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Biomedical subjects

K Murakami

Publications and source records attributed to K Murakami.

At least 109 records · Page 6Linked to original sources
PubMed2000

Involvement of insulin-like growth factor binding protein-3 in the retinoic acid receptor-alpha-mediated inhibition of hepatocellular carcinoma cell proliferation.

We examined the relationship between the expression of retinoic acid receptor-alpha (RAR-alpha) and upregulation of insulin-like growth factor binding protein-3 (IGFBP-3) in the retinoid-induced inhibition of hepatocellular carcinoma (HCC) cell proliferation. HCC cell lines showed a marked expression of RAR-alpha, whereas the expression levels of RAR-beta and RAR-gamma were relatively lower. An RAR-alpha agonist significantly inhibited the HCC cell proliferation both in vitro and in vivo. The RAR-alpha expression closely related to the upregulation of IGFBP-3 as compared with RAR-beta or RAR-alpha expressions. RAR-alpha agonist would be beneficial to inhibit the growth of HCC.

Animals↗
PubMed2000

Social isolation stress enhanced liver metastasis of murine colon 26-L5 carcinoma cells by suppressing immune responses in mice.

We investigated the effect of social isolation stress on the formation of experimental liver metastasis resulted from intraportal vein (i.p.v.) injection of colon 26-L5 carcinoma cells in male Balb/c mice, and elucidated some of the underlying mechanism involving the effects of this stress on cellular immunity. Increases in the colony number and tumor burden were observed in the mice socially isolated before and/or after tumor cell challenge, as compared with the group-housed mice. In addition, exposure of mice to 2 weeks of preisolation resulted in decreases in the thymus weight and number of thymocytes by 35.8% and 40.2%, respectively, in comparison with the controls. Reduced proliferative response of splenocytes to various stimuli and suppressed splenic NK activity, as well as decreased macrophage-mediated cytotoxicity, were also found in the mice exposed to social isolation. Thus, these results suggest that social isolation stress enhances tumor metastasis in part via its suppressive effect on the immune system of the host.

Animals↗
PubMed2000

Pregnenolone binds to microtubule-associated protein 2 and stimulates microtubule assembly.

Fetal or adult rat-brain cytosol and fetal rat-brain microtubules contain a high-affinity, low-capacity pregnenolone-binding protein. The equilibrium dissociation constant is in the 30-50 nM range. The best competitors (in decreasing order) are pregnenolone sulfate, progesterone, Delta5-pregnene-3beta,20alpha-diol, and 3beta-hydroxy-5alpha-pregnan-20-one. It was hypothesized that the pregnenolone-binding protein pertained to microtubule-associated proteins (MAPs). Indeed, partial purification of fetal brain cytosol by fast pressure liquid chromatography with sequential ion-exchange and gel-filtration columns yielded two fractions, one of very high molecular mass, >200 kDa, and the other of 40-60 kDa, enriched in [(3)H]pregnenolone-binding activity and in proteins immunolabeled with monoclonal anti-tubulin and anti-MAP2 antibodies. Because many proteins are associated with microtubules, binding assays were repeated with purified calf-brain tubulin, MAP2, and Tau protein. Only the MAP2 fraction showed saturable [(3)H]pregnenolone binding with an affinity very close to that of rat-brain microtubules, but with a much larger concentration of binding sites (16 pmol/mg MAP2), which was increased more than 8-fold after copolymerization of MAP2 with tubulin. Finally, steroid effects on microtubule-assembly kinetics were assayed. Pregnenolone induced a large, dose-related increase of both the rate and extent of MAP2-induced tubulin assembly, whereas progesterone, inactive per se, counteracted the stimulatory effect of pregnenolone. Electron microscopic analysis confirmed that pregnenolone-increased assembly of microtubules produced a completely normal structure. The stimulatory effect on MAP2-tubulin interaction was also observed in fetal rat-brain neuron cultures. Therefore, we propose a mechanism of neurosteroid action, the control of microtubule or, more generally, of neural cytoskeleton dynamics, with potential roles in brain development, plasticity, and aging.

Animals↗
PubMed2000

The dominant role of the prosegment of prorenin in determining the rate of activation by acid or trypsin: studies with molecular chimeras.

