Biomedical subjects

K Noguchi

Publications and source records attributed to K Noguchi.

At least 613 records · Page 34Linked to original sources

PubMedDate not supplied

Comparison of haemodynamic responses to cilnidipine and nicardipine in an experimental model of acute congestive heart failure.

1. The haemodynamic effects of cilnidipine, a new calcium channel blocker, were examined in a canine model of acute congestive heart failure and were compared with those of nicardipine at equihypotensive doses. 2. The model was prepared by injections of saponin into coronary arteries of anaesthetized open-chest dogs followed by volume loading and continuous i.v. infusion of methoxamine. After the treatment, aortic blood flow (AoF) and left ventricular dP/dt markedly decreased, while left ventricular end-diastolic pressure (LVEDP), right atrial pressure and systemic vascular resistance (SVR) increased. Cilnidipine (0.3, 1.0 and 3.0 micrograms/kg per min), nicardipine (0.3, 1.0 and 3.0 micrograms/kg per min) or the respective vehicle was given i.v. after accomplishment of heart failure. 3. These drugs both produced a comparable reduction in aortic pressure and an increase in AoF associated with profound decreases in LVEDP, SVR and coronary vascular resistance. In contrast, administration of nicardipine was associated with significant increases in heart rate and cardiac contractility but that of cilnidipine was not. 4. These results indicate that cilnidipine as well as nicardipine can exert beneficial haemodynamic effects in a model of acute heart failure probably through lessening afterload and cilnidipine may moderate reflex-induced sympathetic stimulation.

Acute Disease↗

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Modulation of multidrug resistance by cepharanthine in fresh human gastrointestinal tumor cells.

Resistance to doxorubicin (DOX) is mainly due to the effect of P-glycoprotein encoded by the multidrug resistance (MDR) gene. Cepharanthine (CEP) has been shown to circumvent multidrug resistance in P-glycoprotein-expressing cell lines. In the present study, we investigated the augmentation of DOX sensitivity by CEP using an MTT assay, and assessed the correlation between DOX sensitivity and P-glycoprotein expression by flow cytometry, in highly purified fresh human tumor cells obtained from 73 cancer patients. DOX sensitivity was decreased in proportion to P-glycoprotein expression. The cytotoxicity of DOX was increased by CEP in tumor cells possessing low DOX sensitivity. Moreover, there was a significant correlation between the effect of CEP on cytotoxicity and P-glycoprotein expression. Thus, CEP might be able to circumvent DOX resistance in cancer patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

P-glycoprotein expression and chemosensitivity in highly purified fresh human gastrointestinal cancer cells.

BACKGROUND/AIMS: Colorectal cancer is one of the tumors most refractory to treatment by chemotherapy. One of the major problems associated with cancer chemotherapy is drug-resistance of tumor cells, and resistance to doxorubicin (DOX) is mainly due to the effect of P-glycoprotein. We have tried to prove the correlation between P-glycoprotein expression and DOX-sensitivity in highly purified fresh human colorectal cancer and, moreover, to prove the differentiation of P-glycoprotein expression between the different kinds of cancers, including gastric cancer. METHODOLOGY: The present study was designed to quantify P-glycoprotein expression by flow cytometry, and DOX-sensitivity by MTT assay in highly purified fresh human tumor cells obtained from 29 cancer patients including 13 colorectal cancers and 16 gastric cancers. RESULTS: DOX-sensitivity decreased in proportion to P-glycoprotein expression in colorectal cancer. P-glycoprotein expression in colorectal cancer was higher than that in gastric cancer. Particularly, P-glycoprotein expression in colorectal cancer in the DOX low-sensitivity group was higher than in the DOX high-sensitivity group. CONCLUSIONS: The chemotherapeutic management of patients with colorectal cancer might be more effective if we can circumvent the effect of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Multidisciplinary treatment for gastric cancer patients by chemoimmunotherapy.

