Search PubMed⌕ Search

Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Adrenomedullin and related peptides].

"Adrenomedullin (AM)" is a novel hypotensive peptide discovered in human pheochromocytoma by monitoring the elevating activity of platelet cAMP. It has potent and long-lasting vasodilator effects in several vascular systems. In addition, a novel 20-residue hypotensive peptide, termed "proadrenomedullin N-terminal 20 peptide" (PAMP), is processed from proadrenomedullin. Although initially isolated from human pheochromocytoma tissue and porcine adrenal medullae, AM mRNA is highly expressed in several organs including cardiovascular tissues. Taken together with its widespread distribution and its ability to influence the bioactivity of cells in situ, AM may function as a paracrine or autocrine hormone rather than a classical endocrine system. Furthermore, ubiquitous expression of AM mRNA may indicate its various biological functions as well as the existence of a novel circulation control system. Plasma AM as well as PAMP concentrations significantly increased in various cardiovascular diseases including hypertension, chronic renal failure and cognestive heart failure. The present review summarizes the recent advances in AM research and showed that AM and PAMP are important vasoactive peptides, such investigations should enable the elucidation of the basic physiologic mechanisms of novel circulatory homeostasis.

Adrenomedullin↗
PubMed1998

Effects of peptidase inhibitors on the enkephalin-induced anti-nociception in rats.

The intra-third-ventricular (i.t.v.) administration of [Met5]-enkephalin (enk) to rats pretreated i.t.v. with three peptidase inhibitors (PIs), amastatin, captopril and phosphoramidon, inhibited the tail-flick response. The enk-induced inhibition was augmented by increasing the doses of the three PIs, with the maximum inhibition being attained at the doses of 10 nmol each. The enk-induced inhibition in rats pretreated with any combination of two PIs, however, were markedly smaller than that in rats pretreated with all three PIs, indicating that three kinds of enzymes all played important roles in the inactivation of enk. The inhibitory effect of enk on the tail-flick response in rats pretreated with the three PIs at doses of 10 nmol each was approximately tenfold higher than that of morphine. The relative anti-nociceptive potencies of enk and morphine were similar to the relative inhibitory potencies obtained previously with the isolated guinea pig ileum pretreated with the three PIs, indicating that the hydrolysis of the i.t.v. administered enk was largely prevented by the three PIs. However, the magnitude of the enk-induced inhibition in rats pretreated s.c. with the three PIs indicated that the hydrolysis of enk injected i.t.v. was not largely prevented by the s.c. administration of three PIs at doses up to 10 micromol each/kg.

Animals↗
PubMed1998

Lipoxygenase-1 from soybean seed inhibiting the activity of pancreatic lipase.

There are some similar characteristics in protein nature between the lipase inhibitor from soybean seed and soybean lipoxygenase-1 (LOX-1). Thus, the inhibiting protein for pancreatic lipase was prepared from defatted soybean meal by the procedure for the isolation of LOX-1 [Axelrod et al., Methods in Enzymology, 71, 441-451 (1981)]. The LOX-1 from soybean seed dose-dependently inhibited the release of fatty acid from a soybean oil emulsion, and the concentration of LOX-1 to cause half inhibition of the lipase activity was 3.2 x 10(-7) M. The LOX-1 obtained from E. coli transfected with a plasmid carrying the soybean LOX-1 gene also inhibited the lipase activity. However, the lipase-inhibiting activity by the LOX-1 was not affected by the presence of nordihydroguaiaretic acid, an inhibitor for LOX, in the reaction mixture. These results show that the soybean LOX-1 inhibits lipase activity regardless of its lipoxygenase activity.

Chromatography, Gel↗
PubMed1998

Decrease in circulating and urine adrenomedullin concentrations in stroke-prone spontaneously hypertensive rats.

