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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 379 records · Page 21Linked to original sources

Chronologic changes in the clinicopathologic findings and survival of gastric cancer patients.

PURPOSE: To determine the chronologic changes in the clinicopathologic features of gastric cancer patients. PATIENTS AND METHODS: The clinicopathologic findings of 1,795 patients with gastric cancer were examined retrospectively from hospital records obtained between 1969 and 1995. The patients were divided into three generations on the basis of chronologic order. The first generation included patients treated over the period 1969 to 1977; the second generation, 1978 to 1986; and the third generation, 1987 to 1995. RESULTS: The chronologic changes in the clinicopathologic findings for all gastric cancers included increases in the superficial type based on macroscopic appearance (P < .005), small-sized tumor (P < .025), superficial depth of invasion (P < .005), and earlier histologic stages (P < .005), in addition to a decrease in lymph node metastasis (P < .005). Overall, the postoperative survival rate has improved over time in gastric cancer patients, with 5-year survival rates of 36.0%, 53.3%, and 68.6% in the first, second, and third generations, respectively. In stages 1,2, and 3, the survival rate in the third generation was the highest of the three generations, whereas in stage 4, the survival rate did not differ between the three generations. Patients who underwent a D2 dissection showed a higher survival rate than those with D1 or D3 dissections, but there was no statistical difference in the survival of patients with D1, D2, and D3 dissections when stage 4 patients were excluded. CONCLUSION: The chronologic changes in gastric cancer patients over the past 27 years have included an increase in the incidence of earlier-staged gastric cancers, which has had a significant impact on the improved postoperative survival rate.

Adult↗

Bone resorption inhibitors from hop extract.

We searched hop extract for active component(s) that inhibited bone resorption in the pit formation assay, and isolated xanthohumol and humulone as active ingredients. Especially humulone had extraordinarily strong inhibitory activity and the IC50 (concentration of 50% inhibition) value was 5.9 x 10(-9)M.

Bone Resorption↗

Changes in cardiac adrenomedullin concentration in renovascular hypertensive rats.

We assessed changes in tissue and plasma adrenomedullin levels in two-kidney, one-clip renovascular hypertensive rats. Four weeks after clipping, adrenomedullin concentrations were significantly higher in the cardiac ventricles and lower in the left atrium than the respective values in sham-operated rats. The left ventricular adrenomedullin concentration significantly correlated with systolic blood pressure and the degree of cardiac hypertrophy. No difference was noted in the adrenomedullin concentrations of the adrenal gland, aorta, lung, kidneys, or plasma between the two groups. These findings indicate possible involvement of cardiac adrenomedullin in this model of hypertension.

Adrenomedullin↗

Inhibition of nitric oxide synthase activity and nitric oxide-dependent calcium influx in renal epithelial cells by cyclic adenosine monophosphate: implications for cell injury.

Cell injury frequently occurs in the setting of tissue destruction and inflammation and is associated with a rise in intracellular calcium (Cai) and increased NO production. The mechanisms that trigger rises in Cai and NO during cell injury are not fully defined, but they may involve activation of G protein-coupled receptors for substances such as bradykinin, Ang II, thromboxane, and thrombin. These receptors act through G proteins from different families that have distinct functions. Receptors for bradykinin and Ang II act through members of the G alpha i and G alpha q families, whereas receptors for thrombin and thromboxane act through members of the G alpha i, G alpha q, and G alpha 12/13 families. These G proteins cooperate to regulate Cai and NO in epithelial cells through distinct mechanisms. In a number of experimental settings, activators of the adenylyl cyclase system reduce the severity of cell injury. To understand the mechanisms by which G protein-dependent signaling systems may contribute to cell injury and to define the role of adenylyl cyclase in ameliorating cell injury, the effects of adenylyl cyclase on bradykinin-stimulated Ca influx and NO in cultured renal epithelial cells that stably overexpress G alpha q and G alpha 13 were studied. This system allowed for the separation of different components of the signals initiated by receptors for thromboxane and thrombin. G alpha 13 increased bradykinin-stimulated Ca influx by a mechanism that depends on NO and cGMP. The increased Ca influx was blocked by inhibitors of NO synthase and guanylyl cyclase and by activation of adenylyl cyclase. NO production was inhibited by activators of cAMP-dependent protein kinase, which indicated that cAMP blocks Ca influx by inhibiting NO production. Expression of G alpha q, the G protein that regulates phospholipase C, also increased bradykinin-stimulated Ca influx, but by an NO, cGMP-independent mechanism that was insensitive to inhibition by adenylyl cyclase. The authors conclude that Ca influx is modulated by NO-dependent and independent mechanisms, and that to the extent that increased NO production contributes to increased Ca influx and cell injury, cell injury may be reduced by agents that activate adenylyl cyclase.

