if the right axillary masses are metastatic from a cancer in the right breast. An intraoperative cytological examination from the bilateral axillary masses revealed adenosis with fibrocystic changes in the accessory breast tissue. We therefore performed a modified radical mastectomy only on the left side. The patient was thus saved from an unnecessary mastectomy of the right breast. Based on our experience, we wish to emphasize that the accessory breast tissue should be considered for a differential diagnosis when evaluating the axillary masses in order to avoid over-surgery, especially when a patient has been diagnosed to have massive breast cancer. An intraoperative cytological examination is strongly recommended to reach a final diagnosis in such confusing cases.

Adult↗
PubMed1995

Immunohistochemical identification of adrenomedullin in human, rat, and porcine tissue.

The histological localization was investigated of adrenomedullin (AM), a novel vasorelaxant peptide originally isolated from human pheochromocytoma. The immunohistological distribution was examined of AM in human, rat, and porcine tissues using a polyclonal antibody to a fragment comprising C-terminal amino acids 40-52 of human adrenomedullin [AM(40-52)NH2]. Almost all of the human pheochromocytoma and normal adrenal medullary cells of all three species were immunostained and found to be intensely positive for AM. Furthermore, AM-immunoreactive cells were present in the pancreatic islets, gastrointestinal neuroendocrine system, anterior pituitary, and choroid plexus with some degree of interspecies heterogeneity. These findings indicate that AM-immunoreactive cells are widely distributed in the endocrine and neuroendocrine system, suggesting that AM plays some important role in the control of systemic and local circulation and also of humoral secretion.

Adrenomedullin↗
PubMed1995

A method to estimate the potency of the mu-component of an opioid having mixed mu-, and kappa- and/or delta-agonist activities.

The SC administration of either typical mu-agonists such as morphine, pethidine, fentanyl and levorphanol or a mixed mu- and delta-agonist like [D-Ala2, D-Leu5]-enkephalin to 10-day-old rats produced loss of righting reflex. Additionally, the loss of righting reflex induced by these opioid agonists was antagonized by naloxone, an opioid antagonist having a preference for mu-receptors, but by neither nor-binaltorphimine nor naltrindole, a specific kappa- or delta-antagonist, respectively, indicating that the loss of righting reflex was produced by the interaction of an opioid with mu-receptors. Moreover, the potency of each opioid agonist relative to that of morphine estimated by the present in vivo method was similar to that determined by the traditional in vitro isolated preparation. In contrast to mu-agonists, neither typical kappa-agonists such as U-50, 488H, ketocyclazocine, pentazocine and butorphanol, nor a selective delta-agonist like [D-Pen2, D-Pen5]-enkephalin affected the righting reflex of 10-day-old rats, indicating that mu-agonists, but neither kappa- nor delta-agonists, produced the naloxone-reversible loss of righting reflex in infant rats. By employing the present in vivo method to estimate the mu-agonist activity of an opioid with mixed agonist activities, it was indicated that the mu-agonist activity of ethylketocyclazocine, which had been employed as a representative kappa-agonist, was essentially the same as that of morphine, a representative mu-agonist.

Animals↗
PubMed1995

Endothelin-1 and big endothelin-1 increase in human endometrium during menstruation.

OBJECTIVES: Although the physiologic and pathologic roles of endothelin-1 in reproduction have been investigated, little is known about human uterine tissue levels. We studied the levels of immunoreactive endothelin-1 and immunoreactive big endothelin-1 in human endometrium and myometrium during each menstrual phase. STUDY DESIGN: Materials were obtained at hysterectomy (endometrium, n = 33; myometrium, n = 27). We measured immunoreactive endothelin-1 and immunoreactive big endothelin-1 by radioimmunoassay and performed an immunohistochemical study of the tissue. Data were analyzed by the Mann-Whitney U test. RESULTS: We detected larger amounts of immunoreactive endothelin-1 and immunoreactive big endothelin-1 in the endometrium than in the myometrium throughout the menstrual, proliferative, and secretory phases. Endometrial immunoreactive endothelin-1 and immunoreactive endothelin-1 were significantly increased in the menstrual phase (endothelin-1 68.8 +/- 23.3 pg/mg protein, n = 5, p < 0.005; big endothelin-1 45.2 +/- 5.7 pg/mg protein, n = 5, p < 0.003) compared with the other phases (endothelin-1 30.7 +/- 9.5 and 30.5 +/- 14.0 pg/mg protein; big endothelin-1 19.9 +/- 6.7 and 24.1 +/- 7.4 pg/mg protein). Immunohistochemistry demonstrated that the endometrial stromal cells were positive for antiendothelin monoclonal antibody only in the premenstrual and menstrual phases. CONCLUSION: Levels of immunoreactive endothelin-1 and immunoreactive big endothelin-1 are different in each type of uterine tissue and in each phase of the menstrual cycle. These changes may indicate some role of endothelin-1 in menstruation.

Antibodies↗
PubMed1995

An immunohistochemical and ultrastructural study of vasomotor nerves in the microvasculature of human dental pulp.

Immunohistochemical methods for S-100 protein and neurone-specific enolase showed two types of nerve endings around the pulp microvasculature: the free endings, which comprise the major neural component and are distributed in all types of microvessel such as arterioles, venules and capillaries; and the varicose endings. The varicose ending was a less frequent, minor component observed only in the arterioles. Both immunohistochemical and ultrastructural observations confirmed that the varicose endings were the terminal axons of efferent vasomotor nerves. Further extensive ultrastructural examinations on the vasomotor nerves added the following new findings to our previous reports. Vasomotor nerves sometimes ramified into more than two terminal axons around arterioles, and most of these ramified axons ended in the adventitia-media junction of the arteriolar wall; however, nerve endings occasionally penetrated into the media. These findings suggest an intimate structural association between vasomotor nerves and arterioles in regulating the arteriolar microcirculation in human dental pulp by stimulating smooth-muscle cells not only of the outermost but also of the inner layers. Furthermore, the deep penetration of terminal axons into the arteriolar wall seems to provide effective regulation of pulpal blood flow under physiological and pathological conditions.

Adult↗
PubMed1995

Ultrastructural relation between nerve terminals and dentine bridge formation after pulpotomy in human teeth.

Close association between nerve terminals and preodontoblasts, odontoblasts and predentine was observed during healing after pulpotomy. The nerve terminals frequently contained large numbers of synaptic vesicles. Terminals with many vesicles tended to be fewer in the predentine than in the odontoblastic layer. The distribution of terminals was more dense at the stage before the regenerated odontoblasts became arranged regularly beneath the predentine. It is suggested that these terminals have some efferent role(s), especially during collagen synthesis at the early stage of dentinogenesis. The nerves may release their abundant synaptic vesicles, in addition to serving a sensory role for monitoring the increased sensitivity in the injured areas.

Dentin, Secondary↗