Adrenomedullin (AM) is a peptide with potent vasodilatory and hypotensive properties. Plasma AM levels in rats with experimentally induced hypertension, such as Dahl salt-sensitive rats and two-kidney, one-clip hypertensive rats, are higher than those in normotensive rats. We previously noted, however, that plasma AM levels in spontaneously hypertensive rats (SHR) are similar to those in Wistar-Kyoto rats. To define the role of AM in rats with severe hypertension, we investigated changes in circulating and tissue AM levels in stroke-prone spontaneously hypertensive rats (SHRSP/Izm). The immunoreactive rat AM levels in plasma, urine, and tissue measured with a sensitive radioimmunoassay, and the AM mRNA levels in various tissues in 15-wk-old SHRSP/Izm were compared with those in age-matched Wistar-Kyoto rats (WKY/Izm). The plasma and urinary AM levels in SHRSP/Izm were significantly lower than those in WKY/Izm [plasma AM, 2.14+/-0.06 (SE) vs. 3.24+/-0.16 fmol/ml, p< 0.001; urinary AM, 16.36+/-3.21 vs. 36.12+/-6.09 fmol/ml, p< 0.01]. A negative correlation was found between the plasma AM level and the systolic blood pressure in both SHRSP/Izm and WKY/Izm. Reverse-phase high-performance liquid chromatography showed that the molecular components of plasma immunoreactive AM in SHRSP/Izm were similar to those in WKY/Izm. Furthermore, tissue AM levels in various organs in SHRSP/Izm were not lower than those in WKY/Izm. In conclusion, low levels of circulating AM may contribute to the maintenance of high blood pressure in 15-wk-old SHRSP/Izm. These low plasma AM levels may be caused by accelerated metabolism of circulating AM in SHRSP/Izm.

Adrenomedullin↗
PubMed1998

Responses of trabecular and cortical bone turnover and bone mass and strength to bisphosphonate YH529 in ovariohysterectomized beagles with calcium restriction.

Thirty-six beagles, 18 months of age, underwent ovariohysterectomy (OHX) or a sham operation. Sham-operated animals were given a diet with standard calcium (1.4%) (group 1, n = 6) or a restricted calcium diet (0.14%) (group 2, n = 6). The OHX animals were given the restricted calcium diet and YH529 orally with respective daily doses of 0, 0.02, 0.1, and 0.5 mg/kg of body weight (groups 3-6, n = 6 each) for 12 months. At the end of this period, the lumbar bone mineral densities (BMDs) in groups 2 and 3 and the load values for group 3 were significantly smaller than those for group 1. The midfemur BMD did not differ among the groups. The urinary deoxypyridinoline (U-Dpy) and bone formation rates (BFR/BS, BFR/BV) in groups 2 and 3 and the osteonal BFR/BS and trabecular osteoclast number (Oc.N/BS) in group 3 were significantly larger than the respective values for group 1. However, these parameters did not significantly differ between groups 2 and 3. The serum osteocalcin (OC) level, wall thickness (W.Th), and mineral apposition rate values for group 3 were significantly larger than those for group 2. In group 2, the trabecular activation frequency (Ac.F) increased by 3.11 times, and the percent values of the number of labeled osteons (L-Ot.N/T-Ot.N, %) in the tibia by 3.28 times over those for group 1. In group 3, the Ac.F increased by 3.20 times and the number of labeled osteons by 3.77 times over those for group 1. In groups 4-6, the U-Dpy and Oc.N/BS values were smaller, but their OC levels did not significantly differ from the level for group 3. The lumbar BMD, the load, and W.Th were dose-dependently significantly larger than those for group 3. The Ac.F values were significantly smaller, and the respective value in groups 4-6 was 67.9, 25.5, and 10.2% of that in group 3. The BMDs of the midfemur in groups 4-6 were significantly larger than those in group 3, but the ultimate load values did not significantly differ. The L-Ot.N/T-Ot.N values were also significantly smaller, and the respective value in groups 4-6 was 82.0, 48.5, and 55.2% of that in group 3. The tibial endocortical and periosteal BFR/BSs did not differ significantly. These data demonstrate that the effects of OHX on bone mass and turnover were small in the beagles fed a restricted calcium diet. YH529 maintained the mass and strength of the lumbar bone by reducing the bone resorption. The cortical bone appeared to be less sensitive to the agent than the trabecular bone in this animal model.

Administration, Oral↗
PubMed1998

Plasma adrenomedullin levels in patients with non-insulin dependent diabetes mellitus: close relationships with diabetic complications.

