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Biomedical subjects

R Oka

Publications and source records attributed to R Oka.

At least 19 recordsLinked to original sources

Large decreases in insulin requirement occurred repeatedly in two pregnancies in a type 1 diabetic woman.

Whereas the increase in insulin requirement in late gestation is well described in diabetic pregnancy, a decrease in insulin dosage in the end of the third trimester has also been noted in clinical experience and the prevention of hypoglycaemia is important. Here we report a large decrease (over 50%) in the final few weeks of her two gestations in a woman with type 1 diabetes mellitus.

Adolescent↗

Alzheimer's beta-secretase, beta-site amyloid precursor protein-cleaving enzyme, is responsible for cleavage secretion of a Golgi-resident sialyltransferase.

The deposition of amyloid beta-peptide (A beta) in the brain is closely associated with the development of Alzheimer's disease. A beta is generated from the amyloid precursor protein (APP) by sequential action of beta-secretase (BACE1) and gamma-secretase. Although BACE1 is distributed among various other tissues, its physiological substrates other than APP have yet to be identified. ST6Gal I is a sialyltransferase that produces a sialyl alpha 2,6galactose residue, and the enzyme is secreted out of the cell after proteolytic cleavage. We report here that BACE1 is involved in the proteolytic cleavage of ST6Gal I, on the basis of the following observations. ST6Gal I was colocalized with BACE1 in the Golgi apparatus by immunofluorescence microscopy, suggesting that BACE1 acts on ST6Gal I within the same intracellular compartment. When BACE1 was overexpressed with ST6Gal I in COS cells, the secretion of ST6Gal I markedly increased. When APP(SW) (Swedish familial Alzheimer's disease mutation), a preferable substrate for BACE1, was coexpressed with ST6Gal I in COS cells, the secretion of ST6Gal I significantly decreased, suggesting that that the beta-cleavage of overexpressed APP(SW) competes with ST6Gal I processing. In addition, BACE1-Fc (Fc, the hinge and constant region of IgG) chimera cleaved protein A-ST6Gal I fusion protein in vitro. Thus, we conclude that BACE1 is responsible for the cleavage and secretion of ST6Gal I.

Alzheimer Disease↗

Reduction in the local expression of complement component 6 (C6) and 7 (C7) mRNAs in oesophageal carcinoma.

Differential displays of tumour/normal pair specimens of human oesophagus identified complement component 7 (C7) as being enhanced in normal tissues, but remarkably reduced in carcinoma tissues. In situ hybridisation confirmed the localisation of C7 mRNA in normal oesophageal epithelial cells and its disappearance in tumour cells. When mRNA expressions of other components were examined by means of semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in 10 tumour/normal pair specimens, significant reductions in C6 and C7 mRNAs were observed, while C3 and C5 mRNAs were enhanced in both normal and tumour tissues. A similar reduction was observed in colon and kidney cancers using the tumour/normal expression array analysis. Gene deletion of C7 was not found in the cell lines by Southern blot analysis. Our findings suggest a possible relationship between oesophageal tumorigenesis and reduced expression of C6 and C7 mRNAs, which is probably caused by a change in gene expression regulation and not by genetic loss of the locus.

Animals↗

Overexpression of latent transforming growth factor-beta 1 (TGF-beta 1) binding protein 1 (LTBP-1) in association with TGF-beta 1 in ovarian carcinoma.

