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Biomedical subjects

N Kitamura

Publications and source records attributed to N Kitamura.

At least 163 records · Page 9Linked to original sources
PubMed1998

The very low- and intermediate-density lipoprotein fraction isolated from apolipoprotein E-knockout mice transforms macrophages to foam cells through an apolipoprotein E-independent pathway.

Apolipoprotein E (apoE)-knockout mice develop severe atherosclerosis associated with high levels of very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) in plasma. To investigate the atherogenic role of VLDL and IDL, the lipoprotein fraction containing both VLDL and IDL (apoEko-VLDL/IDL) was isolated from plasma of apoE-knockout mice by ultracentrifugation, and its interaction with macrophages was studied. When peritoneal macrophages obtained from apoE-knockout mice were incubated with apoEko-VLDL/IDL, the level of cellular cholesteryl esters (CE) increased with the concentration of apoEko-VLDL/IDL. The level of cellular cholesteryl [3H]oleate formed reached 15.1 nmol/mg of cell protein upon incubation with 50 microg/mL apoEko-VLDL/IDL for 18 h, which was an 8.4-fold increase over the corresponding level induced by low-density lipoprotein (LDL). The cellular CE mass was also significantly increased by apoEko-VLDL/IDL. Morphologically, after exposure to apoEko-VLDL/IDL, macrophages became strongly stained with Sudan black B. The total binding of [125I]apoEko-VLDL/IDL to macrophages was effectively replaced by more than 80% by an excess of the unlabeled ligand. Specific binding, calculated by subtracting the nonspecific binding from the total binding, exhibited a saturation pattern. Similar results were obtained with cell association and degradation experiments. In addition, the endocytic degradation of [125I]apoEko-VLDL/IDL was partially inhibited by LDL, whereas acetyl-LDL did not show any effect. These results indicated that apoEko-VLDL/IDL in its unmodified form produced significant CE accumulation in macrophages through a specific and apoE-independent pathway. This pathway may explain, in part, the mechanisms of foam cell formation in arterial walls and the subsequent development of atherosclerosis in apoE-knockout mice.

Animals↗
PubMed1998

Functional characterization of Kunitz domains in hepatocyte growth factor activator inhibitor type 2.

Hepatocyte growth factor activator inhibitor type 2 (HAI-2) was identified as a potent inhibitor of hepatocyte growth factor activator (HGF activator). The primary translation product of HAI-2 contains two Kunitz domains. To characterize their function, we introduced a point mutation into the reactive site of each Kunitz domain, and assayed the mutants for their HGF activator inhibitory activity. A point mutation in the COOH-terminal Kunitz domain did not affect the activity of HAI-2, whereas a point mutation in the NH2-terminal Kunitz domain markedly reduced the activity. These results suggest that the NH2-terminal Kunitz domain is mainly responsible for the HGF activator inhibitory activity of HAI-2.

Amino Acid Sequence↗
PubMed1998

Increased expression of CD44v6 mRNA significantly correlates with distant metastasis and poor prognosis in gastric cancer.

Expression of CD44 and its variants is associated with clinically aggressive behavior of some human cancers. The present study was undertaken to determine the expression level of these CD44 mRNAs in relation to the clinicopathologic features and prognosis of gastric cancer. Using reverse transcription polymerase chain reaction followed by Southern blotting, we examined the expression of the standard and variant (v6 and v9) forms of CD44 mRNA in 73 cases of gastric cancer. We determined the ratio of mRNA expression in cancer tissue to normal tissue (T/N ratio) and evaluated the correlations of the ratio with clinico-pathologic features, tumor progression and prognosis. The expression level of the standard form of CD44 (CD44s) mRNA correlated with peritoneal dissemination only, and that of CD44v9 mRNA did not significantly correlate with any clinicopathologic factor. The expression level of CD44v6 mRNA was significantly higher in patients with lymph node metastasis and liver metastasis. In 48 curatively resected patients, the expression level of CD44v6 mRNA correlated with the site of recurrence. Furthermore, there was a significant survival advantage in patients with low expression of CD44v6 mRNA compared with those with high expression. The level of CD44v6 mRNA expression may be a potential prognostic indicator and may be useful as a predictor for distant metastasis and recurrence in patients with gastric cancer.

Adult↗
PubMed1998

Evaluation of hepatocyte growth factor activator inhibitor expression in normal and malignant colonic mucosa.