Human prorenin activation by acid or trypsin is faster than rat prorenin by two orders of magnitude. No plausible mechanism exists to explain the difference. Two chimeric mutant prorenins were produced in CHO cells. A chimera, hPro/rRen, composed of human prorenin prosegment and rat active renin segment, was activated as fast as wild-type human prorenin at pH 3.3 and 25 degrees C or by trypsin (1 microg/ml). The other chimera, rPro/hRen, composed of rat prorenin prosegment and human active renin segment, was activated as slowly as wild-type rat prorenin at pH 3.3 and 25 degrees C or by trypsin (50 microg/ml). These results indicate that the rate of activation of prorenin is predominantly determined by the N-terminal pro-sequence. Plausible mechanisms are discussed.

Amino Acid Sequence↗
PubMed2000

Renin-dependent cardiovascular functions and renin-independent blood-brain barrier functions revealed by renin-deficient mice.

Renin plays a key role in controlling blood pressure through its specific cleavage of angiotensinogen to generate angiotensin I (AI). Although possible existence of the other angiotensin forming enzymes has been discussed to date, its in vivo function remains to be elucidated. To address the contribution of renin, we generated renin knockout mice. Homozygous mutant mice show neither detectable levels of plasma renin activity nor plasma AI, lowered blood pressure 20-30 mm Hg less than normal, increased urine and drinking volume, and altered renal morphology as those observed in angiotensinogen-deficient mice. We recently found the decreased density in granular layer cells of hippocampus and the impaired blood-brain barrier function in angiotensinogen-deficient mice. Surprisingly, however, such brain phenotypes were not observed in renin-deficient mice. Our results demonstrate an indispensable role for renin in the circulating angiotensin generation and in the maintenance of blood pressure, but suggest a dispensable role for renin in the blood-brain barrier function.

Angiotensin I↗
PubMed2000

Pilot study on sentinel node biopsy in breast cancer.

BACKGROUND AND OBJECTIVES: Sentinel node biopsy (SNB) in breast cancer using indigo carmine was started in January 1998, and this method has proved feasible and reliable. From our initial experience, sentinel lymph nodes (SLNs) were identified in 65 of 88 cases of breast cancer (74%). METHODS: Lymphatic mapping in breast cancer was assessed using radionuclide, technetium-99m human serum albumin or technetium-99m tin colloid. A pilot study on SNB with dye or a combined method was performed between August 1998 and January 1999. RESULTS: SLNs were identified in 55 of 59 cases (93%). False-negative SLNs were found in 2 cases. The sensitivity and accuracy in all cases were 92% and 96%. SLNs in 52 cases were also diagnosed by immediate frozen sectioning. The sensitivity and accuracy were 89% and 96%. CONCLUSIONS: SNB in the combined method was the best way to identify SLNs in breast cancer.

Axilla↗
PubMed2000

Stenotrophomonas maltophilia endophthalmitis after intraocular lens implantation.

BACKGROUND: Stenotrophomonas maltophilia is an opportunistic, gram-negative bacillus. Endophthalmitis induced by S. maltophilia has been described in only two cases after intraocular lens implantation. We report S. maltophilia endophthalmitis in two patients with diabetes mellitus after intraocular lens implantation and compare the characteristics of the S. maltophilia-induced endophthalmitis with two previous cases. METHODS: A 68-year-old woman and a 74-year-old man with diabetes mellitus developed S. maltophilia endophthalmitis within 5 days of intraocular lens implantation. We performed intraocular lens removal and vitrectomy, which resolved the inflammation. No recurrences were found. RESULTS: Cultures grew S. maltophilia in both cases, and one of the organisms was multi-resistant. The final visual acuity was counting fingers and 0.3. The first case revealed a tractional retinal detachment during vitrectomy. CONCLUSIONS: S. maltophilia is a potential opportunistic intraocular pathogen, and the incidence of multiresistant S. maltophilia is increasing. S. maltophilia causes acute endophthalmitis, and its prognosis may not be poor unless the eye has a history of serious disease before the cataract surgery. The combined procedure of intraocular lens removal and vitrectomy was useful in resolving the inflammation and preventing recurrences.

Aged↗
PubMed2000

Characterization of a bovine herpesvirus type 4 isolated from the spinal cord of a cow with astasia.