Using the differential display method, latent transforming growth factor-beta 1 (TGF-beta 1) binding protein 1 (LTBP-1) mRNA was identified as one of the enriched mRNAs in ovarian carcinoma tissues after isolation of genes responsible for the development of ovarian cancer. Semi-quantitative reverse transcription (RT)-PCR analysis showed that expression of LTBP-1 and TGF-beta 1 mRNAs was much higher in both serous and mucinous adenocarcinomas than in their benign counterparts, including serous and mucinous cystadenomas and cystadenomas of low malignant potential (LMPs). Immunohistochemical analysis demonstrated that only proliferating benign adenoma cells were immunoreactive for both LTBP-1 and TGF-beta 1 proteins. In contrast, most serous and mucinous adenocarcinoma cells and their surrounding stroma were intensely immunoreactive for LTBP-1 and TGF-beta 1. LTBP-1 and TGF-beta 1 proteins, and their complex forms were identified in ovarian carcinoma cell lines and in their culture media by western blot analysis, suggesting these products were produced in ovarian carcinoma cells. RT-PCR analysis demonstrated that LTBP-1L, one of the LTBP-1 transcripts that has a strong activity in targeting the latent form of TGF-beta 1 to extracellular matrix (ECM), was predominantly expressed in ovarian carcinomas. Taken together, the results suggest that upregulation of LTBP-1 in ovarian carcinoma cells may have an important role in distributing TGF-beta1 in the stromal tissues surrounding carcinoma cells.

Adenocarcinoma, Mucinous↗

Central serotonergic mechanisms on head twitch response induced by benzodiazepine receptor agonists.

Intraperitoneal injection of benzodiazepine receptor agonists (estazolam, zopiclone, triazolam: 0.03-0.24 mmol/kg) induces the head twitch response (HTR). The present study was undertaken to examine the possible participation of the serotonergic system in the mechanism of head twitches induced by benzodiazepine receptor agonists (BZ-RAs). The HTR induced by BZ-RAs was suppressed by pretreatment with ketanserine (1 mg/kg, i.p.), a selective 5-HT(2) receptor antagonist. Pretreatment with fluoxetine (10 mg/kg, i.p.), a 5-HT reuptake inhibitor, and 8-hydroxy-2-(di-n-propylamino)tetralin, a 5-HT(1A) receptor agonist, also suppressed the HTR induced by BZ-RAs. These results suggest that the HTR induced by BZ-RAs may be the result of an activation of postsynaptic 5-HT(2) receptors, probably due to direct action.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Fos induction in the brain of mice exhibiting behavioral abnormalities following administration of allylnitrile or crotononitrile.

Allylnitrile and crotononitrile induce behavioral abnormalities in mice. To explore the possible involvement of the vestibular system in these behavioral abnormalities, the expression of Fos protein, used as an indicator of neuronal activity, was examined within various brain structures in allylnitrile-, crotononitrile- and vehicle-treated mice. In each nitrile-treated mouse, Fos expression was observed in brain structures, which were divided into two groups. The structures in group 1 showed Fos expression between 1.5 h and 2 days postdosings, and in those in group 2 expression remained for up to 30 days postdosing. As most of these structures, especially in group 2, were identical to some Fos-positive structures observed after unilabyrinthectomy, the present results indicate that each nitrile induces Fos expression by causing a change in the peripheral vestibular system, resulting in behavioral abnormalities.

Animals↗

Comparative effects of two physical activity programs on measured and perceived physical functioning and other health-related quality of life outcomes in older adults.

BACKGROUND: Although inactivity is an important contributor to impaired functioning and disability with age, little is known concerning how improvements in physical functioning and well-being in older adults vary with the type of physical activity undertaken. METHODS: One hundred three adults age 65 years and older, recruited via population-based methods, were randomized to 12 months of community-based, moderate-intensity endurance and strengthening exercises (Fit & Firm) or stretching and flexibility exercises (Stretch & Flex). A combination of class- and home-based exercise formats was used. Measured and self-rated physical performance along with perceived functioning and well-being were assessed pre- and postintervention. RESULTS: Fit & Firm subjects showed greater 12-month improvements in both measured and self-rated endurance and strength compared to Stretch & Flex subjects. Stretch & Flex subjects reported greater improvements in bodily pain, and Stretch & Flex men evidenced greater improvements in flexibility relative to Fit & Firm subjects. Although overall exercise adherence was high in both exercise conditions (approximately 80%), subjects in both conditions showed better adherence to the home- versus class-based portions of their exercise prescriptions. CONCLUSIONS: Community-based programs focusing on moderate-intensity endurance and strengthening exercises or flexibility exercises can be delivered through a combination of formats that result in improvement in important functional and well-being outcomes. This represents one of the first studies to report significant improvements in an important quality of life outcome-bodily pain-with a regular regimen of stretching and flexibility exercises in a community-based sample of older adults.