Gene expression of hepatocyte growth factor activator inhibitor (HAI), a recently identified Kunitz-type serine proteinase inhibitor, was analyzed in a series of human colorectal carcinoma cell lines and in human colorectal tissues. All of the 14 cell lines derived from adenocarcinoma of the colorectum expressed HAI in vitro, whereas a colon carcinoma cell line of neuroendocrine origin did not. In vivo, HAI was consistently expressed in the normal colorectal mucosa. Although the expression of HAI mRNA was conserved in adenocarcinoma tissues of the colorectum, the levels of expression were decreased in the adenocarcinoma tissues compared to the normal counterparts. There was a tendency towards an inverse correlation, albeit not well defined, between the amounts of HAI mRNA and the tumor progression. Immunohistochemical study indicated that HAI protein is present predominantly on the surface of epithelial cells of the colon and the immunoreactivity was decreased in the adenocarcinoma cells.

Adult↗
PubMed1998

Human Hrs, a tyrosine kinase substrate in growth factor-stimulated cells: cDNA cloning and mapping of the gene to chromosome 17.

Hrs is a 115kDa zinc finger protein which is rapidly tyrosine phosphorylated in cells stimulated with various growth factors. We previously purified the protein from a mouse cell line and cloned its cDNA. In the present study, we cloned a human Hrs cDNA from a human placenta cDNA library by cross-hybridization, using the mouse cDNA as a probe, and determined its nucleotide sequence. The human Hrs cDNA encoded a 777-amino-acid protein whose sequence was 93% identical to that of mouse Hrs. Northern blot analysis showed that the Hrs mRNA was about 3.0kb long and was expressed in all the human adult and fetal tissues tested. In addition, we showed by genomic Southern blot analysis that the human Hrs gene was a single-copy gene with a size of about 20kb. Furthermore, the human Hrs gene was mapped to chromosome 17 by Southern blotting of genomic DNAs from human/rodent somatic cell hybrids.

Adult↗
PubMed1998

Asymmetrical changes in the fodrin alpha subunit in the superior temporal cortices in schizophrenia.

BACKGROUND: We examined possible abnormalities in neural structural proteins that may underlie morphometric changes reported in the left superior temporal cortices (Brodmann's area 22) of schizophrenics. METHODS: Particulate proteins of the superior temporal cortices taken at autopsy from 11 schizophrenic and 9 control brains were fractionated by gel electrophoresis. Target proteins, identified by reading their amino acid sequences, were immunoquantified using the specific antibody. RESULTS: Amino acid sequences of the 150-kDa proteins on sodium dodecyl sulfate/polyacrylamide gel electrophoresis, which were significantly increased on the left side of schizophrenic superior temporal cortices, revealed that they were proteolytic fragments of the alpha subunit of fodrin, a major cytoskeletal protein underlying the plasma membrane. Immunoquantification using the specific antibodies against alpha and beta subunits of fodrin indicated that there exist concomitant decreases in the full-length 240-kDa form and increases in the 150-kDa form of alpha-fodrin with no changes of the 235-kDa form of beta-fodrin in the left superior temporal cortices of the schizophrenic brains. CONCLUSIONS: The findings may be a possible molecular basis for linking morphometric changes to neurochemical pathophysiology in schizophrenia.

Aged↗
PubMed1998

Isotype-specific G protein abnormalities in the left superior temporal cortex and limbic structures of patients with chronic schizophrenia.

BACKGROUND: The potential role of signal transducing guanine nucleotide-binding regulatory protein (G protein) in schizophrenia is largely unknown. METHODS: We immunoquantified isotypes of G protein using specific antisera against alpha and beta subunits of G protein in the superior temporal, prefrontal, and entorhinal cortices as well as the nucleus accumbens and amygdala of postmortem brains from 19 schizophrenic and 28 control subjects. RESULTS: In the left hemisphere of schizophrenics, the amount of Gi alpha, Go alpha, and Gq alpha but not that of Gs alpha or G beta decreased in the superior temporal cortex by 27%, 27%, and 16%, respectively, as compared with the values in ipsilateral controls; the amount of any G protein isotype in the prefrontal and entorhinal cortices was not changed. In the nucleus accumbens and amygdala, the paranoid type schizophrenics showed a smaller amount of Gi alpha and Go alpha than the disorganized type schizophrenics. In the right superior temporal cortex, the isotype amount did not differ between the schizophrenic and control groups. CONCLUSIONS: The decreased Gq alpha immunoreactivity in the schizophrenic left superior temporal cortex may reflect the down-regulation of Gq alpha, resulting from chronic stimulation of Gq alpha-coupled receptors, while the decreased Gi alpha and Go alpha in the nucleus accumbens and amygdala of paranoid type schizophrenics may be related to the dopaminergic hyperactivity via dopamine D2 receptors.

Aged↗
PubMed1998

Hepatocyte growth factor stimulates synthesis of lipids and secretion of lipoproteins in rat hepatocytes.