A bovine herpesvirus (BHV) strain designated B11-41, was recently isolated from the spinal cord of a cow with astasia. By BHV type specific polymerase chain reaction (PCR), a BHV-4 specific fragment was amplified from the DNA of strain B11-41. The nucleotide sequence of the PCR product revealed high homologies (98.4% and 99.8%) with those of two BHV-4 strains (Movar 33/63 and 86-068). The BamHI restriction endonuclease cleavage patterns of the B11-41 were more similar to those of BHV-4 than those of other types of BHV. BHV-4 is divided into two groups, European and American. The EcoRI, and BamHI, and HindIII restriction endonuclease analysis demonstrated that strain B11-41 was closely related to the American type of BHV-4. It was concluded that B11-41 was identified as a BHV-4 that belongs to the American group. Additionally, the results of this study may indicate that the nervous system is one of the sites of viral latency in natural infection.

Animals↗
PubMed2000

Tissue-specific actions of antidiabetic thiazolidinediones on the reduced fatty acid oxidation in skeletal muscle and liver of Zucker diabetic fatty rats.

Fatty acid overload has been proposed as a cause of decreased responsiveness in the major insulin target tissues of the body such as muscle and liver tissue. We therefore investigated fatty acid oxidation in soleus muscle and liver isolated from Zucker diabetic fatty (ZDF) rats treated with thiazolidinediones, a new class of antidiabetic agents. 14CO2 production from [14C]palmitic (C16:0) acid was lower in the soleus muscle and liver of ZDF rats versus lean rats (P < .05). When administered orally to ZDF rats for 2 weeks, the thiazolidinediones troglitazone (300 mg/kg) and KRP-297 (10 mg/kg) increased palmitic acid oxidation in the soleus muscle of ZDF rats (P < .05). KRP-297, but not troglitazone, increased palmitic acid oxidation in the liver of ZDF rats (P < .05), and both troglitazone and KRP-297 inhibited triglyceride accumulation in the skeletal muscle of ZDF rats. Hepatic triglyceride accumulation in ZDF rats was inhibited by KRP-297, but not by troglitazone. A reduction of fatty acid oxidation in the liver of ZDF rats and an increase in response to KRP-297 were observed only when C16:0 and C18:0 fatty acids, not C8:0, were used as substrates. Thus, there were defects in fatty acid catabolic activity and triglyceride accumulation in the soleus muscle and liver of ZDF rats. These results indicate that KRP-297 has advantages over troglitazone in the amelioration of these lipid metabolic abnormalities in insulin resistance associated with obesity.

Administration, Oral↗
PubMed2000

Social isolation stress augments angiogenesis induced by colon 26-L5 carcinoma cells in mice.

We have previously shown that tumor necrosis factor-alpha (TNF-alpha), which is an important angiogenesis-related factor, was over-secreted in male BALB/c mice under social isolation stress as compared with the control, and closely associated with a remarkable elevation of tumor invasion and metastasis of colon 26-L5 carcinoma cells. In the present study, we explored the effect of isolation stress on the angiogenesis caused by colon 26-L5 carcinoma cells in vivo and in vitro. Social isolation lead to the enhancement of tumor growth after intrahepatic implantation with a fragment of colon 26-L5 tumor. Angiogenic response (number of vessels oriented towards tumor mass) and tumor growth (size) were significantly increased in the socially isolated mouse relative to that in the group-housed mice. Furthermore, higher protein level of hepatic TNF-alpha was found in the stressed mice than that in the control. Expression of mRNA for vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were also elevated in the tumor regions and liver tissues of the stressed mice in comparison with that in group-housed mice. On the other hand, hepatic sinusoidal endothelial (HSE) cells treated with TNF-alpha exhibited a marked promotion of the migration, invasion, expression of mRNA for matrix metalloproteinase (MMP)-9, and tube-like formation, but no cytotoxicity against the cells in vitro. The above data suggest that the social isolation stress augmented the tumor-induced angiogenesis probably by up-regulating the angiogenesis-related factors, including TNF-alpha, VEGF and HGF, and consequently mediating the functions of endothelial cells such as migration, invasion, and tube-like formation.