The present study was undertaken to determine plasma adrenomedullin levels in patients with non-insulin dependent diabetes mellitus (NIDDM) to elucidate the potential involvement in the pathogenesis of diabetic complications. The patients were 24 males and 21 females with ages of 55 +/- 2.1 years (mean +/- SEM). Plasma adrenomedullin levels were 5.94 +/- 0.44 pmol/l in patients with NIDDM, and were not affected by plasma glucose concentration. The plasma adrenomedullin increased dependent on the severity of diabetic nephropathy and retinopathy. Plasma levels of adrenomedullin positively correlated with various parameters, including serum creatinine levels, urinary excretion of protein, and systolic blood pressure. In contrast, there were negative correlations between the coefficient variation (CV) of RR intervals and plasma adrenomedullin, and between the conduction velocity of ulnar nerves and plasma adrenomedullin levels. These results indicate that the increase in plasma adrenomedullin was closely related to diabetic complications, which may be dependent on the development of microangiopathy.

Adrenomedullin↗
PubMed1998

Dissociation of adrenomedullin concentrations in plasma and cerebrospinal fluid in pregnant and non-pregnant women.

Adrenomedullin (AM), a potent vasodilator peptide, has been shown to act within the central nervous system to modulate fluid and electrolyte balance. AM-immunoreactive cells have been found in the anterior pituitary gland and the choroid plexus of humans. In addition, AM activity has been implicated in the regulation of maternal circulation during pregnancy. To determine the relationship between AM concentration in the cerebrospinal fluid (CSF) and plasma, we measured AM levels in CSF and plasma of pregnant (group P, n = 12) and non-pregnant (group NP, n = 10) women scheduled to undergo gynecologic or obstetric surgery. In both groups, the concentration of AM in the plasma exceeded that in the CSF. Plasma AM concentration was significantly higher in pregnant than non-pregnant women (17.3+/-5.8 vs 5.1+/-1.4 pmol/l, mean +/- S.D.; P<0.01), whereas CSF AM concentration did not differ between the two groups (1.3+/-0.9 and 0.9+/-0.4 pmol/l in groups P and NP respectively). No significant correlation was found between AM concentrations in the CSF and plasma. The present findings suggest that AM is present in the CSF and that its concentration in the CSF is regulated independently from that in the plasma.

Adrenomedullin↗
PubMed1998

Improvement of a mouse feeder for chemical toxicology testing.

A mouse feeder in common use in the US was modified to eliminate spillage, contamination by excreta and formation of food aggregates. The improved feeder consists of a glass jar which holds 100 g of meal-type feed, an inner metal mesh tube, a marble placed inside the inner mesh tube, and a snap-on metal lid. Female mice [B6C3F1 and CD-1(ICR)] were housed 5 animals/cage. Only slight contamination by feces, but not by urine, was observed in a 13-week feeding study with Japanese meal-type food and the improved feeder. Food spillage also decreased. Food consumption was significantly higher in cages with the conventional Japanese feeder than in the improved one, but no difference was observed between the two feeders in body weight gain.

Animal Feed↗
PubMed1998

Role of endothelium and adventitia on eugenol-induced relaxation of rabbit ear artery precontracted by histamine.

Eugenol (> or = 0.1 mM) inhibited the contractions induced by various stimulants, such as 90 mM extracellular K+ solution ([K+]0), histamine and noradrenaline in the rabbit ear artery. Inhibitory actions of eugenol occurred in a concentration-dependent manner, however, eugenol more dominantly inhibited the histamine-induced contraction than those induced by either 90 mM [K+]0 solution or noradrenaline. Removal of both endothelium and adventitia did not change the inhibitory actions of eugenol on the 90 mM [K+]0- and noradrenaline-induced contractions, however, attenuated those on the histamine-induced contraction. Chlorphenylamine abolished the histamine-induced contraction, but neither cimetidine, ranitidine nor thioperamide modified the eugenol actions on the contractions induced by histamine. Pretreatment with nitric oxide syntheses inhibitor NG-nitro-L-arginine (LNNA; 100 microM), but not soluble guanylate cyclase inhibitor methylene blue (MB; 10 microM), prevented endothelium/adventitia-dependent augmentation of the eugenol-induced relaxation on the histamine-induced contraction. When an intact tissue, but not an endothelium/adventitia-denuded tissue, was placed at the up-stream close to the other denuded preparation (test preparation), histamine-induced contraction observed in the test preparation tended to be augmented. Similarly, eugenol-induced relaxation was also augmented by the same treatment. Eugenol (0.3 mM) inhibited the excitatory junction potentials (EJPs) without hyperpolarization of the membrane. However, a high concentration of eugenol (1 mM) slightly hyperpolarized the membrane (ca. 5 mV). No transient enhancement of amplitude of EJP was recorded. These results suggest that eugenol may inhibit the histamine-induced muscle contraction directly, and the inhibition is augmented by the adventitia and endothelium partly by vasoactive substances, which were released from the adventitia/endothelium-derived substances in rabbit ear artery.

