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Biomedical subjects

H Onishi

Publications and source records attributed to H Onishi.

At least 55 records · Page 3Linked to original sources

Lack of association in Japanese patients between neuroleptic malignant syndrome and a debrisoquine 4-hydroxylase genotype with low enzyme activity.

Decreased activity of debrisoquine 4-hydroxylase (CYP2D6), which participates in hepatic metabolism of several frequently used neuroleptics and antidepressants, is inherited as an autosomal recessive trait through polymorphic CYP2D6 gene alleles. In eastern Orientals, a C --> T substitution at nucleotide 188 (Pro34Ser) is primarily responsible for decreased ability to metabolize CYP2D6 substrates. We therefore studied a possible association between neuroleptic malignant syndrome (NMS) and the C188T mutation. We examined the frequency of the C188T mutation by polymerase chain reaction and restriction fragment length polymorphism analysis in 36 Japanese patients previously diagnosed with NMS and 107 neuroleptic-treated schizophrenic patients with no NMS history. The C188T allele frequency was 0.417 in NMS patients and 0.463 in patients without NMS. No significant allele or genotype associations were observed. We cannot conclude that low CYP2D6 activity genotype causes susceptibility to NMS in Japanese patients.

Adult↗

[Chest radiograph of atypical pneumonia: comparison among Chlamydia pneumoniae. Pneumonia, ornithosis, and Mycoplasma pneumoniae pneumonia].

No report has been found comparing Chlamydia pneumoniae (C. pneumoniae) pneumonia radiographically with other atypical pneumonias, Chlamydia psittaci (C. psittaci) pneumonia and Mycoplasma pneumoniae (M. pneumoniae) pneumonia. We described the chest radiographs of three kinds of pneumonia cases: 46 cases of C. pneumoniae pneumonia, 39 cases of C. psittaci pneumonia, and 131 cases of M. pneumoniae pneumonia. Radiographic shadows were categorized into main shadows and sub-shadows. The main shadows are classified from the viewpoint of the characteristics; air space consolidation(AS), ground-glass opacity(GG), reticular shadow(RS), bronchopneumonia(BP), and small nodular shadows (SN). The size, the site, and the number of the main shadows were also analyzed. In comparison among the three pneumonias, BP was the most frequent in M. pneumoniae pneumonia (0.40/case). AS predominated in C. pneumoniae pneumonia (0.67/case), and GG in C. psittaci pneumonia (0.62/case). The number of main shadows was equal, about 1.4/case in three pneumonias. Large shadows were less frequent in M. pneumoniae pneumonia than C. pneumoniae pneumonia (p = 0.02) and C. psittaci pneumonia (p = 0.01). Main shadows were more frequent in the outer zone in M. pneumoniae pneumonia than C. psittaci pneumonia (p = 0.01), and in the middle zone in C. psittaci pneumonia than in M. pneumoniae pneumonia (p = 0.02). Cases with bilateral main shadows were less common in M. pneumoniae pneumonia (9%) than C. pneumoniae pneumonia(33%, p = 0.001) and C. psittaci pneumonia(30%, p = 0.005). Thickening of bronchovascular bundles as a sub-shadow was most frequently noted in M. pneumoniae pneumonia. Some differences among the three atypical pneumonias were seen in the chest radiograph. However, no specific findings of C. pneumoniae pneumonia were shown radiographically in this study.

Aged↗

Biological fate of highly-succinylated N-succinyl-chitosan and antitumor characteristics of its water-soluble conjugate with mitomycin C at i.v. and i.p. administration into tumor-bearing mice.

Highly-succinylated N-succinyl-chitosan (Suc) was fluorescein-labeled, and the labeled product (Suc-FTC) was examined for biodisposition in Sarcoma 180-bearing mice after i.v. and i.p. administration. Suc-FTC injected intravenously was sustained at a high level in the blood circulation and showed little distribution to tissues other than tumor. On the other hand, it took a few hours for Suc-FTC to be transferred to the blood circulation after i.p. administration. There were no marked differences in the distribution of Suc-FTC between i.v. and i.p. administration routes except in the early stage. The urinary excretion of Suc-FTC following both i.v. and i.p. administration was small, but the excretion tended to be suppressed after i.p. administration. Water-soluble Sucmitomycin C conjugate (Suc-MMC) prepared using water-soluble carbodiimide exhibited marked effect at a high dose and suppressed the acute toxic side effect of MMC. Suc-MMC tended to be more toxic at i.p. administration than at i.v. administration. The difference in biodisposition between the two administrations was thought to affect the toxic side effect. The plasma levels of conjugated and free MMCs at 8 h after i.v. administration were higher than those at 8 h after i.p. administration. These suggested more localization of the conjugate in peripheral tissues and less excretion at i.p. administration, which might result in greater toxicity.