Animals↗
PubMed2000

Incidence of Type 1 diabetes mellitus in children aged 0-14 in Japan, 1986-1990, including an analysis for seasonality of onset and month of birth: JDS study. The Data Committee for Childhood Diabetes of the Japan Diabetes Society (JDS).

AIMS: To detect the incidence of childhood Type 1 diabetes mellitus (DM) (0-14 years) in Japan and to find out whether there is a seasonal pattern in the onset of disease and month of birth of children with diabetes. METHODS: Ascertained data for the period 1986-1990 could be collected in 35 out of 47 local government areas representing 69.4% of the childhood population (aged 0-14 years) of Japan. RESULTS: A total of 1,260 children with Type 1 DM were identified (738 girls, 522 boys). With age there was a progressive increase in incidence from 0.7 to 2.1/10(5) in boys and from 0.6 to 3.5/10(5) in girls. With the exception of 1987, when a coxsackie B3 virus epidemic was registered, no seasonal variation in the month of onset was observed, nor was a seasonal pattern of the month of birth registered in this cohort. CONCLUSIONS: Compared to European countries, the USA and Israel, the Japanese cohort of children with diabetes presents the following differences: the incidence is much lower, there is a preponderance of girls and there is (with one exception) no seasonal pattern.

Adolescent↗
PubMed2000

Outcome of arthroscopic surgery for internal derangement of the temporomandibular joint: long-term results covering 10 years.

OBJECTIVES: To investigate the long-term success (10-year results) of arthroscopic surgery of the temporomandibular joint. PATIENTS AND METHOD: A survey was undertaken of 37 patients who had been treated with arthroscopic surgery for TMJ internal derangement from 1986 to 1990. Thirty-three patients responded, of whom 30 were women and three men, whose age at surgery ranged from 14 to 77 years (mean: 35.1 years). The mean follow-up period was 10 years and 2 months. All patients rated their pain level on a visual analogue scale (VAS), and also recorded pain, jaw dysfunction, and activities of daily living (ADL) before surgery, and at the time of the survey. Interincisal opening was self-assessed (mm). Pre- and postoperative pain, dysfunction and ADL scores were compared for outcome and statistically analyzed with the Student's t-test. RESULTS: Intensity of pain as rated on the VAS was significantly reduced from 5.15 to 0.34 (p<0.01). Pain, dysfunction and ADL scores also decreased from 8.25 to 1.09, 6.5 to 1.93, and 9.1 to 1.32, respectively (p<0.01). At the preoperative examination, 36 of the 37 patients showed limited jaw opening of less than 38 mm, reduced to only three postoperatively. For the success rate of TMJ surgery, the responding 33 plus data of one re-operated patient were assessed. Of these, 27 were rated as excellent, four as good, and three (including two re-operated patients) as poor. The success rate was 83.8% when three patients who did not respond were included in the data. CONCLUSION: The long-term, 10 year outcome of TMJ arthroscopic surgery was considered to be acceptable and stable when compared with other surgical procedures and with the results of previously published middle to long-term treatment outcome studies.

Activities of Daily Living↗
PubMed2000

Prolonged mandibular hypomobility patient with a "square mandible" configuration with coronoid process and angle hyperplasia.

The objective of this study was the surgical management of chronic severe mandibular hypomobility patients associated with square mandible morphology with coronoid process and angle hyperplasia, and one-year follow-up data is reported. Ten patients were studied. All patients were female and had a history of gradual severe jaw hypomobility. Clinical findings were similar to those of a "closed lock" patient. However, the facial appearance in these patients showed a characteristic square mandible facial configuration. Coronoid process thickening and overgrowth of the mandibular angle was evident in the radiographic findings. Diagnostic imaging scarcely depicted any disk derangement, but a severely limited jaw opening was noted in spite of acceptable excursive jaw movements. Bilateral coronoidotomy or coronoidectomy was done initially, and then masseter muscle stripping via the intraoral approach. After successful reduction of jaw hypomobility, a selective mandibular anglectomy was completed. Physical therapy began within three to five days after the surgery. Postoperatively, all patients were questioned about their jaw function and their subjective assessment of the treatment. Interincisal jaw opening was recorded with a ruler marked in millimeters. Bilateral coronoidotomy or coronoidectomy and masseter muscle stripping were done for all patients; the mandibular anglectomy was performed in seven of the cases at 13 sites. Simultaneous TMJ surgery was done on three joints for three patients. Most patients reported improvement of jaw function, and the patients' subjective assessment revealed an average satisfaction rate of 74.6%. A preoperative mean jaw opening distance of 25.6 mm increased to 36.6 mm postoperatively at a one-year follow-up (p < 0.05). The conclusion was that surgical intervention is indicated when nonsurgical treatment is unsuccessful. Etiology is unknown, but masseter and temporal muscle contracture associated with mandibular coronoid and angle hyperplasia may be a strong component of the pathophysiology.