BACKGROUND/AIMS: Gastric cancer is a virulent disease with a poor prognosis despite multidisciplinary treatment. The present study was designed to clarify the clinical effects of chemoimmunotherapy for patients with advanced gastric cancer. METHODOLOGY: The enrolled gastric cancer patients had distant metastases including liver (n = 2) and peritoneal dissemination (n = 21). The patients had received the chemotherapy according to the results of chemosensitivity test and adoptive immunotherapy by activated killer cells. RESULTS: There were no severe toxicities, except fever and mild myelo-suppression. Four patients had complete response (17.4%) and 10 patients had partial response (43.5%). The performance status was improved in responders (p < 0.01, from 2.6 +/- 0.5 to 1.4 +/- 0.7); however, this was not changed in non-responders (from 2.2 +/- 0.9 to 2.0 +/- 1.2). The survival of responders was longer than that of non-responders (p < 0.05, 198 +/- 69 days vs. 104 +/- 68 days). CONCLUSIONS: It was clarified that responders by chemoimmunotherapy had a good quality of life and longer survival.

Aged↗

PubMedDate not supplied

Neutrophil functions and cytokine production in patients with gastric cancer.

BACKGROUND/AIMS: One of the most important factors in the prevention of postoperative infection is the patient's own capacity to protect against infection. Neutrophils play a major role in this protection through phagocytosis and superoxide generation. Inflammatory cytokines are suitable for estimating the degree of surgical stress. The present study was designed to elucidate whether neutrophil functions are impaired in gastric cancer patients, and are related with cytokine production after surgery. METHODOLOGY: Phagocytosis and superoxide generation by neutrophils was studied in 84 patients with gastric cancer by flow cytometry. IL-6, IL-8 and tumor necrosis factor alpha were studied in 18 patients with gastric cancer by enzyme-linked immunosolubent assay. RESULTS: In gastric cancer patients phagocytosis was not impaired, whereas superoxide generation was lower than benign diseases and it was inhibited relative to the clinical stage. Moreover, superoxide generation was correlated with the nutritional parameters and was more suppressed in 7 patients who suffered from postoperative infection than in 40 patients whose postoperative course were uneventful. The fluctuation of superoxide generation correlated well with the serum cytokine levels in the postoperative course and its correlation was clarified in vitro. Nine patients with gastric cancer received intravenous hyperalimentation, and their superoxide generation was increased. CONCLUSIONS: Superoxide generation by neutrophils was suppressed in gastric cancer patients and it is suggested that nutritional support prevents postoperative infection via the augmentation of superoxide generation.

Aged↗

PubMedDate not supplied

Beta-lipoproteins influence the serum level of hepatitis C virus.

Low density lipoprotein receptor (LDLR) has been proposed as a candidate receptor for hepatitis C virus (HCV). According to previous reports, free beta-lipoproteins in a human serum may regulate the rate of hepatocyte infection by competing with the virus. Therefore, serum HCV levels should be regulated by the rise and fall of serum beta-lipoproteins since the infection rate of virions influences HCV replication in hepatocytes and release of virions by hepatocytes. In this study, we examined the relationship between serum beta-lipoproteins and HCV-antigen (Ag) levels in patients with chronic type C hepatitis. Patients were selected based on strict criteria to eliminate other factors that might influence serum HCV levels. Serum concentrations of beta-lipoproteins and HCV-Ag were measured two or more times within 3 months for each patient. The result showed that HCV-Ag levels were negatively correlated with the increased beta-lipoproteins. The results support the concept that LDLR is a HCV receptor and that beta-lipoproteins competitively inhibit the infection of hepatocytes with HCV through the LDLR.

Binding, Competitive↗

PubMedDate not supplied

Simultaneous measurement of renal blood flow of the outer and inner cortex by laser-Doppler flowmetry in anesthetized dogs: effect of enalapril diacid.

Renal hemodynamic effects of the angiotensin-converting enzyme inhibitor enalapril diacid (30 micrograms/kg, i.v.; n = 8) were examined using laser-Doppler flowmetry in anesthetized dogs. Two laser-Doppler flowmetry probes were applied simultaneously to measure the renal blood flow of the outer and inner cortex. Changes in cortical renal blood flow, obtained by the laser-Doppler flowmetry method, were intimately related to those in total renal blood flow measured with the electromagnetic flow probe during occlusion of the abdominal aorta or after administration of angiotensin II, norepinephrine, acetylcholine or dopamine. Enalapril diacid produced a significant increase in total renal blood flow, despite moderate hypotension. The blood flow of the inner cortex significantly increased by 21% following enalapril diacid, while that of the outer cortex did not. These data indicate that there may be a regional difference in the intrarenal vasodilating effect of enalapril diacid. These results also demonstrate that the laser-Doppler flowmetry method is suitable for the continuous measurement of directional changes in both outer and inner cortical blood flows.