Adenylyl Cyclases↗

Different secretion patterns of adrenomedullin, brain natriuretic peptide, and atrial natriuretic peptide during exercise in hypertensive and normotensive subjects.

The purpose of this study was to investigate the effect of exercise on plasma concentrations of adrenomedullin, brain natriuretic peptide (BNP), and atrial natriuretic peptide (ANP) in patients with essential hypertension (n = 15) and in normotensive controls (n = 10). Exercise consisted of two fixed workloads, 40 and 80 watts of work load using a supine bicycle ergometer. Plasma levels of all three peptides at rest were significantly higher in hypertensives than in controls. Plasma concentrations of ANP increased with exercise in both groups and had greater increments in hypertensive patients than in normotensives. Plasma concentrations of BNP increased only in patients with hypertension and the levels of increase correlated with basal plasma BNP levels (r = 0.94, p < 0.001) and with left ventricular mass (r = 0.62, p < 0.01) determined by echocardiography. In contrast, plasma adrenomedullin did not change with exercise in either group. These results suggest that secretion patterns of these peptides are regulated by different mechanisms and that the amount and kind of peptides mobilized by exercise may depend on the underlying diseases or pathophysiologic condition.

Adrenomedullin↗

[A pilot study of mass screening program for prostatic cancer by means of prostate specific antigen (PSA) filter paper method].

BACKGROUND: Mass screening program for prostatic cancer (PC) using prostate specific antigen (PSA) filter paper method was performed in an urban area of Kyoto in 1995. METHODS: In the primary study, males more than the age of 55 years were examined by PSA (Delfia PSA kit) with blood samples on a filter paper. The cut-off values were set at 4 and 10 ng/ ml. Subjects whose PSA level ranged from 4.1 to 10.0 ng/ml (gray zone) were examined by digital rectal examination (DRE), transrectal sonography (TRS) and PSA density (PSAD; more than 0.15) in the secondary study, then the suspected subjects of PC underwent 6 sextant biopsies under interventional ultrasound. Subjects whose PSA level were more than 10.1 ng/ml were biopsied directly. RESULTS: Of 3,749 males who took the annual health checkup system organized by the government, 2,387 males wished to submit this screening. Among them, 2,217 (92.9%) showed a negative PSA, 107 belonged to the gray zone and 43 had a PSA more than 10.1 ng/ml. Of these, 102 subjects underwent biopsy. PC was finally detected in 28 (1.2%). The positive predictive value for positive PSA and gray zone PSA was 46.3% and 8.4%, respectively. In the detected cancers, 17 cases (60.7%) belonged to Stage B, 5 (17.9%) to Stage C and 6 (21.4%) to Stage D. CONCLUSION: The results suggested that this system of mass screening program for PC combined with the annual health checkup was suitable for the future "national-level" screening.

Aged↗

Gene expressions and activities of protein phosphatases 1 alpha, 2A and 2C in hepatocarcinogenesis and regeneration after partial hepatectomy.

The mRNA levels of protein phosphatases (PP) 1 alpha, 2A, and 2C were determined both in hepatocarcinogenesis and in liver regeneration. In the precancerous stage and during regeneration, the mRNA levels of PP1 alpha, PP2A, and PP2C were markedly increased compared with those in normal livers. In primary hepatomas, all three of these mRNA levels were decreased to the control levels. In poorly differentiated hepatomas, however, only PP1 alpha mRNA was specifically increased, in contrast to PP2A and PP2C, which were at the control levels or below. While PP1 activity in the non-nuclear fraction of partially hepatectomized livers was nearly constant, the activity in nuclei was increased about 2.5-fold over control levels at 12 h after partial hepatectomy, the time that corresponds to the G1 to S transition in the cell cycle of hepatocytes. On the other hand, PP2A activity in both fractions was nearly constant throughout. These results appear to suggest some involvement of protein phosphatases in regulation of hepatocyte proliferation.

3T3 Cells↗

Effect of cilnidipine, a novel dihydropyridine Ca++-channel antagonist, on N-type Ca++ channel in rat dorsal root ganglion neurons.