Animals↗

Solid and cystic tumor of the pancreas: clinicopathologic and genetic studies of four cases.

BACKGROUND: Solid and cystic tumor (SCT) of the pancreas can be distinguished from other pancreatic neoplasms by its nearly exclusive occurrence in young women, and its favorable prognosis after complete resection. METHODS: We experienced four cases with SCT of the pancreas, and analyzed these tumors by immunohistochemical and electron microscopic studies, as well as genetic analysis of ras oncogene mutation. RESULTS: The presented cases expressed the neuron-specific enolase in two cases, alpha1-antitrypsin and alpha1-antichymotrypsin in two cases, and vimentin in one case, which indicated that this tumor originates from pleuripotential embryonic stem cells. No patients had mutations of K-ras gene in codon 12, and further genetic analysis is required to predict the malignant potential. CONCLUSION: SCT of the pancreas appears to have limited malignant potential and the metastatic ratio is not high, although the tumor has local invasion. Therefore, an aggressive surgical approach seems fully justified.

Adult↗

SH1 (cysteine 717) of smooth muscle myosin: its role in motor function.

To determine if a thiol group called SH1 has an important role in myosin's motor function, we made a mutant heavy meromyosin (HMM) without the thiol group and analyzed its properties. In chicken gizzard myosin, SH1 is located on the cysteine residue at position 717. By using genetic engineering techniques, this cysteine was substituted with threonine in chicken gizzard HMM, and that mutant HMM and unmutated HMM were expressed in biochemical quantities using a baculovirus system. The basal EDTA-, Ca(2+)-, and Mg(2+)-ATPase activities of the mutant were similar to those of HMM whose SH1 was modified by N-iodoacetyl-N'-(5-sulfo-1-naphthyl)ethylenediamine (IAEDANS). However, while the chemically modified HMM lost the function of the light chain phosphorylation-dependent regulation of the actin-activated ATPase activity, the mutant HMM exhibited the normal light chain-regulated actin-activated ATPase activity. Using an in vitro motility assay system, we found that the IAEDANS-modified HMM was unable to propel actin filaments but that the mutant HMM was able to move actin filaments in a manner indistinguishable from filament sliding generated by unmutated HMM. These results indicate that SH1 itself is not essential for the motor function of myosin and suggest that various effects observed with HMM modified by thiol reagents such as IAEDANS are caused by the bulkiness of the attached probes, which interferes with the swinging motion generated during ATP hydrolysis.

Amino Acid Sequence↗

Preparation and evaluation of double-phased mucoadhesive suppositories of lidocaine utilizing Carbopol and white beeswax.

In an attempt to restrict drug absorption from suppositories to only the lower rectum, mucoadhesive lidocaine (LID) suppositories were prepared using Witepsol H-15 as a base, and Carbopol 934P (CP) and white beeswax (WAX) as additives. CP has a mucoadhesive property and WAX gives the suppositories stiffness. The suppositories containing 10% CP and 20% WAX stayed in the lower recta of rats for at least 2 h. Double-phased suppositories consisting of a front layer containing 10% CP and 20% WAX and a terminal layer containing LID and various amounts of CP were prepared. In vitro release profiles of LID from double-phased suppositories were similar to conventional single-phased suppositories containing CP alone. Values of AUC(0-6 h) and MRT of LID after administration of double-phased suppositories to rabbits were larger than those for single-phased suppositories with or without CP. On the other hand, the initial plasma metabolites concentrations after administration of double-phased suppositories were significantly lower and tended to exhibit delayed T(max) compared to single-phased suppositories. These results suggest that the double-phased mucoadhesive suppositories suppress initial metabolism of LID, and may be useful for improving bioavailabilities of drugs, like LID, which accept first-pass effect considerably.

Acrylic Resins↗

A novel missense mutation (G209R) in exon 8 of the presenilin 1 gene in a Japanese family with presenile familial Alzheimer's disease. Mutation in brief no. 254. Online.

Over fifty missense mutations in the presenilin-1 (PSEN1) gene have been reported in families with presenile familial Alzheimer's disease (FAD). We describe a novel missense mutation (G209R) within the predicted fourth transmembrane domain of the PSEN1 in a Japanese family with presenile FAD. The affected cases showed similar disease histories with the mean age at onset of 49.6 +/- 3.1 years and rapid progressive dementia characterized by memory impairment, amnestic aphasia, disorientation and personality change, but lacking parietal focal symptoms such as apraxia or agnosia. Compared with the previously reported cases of same Gly209 mutation (G209V), the clinical features of the G209R-FAD cases appear to be less critical than those of G209V-FAD cases, although the Gly to Arg mutation is considered to be less conservative than the Gly to Val mutation. These findings may suggest the possible existence of other genetic and/or environmental factors or the possibility that these two different Gly209 mutations may underlie different pathomechanisms in the development of presenile FAD.

