Biomedical subjects

M Kato

Publications and source records attributed to M Kato.

At least 901 records · Page 50Linked to original sources

PubMed1996

Genetic change in transforming growth factor beta (TGF-beta) receptor type I gene correlates with insensitivity to TGF-beta 1 in human prostate cancer cells.

Transforming growth factor beta 1 (TGF-beta 1), a potential regulator of growth of prostate cancer cells, exerts its effects through interaction with membrane receptors. In the present study, an attempt was made to establish a correlation between TGF-beta 1 sensitivity and TGF-beta receptor expression in three prostate cancer cell lines (PC3, DU145, and LNCaP). In a dose-dependent manner, TGF-beta 1 inhibited the proliferation of PC3 and DU145 cells but not LNCaP cells. Since TGF-beta signals through a heteromeric complex composed of TGF-beta receptors type II and type I, the expression of these receptors was investigated by Western blot analysis and reverse transcriptase-PCR. These studies demonstrated that all three prostate cancer cell lines express type II receptor. In contrast, type I receptor was detected only in the TGF-beta 1-sensitive PC3 and DU145 cells but not in the TGF-beta 1-insensitive LNCaP cells. To investigate the possibility that the undetectable expression of type I receptor in LNCaP cells is due to a change in the respective gene, Southern blot analysis was performed. The result demonstrated that there was a genetic change in type I receptor gene in these cells. Subsequently, when LNCaP cells were transiently transfected with T beta R-I cDNA, sensitivity to TGF-beta 1 was restored. These observations indicate that LNCaP cells contain a defective T beta R-I gene which rendered these cells insensitive to the action of TGF-beta 1.

Base Sequence↗

PubMed1996

Dynamics of soluble adhesion molecule levels in patients with pollinosis.

OBJECTIVES: To define the dynamics of systemic and local soluble adhesion molecule levels and to discuss the role of these molecules in the pathogenesis of allergic rhinitis. DESIGN: Randomized control trial. SUBJECTS: Twelve volunteers with Japanese cedar pollinosis and 7 healthy volunteers. INTERVENTIONS: The levels of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble E-selectin, and soluble L-selectin in serum samples and nasal epithelial lining fluids (ELF) from 12 patients with pollinosis were measured 5 times throughout the allergy preseason to postseason, and the results were compared with those from 7 healthy subjects. RESULTS: The levels of sICAM-1 (P < .05) and sVCAM-1 (P < .05) in sera were up-regulated, and the levels of soluble L-selectin (P < .01) in sera were down-regulated during the early stage of the season in the allergic subjects. The difference between the levels of sICAM-1 and sVCAM-1 in sera in the early and mid-season was statistically significant in the allergic subjects (P < .05). The levels of sICAM-1 in ELF were up-regulated during the early and mid-season. The levels of sVCAM-1, soluble E-selectin, and soluble L-selectin in ELF were undetectably low throughout the preseason to postseason. CONCLUSION: There is evidence of the unique stage-dependent differential contributions of various soluble adhesion molecules in the pathogenesis of seasonal allergic rhinitis with a small amount of natural allergen provocation.

Adult↗

PubMed1996

Low expression of erythrocyte complement receptor type 1 in chronic hepatitis C patients.

Primate erythrocyte complement receptor type 1 (CR1) plays an essential role in complement-associated immune complex clearance by transporting complexes to macrophages in the liver and/or spleen. Antibody-bound hepatitis C virus, which consists of immune complexes, is observed in patients with chronic hepatitis C. The aim of this study was to clarify the pathophysiological roles of erythrocyte CR1 in hepatitis C virus-infected individuals. We quantified the expression of erythrocyte CR1 with a fluorescence-activated cell sorter system in 57 chronic hepatitis C and 37 chronic hepatitis B cases and 20 normal volunteers. Complement-bound immune complexes were quantified by means of an enzyme-linked immunosorbent assay using anti-C1q and anti-C3d antibodies. Hepatitis C virus-infected patients showed lower erythrocyte CR1 and higher C3d immune complex levels than volunteers (P < 0.01 and P < 0.05, respectively). An inverse correlation was observed between the erythrocyte CR1 and C3d immune complex levels in hepatitis C virus infection (r = -0.300, P = 0.032). The erythrocyte CR1 levels in hepatitis C virus infection were lower in patients with severe liver inflammation, cirrhosis, or hepatocellular carcinoma than in those with mild inflammation, whereas the levels did not differ regardless of the disease stage in hepatitis B virus infection. These findings demonstrate that the expression of erythrocyte CR1 is related to immune complex quantity and the severity of liver disease in hepatitis C virus infection.