We investigated the effects of cilnidipine, a dihydropyridine derivative, on neuronal Ca++ channels in rat dorsal root ganglion neurons. Voltage-dependent Ca++-channel currents were recorded, using 5 mM Ba++ as the charge carrier, by means of the whole-cell patch-clamp technique. The Ba++ current was subdivided pharmacologically into calciseptine-sensitive (L-type), omega-conotoxin GVIA- (omegaCgTx) sensitive (N-type), omega-agatoxin IVA- (omegaAgTx) sensitive (P/Q-type) and toxin-resistant currents. Cilnidipine inhibited the L-type current with an IC50 of 100 nM in neurons pretreated with omegaCgTx plus omegaAgTx. In neurons pretreated with Cal plus omegaAgTx, cilnidipine induced a potent inhibition of the N-type current, but was unable to block the residual Ba++ current. The IC50 for cilnidipine in respect of the N-type current was 200 nM. Cilnidipine (300-500 nM) modified neither the voltage-dependent inactivation curve nor the decay of the N-type current. Furthermore, elevation of the holding potential did not enhance the inhibitory action of cilnidipine (300 nM) on the N-type current. No effect was induced by 100 nM cilnidipine on the P/Q-type current. However, nicardipine (1 microM) barely inhibited the N-type current at a concentration that almost completely blocked the L-type current. In conclusion, cilnidipine has potent inhibitory actions on N-type as well as L-type voltage-dependent Ca++-channel in rat dorsal root ganglion neurons. The former action may bestow an additional clinical advantage for the treatment of hypertension, such as suppression of reflex tachycardia.

Animals↗

[Pharmacokinetic and clinical evaluation of azithromycin in the pediatric field].

35 children between 9 months and 12 years of ages were given 9.1 to 12.2 mg/kg of azithromycin (AZM) once a day for 3 days. In the treatment of pediatric infectious diseases, we studied pharmacokinetics, efficacy and safetiness of AZM. After administration of 10 mg/kg/day of AZM for 3 days, the elimination half-life was calculated to be 3.8 +/- 16.3 hours (n = 6, mean +/- S.D.). The excretion rate of AZM in the urine within 120 hours of administration was 9.0 +/- 2.3% (n = 5). For the evaluation of efficacy of AZM, we treated 33 cases of children with pharyngotonsillitis, bronchitis, mycoplasma bronchitis, pneumonia, mycoplasma pneumonia, atypical pneumonia, and SSTI. The efficacy rate of these cases were 93.9%. 6 strains of bacteria were identified as causative agents. All strains were eradicated upon the treatment. One case of elevated GOT and GPT and two cases of elevated GPT were observed. No clinical adverse reactions were observed. In conclusion, AZM was useful for the treatment of pediatric infectious diseases were examined.

Anti-Bacterial Agents↗

[Continuous infusion high-dose leucovorin with cisplatin and 5-fluorouracil for a recurrent oropharynx carcinoma].

Cisplatin and leucovorin heighten the activity of 5-fluorouracil by increasing the intracellular concentration of reduced folates. Therefore, we treated the recurrent oropharynx carcinoma case, who had received concurrent chemotherapy with low-dose cisplatin and radiotherapy, with continuous infusion high-dose leucovorin with cisplatin and 5-fluorouracil. Chemotherapy included continuous intravenous infusion of cisplatin (25 mg/m2, days 1 through 5); 5-fluorouracil (600 mg/m2, days 2 through 6); and leucovorin (200 mg/m2, days 1 through 6) administered once about every 4 weeks. Three cycles were performed, and a complete response was achieved. Grade 3 to 4 mucositis, nausea-vomiting, anemia, neutropenia, and thrombocytopenia occurred. Continuous infusion high-dose leucovorin with cisplatin and 5-fluorouracil was effective for this recurrent head and neck carcinoma. However, one must be cautious when comparing this chemotherapy in terms of toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

Almost complete protection from [Met5]-enkephalin-Arg6-Gly7-Leu8 (Met-enk-RGL) hydrolysis in membrane preparations by the combination of amastatin, captopril and phosphoramidon.

