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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 73 records · Page 4Linked to original sources

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

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

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

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

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

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

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

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

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

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

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

Stimulatory effect of angiotensin II on calcium efflux from cultured bovine adrenal chromaffin cells.

The effect of angiotensin II on Ca2+ mobilization in cultured bovine adrenal chromaffin cells was examined. Angiotensin II (10(-7)M) increased the intracellular free Ca2+ level ([Ca2+]i) to a peak in the presence or absence of extracellular Ca2+, followed by decrease with time. Angiotensin II (10(-9)-10(-6)M) also stimulated 45Ca2+ efflux from cultured bovine adrenal chromaffin cells in a concentration-dependent manner. Its stimulatory effect on 45Ca2+ efflux was inhibited by the angiotensin II antagonist [Sar1, Ile8]-angiotensin II or [Sar1, Val5, Ala8]-angiotensin II. The increase in angiotensin II-stimulated 45Ca2+ efflux was dependent on the extracellular Na+ concentration. Angiotensin II also increased 22Na+ influx into the cells. These results indicate that stimulation of the angiotensin II receptor induces extracellular Na(+)-dependent Ca2+ efflux from cultured bovine adrenal chromaffin cells, probably by acceleration of Na+/Ca2+ exchange.

Adrenal Medulla

Calcium efflux from cultured bovine adrenal chromaffin cells induced by pituitary adenylate cyclase-activating polypeptide (PACAP): possible involvement of an Na+/Ca2+ exchange mechanism.

The effect of pituitary adenylate cyclase-activating polypeptide 1-38 (PACAP1-38) on Ca2+ efflux from cultured bovine adrenal chromaffin cells was examined. PACAP1-38 stimulated the efflux of 45Ca2+ from the cells in a concentration dependent manner (10(-9)-10(-7)M). This effect was inhibited by its potent receptor antagonist PACAP6-38. PACAP1-38 increased the formation of [3H]inositol phosphates and cyclic AMP in the cells. Forskolin, an activator of adenylate cyclase, also stimulated the efflux of 45Ca2+ from the cells. 3-Isobutyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterase, enhanced PACAP1-38-induced 45Ca2+ efflux from the cells. Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, had no effect on the efflux of 45Ca2+ from the cells. The increases in 45Ca2+ efflux induced by PACAP1-38 and forskolin were reduced by deprivation of extracellular Na+ and the Na+/Ca2+ exchange inhibitor amiloride. In addition, PACAP1-38 stimulated 22Na+ influx into the cells, and this action was inhibited by amiloride. These results suggest that PACAP1-38 stimulates an Na+/Ca2+ exchange mechanism through activation of adenylate cyclase in cultured bovine adrenal chromaffin cells.

1-Methyl-3-isobutylxanthine

Augmented adrenomedullin concentrations in right ventricle and plasma of experimental pulmonary hypertension.

Adrenomedullin is a strong vasorelaxing peptide discovered in pheochromocytoma tissue. Monocrotaline, a pyrrolizidine alkaloid derived from Crotalaria spectabilis, is known to cause pulmonary hypertension. To test the hypothesis that adrenomedullin plays a role similar to that of atrial natriuretic peptide or brain natriuretic peptide in modulating right ventricular responses to pulmonary hypertension, we have compared concentrations of immunoreactive rat adrenomedullin and adrenomedullin messenger RNA levels in tissues of monocrotaline treated rats with those of control rats. We also measured the effect of pulmonary hypertension on plasma level of the peptide. The concentrations of adrenomedullin immunoreactivity in right ventricle and plasma were significantly higher in monocrotaline treated rats than in control rats. The messenger RNA level of adrenomedullin in right ventricle was also higher in monocrotaline treated rats than in control rats. These results suggest that adrenomedullin participates in the mechanism to counteract the high blood pressure in pulmonary circulation.

Adrenomedullin

The incidence of internal malignancies in pemphigus and bullous pemphigoid in Japan.