Animals↗
PubMed1998

Simultaneous activation of Ca(2+)-dependent K+ and Cl- currents by various forms of stimulation in the membrane of smooth muscle cells from the rabbit basilar artery.

In smooth muscle cells isolated from cerebral blood vessels, histamine activates Cl- channels through an elevation of intracellular Ca2+. We investigated whether Cl- currents were also evoked by adenosine triphosphate (ATP) or caffeine in isolated smooth muscle cells from the rabbit basilar artery using the perforated patch-clamp technique. Bath application of 10 microM ATP or 1 mM caffeine (holding potential -60 mV) activated transient inward currents. With prolonged bath application of 10 microM ATP or 1 mM caffeine, oscillatory inward current were sporadically generated. At a holding potential of -40 mV, transient Cl- currents were induced by 10 microM histamine, 10 microM ATP, and 1 mM caffeine, following activation of a K+ current. At -10 or -20 mV, histamine predominantly activated the K+ current. A repetitively activated outward current was induced by membrane depolarization. These results suggest that oscillations in intracellular Ca2+ induced by histamine, ATP, and caffeine caused Cl(-)-current activation at the resting membrane potential. This Cl- current may depolarize the membrane and, thus activate voltage-dependent currents, including a Ca(2+)-dependent K+ current. Both the Ca(2+)-dependent K+ and Cl- currents induced by various stimuli may contribute to the modulation of Ca2+ influx by reinforcing membrane depolarization.

Adenosine Triphosphate↗
PubMed1998

Mp colorectal cancer should be defined as early colorectal cancer.

Little is known about the clinicopathologic features of mp colorectal cancer, defined as a cancer where the depth of invasion is limited to within the mucosa, the submucosa and the proper muscle. This study was designed to determine the clinicopathologic features of mp colorectal cancers. From 1973 to 1993, 83 mp colorectal cancer and 66 sm colorectal cancer patients were treated in our department and were enrolled in this study. During the same period, 66 patients with sm colorectal cancer defined as a cancer where the depth of invasion is limited to within the mucosa and the submucosa, were treated. The clinicopathologic findings of these patients were determined retrospectively from their hospital records. Clinicopathologic differences in sm and mp colorectal cancers were compared with sm and mp gastric cancers. The incidence of mp colorectal cancer increased from 7.9% in 1973-1977 to 16.2% in 1988-1993. An advanced macroscopic appearance, a larger tumor size, lymph node metastasis and lymph vessel invasion were more predominant in mp than sm colorectal cancer. Multivariate analysis demonstrated that these clinicopathologic factors were not statistically independent prognostic factors for mp colorectal cancer patients. There was no statistical difference in postoperative survival between sm and mp colorectal cancer patients. Mp colorectal cancer should be defined as early colorectal cancer, because the postoperative survival rate does not differ between mp and sm colorectal cancers, and the clinicopathologic differences between these two are negligible.

Colorectal Neoplasms↗
PubMed1998

Disturbance of consciousness associated with hypophosphatemia in a chronically alcoholic patient.

A 69-year-old man with chronic alcoholism was admitted to our hospital due to disturbance of consciousness and oliguria. Emergency laboratory examination revealed metabolic acidosis, hypoglycemia, hyponatremia, mild liver dysfunction, acute renal failure and rhabdomyolysis. After administration of fluids and nutrients and continuous hemodiafiltration, he recovered from all signs and symptoms except for disturbance of consciousness after 7 days. Since severe hypophosphatemia persisted, we administered adequate phosphates, and then his level of consciousness normalized. We discuss the relationships among alcohol abuse, hypophosphatemia and disturbance of consciousness, and recommend that hypophosphatemia be considered a potential cause of disturbance of consciousness in alcoholic patients.

Acidosis↗
PubMed1998

[Topical treatment of onychomycosis by occlusive dressing using bifonazole cream containing 40% urea].