Adult↗

PubMed1996

Applicability of monoclonal antibody Fab fragments as a carrier of neocarzinostatin in targeting chemotherapy.

Two types of fragments of MAb A7 were produced to improve the efficacy and safety in targeting chemotherapy with neocarzinostatin. In this study, 125I-labeled F(ab')2 and Fab fragments of MAb A7 and 125I-labeled MAb A7 were injected intravenously into mice with pancreatic carcinoma xenografts, and the accumulation of each antibody in the tumors was compared. A greater amount of the 125I-labeled Fab fragments of MAb A7 localized in the tumor 2 h following the injection than was observed with the other probes. Relatively less 125I-labeled MAb A7 localized in the tumor 2 h following the injection than was observed with the other two probes. Moreover, reaction of rabbit antimouse IgC with the Fc portion, which is the most immunopotent region of the Fab and F(ab')2 fragments of MAb A7 and MAb A7, was determined by ELISA; the weakest reaction was observed with the Fab fragments of MAb A7. These results suggest that the Fab fragments of MAb A7 may be more suitable carriers of an anticancer drug that is inactivated rapidly in the blood, such as NCS, in targeting chemotherapy than either intact MAb A7 or the F(ab')2 fragments of MAb A7.

Animals↗

PubMed1996

Significance of free prostate-specific antigen and gamma-seminoprotein in the screening of prostate cancer.

BACKGROUND: Since free prostate-specific antigen (PSA) and gamma-seminoprotein (gamma-SM) recognize similar epitope(s) of PSA, the significance of serum-free PSA and gamma-SM in the early detection of prostate cancer was compared. METHODS: A prospective clinical trial was conducted on 701 male volunteers, age 50 years or older. Free PSA (Tandem-R free PSA, Hybritech) and gamma-SM (gamma-SM, Chugai) levels were determined, and biopsies were performed if the PSA (Tandem-R, Hybritech) level was > 4 ng/ml, or if digital rectal examination (DRE) was suspicious. RESULTS: One hundred and eighty-seven men (27%) had either a PSA level > 4 ng/ml or a suspicious DRE. Of 116 biopsies performed, cancer was detected in 13 (1.9%, 13/701). Receiver-operating characteristic analysis of free PSA to PSA ratio (free PSA ratio, %) and gamma-SM to PSA ratio (gamma-SM ratio), to differentiate normal biopsy findings from cancer, showed that the optimal values were 12% and 0.38, respectively. Positive predictive value for cancer was 24% (12 cancers/50 biopsies) for PSA alone, 42% (8/19) for the combination of PSA and DRE, 45.5% (10/22) for the combination of PSA and gamma-SM ratio, and 50% (10/20) for the combination of PSA and free PSA ratio. Regression analysis showed that gamma-SM highly correlated with free PSA, but that the analytical detection limit of gamma-SM was 1 ng/ml, significantly higher than that of free PSA. CONCLUSIONS: Free PSA determination might effectively eliminate unnecessary biopsies in subjects with PSA > 4 ng/ml, and gamma-SM might provide a complementary index to free PSA, but its validity should be further studied in other settings, such as after radical prostatectomy or during endocrine treatment.

Aged↗

PubMed1996

Mercuric chloride mediates a protein sulfhydryl modification-based pathway of signal transduction for activating Src kinase which is independent of the phosphorylation/dephosphorylation of a carboxyl terminal tyrosine.