Alzheimer Disease↗

Pelizaeus-Merzbacher disease: three novel mutations and implication for locus heterogeneity.

We report a mutational and polymorphic analysis of the proteolipid protein gene in members of 27 Japanese families with Pelizaeus-Merzbacher disease. We found causative mutations in 6 members of 27 families (22.2%); 5 of the 6 mutations, including two novel mutations, Leu45Arg and 231 + 2T --> G, resulted in the typically severe clinical symptoms. Paradoxically, the Cys219Tyr mutation, presumed to disrupt the tertiary structure of proteolipid protein by removing the disulfide bond between Cys200 and Cys219, was associated with a mild clinical presentation wherein the patient could walk with assistance and speak. It was inferred that the structural change prevented the toxicity associated with a gain of function mutation. Moreover, in one family 3 patients exhibited a intragenic polymorphism that did not segregate with the disease, suggesting a locus heterogeneity for Pelizaeus-Merzbacher disease.

Adult↗

Granulomatous nephritis as a complication of intrarenal bacille Calmette-Guérin therapy.

A case of granulomatous nephritis after intrarenal bacille Calmette-Guérin (BCG) therapy is reported. High fever greater than 38.5 degrees C lasted for 1 month, without response to conservative therapy. Standard nephroureterectomy was subsequently carried out. Histopathologic findings from the surgical specimen were compatible with BCG-induced granulomatous nephritis. The use of a syringe pump for retrograde instillation of BCG was thought to be the major cause of this severe complication.

Aged↗

Biodegradation and distribution of water-soluble chitosan in mice.

Randomly 50% deacetylated chitin, called Chi, was examined on the biodegradability, body distribution and urinary excretion after the intraperitoneal (ip) administration to mice. These characteristics were investigated using fluorescein isothiocyanate (FITC)-labeled Chi (FTC-Chi). The in vitro biodegradability was investigated by incubation with lysozyme and murine plasma and urine. The degradation of Chi or FTC-Chi was accelerated by lysozyme, plasma and urine. The molecular weight was checked by gel-chromatography. The degradation product showed a fairly small molecular weight and contained no FTC-Chi of a large one. The body distribution and urinary excretion of FTC-Chi were investigated at 1, 14 and 24 h after the ip injection to mice. FTC-Chi moved fast to the kidney and urine, and was scarcely distributed to the liver, spleen, abdominal dropsy and plasma. Most of FTC-Chi was excreted into urine after 14 h, and the molecular weight of the excreted FTC-Chi was as small as that of the product obtained by the long in vitro incubation. Therefore, Chi is considered to be highly biodegradable and easily excreted in urine, and further it is suggested to have no problem on accumulation in the body; however, at the same time, Chi is found not to operate as a polymer support showing long retention in the body.

Acetylation↗

Reduction in subluxation and improved muscle function of the hemiplegic shoulder joint after therapeutic electrical stimulation.

Seventeen hemiplegic patients with chronic shoulder subluxation secondary to a cerebrovascular accident (CVA) were divided into three groups, two of which were subjected to 6 weeks of therapeutic electrical stimulation (TES) for 15 minutes twice a day, in order to assess the effectiveness of the treatment in reducing subluxation, and in improving shoulder abduction function. The third group was used as a control (C group). After 6 weeks of electrical stimulation of the supraspinatus (S group) and deltoid (D group), a significant (p<0.05) reduction in subluxation was observed in both groups when compared to the C group. The maximal force of shoulder abduction showed a tendency to increase in the S group (p<0.10). A significant increase in maximal force was also observed in the D group. In most of the TES-treated muscles, the interference pattern of EMG at maximum voluntary contraction increased. The amplitude of the EMG activity of the stimulated muscle also increased. Thus, we concluded that electrical stimulation therapy of the supraspinatus and the deltoid muscle is an effective treatment modality for shoulder subluxation and shoulder abduction function in hemiplegic patients.

Chronic Disease↗

Biodisposition characteristics of N-succinyl-chitosan and glycol-chitosan in normal and tumor-bearing mice.