Adolescent↗
PubMed2000

Regulation of mast cell signaling through high-affinity IgE receptor by CD45 protein tyrosine phosphatase.

The transmembrane tyrosine phosphatase CD45 regulates the activity of src family protein tyrosine kinases (PTK) and thereby influences the signaling via such receptors as T and B cell antigen receptors associated with these PTK. However, its implication in signaling through the mast cell receptor with high affinity for IgE (FcepsilonRI) is less clear, although Lyn, a member of the src family, plays an important role in FcepsilonRI-mediated signaling. To define a role for CD45 in FcepsilonRI signal transduction, we established CD45 high expressing rat basophilic leukemia cell lines (RBL-CD45H) and cell lines expressing trace amounts of CD45 (RBL-CD45L). We demonstrate that although all RBL-CD45L cell lines degranulate following IgE- and antigen-induced FcepsilonRI aggregation, the response is significantly reduced at a low dose of antigen. The cells show a delayed and slowed Ca(2+) mobilization even though at a higher dose where the cells degranulate to a similar extent as RBL-CD45H. This diminished Ca(2+) response is restored by reconstitution of RBL-CD45L with a chimeric molecule containing the cytoplasmic phosphatase domains of rat CD45. Furthermore, tyrosine phosphorylation of FcepsilonRI, association of FcepsilonRI with Lyn and PTK activity associated with FcepsilonRI, all of which are enhanced upon FcepsilonRI aggregation in RBL-CD45H, are impaired in RBL-CD45L. Finally, we show that FcepsilonRI is physically associated with CD45 in RBL-CD45H prior to receptor aggregation. Thus, we propose that, although not indispensable in mast cell degranulation, CD45 positively regulates the signaling through FcepsilonRI by promoting the activation of FcepsilonRI-associated Lyn.

Animals↗
PubMed2000

The 7alpha-methoxy substituent in cephem or oxacephem antibiotics enhances in vivo anti-Helicobacter felis activity in mice after oral administration.

The in vivo antibacterial activities of 7alpha-methoxy-cephems or 7alpha-methoxy-1-oxacephems and their demethoxy congeners after oral administration were compared in a mouse model of gastric infection with Helicobacter felis. The MICs of all four pairs of compounds with and without the 7alpha-methoxy substituent were within one two-fold dilution for H. felis and Helicobacter pylori, but the 7alpha-methoxy compounds were at least four-fold more active at bacterial eradication than their demethoxy congeners. Since these compounds are not absorbed after oral administration, they are likely to have gained direct access to the bacteria from the gastric cavity. Thus the 7alpha-methoxy substituent may enhance in vivo activity by promoting the gastric mucus permeability of the compounds or by allowing the compounds to remain longer in the gastric cavity.

Animals↗
PubMed2000

Efficacy of a novel tetracycline derivative, glycylcycline, against penicillin-resistant Streptococcus pneumoniae in a mouse model of pneumonia.

The MIC90 of glycylcycline (< or =0.06 mg/L) against 55 strains of Streptococcus pneumoniae was 100-fold lower than that of minocycline or tetracycline. In a mouse model of penicillin-resistant S. pneumoniae (PRSP) pneumonia, glycylcycline (10 mg/kg) decreased bacterial counts in the lungs from 10(6) cfu to <10(2) cfu, whereas no apparent reduction of bacterial numbers was observed with minocycline or penicillin G. Pharmacokinetic studies showed that the half-life and area under the curve of glycylcycline were superior to those of minocycline and penicillin G in the lungs. These results show a preferential distribution of glycylcycline in the lungs and potent in vivo bactericidal activity in PRSP pneumonia.

Animals↗