Activities of Daily Living↗

Behavioral abnormalities and apoptotic changes in neurons in mice brain following a single administration of allylnitrile.

A single dose of allylnitrile in mice might induce persistent behavioral abnormalities, of which the mechanism is not yet known. The present study was undertaken to explore the relationship between behavioral abnormalities and pathological changes in the brain of mice following exposure to allylnitrile. Exposure to allylnitrile (63, 84, and 112 mg/kg, p.o.) resulted in dose-dependent changes in behavioral abnormalities, including increased locomotor activity, circling, retropulsion, head twitching, and alteration in reflexive behavior, which appeared at day 2 postdosing and were persistent throughout the experimental period (60 days) at the higher dose levels. Allylnitrile produced neuronal retraction including hyperchromasia of the nuclei in the raphe nuclei, cerebral cortex, hypothalamus, hippocampal CA1 and dentate gyrus later than 30 days. No gliosis was observed in these regions. Not all but a significant number of neurons in the hippocampal CA1, medial habenula and raphe nuclei were immuno-reactive to CPP32 (Caspase-3) even at day 2. These neurons were also positive to Hoechst 33258 staining, indicating allylnitrile caused apoptotic changes in specific neurons when neuronal behaviors became apparent. These apoptotic changes were persistent even in the area without neuronal contraction such as medial habenula. However, almost all neurons in these areas were also positive to terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL). It is conceivable that allylnitrile caused apoptotic changes in neurons but did not always lead them to cell death immediately. Moreover, even when neuronal contraction resulted in retention of behavioral abnormalities, onset of these abnormalities seems to be associated with the impairment in the habenulo-raphe relay due to activation of apoptotic cascade in neurons.

Animals↗

Relationship of anesthetic activity of alkyl acetates to hydrophobicity and in vivo effect on membrane fluidity in mice.

In vivo anesthetic activity of alkyl acetates in mice was studied in relation to hydrophobicity and the in vivo effect on membrane fluidity. The anesthetic potency (AD50) of alkyl acetates was determined; AD50 shows the i.p. dose required to anesthetize 50% of mice from the treated group. We used log P (n-octanol/water partition coefficient) as an operational definition of hydrophobicity. Membrane fluidity was determined using 1,6-diphenyl-1,3,5-hexatriene (DPH) as fluorescence probe. Log (1/AD50) was a parabolic function of log P, and the value of log P that corresponds to the minimum AD50 was estimated to be 2.08. Brain synaptosomal membranes were prepared from mice 30 min after dosing with each of the three alkyl acetates applied at 1.5-fold AD50: n-butyl, n-amyl, and n-hexyl acetate. In each alkyl acetate group, most of the animals were anesthetized (> 68%). Decreased membrane fluidity was observed for the animals that were anesthetized while no change in the fluidity was seen for the animals that were not anesthetized. The results suggest an involvement of decreased DPH fluidity in alkyl acetate-induced anesthesia.

Acetates↗

Pharmaceutical and bacteriological study on povidone-iodine sugar ointment.