Little is known about the regulatory mechanism of c-Src kinase in cells except the suggested regulation through phosphorylation and dephosphorylation of its carboxyl terminal tyrosine residue (Y527). We here demonstrated that exposure of NIH3T3 cells to mercuric chloride (HgCl2) induces both aggregation and activation of Src kinase protein through a redox-linked mechanism. The aggregation of Src proteins was suggested to be induced by the sulfhydryl groups-to-Hg2+ reaction-mediated polymerization of cell membrane proteins to which the Src proteins associate noncovalently. The possibility was ruled out that the aggregation occurred secondarily to the promotion of protein tyrosine phosphorylation. Further study revealed that the Src kinase was activated by HgCl2 at least in part independent of the known Csk kinase-linked or Y527-phosphorylation/dephosphorylation-mediated control. Correspondingly, CNBr cleavage mapping of phosphopeptides for autophosphorylated c-Src protein demonstrated selective promotion of phosphorylation at Y416 in HgCl2-treated cells without obvious change in the phosphorylation level at Y527. These results suggest a unique protein sulfhydryl modification-based pathway of signal transduction for activating Src kinase in NIH3T3 cells.

3T3 Cells↗

PubMed1996

Optimal conditions for collection of blood samples for assay of alpha 2-macroglobulin-trypsin complex-like substance (MTLS).

We have developed an enzyme-linked immunosorbent assay (ELISA) for the specific quantification of alpha 2-macroglobulin-trypsin complex-like substance (MTLS). To exclude artifacts in measured values of MTLS, the conditions for collection of blood samples are critical. In the present study, we have determined the optimal conditions for blood collection and investigated the role of MTLS as a clinical tool for diagnosis in pancreatitis. Results obtained are as follows: (1) MTLS levels of all sera were more than 10-fold higher than the corresponding plasma; (2) MTLS levels of heparinized plasma were the lowest among plasma with three anticoagulants (sodium citrate, sodium EDTA and heparin); (3) some kinds of blood collection tubes containing heparin were not suitable for the sampling; (4) MTLS values of plasma obtained by blood collection tubes containing Trasylol and sodium EDTA were demonstrated more stable and lower than those obtained by heparin tubes; and (5) under these conditions, we can exclude elevation of MTLS values caused by inappropriate blood sampling and find the time course of the elevation reflecting clinical course of a patient with acute pancreatitis and a patient after endoscopic retrograde cholangiopancreatography (ERCP). The optimal conditions for collection of blood samples were as follows. Blood sampling should be performed by blood collection tubes containing Trasylol (50 microliters/ml blood) and sodium EDTA (1.5 mg/ml blood). The samples were immediately stored at 4 degrees C and centrifuged at 3,000 rpm for 15 min. The plasma were stored in plastic tubes at 4 degrees C until assayed.

Anticoagulants↗

PubMed1996

Plasma alpha 2-macroglobulin-trypsin complexlike substance (MTLS) in pancreatic disease.

alpha 2-macroglobulin-trypsin complexlike substance (MTLS) was determined in plasma of pancreatic and nonpancreatic diseases using a two-step enzyme immunoassay to study the diagnostic and pathophysiological significance of MTLS. Plasma levels of MTLS in acute pancreatitis (mean +/- SD = 265.6 +/- 346.2 ng/ ml, n = 9), calcified chronic pancreatitis (128.6 +/- 257.4, n = 13), and noncalcified chronic pancreatitis (13.5 +/- 12.5, n = 10) were significantly higher than that in controls (3.6 +/- 1.8, n = 81). In other diseases such as gastric cancer, hepatoma, diabetes mellitus, and gallstones, MTLS values were not different from those of control. Plasma MTLS values showed low correlation with serum trypsin, elastase 1, pancreatic amylase, lipase, and pancreatic secretory trypsin inhibitor (PSTI). The elevation of plasma MTLS values in acute pancreatitis suggests that plasma MTLS levels reflect that protease is inappropriately activated in pancreatic acinar cell and released into the circulation and that the determination of MTLS can be useful for diagnosis and pathophysiology of acute pancreatitis and chronic pancreatitis.

Adult↗

PubMed1996

Loss of tuberin from cerebral tissues with tuberous sclerosis and astrocytoma.