Topical treatment with an antifungal agent was performed in 70 cases of onychomycosis (69 cases of tinea unguium and 1 case of Candida onychomycosis). The patients were treated every night by occlusive dressing using bifonazole cream containing 40% urea, and then by simple application of 1% bifonazole solution in the morning. During the treatment period, the softened affected nails were removed as completely as possible with nail clippers and files. The nails were observed every two weeks, and the efficacy was evaluated after 12 weeks. Two cases were excluded and 28 cases dropped out leaving 40 cases for efficacy evaluation. Among the 40 patients, 20 appeared to be mycologically negative (mycological cure rate: 50.0%). Clinical response was judged by the changes in opacity and thickness of the nails. Nine patients were evaluated as showing "marked improvement" and 16 as showing "improvement" (improvement rate: 62.5%). Erosion was noted as an adverse reaction in 2 patients. In one patient, treatment was stopped and the lesion was improved by antibiotic ointment, and in another, treatment was resumed when erosion was cured by discontinuation of the treatment. These results suggest that the topical treatment of onychomycosis by occlusive dressing is a useful method for those patients who have difficulties in or do not wish to be treated with oral antifungal agents.

Administration, Topical↗
PubMed1998

[Prefectural health administration's view on otorhinolaryngological care in medical rural areas].

In a previous study, we investigated otorhinolaryngological care by the general practitioners in medical rural areas and demonstrated that a close relationship between general practitioners and otorhinolaryngologists was necessary. In the present study, a survey of prefectural health administration's views on otorhinolaryngological care in medical rural areas was performed. A questionnaire for otorhinolaryngological care in medical rural areas was sent to the divisions of health administration in the 47 prefectures of Japan. Of these prefectures, 46 (97.9%) responded. About 80% of respondents have medical rural areas, and the otorhinolaryngological care is inadequate in most areas. General practitioners of internal medicine or surgery are primarily demanded in about 75% of the prefectures. Otorhinolaryngological care in medical rural areas has never been considered in most prefectures. Because the need for otorhinolaryngological medical care will increase, prefectural health administrations need to pay more attention to otorhinolaryngological care in medical rural areas, and a close relationship between general practitioners, otorhinolaryngologists, and the administration should be established.

Community Health Services↗
PubMed1998

[Mediastinal neurilemmoma originating in the right phrenic nerve: a case report].

We report on a 31-year-old man with a mediastinal neurilemmoma originating in the right phrenic nerve. The patient was admitted because of abnormal chest X-ray shadows observed during a routine checkup. A preoperative diagnosis of bronchial cyst in the mediastinum was made. The tumor was resected by video-assisted thoracic surgery. It was 3 x 4 x 3 cm in size, weighted 15 g, and originated in the right phrenic nerve. The histopathologic diagnosis was mediastinal neurilemmoma. Only 14 cases have been reported in the Japanese literature.

Adult↗
PubMed1998

[Application of monoclonal antibody for drug delivery system--missile therapy for cancer].

Clinical applications of monoclonal antibody for selective delivery of anticancer drug, toxin and radioisotope were reviewed. The difficulties in preparation and clinical application of chemoimmunoconjugate were pointed out. Also the difficulties of immunotoxin in clinical trial due to its high toxicity had been discussed and it is assumed that development of blocked ricin may overcome many problems related to toxicities. Clinically most advanced immunoconjugate seems to be radioimmunoconjugate. Among three types of immunoconjugates preparation of radioimmunoconjugate is easiest and some promising clinical trials were introduced in this review.

Animals↗
PubMed1998

Activation of protein phosphatase 1alpha promoter in ascites hepatoma cells.

We have already reported the nucleotide sequence of 5'-flanking region of rat PP1alpha gene and identified the promoter region in NIH3T3 cells. Here we determined the promoter activity of PP1alpha gene in ascites hepatoma cells and compared with that of hepatocytes. Reporter analysis showed that the promoter activity was enhanced in an ascites hepatoma AH13 compared with normal hepatocytes at two regions, -37 to -198 bp and -492 to -848 bp upstream of the translation start site. At -37 to -198 bp region with high GC content, binding of Sp1 was markedly increased in all of five ascites hepatomas examined. At -492 to -848 bp region, two bands were clearly detected in two of the five ascites hepatomas, AH13 and AH7974F, by gel shift analysis. These results strongly suggest that the increase in PP1alpha mRNA expression in ascites hepatomas is at least in part due to the enhanced promoter activity of PP1alpha gene.

Animals↗