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Biomedical subjects

H Onishi

Publications and source records attributed to H Onishi.

At least 91 records · Page 5Linked to original sources

Nuclear polyadenylate polymerase activity in the brain of seizure-prone EL mice.

Nuclear polyadenylate polymerase from I activity in the brains of seizure-prone EL mice was significantly higher than in seizure-non-susceptible progenitor ddY mice. This finding may be essential in acquiring susceptibility to seizures, since there was no significant difference between EL(S) mice and those that did not receive stimulation, EL(NS) mice. Lower form II enzymatic activity was observed in both groups of EL mice but not in ddY mice. Moreover, significantly lower activities of form II 7 days after seizures were found in EL(S) mice compared with EL(NS) mice, suggesting that this is a consequence of repeated seizures. The activity of form I enzyme decreased immediately and at 30 and 60 min after seizures, then returned to control levels at 100 min. Form II enzymatic activity was significantly decreased only at 30 min after seizures, implying that seizures exerted a later effect on form II enzyme. These changes may cause a decrease in the rate of polyadenylation in the brain; thus, alteration of post-transcriptional events, including messenger RNA processing and transport, may occur during epileptic seizures.

Animals↗

A case of Turner syndrome with schizophrenia: genetic relationship between Turner syndrome and psychosis.

An 82-year-old woman with Turner syndrome and schizophrenia, and her 46-year-old daughter with schizophrenia are described. 45X/46XX chromosomal mosaicism was identified in the peripheral leukocytes of the mother, who showed several Turner dysmorphisms and cavum septi pellucidum in the brain. She had a normal reproductive life-span. The daughter resembled the mother in terms of schizophrenic symptoms, but she did not show any signs of Turner dysmorphism or chromosomal abnormality. The phenotype-karyotype relationship of Turner syndrome and the genetic relationship with psychosis are discussed.

Aged↗

Biological properties of conjugates of mitomycin C with estradiol benzoate and estradiol: their stability characteristics in biological media and their binding abilities to estrogen receptor.

Conjugates of mitomycin C (MMC) with estradiol benzoate and estradiol via glutaric acid, abbreviated to EB-glu-MMC and E-glu-MMC, respectively, were investigated in vitro to determine their stability and MMC regeneration properties in biological media and on their binding to estrogen receptor. EB-glu-MMC and E-glu-MMC were added into a mixture of 1/15 M phosphate buffer, pH 7.4 (ionic strength = 0.3), propylene glycol (PG) and rat plasma (4:5:1, v/v/v), named 10% plasma, or into a mixture of the buffer, PG and rat liver homogenate (9:10:1, v/v/w), named 5% liver homogenate, and each was incubated at 37 degrees C. The conversion characteristics of EB-glu-MMC and E-glu-MMC were compared with those in the buffer-PG (1:1, v/v) mixture previously reported. In 10% plasma, the change of EB-glu-MMC to E-glu-MMC was accelerated enzymatically to some extent, while the enzymatic degradation of E-glu-MMC was not accelerated at all. In 5% liver homogenate, EB-glu-MMC changed quickly to E-glu-MMC, whereas the degradation of E-glu-MMC was accelerated very little. E-glu-MMC was considered to be rather stable against enzyme in the biological media. Competitive binding studies using the rat uterine estrogen receptor showed that the specific binding affinity of E-glu-MMC was 0.81% to that of estradiol, while EB-glu-MMC hardly exhibited specific binding. E-glu-MMC was regarded as a hormone-drug conjugate showing a small specific binding affinity to the estrogen receptor. E-glu-MMC is considered to be an effective antitumor agent which gradually generates MMC in the body, and its receptor-mediated action to target cells such as estrogen receptor-positive tumor cells might be possible.

Animals↗

[Trial for transdermal administration of sulfonylureas].

Sulfonylureas are widely used as oral hypoglycemic drugs in the treatment of non insulin dependent diabetes mellitus (NIDDM). Since sulfonylureas are usually taken for a long period, the compliance of the patients is very important. Therefore, for the improvement of the compliance of the patients, the development of a transdermal dosage form of sulfonylureas was attempted in this study. Glibenclamide (GLI) or chlorpropamide (CHL) was chosen as a principal agent and ointments were prepared by mixing 5% of GLI or CHL with a FAPG ointment base. Penetration and shearing stresses of the ointments were determined as physical characteristics of the ointments. There was no obvious difference of characteristics between the GLI ointment, or the CHL ointment and the FAPG ointment base. In drug release tests, the CHL ointment showed better release of the drug than the GLI ointment. In both ointments, comparatively rapid release of drug was observed in the initial 1 h, and continuous slow release was observed thereafter. When the ointments were applied on the back of male Wistar rats and the plasma glucose level was measured, both CHL and GLI ointments gave lower blood glucose levels than the control (FAPG base). At the all measuring points, the GLI ointment brought about significantly lower blood glucose levels than the control (p < 0.01). Thus, it was demonstrated that sulfonylureas were absorbed through the skin and lowered the blood glucose levels. The results suggest the possibility of transdermal administration of sulfonylureas for the treatment of NIDDM.