Povidone-iodine sugar ointment is an excellent preparation for the treatment of decubitus. It has been used as an intrahospital preparation made according to the formula each hospital decided on from experience. Although commercial products have also been developed and used, they are too expensive. The efficacy of a povidone-iodine sugar ointment formulation which can be prepared by a single method and which has the stability and antibacterial activity equal to commercially available products was evaluated. As the test drugs, one commercially available product (UP), and three preparations with different formulas (P-1, P-2 and P-3) were used. All of these test drugs were stored at 20 and 40 degrees C. Specimens were sampled immediately after storage and after 20, 60, 90, 120 and 150 days and examined pharmaceutically (measurement of pH value and determinations of available iodine and sucrose levels). For the determination of bacteriological effects, 5 standard strains of 5 genera and 5 strains of methicillin-resistant Staphylococcus aureus (MRSA) were used and the time required to kill the bacteria was determined. For UP and P-3, no changes were seen pharmaceutically after 150 days of storage at 20 and 40 degrees C. However, MRSA could not be killed within 30 min. P-1 and P-2 showed remarkable changes pharmaceutically after 60 days of storage at 40 degrees C and could not be used any more. It became possible to make a preparation of povidone-iodine sugar ointment which has a stability almost similar to that of UP. Moreover, such a preparation can be made at low cost. However, since the bactericidal activity against MRSA was not higher than those of other drugs, the future task is to improve the bactericidal activity.

Anti-Infective Agents, Local↗

[Congenital coronary arterial fistula drained to the coronary sinus--a case report].

We report a very rare case of an infant with coronary arterial fistula in whom the communication between a dilated right coronary artery and the coronary sinus was found. The patient was 1-year-old. She had pulmonary congestion and cardiomegaly due to the left-to-right shunt through the fistula, and underwent ligations of the fistula. Ligations of the fistula was indicated because the patient was too small to undergo a fistula resection and coronary arterial bypass grafting. Although the patient had a successful post-operative course, we are paying attention to the aneurysmal change of the dilated right coronary artery proximal to the site of ligations.

Arteriovenous Fistula↗

["Extended aortic arch anastomosis" in Shone's anomaly--a case report].

We report a case of a newborn with Shone's anomaly in whom the parachute mitral valve, mild subaortic stenosis, hypoplastic aortic arch, and severe coarctation of the aorta were found. The patient was 10 days old, who had symptoms of low output syndrome due to the progressive obstruction of patent ductus arteriosus, underwent "extended aortic arch anastomosis" to repair the hypoplastic aortic arch and severe coarctation of the aorta. This surgical procedure, resulting in a successful post-operative course of the patient, might be effective in such anomalies.

Anastomosis, Surgical↗

Skeletal muscle size: relationship to muscle function in heart failure.

Abnormalities of skeletal muscle function and metabolism are common in patients with congestive heart failure (CHF) and appear to contribute to systemic exercise limitation. Although the mechanism for these differences is unclear, one possibility is skeletal muscle atrophy. In 21 CHF patients and 12 sex- and age-matched sedentary control subjects, we quantified muscle size as maximal cross-sectional area (MCSA) of thigh muscles measured by magnetic resonance imaging and determined the relationship between muscle size and muscle function. Muscle strength was measured as maximum force developed during isometric contractions, and muscle endurance was quantified as the decline in force during 15 consecutive isokinetic knee extensions (measured as ratio of mean peak torque of last 3 and first 3 extensions). MCSAs of thigh muscles (141 +/- 28 vs. 167 +/- 47 cm2, P < 0.05) and knee extensors (62 +/- 13 vs. 75 +/- 13 cm2; P < 0.05) were both significantly smaller in patients than in control subjects. These differences persisted after normalization for body size. Isometric strength was less, but not significantly so, in patients (126 +/- 39 vs. 135 +/- 43 Nm; P = NS), but muscle endurance was markedly impaired (endurance ratio 0.67 +/- 0.14 vs. 0.83 +/- 0.11; P < 0.05). A strong correlation was found between isometric strength (r = 0.76) and MCSA of knee extensors, but only a weak correlation between dynamic endurance and MCSA was seen. We conclude that muscle size is smaller in CHF patients but that maximal force generated per area of muscle is not impaired.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