We studied the expression of tuberin, the TSC2 gene product, in cerebra with or without tuberous sclerosis. Tuberin was abundant in the gray matter of normal cerebra, but was undetectable in the subependymal astrocytomas from 3 patients with tuberous sclerosis. In 1 patient, cortical tubers and normally appearing cortical tissue also showed a marked loss of tuberin. These results indicate the critical role of tuberin in the neuropathology of tuberous sclerosis.

Adolescent↗

PubMed1996

Prognostic value of monolayer culture patterning in primary cell culture of oesophageal cancer.

The growth of primary cell cultures of oesophageal cancer was compared with the clinical outcome of patients from whom the cancers were taken. Ninety-three patients underwent curative resection, with no operative deaths, and were divided into three groups according to the monolayer culture pattern of the primary cell culture: culture from 43 patients (46 per cent) grew no malignant cells (group 1), 21 (23 per cent) produced monolayer epithelial growth (group 2) and the rest (from 29 patients) established cell lines (group 3). The 5-year survival rate of patients in group 2 (29 per cent) and group 3 (23 per cent) was significantly lower (P < 0.005) than that of those in group 1 (51 per cent). Monolayer epithelial growth potential is a significant prognostic factor in patients with oesophageal cancer.

Adult↗

PubMed1996

Effect of bile duct ligation and unilateral nephrectomy on brain concentration and convulsant potential of the quinolone antibacterial agent levofloxacin in rats.

To mimic the excretion route of the quinolone antibacterial agent levofloxacin (LVFX) in humans, we produced an excretion-limited (EL) model in male Sprague-Dawley rats by bile duct ligation and unilateral nephrectomy. We then examined the relationship between brain levels of LVFX and its convulsant effects in control and EL animals. Serum concentrations of LVFX in EL animals (EL + LVFX) were 2.38- and 1.59-fold and brain concentrations were 1.33- and 1.19-fold those of the controls (control + LVFX) at 30 min after a single intravenous injection of 10 and 100 mg/kg LVFX, respectively. Furthermore EL animals became more susceptible to the convulsant effect of LVFX with a 1.28-fold decrease in convulsion-inducing dose. In combination with oral pretreatment with 400 mg/kg 4-biphenylacetic acid (BPAA), convulsion-inducing doses in the control (control + LVFX + BPAA) and EL (EL + LVFX + BPAA) groups were markedly decreased by 2.25 and 9 times that of the control + LVFX group. EL operation and BPAA pretreatment slowed the elimination of LVFX in the serum and brain 4 hr later in the following order: EL + LVFX + BPAA, control + LVFX + BPAA, EL + LVFX, and control + LVFX groups. This order reflects that for the convulsion-inducing doses. These results suggest that EL rats may be a useful model for humans and that the convulsant effect of LVFX with or without BPAA arises not only from the attainment of maximum brain concentration but also from delayed disappearance from the brain.

Administration, Oral↗

PubMed1996

Effect of antioxidants, anti-inflammatory drugs, and histamine antagonists on sparfloxacin-induced phototoxicity in mice.

We examined the effects of antioxidants, anti-inflammatory drugs, and histamine antagonists on auricular inflammation and retinal degeneration induced by the phototoxicity of sparfloxacin (SPFX), a quinolone antibacterial agent. Catalase (CAT), dimethyl sulfoxide (DMS0), dexamethasone (DM), indomethacin (IM), phenidone (PD), AA-861 (AA), pyrilamine maleate (PY), or cimetidine (CM) was continuously administered to female Balb/c mice using microosmotic pumps for 72 hr and intraperitoneally once before SPFX administration. The mice were given a single oral administration of 50 or 100 mg/kg SPFX and irradiated with ultraviolet-A (UVA) light at 1.5 mW/cm(2) for 4 hr. SPFX administration plus UVA irradiation induced thickening and inflammation of the auricular skin and retinal degeneration in the eye. CAT and DMS0 significantly inhibited the auricular thickening only 4 hr after SPFX administration. DM, IM, and PD also inhibited this toxicity from 4 to 48 or 72 hr. On the other hand, PY and CM showed no effect on this change. With regard to the eye, CAT and DMSO completely inhibited the occurrence of retinal degeneration and IM and PD tended to decrease its incidence, whereas DM, AA, PY, and CM showed no or an exacerbating effect. These results suggest that reactive oxygen species contribute to the initiation of auricular inflammation and retinal degeneration and that cyclooxygenase products are also involved in the initiation and later progression of auricular inflammation. They also show that histamine and 5-lipoxygenase products are not involved in either phototoxic lesion.