Animals↗

EMG power spectrum and integrated EMG of ankle plantarflexors during stepwise and ramp contractions.

The aim of this study was to investigate whether the median frequencies (MF) of the electromyogram (EMG) and the integrated EMG (IEMG) of histochemically differentiated ankle plantarflexors, the gastrocnemius and soleus, were force dependent. Bipolar intramuscular wire electrodes were used to measure EMG of the soleus (SO), medial head of gastrocnemius (GM), and lateral head of gastrocnemius (GL) during ramp (single ongoing contractions) with the force increasing linearly from 0 to 100% of maximum voluntary contraction (MVC) and stepwise (steady force levels) ankle plantarflexion at 10, 20, 30, 40, 60, and 80% MVC. EMG and force were measured simultaneously. Power spectral analysis of these signals was performed to calculate MF on 1024-point by fast Fourier transform (FFT) technique. IEMG value of each muscle was also obtained at the same levels of force. While IEMG of three heads of triceps surae in both stepwise and ramp contractions increased significantly with increasing force, MF values of GL during stepwise contraction increased significantly (20, 40, 60, 80% MVC). These results suggest that the sensitivity of EMG power spectrum might be influenced by the proportion of fast twitch muscle fibers, which histochemically corresponds to type II fibers.

Adult↗

Plasma neuropeptide Y in patients with major depressive disorder.

It has been suggested that neuropeptide Y (NPY) is involved in the pathophysiology of depression. Plasma peptide-rich fraction from patients with major depressive disorder and control subjects was eluted with high performance liquid chromatography (HPLC), followed by radioimmunoassay of NPY. The screening patterns of the NPY-like immunoreactivity in 50 fractions eluted by HPLC from the plasma peptide-rich fraction were different between the two groups. The values of NPY in the 16 controls and the 14 patients were 427 +/- 38 and 310 +/- 27 fmol/ml plasma (P < 0.05), respectively. These results suggest that impaired metabolism of plasma NPY and the reduced plasma NPY in patients with major depressive disorder could be involved in the pathogenesis or pathophysiology of major depressive disorder.

Adult↗

HLA DRB1 and DQB1 alleles and haplotypes influencing the progression of hepatitis C.

Some HLA class II alleles and haplotypes were examined by restriction fragment length polymorphism of corresponding DNA fragments amplified by the polymerase chain reaction in 117 patients with chronic hepatitis C in Japan. The prevalence rates were compared between patients and 1216 controls and in 67 patients with liver cirrhosis, of whom 20 had hepatocellular carcinoma and 50 patients with chronic hepatitis who did not have cirrhosis or hepatocellular carcinoma. Notably, DRB1*0405 (49% [95% confidence range 38-60%] vs. 26% [16-40%]; P < 0.05, relative risk [rr] = 2.8) and DQB1*0401 (43% [33-54%] vs. 22% [13-34%]; P < 0.05, rr = 2.1) were detected more frequently in patients with cirrhosis than in those without cirrhosis. By contrast, DRB1*0901 (11% [6-19%] vs. 28% [18-40%]; P < 0.05; rr = 0.3) and DQB1*0303 (11% [6-19%] vs. 36% [25-49%]; P < 0.01; rr = 0.2) were detected less frequently in patients with cirrhosis than those without cirrhosis. Accordingly, the DRB1*0405-DQB1*0401 haplotype was more common (43% [33-54%] vs. 22% [13-34%]; P < 0.05; rr = 2.7), while the DRB1*0901-DQB1*0303 haplotype was less common (9% [4-17%] vs. 28% [18-40%]; P < 0.05; rr = 0.3) in patients with cirrhosis than in those without cirrhosis. These results suggest that there would be HLA class II alleles and haplotypes which may be associated with an accelerated or slower progression of chronic hepatitis C towards cirrhosis and eventually to hepatocellular carcinoma.

Alleles↗

Neuropathological evaluation and apolipoprotein E gene polymorphism analysis in diffuse Lewy body disease.

We performed a quantitative neuropathological investigation of senile plaques and neurofibrillary tangles in the brains of 14 Japanese patients with diffuse Lewy body disease (DLBD), and examined apolipoprotein E (APOE) gene polymorphism in these patients. Most DLBD brains had as many senile plaques as those with Alzheimer-type dementia (ATD), but fewer neurofibrillary tangles. The APOE epsilon 4 allele frequency in DLBD was 39.3%, similar to that previously reported in pathologically diagnosed ATD. DLBD and ATD are clinically and pathologically distinct, but may have common mechanisms with regard to the formation of amyloid deposition based on these findings. Future investigation of the pure form of DLBD may clarify the association between Lewy body dementia and APOE.

Aged↗

In vivo drug release and antitumor characteristics of water-soluble conjugates of mitomycin C with glycol-chitosan and N-succinyl-chitosan.