The contents of [Met5]-enkephalin-Arg6-Gly7-Leu8 (met-enk-RGL) and its seven hydrolysis products-Y, YG, YGG, YGGF, YGGFM, YGGFMR, and YGGFMRG-were estimated after incubating met-enk-RGL with a membrane fraction from either guinea pig ileum or striatum for various times at 37 degrees C. After 15 min of incubation, met-enk-RGL was completely hydrolyzed in both the ileal and the striatal membrane preparations. The major hydrolysis products were YGGFMR, YGGF and Y, which indicates that dipeptidyl carboxypeptidase and aminopeptidase activities were mainly involved in the hydrolysis. Additionally, even when the ileal and the striatal preparations were incubated for 60 min in the presence of both captopril, a dipeptidyl carboxypeptidase inhibitor, and amastatin, an aminopeptidase inhibitor, 24% and 44% of enkephalin octapeptide, respectively, were hydrolyzed. The YGG fragment was the major hydrolysis product in both preparations. When the ileal and the striatal membrane fractions were incubated with met-enk-RGL in the presence of three peptidase inhibitors-captopril, amastatin, and phosphoramidon (an inhibitor of endopeptidase-24.11)-approximately 95% of the enkephalin octapeptide, remained intact in both cases. This shows that met-enk-RGL was almost exclusively hydrolyzed by three enzymes, amastatin-sensitive aminopeptidase, captopril-sensitive dipeptidyl carboxypeptidase I and phosphoramidon-sensitive endopeptidase-24.11, in both ileal and striatal membranes. We also reported the potencies of several opioids relative to that of met-enk-RGL in guinea pig ileum pretreated with the three peptidase inhibitors.

Animals↗

[A simultaneous operation of aortic root, arch replacement, and sternal elevation for Marfan's syndrome--a case report].

A 42-year-old male was transferred to our institution by his family doctor because of suspected type A aortic dissection with cardiac tamponade. His physical constitution gave the appearance of Marfan's syndrome. Contrast CT revealed DeBaky type 1 aortic dissection. Angiography detected an Annulo-aortic ectasia complicated by an aortic regurgitation (AR) grade IV. He also suffered from a severe funnel chest. We performed simultaneous procedures of aortic root, arch replacement, and sternal elevation. Upon operation, a staged aortic clamp technique was employed to reduce the period of cardiac arrest. In the sternal elevation, the bilateral internal thoracic arteries were preserved. Post operative course was uneventful. We consider it effective to employ the staged aortic clamp technique in a reconstruction of the entire thoracic aorta in the case of poor cardiac function and to preserve the bilateral internal thoracic arteries in sternal elevation in order to prevent infection.

Adult↗

[Mass screening for prostatic cancer].

Two mass screening programs for prostatic cancer (PC) have been conducted at our institution. The first program, based on transrectal ultrasonography (TRUS), was performed between 1975 and 1995 in a total of 16,313 men over 55 years of age. Those showing abnormal findings on TRUS were referred to the secondary urological examination including needle biopsy of the prostate. PC was detected in 93 men (0.6%) and 43 of them were in the early stage. In 1995, a new mass screening program for PC was performed in an urban area of Kyoto. Of 3,749 men over 55 years of age who took the annual health checkup organized by the government, 2,387 wished to receive this screening. The primary examination consisted of Delfia prostate specific antigen (PSA) assay of dried blood samples on a filter paper. Men with PSA levels > 4.0 and < or = 10.0 ng/ml showing abnormal findings on TRUS and/or digital rectal examination, or PSA density > 0.15, underwent 6 sextant biopsies under transrectal ultrasonography, as well as men with PSA levels > 10.0 ng/ml. PSA levels were < or = 4.0 in 2,217 men, > 4.0 and < or = 10.0 in 107, and > 10.0 in 43. Prostatic biopsy was performed in 102 men. PC was detected in 28 men (1.2%) and 17 of them were in the early stage. These findings suggest that the PSA-based mass screening program for PC combined with the annual health checkup is suitable for future "national-level" screening.

Adult↗

[A case of primary fibrous histiocytoma of the lung].

Fibrous histiocytoma is non-epithelial malignant tumor mainly arising from soft tissue in extremities and body. Those derived from lung are rare. A 71-year-old female was admitted to our hospital because of an abnormal shadow on chest X-ray film. Preoperative diagnosis was not obtained by various examination. The tumor was located in right upper lobe (S2) and partial resection of right upper lobe was performed. Pathological diagnosis was fibrous histiocytoma of borderline malignancy. After the operation, adjuvant therapy was not done. The patient is doing well without recurrence and metastasis, during 4 years after the operation. However, careful follow-up should be necessary for long term.