Animals↗

PubMed1996

Postprandial responses of liver blood flow prior to and following hepatectomy in conscious dogs.

The responses of the portal and hepatic arterial blood flows to various diets and nutrients were measured simultaneously in conscious dogs prior to and following hepatic resection. Prior to hepatectomy, the increase in the portal blood flow was significantly larger in response to an elemental diet, fats, or amino acids than to glucose or water. The peak increase was 60.2 +/- 14.4 ml for water, 144.7 +/- 22.1 ml for a 150-cal elemental diet, 168.5 +/- 16.1 ml for a 300-cal elemental diet, 86.7 +/- 14.0 ml for a glucose solution, 159.3 +/- 16.7 ml for an amino acid meal, and 188.5 +/- 25.3 ml for a fat meal. Following partial hepatectomy, fats and amino acids induced an increase in the portal blood flow similar to that prior to hepatectomy. Glucose and the elemental diet, on the other hand, induced a significantly larger increase in portal blood flow following the surgery although water did not. The peak increase was 144.4 +/- 27.8 ml for glucose (166% of the peak increase prior to hepatectomy) and 221.8 +/- 32.5 ml for the 300-cal elemental diet (132%). The postprandial response of the hepatic artery to every diet was quite different among the dogs and there were no significant changes both prior to and following surgery. The different response of the portal flow to intraluminal glucose following partial hepatectomy may be due to alterations in glucose metabolism following hepatectomy. We have shown that the postprandial response of the portal blood flow varies with the type of nutrient, and it can be altered by hepatectomy.

Animals↗

PubMed1996

Intravenous catecholamines alter hepatic blood flow in conscious dogs with experimental hepatic denervation.

Hepatic blood flow is regulated by the autonomic nervous system; however, blood flow through the denervated liver has been controversial. The purpose of this study is to evaluate the changes in hepatic blood flow caused by experimental hepatic denervation during the intravenous infusions of catecholamines (dopamine or dobutamine) with or without prior administration of alpha-adrenoceptor antagonist (phenoxybenzamine) or beta-adrenoceptor antagonist (propranolol). The liver blood flow was measured using transit time ultrasonic flow meter probes at the portal vein and hepatic artery in conscious dogs which (a) underwent hepatic denervation (denervation group, n = 9) and (b) were intact (control group, n = 10). Norepinephrine concentrations in the liver were determined to evaluate the effects of hepatic denervation and were decreased at 1 week and 4 weeks after hepatic denervation. In the control group, dopamine and dobutamine produced an increase of portal venous blood flow (PVF). Conversely, hepatic denervation reduced the increase in PVF by dopamine and dobutamine. Dopamine with prior administration of phenoxybenzamine produced a much larger increase in PVF in both groups. Pretreatment of propranolol in both groups abolished the increasing effects of dopamine and dobutamine in PVF. Dopamine reduced the hepatic arterial blood flow (HAF) regardless of hepatic denervation. During dobutamine infusion, HAF was decreased by hepatic denervation and prior administration of propranolol. These results suggest that hepatic denervation reduces the increasing effects of catecholamines on the hepatic blood flow through greater enhancement of alpha-adrenergic effects than of beta-adrenergic effects in the hepatic vascular autonomic nerve response.

Animals↗

PubMed1996

Anomalous left main coronary artery arising from the pulmonary artery in an adult: treatment by direct reimplantation.

