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Biomedical subjects

K Ohara

Publications and source records attributed to K Ohara.

At least 163 records · Page 9Linked to original sources
PubMed1994

Dopamine D4 receptor repeat: analysis of different native and mutant forms of the human and rat genes.

Recent molecular characterization of the human D4 gene has revealed the existence of various polymorphic forms of this receptor. These variations are found in the putative third cytoplasmic loop region and encode a variable number of repeats of 16 amino acids in length. In the present study we have compared the pharmacological binding profiles of seven different polymorphic variants of the human D4 receptor, the rat D4 receptor, and two different human D4 receptor mutants that were deleted in the repeat sequence. For this purpose we cloned the rat D4 receptor gene and compared its gene structure and its pharmacological binding profile with those of the D4.4 and D4.7 genes. The rat and human D4 genes display a high degree of sequence similarity, especially in the coding regions. An Alu repeat sequence was identified in the first intron of the human D4 gene but is not present in the rat D4 gene. Furthermore, using the polymerase chain reaction we cloned 3-, 5-, 6-, and 9-fold repeat sequences. These cloned repeat sequences were used for the reconstruction of full length cDNAs encoding D4.3, D4.5, D4.6, and D4.9, respectively. These novel forms of the human D4 receptor, as well as the previously cloned D4.2, D4.4, and D4.7 forms, were transiently expressed in COS-7 cells. All of the different forms of the human and rat D4 receptors and repeat deletion mutants displayed similar binding profiles for all ligands tested, although small differences were observed. The affinity for dopamine could be decreased by guanosine-5'-(beta, gamma-imido)triphosphate with the different forms of the D4 receptor, including the two receptor mutants that were deleted in the repeat sequence. These data suggest that the polymorphic repeat sequence has little influence on D4 binding profiles and might not be essential for G protein interaction.

Amino Acid Sequence↗
PubMed1994

[Short-term intensive consolidation chemotherapy in the treatment of acute nonlymphocytic leukemia].

Thirty-four adults with AML were treated with conventional remission induction chemotherapy consisting of Ara-C and daunorubicin. The median age was 55 years. Thirty (88%) patients showing complete remission (CR) were treated with four courses of intensive consolidation chemotherapy: course 1 with 7 days Ara-C and 4 days of mitoxantrone; course 2 and 7 days Ara-C, 5 days of etoposide, vincristine day 10 and vinblastine day 12 (A-Triple-V); course 3 with 7 days Ara-C and 3 days of aclacinomycin; course 4 with 7 days Ara-C and 3 days of daunorubicin. Then patients were observed without further therapy until relapse. The median duration of relapse-free survival for patients < 60 years of age was 13 months, with 49% patients projected to continue first CR at 52 months. In contrast, only 19% of patients 60 years or older were projected to be in CR at 22 months. Most patients experienced significant side effects including fever, liver dysfunction, pneumonia and septicemia during consolidation therapies. Short-term intensive consolidation therapy appeared to be efficacious for patients < 60 years of age. The results in older individuals were worse than expected, and the use of G-CSF was suggested to improve this problem.

Aclarubicin↗
PubMed1993

An assay of flavin-containing monooxygenase activity with benzydamine N-oxidation.

An assay system of flavin-containing monooxygenase was developed by fluorometric determination of benzydamine (BZY) N-oxidation with HPLC. The apparent Km value for the formation of BZY N-oxide from BZY by rat liver microsomes was similar to that by purified FMO. The Km and Vmax values for the formation of N-desmethylbenzydamine (Nor-BZY) by rat liver microsomes were about 50 times greater and 2000 times less, respectively, than those of BZY N-oxide. Nor-BZY was not formed upon incubation with purified enzyme. BZY N-oxidation activity was completely inhibited both in the absence of NADPH and by heat inactivation. The reaction was inhibited in the presence of 0.5 mM thiourea, but 2 mM SKF-525A did not affect BZY N-oxidation. Moreover, rabbit antibody raised against the rat enzyme inhibited BZY N-oxidation. These results are in accord with a simple, rapid, and sensitive assay for the enzyme.

Animals↗
PubMed1993

Transbronchial lung biopsy in the diagnosis of suspected ocular sarcoidosis.

We conducted clinical research using transbronchial lung biopsy in 60 patients with suspected ocular sarcoidosis who showed no bilateral hilar lymphadenopathy and sparse contributory evidence for sarcoidosis. The patients had a combination of granulomatous iritis with mutton-fat keratic precipitates or iris nodules, trabecular nodules, tent-like peripheral anterior synechiae, snowball or string-of-pearls vitreous opacities, retinal perivasculitis, and spotty retinochoroidal exudates. The transbronchial lung biopsy specimen showed noncaseating epithelioid granuloma in 37 patients (61.7%); these patients were diagnosed as having sarcoidosis. Bronchoalveolar lavage showed a high percentage of patients with an increased lymphocyte fraction among those with positive transbronchial lung biopsy results. The present results may serve as a basis for a clinical diagnosis of sarcoidosis in patients with suspected sarcoidosis without apparent extraocular manifestations.

Adolescent↗
PubMed1993

Clinical results of fractionated proton therapy.

