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Biomedical subjects

M Chiba

Publications and source records attributed to M Chiba.

At least 145 records · Page 8Linked to original sources
PubMed1997

Controlled protein delivery from biodegradable tyrosine-containing poly(anhydride-co-imide) microspheres.

Polymer microspheres capable of the controlled release of macromolecules for periods ranging from days to over a month were developed. The microspheres were made using a new family of anhydride polymers: tyrosine-containing poly(anhydride-co-imides), specifically poly[trimellitylimido-L-tyrosine-co-sebacic acid-co-1,3-bis(carboxphenoxy)propane] anhydrides [poly(TMA-Tyr:SA:CPP)]. These polymers may be of particular interest for controlled delivery of vaccine antigens due to the incorporation of an immunological adjuvant, L-tyrosine, into their backbone. Microspheres were produced from a variety of polymer compositions using a double-emulsion solvent-evaporation technique, and tested for their ability to provide controlled release of a model protein, bovine serum albumin, in vitro. The microspheres are spherical with smooth surfaces and encapsulate greater than 70% of the protein. Protein release rates from polymers of identical composition could be varied from 0.3 to over 125 micrograms per mg spheres per month by changing the amount of protein encapsulated. This effect can be magnified by using polymers with various monomer ratios. A close correlation between protein release and polymer weight loss was observed, suggesting a release mechanism controlled mainly by polymer erosion. Bovine serum albumin release from poly(TMA-Tyr:SA:CPP) microspheres is also pH sensitive, being enhanced at high pH and depressed under acidic conditions.

Anhydrides↗
PubMed1997

Huge solitary osteochondroma at T11 level causing myelopathy: case report.

A solitary osteochondroma of the vertebral column is rare, and also it will rarely cause neurological deficits. Myelopathy from a tumour usually presents insidiously with neurological deficits. We report a case of a huge solitary osteochondroma at T11 level with an acute onset of myelopathy induced by a minor trauma. MRI findings of a spinal osteochondroma has rarely been described. In our patient, the MRI demonstrated an outer osteochondral layer and an ossified centre of the mass. A literature review has also been undertaken.

Bone Neoplasms↗
PubMed1997

Occurrence of nonenzymatic N-acetylation of sphinganine with acetyl coenzyme A producing C2-H2-ceramide and its inconvertibility to apoptotic C2-ceramide.

Sphinganine, a biosynthetic precursor of ceramide, was non-enzymatically acetylated with acetyl coenzyme A at the C-2-amino residue to produce C2-H2-ceramide (N-acetyl sphinganine) in an organic solvent and in an aqueous solution with a high yield, whereas sphingenine was only acetylated slightly. The structure of the N-acetyl sphinganine was identified with mass spectrum, and with chromatography using an authentic N-acetylated substance. Furthermore, the C2-H2-ceramide was examined for enzymatic desaturation to determine whether C2-ceramide, a cell-permeable ceramide responsible for apoptosis of cells, was produced, revealing an inferior substrate for H2-ceramide desaturase of horse brain microsomes.

Acetyl Coenzyme A↗
PubMed1997

In vitro measurement of orthodontic tooth movement in rats given beta-aminopropionitrile or hydrocortisone using a time-lapse videotape recorder.

In vitro tooth movement of rat molars in response to an orthodontic force was recorded using a time-lapse videotape recorder and analysed by a computer system. Rats received daily s.c. injections of beta-aminopropionitrile (BAPN, 300 mg/kg/day) or hydrocortisone (10 mg/kg/day) for a period of 7 days. After drug administration, the animals were killed and the mandibles dissected. The jaw was then held under a stereomicroscope with a haemostatic clamp and an elastic band was inserted between the first and second molars. The movements of reference points on the occlusal surfaces of the first and second molars were recorded for 20 hours using a time-lapse videotape recorder. Mesiolingual movement of the first molar and distobuccal movement of the second molar were observed. During the experimental period, the greatest amount of total tooth movement in the first and second molars was seen in the group pretreated with BAPN, less movement was observed in the control group, and the group pretreated with hydrocortisone exhibited the least amount of movement. The highest rates of tooth movement were observed during the initial hour in each of the groups, and decreased thereafter. The initial rates of movement were also greatest in the BAPN group, less in the control group, and least in the hydrocortisone group. These results indicate that treatment with BAPN accelerated experimental tooth movements in vitro and hydrocortisone treatment inhibited the movements, suggesting that, although a part of the tooth movement measured in this experiment was due to deformation of the alveolar bone, the mechanical properties of the periodontal ligament play an important role in the regulation of orthodontic tooth movement.