Acetylcholine↗

PubMedDate not supplied

Intracranial dural arteriovenous fistulas with retrograde cortical venous drainage: assessment with cerebral blood volume by dynamic susceptibility contrast magnetic resonance imaging.

BACKGROUND AND PURPOSE: Retrograde cortical venous drainage (RCVD) is the most major risk factor for aggressive behavior of intracranial dural arteriovenous fistulas (DAVF). The purpose of this study was to assess the efficacy of relative cerebral blood volume (rCBV) map for RCVD in patients with DAVF. METHODS: Ten patients with angiographically proven DAVF with RCVD, 2 reference patients with DAVF without RCVD, and 10 control subjects underwent examinations with dynamic susceptibility contrast (DSC)-MR imaging. Four patients with DAVF with unilateral RCVD were evaluated, before and after treatment. The calculation of mean rCBV ratio was performed on a hemispheric basis. The mean rCBV ratio was defined as the value on one side (higher value side) divided by that on the other side (lower value side). RESULTS: In all patients with DAVF with RCVD, the rCBV map showed an increase in rCBV of the angiographically proved affected hemisphere. In 2 reference patients with DAVF without RCVD and all control subjects, the rCBV map showed no increase of rCBV. The mean rCBV ratio in patients with DAVF with RCVD was significantly higher than that of control subjects (P = .0002). Treatment response for RCVD was indicated by a decrease of CBV on the rCBV map and by a decrease of 22% in the mean rCBV ratio. CONCLUSIONS: Increased rCBV by DSC-MR correlated with RCVD in patients with DVAF. The assessment with rCBV for RCVD may be more quantitative than that with angiogram.

Aged↗

PubMedDate not supplied

Regional vasodilating effects of spirapril diacid and enalapril diacid in anesthetized dogs.

The acute regional hemodynamic effects of spirapril diacid, a novel nonsulfhydryl angiotensin-converting enzyme inhibitor, and enalapril diacid at an equidepressor dose were examined in anesthetized dogs by simultaneously measuring renal, coronary, vertebral arterial and aortic blood flow. Spirapril diacid (30 micrograms/kg, i.v.) lowered aortic pressure and increased aortic and renal blood flow associated with no marked change in heart rate, myocardial contractility, vertebral and coronary blood flow in a similar manner to enalapril diacid (30 micrograms/kg, i.v.). Both inhibitors thus produced an increase in stroke volume and a decrease of the rate-pressure product. The decrease of renal vascular resistance after administration of both agents was greater than that in vertebral and coronary vascular beds. A relatively more prolonged renal vasodilatation and a shortened coronary vasodilatation were seen with spirapril diacid as compared with enalapril diacid, despite practically identical reductions in total peripheral resistance. Each of the drugs markedly inhibited the pressor and renal vasoconstrictor responses to angiotensin I. These results indicate that the two inhibitors exhibit a similar profile of regional differences in vasodilatory effects, although they might display different durations of regional vasodilatation.

Anesthesia↗

PubMedDate not supplied

Demonstration of rat preprotachykinin A mRNA in the rat trigeminal ganglion by in situ hybridization histochemistry.

The localization of gamma-preprotachykinin A mRNAs in the rat trigeminal ganglion was demonstrated by in situ hybridization histochemistry using the 32P and 35S labelled gamma-preprotachykinin A complementary DNA. In situ hybridization using 32P allowed shorter exposure times, whereas higher resolution of the hybridization signal on both film and emulsion autoradiograms was obtained using 35S. Preprotachykinin A mRNA detected by the gamma-preprotachykinin A probe was localized in about 15 per cent of the trigeminal ganglion cells, most of which were small or medium sized. Immunohistochemical studies using anti-substance P antibodies demonstrated that 15-20 per cent of total trigeminal ganglion cells were positive. These cells were small or medium sized. The result of immunohistochemistry coincided well with that of in situ hybridization histochemistry. The present study showed that the cellular localization of preprotachykinin A mRNA could be analysed by in situ hybridization histochemistry.