We herein report the case of a 37-year-old woman in whom an anomalous origin of the left coronary artery from the pulmonary artery was surgically corrected. A magnetic resonance angiogram showed the left main coronary artery connecting to the right posterior portion of the pulmonary trunk, and exercise-stressed thallium-201 perfusion scintigrams demonstrated a large reversible anterior defect. She was successfully treated by direct aortic reimplantation of the abnormal left coronary artery. We were able to obtain a sufficient length of the left main trunk by excising the large cuff of pulmonary artery wall surrounding the ostium of the anomalous left coronary artery while transecting the pulmonary artery. Postoperative angiograms demonstrated a widely patent left coronary artery, a decrease in the size of the right coronary artery, and no collaterals, and exercise-stressed thallium-201 perfusion scintigrams demonstrated no remaining ischemic defect at all. Direct aortic reimplantation is an ideal operation but is still limited by the anatomical position of the left coronary artery. In this case, magnetic resonance angiography was an excellent method for deciding the optimum operative procedure for the anomalous left coronary artery. In addition, exercise thallium-201 scintigraphy was found to be useful in recognizing the revascularized effect of the left ventricle.

Adult↗

PubMed1996

Changes in liver blood flow after hepatectomy in conscious dogs.

Hepatic circulation after hepatectomy was investigated in conscious dogs under fasting and feeding conditions. After a 40% hepatectomy, both the hepatic arterial and portal blood flow were measured simultaneously using ultrasonic transit time flowmeters. During fasting, the total hepatic blood flow (i.e., the sum of arterial and portal blood flow) changed in a biphasic pattern after hepatectomy. The first peak (517.9 +/- 42.7 ml/min; 130.1% of preoperative flow) was seen on the 1st postoperative day (POD) and the second peak (444.8 +/- 25.6 ml/min; 112.7% of preoperative flow) occurred on the 7th POD. The portal flow demonstrated the same biphasic changes as the total hepatic flow, although the hepatic arterial flow showed only the first peak. A heart rate analysis suggested that the first peak was probably due to hyperdynamic circulatory conditions, as has been previously reported. In addition, the existence of the second peak was established by the present study. The postprandial hepatic blood flow decreased during the first 2 weeks postoperatively, but exceeded the presurgical levels on PODs 21 and 28.

Animals↗

PubMed1996

Successful coronary artery bypass grafting for a patient with myelodysplastic syndrome: report of a case.

We report herein the case of a 61-year-old man with myelodysplastic syndrome causing pancytopenia who underwent successful coronary artery bypass grafting (CABG). Preoperatively, his hemoglobin (Hb) value was 10.4 g/dl while receiving transfusions of 1 or 2 units of red blood cells (RBC) every 2 weeks, his white blood cell (WBC) count was 8200/microliter with injections of 100 micrograms granulocyte colony-stimulating factor (G-SCF) every 5 days, and his platelet count was 4.5 x 10(4)/ microliter without platelet transfusion. From the time the pancytopenia was diagnosed in his peripheral blood, he had received a total of 104 units of RBC and 472 units of platelets, following which he developed an antiplatelet antibody, not for a platelet-specific antigen, but for an HLA antigen. Thus, HLA-matched platelets were prepared to prevent bleeding caused by thrombocytopenia, and the WBC count was elevated preoperatively by G-CSF injections. Thereafter, CABG was performed on three vessels. The HLA-matched platelets were transfused as the patient was weaned from the extracorporeal circulation. As a result of these preparations, we were able to protect the patient against bleeding and infection.

Antibodies↗

PubMed1996

Methylation status of Sillago japonica satellite DNA examined by bisulfite modification.

A member of Sillago japonica satellite DNA contained internal subrepeats in its 174 bp unit. S. Japonica genomic DNA isolated from liver tissue was subjected to bisulfite modification, and the DNA sequences of about 40 bp flanked by both subrepeats were amplified by polymerase chain reaction (PCR). This protocol, combination of bisulfite reaction and PCR, converts cytosines in the genomic DNA to thymines in the amplified DNA, whereas 5-methylcytosines in the genomic DNA remain as cytosines. Sequence analysis of the amplified DNA fragments revealed that most of the cytosine residues at CpG were methylated in this region.

Animals↗