Alveolar Process↗
PubMed1997

Improvement in lower limb vasodilatory reserve and exercise capacity in patients with chronic heart failure due to valvular heart disease.

AIMS: Reduced skeletal muscle blood flow during exercise is an important factor contributing to exercise intolerance in patients with chronic heart failure. Reactive hyperaemic blood flow is the maximum flow response necessary to protect tissue against ischaemia and hypoperfusion. We examined the vasodilatory response of the lower limb to ascertain whether response was increased with the improvement in exercise capacity observed after intracardiac surgery in patients with chronic heart failure due to valvular heart disease. METHODS AND RESULTS: Calf blood flow in 23 patients was measured by venous occlusion plethysmography at rest and after a 5 min period of femoral occlusion. Immediately after this evaluation, peak oxygen uptake and anaerobic threshold were assessed by a symptom-limited cardiopulmonary exercise test using a bicycle ergometer. Both baseline calf blood flow and peak calf blood flow during reactive hyperaemia were significantly increased after surgery (baseline calf blood flow; from 2.6 +/- 0.2 to 3.8 +/- 0.4 ml.min-1 per 100 ml calf volume, P < 0.05: peak calf blood flow; from 17.5 +/- 1.3 to 25.4 +/- 2.6 ml.min-1 per 100 ml calf volume, P < 0.01). There was a significant correlation between changes in peak calf blood flow and improvement in exercise capacity (peak oxygen uptake; r = 0.42, P < 0.05; anaerobic threshold; r = 0.68, P < 0.0010). CONCLUSION: These results indicate that exercise tolerance is improved with increased lower limb vasodilatory capacity after recovery from chronic heart failure.

Aged↗
PubMed1997

Utility of hepatitis C virus RNA levels for predicting the therapeutic efficacy of interferon.

We studied the levels of serum hepatitis C virus (HCV)-RNA, the HCV genotype before interferon therapy, and the kinetics of serum HCV-RNA at the initial stages of therapy to determine their utility in predicting the therapeutic efficacy of interferon in 44 patients with chronic hepatitis C infection. We also looked at the efficacy of repeated interferon treatment in relation to the kinetics of serum HCV-RNA. The level of serum HCV-RNA determined by a branched DNA probe assay before interferon treatment and that by a reverse transcription nested polymerase chain reaction assay during the initial stages of interferon administration were useful for predicting the efficacy of treatment. Furthermore, detection of serum HCV-RNA by the reverse transcription nested polymerase chain reaction assay after the completion of interferon therapy indicated relapse at its earliest stage. In patients who experience relapse, repeated treatment with an appropriate dose of interferon before an increase in viral levels may increase the proportion of complete responses.

Adult↗
PubMed1997

A case of tick-borne encephalitis in Japan and isolation of the the virus.

A case of tick-borne encephalitis (TBE) has not been reported for many years in Japan, although a serological survey of sera from domestic animals suggested the presence of TBE foci in Hokkaido, the northern island of Japan. Studies were conducted to prove the presence of an endemic focus of TBE virus in Japan by means of serology and virus isolation. In October 1993 in Hokkaido, a severe case of encephalitis in a dairy farmer's wife was diagnosed as TBE. Serological examination of paired serum specimens showed a rise in the neutralization antibody titer to Russian spring summer encephalitis virus. A seroepizootiological survey of dogs showed that the TBE-related virus was prevalent in the area. Three virus isolates were obtained from the blood of sentinel dogs, and antigenic analysis grouped the isolates into TBE-related viruses. Sequence analysis of the envelope protein gene identified one of the isolates as being of the same subtype as the Russian spring summer encephalitis (Far Eastern TBE) virus. The results provide evidence that TBE is endemic in a certain area of Japan.

Animals↗
PubMed1997

A multicentre randomized controlled trial of recombinant interferon-alpha-2a in the treatment of patients with chronic hepatitis C.

Sixty-one chronic hepatitis C patients were randomly assigned to receive either 6 x 10(6) or 9 x 10(6) U of recombinant interferon-alpha-2a (IFN alpha-2a) six days a week for the first two weeks of treatment, followed in both cases by 6 x 10(6) U three days a week for the next 22 weeks. In the low dose group, 11 patients showed a complete response maintained for at least six months, 12 responded but then relapsed and nine did not respond; the corresponding figures in the high dose group were 10, 15 and five patients, respectively. The differences between groups are not statistically significant. Thus, this study provides no evidence of therapeutic benefit from increasing the initial dose of IFN alpha-2a. In both treatment groups, complete responders had significantly lower pretreatment viral titres than nonresponders and were significantly more likely to be infected by type 2a versus type 1b virus.