Aged↗

[The HIV/AIDS Epidemic in Cambodia].

In December 1995 and March 1996, we visited institutes which were conducting epidemiological studied of HIV/AIDS in Cambodia, and obtained data for further collaborative study between Japan and Cambodia. Data included information on AIDS patients and HIV infected persons, and behavioral epidemiology of CSWs (Commercial Sex Workers). The cumulative reported number of AIDS patients and HIV infected persons in Cambodia was 86 and 2,536 cases respectively in 1995. The cause of infection was mostly heterosexual contact with very few cases from injecting drug use (IDU) and other causes. The seroprevalence rate of HIV antibody among donated blood rapidly increased from 0.08% in 1991 to 4.47% in 1995, and those among CSWs and pregnant women were 37.9% and 2.6%, respectively, in 1995. The average rate of condom use among CSWs was 66%, but the rate of usual usage was only 14%. These results indicate that the HIV/AIDS epidemic had spread rapidly through CSWs, that it had been spread among peoples in communities, and that usage of condoms among CSWs was insufficient in Cambodia. Without strong countermeasures against HIV/AIDS in this country, HIV/AIDS epidemic may spread significantly to not only peoples in this country but also those in neighbouring countries in the future.

Acquired Immunodeficiency Syndrome↗

[Effects of head-up tilting on vagal nerve activity in man].

OBJECTIVES: To evaluate the contribution of the vagal nerve activity in the cardiovascular postural adaptation, effects of decremental head-up tilting (90 degrees, 64 degrees, 53 degrees, 44 degrees, 37 degrees, 30 degrees, 24 degrees, 17 degrees, 12 degrees, 6 degrees and 0 degree) on time- and frequency-domain heart rate variability variables were analyzed in healthy young female. BACKGROUND: During head-up tilting, a hydrostatic venous pooling in the extremities occurs owing to gravity. To pump up the blood toward the upper body, the sympathetic nerve activity has been shown to play an important role. So, to date, few studies evaluated the effects of vagal nerve activity to stabilize the cerebral blood flow during head-up tilting. METHODS: Eight young female volunteers (age, 23.3 +/- 0.8 years; mean +/- SD) were evaluated. The electrocardiogram (ECG) by bipolar chest leads was recorded continuously during procedures, and the bed was tilted at 0.1 interval of sine function of tilting angle from upright position (90 degrees) to supine position (0 degree). The time domain measurements of cycle length variability (co-efficient of variance in percent for R-R intervals [CVRR], number of differences between adjacent R-R intervals that are > 50ms [RR50]) and the frequency domain measurements of low (0.08 to 0.15Hz, LF), high (0.15 to 0.40Hz, HF) and total (0.08 to 0.40, TF) power were performed to assess the cardiac sympathetic and vagal nerve activity. RESULTS: The CVRR showed no significant change during decremental head-up tilting, whereas the RR50 and the square root of HF power, more specific indices of cardiac parasympathetic tone, showed significant negative linear correlations to the sine of the tilting angle. In markers of cardiac sympathetic tone, there were significant positive correlations between the sine of the tilting angle and the normalized LF power or the LF-to-HF power ratio (LF/HF). CONCLUSION: These findings suggest that, in healthy young female, not only cardiac sympathetic nervous system but also cardiac vagal nervous system respond linearly to the change in body axis component of gravity, and they may contribute reciprocally and coordinately to cardiovascular postural adaptation.

Adult↗

[Adrenomedullin and PAMP].

"Adrenomedullin (AM)" is a novel hypotensive peptide which was discovered in human pheochromocytoma by monitoring the elevating activity of platelet cAMP. In addition, a novel 20 residues hypotensive peptide, termed "proadrenomedullin N-terminal 20 peptide" (PAMP) is processed from proadrenomedullin. By RNA blot analysis, AM mRNA was found to be highly expressed in several tissues including ventricle, lung, kidney, aorta and vascular cultured cells as well as in adrenal medulla. Both AM and PAMP shows hypotensive effects in anesthetized rats, but exhibits different hypotensive mechanism. AM possesses multiple biological effects involving in cardiovascular homeostasis. Further, plasma AM as well as PAMP concentrations significantly increased in various cardiovascular diseases including hypertension and congestive heart failure. The present review summarizes the recent advancement of AM research and demonstrated that AM and PAMP are important vasoactive peptides involved in the physiology and pathophysiology of circulation control.

Adrenomedullin↗