Animals↗

PubMedDate not supplied

Comparative effects of the calcium antagonist isradipine and some other dihydropyridine derivatives on regional blood flow in anesthetized open-chest dogs.

The effects of isradipine (PN 200-110), isopropyl 4-(2,1,3-benzoxadiazol-4-yl)-1,4-dihydro-5-methoxycarbonyl-2,6-dim ethyl-3- pyridinecarboxylate, on some cardiovascular parameters and regional blood flow were compared with those of other dihydropyridine derivatives in anesthetized open-chest dogs. Intravenous (i.v.) administrations of isradipine 3 and 10 micrograms/kg, nifedipine 10 micrograms/kg, nicardipine 10 micrograms/kg and nisoldipine 10 micrograms/kg, decreased aortic blood pressure and increased aortic (AoF), vertebral (VBF) and coronary blood flow (CBF), but did not affect heart rate and left ventricular end-diastolic pressure. Renal blood flow was reduced by isradipine 10 micrograms/kg and nifedipine 10 micrograms/kg, but was not influenced by isradipine 3 micrograms/kg, nicardipine 10 micrograms/kg and nisoldipine 10 micrograms/kg. Left ventricular dP/dt was increased by isradipine 3 micrograms/kg, nicardipine 10 micrograms/kg and nisoldipine 10 micrograms/kg, but remained essentially unchanged following isradipine 10 micrograms/kg and nifedipine 10 micrograms/kg. The increase in AoF, VBF and CBF lasted 5-9 min following nifedipine 10 micrograms/kg or nicardipine 10 micrograms/kg, 17-30 min following nifedipine 10 micrograms/kg or nicardipine 10 micrograms/kg, 17-30 min following nisoldipine 10 micrograms/kg, and 16-44 min following isradipine 3 micrograms/kg i.v., but persisted for at least 60 min following isradipine 10 micrograms/kg. Under the experimental conditions and at the doses used in this study, all 4 drugs reduced total peripheral resistance as well as resistance in the vertebral, coronary and renal vascular beds. The results suggest that isradipine exerts cardiovascular effects similar to other calcium antagonists of the dihydropyridine group, but possesses a longer duration of action and shows a greater specificity in reducing coronary vascular resistance than nifedipine, nicardipine and nisoldipine.

Anesthesia↗

PubMedDate not supplied

Non-T cell disturbance causes the suppression of the autologous mixed lymphocyte reaction in patients with gastric carcinoma.

We investigated the accessory function of non-T cells to autoreactive T cells in autologous mixed lymphocyte reaction (AMLR) and clarified the cause of the suppression of autoreactivity in patients with gastric carcinoma. The response of T cells in the AMLR in gastric cancer patients was significantly suppressed compared with that in controls. In patients in whom the AMLR of the spleen was suppressed more than that of the peripheral blood, the degree of stimulation of non-T cells from the spleen was remarkably suppressed, on the other hand, in patients in whom AMLR of the peripheral blood was suppressed more than the spleen, the degree of stimulation from the peripheral blood was remarkably suppressed. The expression of HLA-DR antigens on non-T cells of gastric cancer patients was lower than that of controls. AMLR was considerably decreased in controls by the treatment non-T cells with anti-HLA-DR MoAb, but not in cancer patients. Treatment of non-T cells from the spleen of gastric cancer patients with IFN-gamma remarkably improved T cell proliferation in the AMLR. IFN-gamma also enhanced the expression of HLA-DR antigens on non-T cells. The disturbance of non-T cells was not biased to a specific population. These disturbances of non-T cells suppressed the AMLR independently of stage status. Therefore, the immunological abnormality of non-T cells manifested by reduced accessory function to autoreactive T cells may cause impaired immunological surveillance against tumors and permit cancer cell growth.

Antibodies, Monoclonal↗

PubMedDate not supplied

Unusual widening of Virchow-Robin spaces: MR appearance.