Alanine Transaminase↗
PubMed1997

Pilot study of ofloxacin and interferon-alpha combination therapy for chronic hepatitis C without sustained response to initial interferon administration.

A controlled trial comparing combination therapy with ofloxacin (OFLX) and interferon (IFN) versus IFN monotherapy was conducted in patients with chronic hepatitis C who failed IFN therapy. Twenty patients were assigned randomly to two groups. Equal doses of recombinant IFN alpha-2b were administered to each group for 24 weeks. For the IFN plus OFLX group, OFLX was administered for 12 weeks at a daily dose of 600 mg. Levels of hepatitis C virus RNA declined significantly from the first month after the start of IFN treatment compared with those before administration in both groups. Serum alanine aminotransferase levels were significantly lower in the IFN plus OFLX group at two and six months after the start of treatment than levels in the IFN group. The fraction of subjects whose levels of serum ALT normalized was also higher in the IFN plus OFLX group. Larger clinical trials should be undertaken.

Adult↗
PubMed1997

Mn SOD activity and protein in a patient with chromosome 6-linked autosomal recessive parkinsonism in comparison with Parkinson's disease and control.

We report Mn superoxide dismutase (SOD) protein and activity in a patient with familial autosomal recessive Lewy body-negative parkinsonism in comparison with patients with sporadic Parkinson's disease (PD) and controls. We recently proved linkage of this family with markers of chromosome 6 at 6q25.2-27, which included the Mn SOD gene. We used a novel polymorphic mutation at -9 position of the signal peptide of the Mn SOD precursor protein, which caused valine to alanine substitution. All the affected members of this family showed homozygosity for alanine, whereas nonaffected members, sporadic PD patients, and the control subjects studied showed either heterozygosity of alanine and valine or homozygosity of valine. The Mn SOD activity of this familial patient was the highest among the PD patients and the control subjects studied, and an abundant expression of Mn SOD was found in the substantia nigra. The molecular weight of Mn SOD protein by Western blotting of this patient was essentially similar to that of PD patients and the control subjects. High Mn SOD activity may constitute a genetic risk factor in this familial patient. The difference in the signal peptide sequence may affect the expression of Mn SOD within mitochondria; however, it is unlikely that loss of function type Mn SOD mutation is the cause of this familial parkinsonism. Mn SOD in sporadic PD patients was similar to that in controls.

Adult↗
PubMed1997

Effect of interferon-gamma on lymphocyte cell subsets in human large bowel: a study using organ culture method.

This study was conducted to investigate the effects of interferon (IFN)-gamma on normal colonic lamina propria lymphocyte subsets in humans using organ culture method. Lamina propria lymphocyte subsets in normal colonic biopsy tissues receiving 1 x 10(5) u/ml of IFN-gamma (IFN-gamma-treated group) were investigated in comparison with those cultured in medium only (IFN-gamma-non-treated group) for 24 hr. CD8-positive cells and IgG, IgA1 and IgM-containing cells were elevated in the IFN-gamma-treated group compared with those in the IFN-gamma-non-treated group, which was similar to immunological changes in mucosal lesions of inflammatory bowel disease.

Antibodies, Monoclonal↗
PubMed1997

Diabetes associated with a novel 3264 mitochondrial tRNA(Leu)(UUR) mutation.

OBJECTIVE: To present a novel mitochondrial DNA mutation in a diabetic family RESEARCH DESIGN AND METHODS: The proband was a 64-year-old man. In the family, diabetes was maternally inherited. He had diabetes, cerebellar ataxia, cervical lipoma, hearing loss, olfactory dysfunction, ophthalmoplegia, and facial nerve bilateral palsy. On examination, early insulin secretion was blunted, and the M value on glucose clamp test was low. In muscle, ragged red fibers were not found. T-to-C mutation at position 3264 was detected in the proband (0.5% mutant DNAs in leukocyte and 30% in muscle), but was not detected in 201 normal individuals. RESULTS: Heteroplasmy of mutation, maternal inheritance of diabetes, and symptoms related to mitochondrial dysfunction suggest the pathogenecity of this 3264 mutation. As for diabetes etiology, both impaired insulin secretion and decreased insulin sensitivity seem to be important. In phenotypic characteristics, the combination of cerebellar ataxia and lipoma is a symptom sometimes found in myoclonic epilepsy and ragged red fibers (MERRFs). Ophthamoplegia is a symptom of chronic progressive external ophthalmoplegia (CPEO). These suggest that our proband had phenotypic overlap with MERRF and CPEO. Conversely, facial nerve bilateral palsy is a rare finding. The pictures that focused on his cranial nerves were thus unique, suggesting the heterogeneity of mitochondrial DNA (mtDNA)-related diabetes. CONCLUSIONS: A novel 3264 mitochondrial DNA mutation in diabetes gives new insight to the etiology of mitochondrial diabetes. Its pathogenecity supports the belief that the tRNA(Leu)(UUR) gene is an etiological hot spot of mitochondrial diseases.