The water-soluble conjugates of mitomycin C (MMC) with N-succinyl-chitosan (N-Suc-chitosan) and glycol-chitosan (Gly-chitosan), named N-Suc-chitosan-glu-MMC and Gly-chitosan-glu-MMC, respectively, were characterized mainly by the plasma concentration-time profiles of MMC after intraperitoneal administration and their in vivo antitumor effect against P388 leukemia and Sarcoma 180. Before in vivo evaluation, polymer-drug binding characteristics were checked by gel-chromatography. Gel-chromatographs proposed the covalent binding of 1a-(4-carboxybutyryl)-MMC (glu-MMC) with both the polymer supports. The plasma concentration of MMC showed that each conjugate released MMC in vivo at a similar rate. Kinetic analysis suggested that the in vivo drug release should be considerably faster than the in vitro release in the buffer, pH 7.4, alone. In the treatment against P388 leukemia inoculated intraperitoneally, Gly-chitosan-glu-MMC showed the highest increase in life span (ILS) at 10 mg MMC eq/kg. It was lethally toxic at the dose of 20 mg MMC eq/kg, while N-Suc-chitosan-glu-MMC gave the highest ILS value at this dose. Each conjugate exhibited a little larger ILS value than MMC. For the Sarcoma 180 solid tumor inoculated subcutaneously, the polymer characteristics affected the antitumor effect. Namely, with the intravenous injection, Gly-chitosan-glu-MMC hardly exhibited any tumor growth inhibition, but N-Suc-chitosan-glu-MMC showed significant tumor growth suppression. As to the intratumoral administration, the tendency to suppress tumor growth was observed in MMC and both the conjugates.

Animals↗

Preparation and drug release characteristics of the conjugates of mitomycin C with glycol-chitosan and N-succinyl-chitosan.

Mitomycin C (MMC) was covalently attached to glycol-chitosan (Gly-chitosan) and N-succinyl-chitosan (N-Suc-chitosan) through a spacer of the glutaryl group, and each conjugate was obtained as a water-soluble product. Stability of 1a-(4-carboxybutyryl)-MMC (Glu-MMC) in vitro was investigated by incubation in 1/15 M phosphate buffers of pH 5, 6, 7.4, 8 and 9 at 37 degrees C. The release rate of MMC from Glu-MMC was very slow at neutral pH, gradual at basic pH and relatively fast at acidic pH, but the quick decomposition of MMC proceeded simultaneously at acidic pH. Release of MMC from the conjugates in vitro was investigated by incubation in 1/15 M phosphate buffers of pH 5, 7.4 and 9 at 37 degrees C. The release rate of MMC from the conjugates was slight at acidic pH, accelerated at basic pH, and was gradual at pH 7.4. In a plasma-buffer (pH 7.4) mixture (1:1, v/v), the release rate of MMC from the conjugates was rather similar to that in only the buffer (pH 7.4).

Antibiotics, Antineoplastic↗

A duplicated PLP gene causing Pelizaeus-Merzbacher disease detected by comparative multiplex PCR.

Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder caused by abnormalities in the proteolipid protein (PLP) gene, which is essential for oligodendrocyte differentiation and CNS myelin formation. Although linkage analysis has shown the homogeneity at the PLP locus in patients with PMD, exonic mutations in the PLP gene have been identified in only 10%-25% of all cases, which suggests the presence of other genetic aberrations, including gene duplication. In this study, we examined five families with PMD not carrying exonic mutations in PLP gene, using comparative multiplex PCR (CM-PCR) as a semiquantitative assay of gene dosage. PLP gene duplications were identified in four families by CM-PCR and confirmed in three families by densitometric RFLP analysis. Because a homologous myelin protein gene, PMP22, is duplicated in the majority of patients with Charcot-Marie-Tooth 1A, PLP gene overdosage may be a important genetic abnormality in PMD and affect myelin formation.

Base Sequence↗

[89Sr Therapy for pain relief in patients with bone metastases].

Radioactive strontium chloride (89Sr) was administered for pain relief in 6 patients with bone metastases (4 prostate cancer and 2 breast cancer patients). Out of 6 patients, 2 showed apparent relief of bone pain and improvement of QOL, and 3 showed slight relief of the pain with or without improvement of QOL; that is, 83% was effective. Side effects were seen in 2 patients; transient deterioration of bone pain in one patient and bone marrow suppression in the other patient. The patient who showed bone marrow suppression had rather more lesions of bone metastasis (diffuse metastasis) and least urinary excretion of the radioactivity. Urinary excretion for 2 days varied 5 to 40% of the administered dose and was less in the patients with more metastatic lesions.

Bone Marrow↗

Seroepidemiological studies on Silk Road ethnic groups.

To clarify the origin of the Japanese, the Jomom and/or Yayol, we screened for HTLV-1 and -II antibodies among inhabitants of the Silk Road, the Han, Uygur and Kazaks. We also screened for HIV, HBV, and HCV. The HTLV-I, -II, HIV, and HCV antibody tests were uniformly negative in all the studied groups. In contrast, a significantly higher incidence of HBs antigen was observed in all the groups tested (Northern Han: 11.9%, Uygur: 6.0%, Kazak: 9.1%). These results indicate that these ethnic groups are not the origin of the indigenous Japanese (the Jomon), and that HBV is prevalent in the various groups along the Silk Road.

Antigens, Viral↗