To evaluate the significance of the association of malignancy with autoimmune blistering diseases, we studied the incidence of internal malignancies in pemphigus and bullous pemphigoid based upon 496 cases of pemphigus and 1113 cases of bullous pemphigoid in Japan. Results showed that (1) an association between internal malignancies and pemphigus was observed in 25 out of 496 cases (5.0%), while that with bullous pemphigoid was seen in 64 out of 1113 cases (5.8%). Such association ratios were significantly higher than that of the controls aged over 70 years old (0.61%); (2) The average ages of pemphigus/bullous pemphigoid with malignancy were 64.7 and 69.2 years, respectively. The association ratio of malignancy with pemphigus increased by age, while that with pemphigoid was not correlated with aging; (3) Lung cancer was most common in pemphigus and gastric cancer in bullous pemphigoid; (4) There were no significant differences in the titers of circulating antibody, the presence or extent of mucous involvement or annular erythema between bullous pemphigoid patients with malignancy and without malignancy. Our results indicated that detailed examination for internal malignancy is essential for those patients with pemphigus or bullous pemphigoid.

Aged

The effect of intravenous and intra-tumoural chemotherapy using a monoclonal antibody-drug conjugate in a xenograft model of pancreatic cancer.

In order to investigate the efficacy of the intra-tumoural administration of an anticancer drug-monoclonal antibody conjugate in athymic nude mice bearing xenografts of a human pancreatic carcinoma, we examined the clearance of the murine monoclonal antibody A7 from the xenografts after intravenous or intra-tumoural administration and measured the antitumour effect of neocarzinostatin conjugated to MAb A7 following intravenous or intra-tumoural injection. Compared with 125I-labelled normal mouse IgG, a larger amount of 125I-labelled A7 remained in the tumour after both intravenous and intra-tumoural injection, and a significantly larger amount of 125I-labelled A7 remained in the tumour after intra-tumoural injection than that after intravenous injection. Moreover, a larger amount of 125I-labelled A7-NCS localized in the tumour after intra-tumoural injection than that after intravenous injection. Neocarzinostatin conjugated to MAb A7 showed greater activity against human pancreatic cancer than neocarzinostatin alone after both intravenous and intra-tumoural administration. Tumour growth was suppressed completely by the intra-tumoural administration of A7-NCS at a dose that did not suppress tumour growth via the intravenous route. These observations suggest that the intra-tumoural injection of neocarzinostatin conjugated to MAb A7 offers promise in treating pancreatic carcinoma.

Adenocarcinoma

Induction of bone resorbing-activity by mouse stromal cell line, MC3T3-G2/PA6.

Unfractionated mouse long-bone cells prestimulated with rat parathyroid hormone (PTH) for 7 days (PTH-prestimulated long-bone cells; PTH-psLB cells) contained about 20% tartrate-resistant acid phosphatase (TRAP)-positive mononuclear cells and about 0.2% TRAP-positive multinucleate cells. When PTH-psLB cells (1.0 x 10(5)/slice) were cultured on dentine slices, about 100 resorption lacunae (pits) per slice were formed by 6 h after the start of culture, while the number of TRAP-positive multinucleate cells on the dentine slices did not increase. When the number of inoculated cells was plotted versus the number of pits formed during the 6-h cultivation, a sigmoid curve was generated. When PTH-psLB cells (1.0 x 10(3)/slice) were cocultured with various mouse stromal cell lines, the MC3T3-G2/PA6 line was found to increase the number of pits. Since this activity was manifested within a short period of time (4 h), and as there was no change in the number of TRAP-positive multinucleate cells, we postulate that the activity of MC3T3-G2/PA6 is exerted on mature osteoclastic cells capable of resorbing bone rather than on some differentiation step of the osteoclast cell lineage. With respect to the mechanism of expression of this activity, it is unlikely that MC3T3-G2/PA6 produces a soluble factor, because no activity was seen when MC3T3-G2/PA6 and PTH-psLB cells were cultured separately across a membrane in a Transwell. These results suggest that cell-to-cell contact and communication between PTH-psLB cells and MC3T3-G2/PA6 may be a crucial event for the stimulation of osteoclastic bone resorption by MC3T3-G2/PA6.

Animals