MR in two patients with unusual widening of the Virchow-Robin spaces showed multiple cystic foci up to 2 cm in diameter along the perforating medullary arteries in the cerebral white matter, mainly in one cerebral hemisphere. These areas were of the same signal intensity as cerebrospinal fluid on all pulse sequences. In one patient, the cystic foci in the white matter were biopsied and histologically confirmed to be large Virchow-Robin spaces.

Aged↗

PubMedDate not supplied

Significant role of 5 alpha-reductase on feedback effects of androgen in rat anterior pituitary cells demonstrated with a nonsteroidal 5 alpha-reductase inhibitor ONO-3805.

A 5 alpha-reductase inhibitor with nonsteroidal structure, ONO-3805, has been used to study the role of 5 alpha-reductase on positive and negative feedback effects of androgen on gonadotropin secretion in the rat anterior pituitary gland. Initially, the potential of ONO-3805 to inhibit the formation of 5 alpha-dihydrotestosterone (DHT) was evaluated. The activity of 5 alpha-reductase in rat anterior pituitary gland was approximately one-fourth of that in rat prostate gland or epididymis, with a Michaelis' constant (Km) value for testosterone of 5-6 x 10(-7) M. When homogenates of rat anterior pituitary glands were incubated with 14C-testosterone (14C-T) in the presence of > or = 10(-7) M ONO-3805, the formation of labeled DHT and its metabolite 5 alpha-androstane-3 alpha,17 beta-diol was inhibited by > 90%. The inhibition pattern was non-competitive, and the inhibition constant (Ki value) derived from Lineweaver-Burk plots was 3.9 x 10(-11) M. Dispersed pituitary cells (1-2 x 10(5)/ml) were cultured for 48 hours and then further incubated with or without androgen and/or the inhibitor for 72 hours (basal secretion). After this incubation, the media were saved, and 10 nM of luteinizing hormone-releasing hormone (LH-RH) with the same concentration of androgen and/or the inhibitor as used in the 72-hour incubation was added to the cultures for 6 hours (LH-RH-induced secretion). Secreted follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were assayed by radioimmunoassay (RIA). Both testosterone (T) and DHT stimulated 72-hour basal FSH secretion from cultured pituitary cells in a dose-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMedDate not supplied

Polysaccharide preparation PSK augments the proliferation and cytotoxicity of tumor-infiltrating lymphocytes in vitro.

We have investigated whether or not polysaccharide preparation PSK directly augments the proliferation and cytotoxicity of tumor-infiltrating lymphocytes (TILs). TILs were separated from 10 patients with gastrointestinal cancer (5 gastric cancers, 3 colon cancers and 2 pancreatic cancers). TILs were cultured with IL-2 and PSK for 7 days. The DNA synthesis of TILs was augmented by incubation with 100 micrograms/ml of PSK, which was similar to serum level with oral administration of PSK in cancer patients. The effect of PSK in DNA synthesis was also found by elimination of non-T cells. Furthermore, we established TIL clones and examined the effect of PSK on TILs clones. The DNA synthesis was augmented by PSK in CD4 positive and CD8 positive TIL clones without non-T cells, suggesting that PSK acts directly on TILs. We examined the cytotoxic activities of TILs by the 4-h and 16-h 51Cr release assay. PSK did not affect the cytotoxic activity of TILs against autologous tumor cells and KATO-III cells in the 4h 51Cr release assay, whereas PSK induced high lysability of TILs against autologous tumor cells in the 16-h 51Cr release assay. We studied the ability of PSK to induce cytokines from TILs using a double chamber plate. The DNA synthesis of tumor cells was more suppressed by the mixed-tumor cell culture supernatants of TILs cultured with PSK, compared to that of TILs cultured without PSK. It is suggesting that PSK induced long term killing activity of TILs by induction of cytotoxic cytokines. Thus, PSK augmented the proliferative response of TILs without interaction of T cells and non-T cells and induced cytotoxic cytokines of TILs.

Cell Division↗

PubMedDate not supplied

Cardioprotective effects of hydrolyzed bopindolol against contractile dysfunction produced by coronary stenosis and reperfusion in dogs.