We have reported that infusion of recombinant human hepatocyte growth factor (rhHGF) stimulates liver regeneration after hepatectomy in cirrhotic rats and increases the level of serum lipids and secretion of very-low density lipoprotein (VLDL). Studies were now performed to determine whether rhHGF directly influences lipid synthesis and its secretion in cultured rat hepatocytes. Isolated cells were cultured in the presence or absence of rhHGF (20 ng/mL) for 2 days. During the first 12 hours, rhHGF transiently inhibited the release of lipids (triacylglycerol, total cholesterol, and phospholipids), but stimulated their releases with maximal levels achieved at 36 hours. [3H]-glycerol experiment with the transcriptional and translational inhibitors revealed that rhHGF stimulated de novo synthesis of lipids by affecting activities of lipid metabolic gene. [35S]-Methionine experiment also revealed de novo synthesis of apolipoprotein B by rhHGF. Furthermore, lipid analysis of lipoprotein fractions in the conditioned medium showed that rhHGF enhanced levels of triacylglycerol, total cholesterol, and phospholipids by 50% to 200% in both VLDL and low-density lipoproteins (LDL)/high-density lipoprotein (HDL). Genistein, a tyrosine kinase inhibitor, blocked the secretion of VLDL, as well as synthesis of lipids and apolipoprotein B stimulated by rhHGF. These results indicate that HGF likely stimulates lipid biosynthesis and lipoprotein secretion in hepatocytes through its tyrosine kinase-associated receptor, c-met, and accelerates the progress of cell maturation in liver regeneration.

Androstadienes↗
PubMed1998

Cardiovascular Effects of Bolus-Administered Vasodilators in Elderly Patients with Atherosclerotic Disease: A Comparative Study of Nitroglycerin and Prostaglandin E1

To evaluate the hemodynamic effects of vasodilators in elderly patients with atherosclerotic disease, systemic hemodynamics were examined during cardiac catheterization study. After the intravenous bolus injection of nitroglycerin (NTG, 5 µg/kg, n = 20) or prostaglandin E1 (PGE1, 0.2 µg/kg, n = 20), significant reduction of mean arterial pressure, pulmonary capillary wedge pressure (PCWP), systemic vascular resistance index (SVRI), and rate-pressure product (RPP) was observed. In contrast, cardiac index and stroke index were not significantly deteriorated in either group. In conclusion, bolus-administered NTG and PGE1 had beneficial vasodilating effects without harmful impact on cardiac functions in elder patients with atherosclerotic disease.

Journal Article↗
PubMed1998

Anticoagulant Effects of Argatroban on the Pre-DIC State in Patients with an Aortic Aneurysm: A Comparative Study of Heparin

We compared the efficacy of argatroban, a new synthetic thrombin-specific inhibitor, with that of heparin in pre-DIC state patients with abdominal aortic aneurysm (AAA). A pre-DIC state was diagnosed by a detection of soluble fibrin monomer complex (FM) and increased levels of thrombin-antithrombin III complex (TAT) of more than 20 ng/ml. Twelve patients showing a pre-DIC condition were treated with argatroban (40 mg/day, n = 6) or heparin (10,000 U/day, n = 6) for 5 days. Coagulation and fibrinolytic profiles were analyzed before and after drug administration. FM became negative in two (33%) patients after the argatroban treatment and in all (100%) of the heparin-treated patients. Plasma levels of TAT were significantly decreased after the heparin treatment, however, there was no significant alteration in this parameter after the argatroban treatment. In conclusion, the anticoagulant effects of heparin were superior to those of argatroban in controlling the pre-DIC state associated with AAA.

Journal Article↗
PubMed1998

[Cardiac hemangioma of the right ventricle--report of a case].

A 74-year-old male was admitted to our hospital with a diagnosis of intra-cardiac tumor on echochardiography, CT, and MRI. The tumor was located on the free wall of the right ventricle and protruded into the outflow tract. The surgical excision of the tumor was performed under cardiopulmonary bypass. The size of the tumor was 5 x 5 x 4 cm. Histological examination disclosed cavenous hemangioma. The post opertive course was uneventful. This is the forth case reported in Japan and the fifteenth case in the world.

Aged↗
PubMed1998

[A surgical case for concomitant coronary artery disease and ASO with advanced colon cancer].

We report a successful surgical case of concomitant severe coronary artery disease and ASO with advanced sigmoid colon cancer. This patient underwent two-stage operation. Resection of the sigmoid colon was carried out first, then CABG and aortofemoral bypass was carried out simultaneously. The surgical strategy of a patient with coronary artery disease and malignant neoplasm is still controvertial, however, it should be decided considering the severity and the symptoms of both disease. In this case, ascending aorta was used as a donor artery for aortofemoral bypass. This technique will bring those benefits, i.e., consecutive operation procedures in same operating field, obtaining abundant blood flow to lower limb and safe IABP catheter insertion from subcutaneously tunneled bypass graft.