DNA, Mitochondrial↗
PubMed1997

An innovative method using the Leeds-Keio artificial ligament in the unstable spine.

We have designed two innovative surgical procedures using the Leeds-Keio artificial ligament to solve the difficult problems caused by the difference in physical properties between bone structure and spinal implants, such as pedicle screw systems, used for treating the unstable lumbar spine. The procedures aim at intervertebral immobilization or reinforcement of a posterior lumbar interbody fusion. Twenty-one patients with over 2 years of follow up were evaluated. The clinical results showed these procedures to be advantageous compared with various pedicle screw systems. We conclude that these combined procedures may be applicable to patients with various types of unstable lumbar spine problems who, until now, were treated with instrumentation surgery. The best indications for these two procedures are degenerative spondylolisthesis or degenerative disk lesion with various instabilities, degenerative canal stenosis for which wide laminectomy is essential, and herniated disk with instability during flexion.

Adult↗
PubMed1997

Distribution of terbium and increase of calcium concentration in the organs of mice i.v.-administered with terbium chloride.

To investigate the biological effects of terbium (Tb), male mice were intravenously administered with TbCl3 at 10, 25, or 50 mg Tb/kg. Time-course and dose-related changes in organ distributions of Tb were determined. More than 95% of the Tb in blood was in plasma, and the concentrations decreased rapidly. Contrary to normal pharmacokinetics, Tb concentrations in plasma were higher in the 10 mg/kg group than in the 50 mg/kg group. The concentrations after injection of 25 mg/kg were between 10 and 50 mg/kg injections. Tb was incorporated mainly in liver, lung, and spleen. In all groups more than 80% of Tb administered were found in these three organs. Disappearance of Tb in these organs was very slow. Tb was also found in kidney, heart and other organs. Coincidentally, it was found that the Ca concentration was increased in organs in which Tb was incorporated. After administration of Tb (50 mg/kg) the Ca concentration, compared to the controls, was 70-fold in spleen, 20-fold in lung, and 6-fold in liver. There were highly positive correlations between Tb and Ca concentrations in organs. Excretion of Tb in urine was 0.15-0.3% and that in feces was 1.7-12.5% for up to 7 days. These results indicate that liver, lung, and spleen are the main target organs of Tb administered intravenously, and that the increase in Ca concentrations is one of the important biological effects of Tb in target organs.

Animals↗
PubMed1997

Hepatic microsomal metabolism of montelukast, a potent leukotriene D4 receptor antagonist, in humans.

Montelukast (L-706,631, MK-0476, SINGULAIR), a potent and selective leukotriene D4 (CysLT1) receptor antagonist, is currently under development for the treatment of asthma. In vitro studies were conducted using human liver microsomes to evaluate: 1) the difference in the metabolic kinetics of montelukast between adult and pediatric subjects; 2) the relative contribution of flavin-containing monooxygenase and cytochrome P450 (P450) to the sulfoxidation; and 3) the P450 isoforms responsible for montelukast oxidation. No statistically significant difference was observed in the in vitro kinetics for acyl glucuronidation and oxidative metabolism between the two age groups. Results from studies on heat inactivation of flavin-containing monooxygenase and immunochemical inhibition by an anti-rat NADPH P450 reductase antibody on montelukast oxidation indicated that all oxidative metabolism of montelukast-including diastereomeric sulfoxidations, as well as 21- and methyl-hydroxylations-are catalyzed exclusively by P450. Five in vitro approaches have been used to identify the P450 isoforms responsible for the human liver microsomal oxidation of montelukast. The experimental results consistently indicated that CYP3A4 catalyzes sulfoxidation and 21-hydroxylation, whereas CYP2C9 selectively mediates methyl-hydroxylation.

Acetates↗