The effects of the active metabolite (18-502) of bopindolol, which is a new nonselective beta-adrenoceptor antagonist, were studied on the ischemic changes in myocardial segment shortening, cardiac lactate metabolism and S-T segment of subendocardial electrocardiogram during coronary stenosis and on their recoveries after reperfusion in anesthetized dogs, and were compared with those of propranolol at a dose exhibiting a comparable degree of beta 1-blocking activity. In the presence of coronary stenosis, intravenous administration of 18-502 (5 micrograms/kg) and propranolol (0.2 mg/kg), but not saline, produced significant improvements of regional myocardial dysfunction, lactate production and S-T segment elevations in the ischemic myocardium, which were associated with significant decreases in heart rate and cardiac contractility. After release of the stenosis, administration of 18-502, but not propranolol, resulted in a significantly accelerated recovery of the ischemic segment function as compared with the control group. In rat heart homogenates, 18-502 inhibited the lipid peroxidation approximately 4 times more potently than propranolol. These data show that 18-502 exerts favorable effects during myocardial ischemia produced by coronary stenosis and that it has a cardioprotective action against the contractile dysfunction following reperfusion.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

In vitro augmentation of cytotoxic activity of peripheral blood lymphocytes and spleen cells of cancer patients by ubenimex.

Ubenimex is used for the immunotherapy of malignant diseases as a biological response modifier (BRM) and shows beneficial effects as an adjuvant treatment. In the present study, the in vitro effects of ubenimex on the cytotoxic activity of peripheral blood lymphocytes (PBL) and spleen cells of cancer patients and the mechanism of killer cell activation were investigated. Cytotoxic activity against K562, KATO-III and autologous tumor cells was augmented by in vitro sensitization with ubenimex (p < 0.05). The optimal concentration of ubenimex for induction of cytotoxic activity was 1 micrograms/ml, similar to serum levels after clinical oral administration. The major population of killer cells activated by ubenimex recognizing K562 was CD16+, and those recognizing KATO-III were mainly CDA+ or CD8(5) cels and CD16+ NK cells, while CDA5 or CD8+T cells comprised the majority of killer cells which showed autologous tumor-killing activity. Augmentation of the cytotoxic activity of mononuclear cells by ubenimex was blocked by both anti-IL-1 beta Ab and anti-IL-2 AB. However, the expression of IL-2 receptor (p55, p75) on effector cells was not altered. Ubenimex augmented not only NK activity but also autologous tumor killing activity of PBL and spleen cells via macrophage activation. These activities of ubenimex may be clinically beneficial as an adjuvant treatment.

Adjuvants, Immunologic↗

PubMedDate not supplied

Ubenimex treatment enhances the susceptibility of gastric cancer cell lines to lymphokine-activated killer cells.

We investigated the direct effects of ubenimex on the modification of gastric carcinoma cell lines' susceptibility to killer cells, and the mechanism of its action. The susceptibility of both MKN-45 cells and KATO-III cells to LAK cells was enhanced by treatment with ubenimex for 48 h (p < 0.05), and the optimal concentration for this effect was 10 micrograms/ml. The susceptibility of ubenimex treated KATO-III cells to CD3+ LAK cells, especially to those also expressing CD8, was enhanced. DNA synthesis of tumor cells was not impaired by treatment with ubenimex at all concentrations tested. The binding rate of LAK cells and ubenimex-treated KATO-III cells was similar to that between LAK cells and untreated KATO-III cells. Moreover, no alterations in the expression of any antigen related to mononuclear cell-binding to tumor cells were induced by ubenimex. Lysis or the inhibition of DNA synthesis of tumor cells by LAK cell supernatant was enhanced by ubenimex. These results suggested that the mechanism responsible for the augmentation of tumor cell susceptibility by ubenimex may be a result of the alteration of their sensitivity to some Iytic factors released by LAK cells. Thus ubenimex shows not only an indirect host-mediated anti-tumor activity but also a direct effect on tumor cells, modifying their susceptibility to killer cells, and this may explain why ubenimex shows beneficial clinical effects as an adjuvant treatment.

Adjuvants, Immunologic↗