Two water-soluble chitosan derivatives, N-succinyl-chitosan (Suc-chi; average MW 3x10(5)) and glycol-chitosan (Gly-chi; average MW 1.5x10(5)), were examined concerning their biodisposition characteristics in order to evaluate their possible use as water-soluble drug carriers. Their body distribution and urinary excretion were investigated by i.v. administration of FITC-labeled Suc-chi (FTC-Suc-chi) and FITC-labeled Gly-chi (FTC-Gly-chi) to normal and Sarcoma 180 solid tumor-bearing mice. In normal mice, both polymers showed good retention in blood circulation; especially, FTC-Suc-chi exhibited a long half-life of 51 h, and its distribution to other tissues was very small. FTC-Gly-chi was distributed into the kidney to a relatively high extent. In tumor-bearing mice, FTC-Suc-chi and FTC-Gly-chi were eliminated faster from the blood circulation than in normal mice, that is, with half-lives of 11 and 7 h, respectively. FTC-Suc-chi was less partitioned to the tumor tissue but accumulated more easily into it compared with FTC-Gly-chi. This suggested the enhanced permeability and retention (EPR) effect of Suc-chi and explained the previous result that a water-soluble Suc-chi-mitomycin C conjugate injected intravenously exhibited a good effect against Sarcoma 180 solid tumor. FTC-Gly-chi showed greater distribution to the kidney than in normal mice. Urinary excretion studies indicated the faster excretion of both polymers in tumor-bearing mice. The molecular weight of the products excreted into urine indicated that both polymers should be pretty resistant to the hydrolytic enzyme, lysozyme. Taking toxicities into account, Suc-chi is considered to be available as a drug carrier showing long systemic retention and tumor accumulation.

Animals↗

[A case of metastatic liposarcoma originating in the retroperitoneum successfully treated with combination chemotherapy].

We reported a 36-year-old woman with metastatic liposarcoma originating in the retroperitoneum, which responded well to adjuvant chemotherapy. The primary tumor was removed by surgery. Two months later, the patient developed metastasis to the brain, and to the lung four months later. Metastatic liposarcomas to the brain generally are extremely rare. The patient was treated with combination chemotherapy using cyclophosphamide, vincristine, adriamycin, and dacarbazine (CYVADIC). After she was examined, the former two drugs were alternated with vindesine and ifosfamide, and another regimen with cisplatin and etoposide was given after a three-week interval. As a result, both of the metastases totally disappeared. No recurrent lesion has been noted for two years. Although the role of chemotherapy for liposarcoma has not been well defined and little data support its use in an adjuvant setting, this combination chemotherapy seemed to be effective for advanced liposarcoma.

Adult↗

[Bilateral breast metastases from prostatic carcinoma: a case report].

We report a case of bilateral breast metastases from prostatic carcinoma. A 49-year-old man with stage D2 prostate cancer, who had been treated by chemoendocrine therapy and radiotherapy for 2 years, complained of bilateral enlarged breasts. Oral administration of diethylstilbestrol diphosphate was started 2 months before the onset of this symptom. A firm mass that was not tender was palpable beneath the skin without fixation on each side. A needle biopsy of the masses showed poorly differentiated adenocarcinoma with positive immunohistopathological staining for prostate-specific antigen. The masses were diagnosed as metastatic adenocarcinoma of prostate gland origin. The patient died 3 months after the diagnosis of breast metastases. Autopsy revealed diffuse lymphogenous metastatic disease. Metastatic prostatic carcinoma to the breast is uncommon. Breast metastases in this patient might be associated with diffuse lymphogenous metastases as well as increased local blood and lymphatic supply caused by extrinsic estrogens.

Adenocarcinoma↗

[Laparoscopic nephropexy for symptomatic nephroptosis: a case report].

We present our clinical findings of laparoscopic nephropexy performed on a 32-year-old woman with symptomatic nephroptosis. Supine and erect excretory urography (DIP) revealed right renal descent of 2.5 vertebral bodies with hydronephrosis. Laparoscopic transperitoneal nephropexy was performed using nonabsorbable sutures, polyglactin net, hernial staplers and tissue adhesive. An upright DIP 1 month postoperatively revealed renal descent of only 1 vertebral body and no hydronephrosis. One year postoperatively, the patient is asymptomatic. A laparoscopic procedure, which is safe, effective and causes minimal morbidity, represents an excellent approach for repair of symptomatic nephroptosis.

Adult↗

Phylogenic analysis of echovirus type 30 isolated from a large epidemic of aseptic meningitis in Japan during 1997-1998.

During 1997 to 1998, a nationwide epidemic of aseptic meningitis occurred in Japan. More than 4,500 isolates from patients with aseptic meningitis were identified as echovirus type 30. To investigate the character of these isolates, we examined the nucleotide sequences of thirty-seven geographical representatives and compared them with 50 strains isolated during the past 20 years. The phylogenic analysis used partial sequences from either the VP1 or VP4-VP2 region of the viral capsid. This analysis revealed that the isolates were divided into six genomic groups. All isolates identified during 1997-1998 belonged to only two genomic groups; these two groups are thought to be the causative viral agents involved in the recent epidemic.

Enterovirus B, Human↗