Adenocarcinoma↗
PubMed1998

[Metastatic lung tumor developing 15 years after resection of invasive thymoma].

A 57-year-old man with myasthenia gravis had undergone extended thymothymomectomy for invasive thymoma and postoperative irradiation 15 years ago. At present, an abnormal shadow on his left lung field on chest X-ray and an elevated SCC-Ag level led us to suspect primary lung cancer (squamous cell lung cancer). He underwent left lower lobectomy and partial resection of the upper lobe. After the operation, this tumor was identified pathologically as a thymoma. Comparing this tumor with the previous invasive thymoma, we concluded that the present lesion was a metastasis of the former thymoma. This case suggests that a metastatic lung tumor should be suspected when an abnormal shadow is detected on chest X-ray following extended thymothymomectomy for invasive thymoma.

Humans↗
PubMed1998

[Clinical benefits of normothermic cardiopulmonary bypass on postoperative systemic metabolism].

To evaluate the influence of body temperature during cardiopulmonary bypass (CPB) on postoperative systemic metabolism, 32 patients undergoing elective cardiac surgery were randomly assigned to either hypothermia (n = 16) or normothermia (n = 16). Serial hemodynamic parameters and blood samples were obtained after surgery. CPB and operation times were significantly shorter and the platelet reduction ratio during CPB [ = (platelets before CPB-platelets after CPB)/platelets before CPB] was significantly lower in normothermic patients than in hypothermic patients. The platelet reduction ratio was dependent on the minimum rectal temperature during CPB, the operation time, and the CPB time. In the early postoperative period, hypothermic patients had abnormally high systemic vascular resistance and a reduced cardiac index compared with the normothermic patients. There were no differences between 2 groups in postoperative hepatic and renal functions, changes in oxygen consumption, arterial-venous PCO2 or arterial-venous pH gradient. This study suggested a beneficial influence of normothermic CPB on postoperative hemodynamics. Normothermic CPB was not associated with adverse effects on postoperative metabolic recovery.

Aged↗
PubMed1998

Calcium channel current facilitation in porcine adrenal chromaffin cells.

The mechanisms of depolarizing-prepulse-induced facilitation of Ca2+ channel current were investigated in a study of porcine chromaffin cells. The Ba2+ current evoked by a pulse to 0 mV was increased by a strong depolarizing prepulse (conditioning pulse), termed "facilitation". This facilitation increased with an increase in either the duration or the voltage of the conditioning pulse, and decreased with an increase in the interpulse interval. For example, the Ba2+ current was increased to 1.14 times the control (facilitation ratio) by a 150-ms conditioning pulse to +100 mV followed by a 10-ms interpulse interval. Forskolin, 8-bromo-adenosine 3',5'-cyclic monophosphate (8-bromo-cAMP) and Rp-adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS) did not affect the facilitation of the Ba2+ current, suggesting that a cAMP-dependent mechanism is not involved. Intracellular guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) decreased the Ba2+ current to 0.59 times the control and GDP beta S increased it to 1.19. However, neither GTP gamma S nor guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) changed the amplitude of the Ba2+ current that was facilitated by the conditioning pulse. Thus, GTP gamma S increased the facilitation ratio to 2.05 and GDP beta S decreased it to 1.05. Furthermore, the facilitation of the Ba2+ current was abolished by omega-conotoxin GVIA but not by either omega-agatoxin IVA or nifedipine. These results suggest that, in porcine chromaffin cells, there is a omega-conotoxin GVIA-sensitive N-type Ca2+ channel that is under the inhibitory control of a G protein, which can be relieved by a conditioning pulse.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

Targeted cancer chemotherapy for VX2 tumour implanted in the colon with lipiodol as a carrier.

In this study, we examined the possibility of targeting drug delivery to tumours by dissolving the cytotoxic drug in a lipid fluid that is selectively deposited in tumours. Rabbits bearing VX2 tumour 10-20 mm in diameter in the large bowel received arterial injections of 0.2 ml of mitomycin C (MMC) dissolved in Lipiodol (MMC/Lipiodol), and the antitumour activity and adverse effects were examined. One week after treatment complete necrosis of the tumour was observed in 8 of 10 rabbits that received MMC/Lipiodol (3 mg/ml) without severe adverse effects on the surrounding caecum. In comparison 3/12 control animals that received MMC in saline and Lipiodol also showed complete necrosis. 6 of 7 rabbits killed eight weeks after the injection of MMC/Lipiodol were cured, with no viable tumour cells and with a normal appearance of the surrounding large bowel. In conclusion, MMC dissolved in Lipiodol may be adaptable for the treatment of colon cancer and may achieve antitumour activity without severe adverse effects.

Animals↗