PURPOSE: Preliminary results of a multi-site Phase I-II clinical trial investigating the efficacy of high-energy proton beams in a wide variety of human malignancies are reported. METHODS AND MATERIALS: Since 1983 proton radiotherapy using 250 MeV proton beams produced by a booster synchrotron of the National Laboratory for High Energy Physics has been carried out at Proton Medical Research Center, University of Tsukuba. As of September 1990, a total of 147 patients received a partial or full treatment with proton beams with curative intent; 92 patients (63%) were treated with proton beams alone and 55 patients (37%) with combined photon and proton beams. There were 91 males and the mean age was 61.8 years old. The follow-up observation period ranged from 10 to 97 months. With regard to a total tumor dose, nearly 80% of patients received 70 Gy or more and 53% received 80 Gy or more. While dose-fractionations used depended upon tumor sites, the large majority of patients received substantially high radiation doses in terms of larger total doses (> 70 Gy) and larger fraction sizes (> 2.5 Gy) than those traditionally used. This fractionation regimen has been used because of limited availability of the accelerator or a shortage of machine time (27-30 weeks/year, 3-3.5 hr/day), and also by the expectation that the superior dose distribution possible with protons will permit administration of high radiation doses without increasing morbidities. In connection with this, we have determined the target volume by setting margins around the tumor boundary as practically small as possible, ranging from 5 to 10 mm. RESULTS AND CONCLUSIONS: The current trial has been based on a site and dose searching program, hence a wide variety of tumor sites including the aerodigestive organs has been treated. So far, our judgment is that proton therapy has proven of potential advantage in treatment of the lung, esophageal, liver, uterine cervix, prostate, and head and neck malignancies; and of possible value in treatment of high-grade gliomas, and gastric, urinary bladder, and pediatric tumors.

Adolescent↗
PubMed1993

Oral absorption of FK506 in rats.

The oral absorption of FK506 in solid dispersion formulation was studied in rats. The obtained area under the concentration versus time curve (AUC) increased in a nonlinear fashion with a small dose-dependent increase in the peak blood concentrations (Cmax). The peak concentration time (Tmax) was observed within 30 min after administration in all dosing groups (1-10 mg/kg) with or without feeding, whereas the oral absorption of FK506 was reduced to about 50% by gavage at a dose of 1 mg/kg. Participation of first-pass elimination was suggested by comparing the blood levels after infusion via the portal vein with those after infusion via the femoral vein. Further, in an in vitro stability study and an in situ loop absorption study, FK506 was fairly stable in the gastrointestinal juice and was absorbed predominantly from the upper part of the small intestine.

Administration, Oral↗
PubMed1993

Schizophrenia: dopamine D1 receptor sequence is normal, but has DNA polymorphisms.

Genes that regulate dopamine (DA) receptors may underlie the overactive DA system in schizophrenia. Since it is known that there is an abnormally reduced or absent regulation of the DA D2 receptor by the DA D1 receptor in the postmortem schizophrenia brain, the human DA D1 receptor gene was sequenced from genomic deoxyribonucleic acid (DNA) of seven schizophrenic individuals. The tissues from two schizophrenics had previously been found to have a reduced link between DA D1 and D2 receptors. The D1 receptor genes were amplified by the polymerase chain reaction, subcloned, and sequenced. Although three DNA polymorphisms were found, the deduced amino acid sequence of the DA D1 receptor was normal in these tissues.

Adult↗
PubMed1993

Schizophrenia: normal sequence in the dopamine D2 receptor region that couples to G-proteins. DNA polymorphisms in D2.

Because dopamine (DA) D2 receptors are a target in neuroleptic therapy and have been found to be elevated in schizophrenia, the human DA D2 receptor gene was examined for possible abnormalities in schizophrenia. Moreover, since D2 receptors in psychosis have a reduced coupling to D1 receptors, the cytoplasmic third loop of D2 was chosen for deoxyribonucleic acid (DNA) sequencing, since this region is essential for coupling to G-proteins. This region also contains exon 5, which is expressed in the long form of D2, but not in the short form of D2. In eight schizophrenia cases, this region had normal exon sequences (exons 4, 5 and 6), and normal sequences at its intron-exon junctions. However, exon 6 contained three DNA polymorphic base changes, and introns 4 and 5 revealed three missing bases and two polymorphic base changes, none of which would be expected to alter the D2 receptor protein in schizophrenia.

Amino Acid Sequence↗
PubMed1993

Partial trisomy for short arm of chromosome 5.

We present two unrelated cases of partial trisomy for the short arm of chromosome 5, the first such cases reported in Japan. The features are characterized by hypertelorism, low set ears, arachnodactyly, laryngostenosis, hypotonia and some cerebral malformation. The characteristic facial expression and arachnodactyly are the key features used to diagnose this disorder. A high-resolution chromosome banding technique showed that the karyotype of the first patient was 46,XX,inv dup(5) (p13.1-->p15.3) de novo and that of the second patient was 46,XX,dir dup(5) (p13.3-->p15.2) de novo. The similar symptoms in the two cases, despite the difference in karyotypes, were caused by duplication of 5p including segment 5p13. This would be a key site for this disorder.

Abnormalities, Multiple↗
PubMed1993

Circadian variation in plasma 5-hydroxyindoleacetic acid level during and after alcohol withdrawal: phase advances in alcoholic patients compared with normal subjects.

Alcohol withdrawal symptoms in 19 male alcoholics were objectively evaluated and classified and circadian variation in their plasma 5-hydroxyindoleacetic acid (5-HIAA) concentrations was determined at 3 different intervals after cessation of drinking. Circadian variations in plasma 5-HIAA level exhibited phase advances in alcoholic patients compared with normal controls and were different depending on the severity of alcohol withdrawal symptoms. Plasma 5-HIAA in patients with delirium tremens showed significantly higher levels during the abstention period, possibly suggesting peculiarity in their serotonergic metabolism.

Adult↗
PubMed1993

Genetic development of an inbred rat strain with increased resistance adaptation to a hot environment.

The purpose of this study was to demonstrate resistance adaptation based on genotypic adaptation and to develop an inbred rat strain with genotypic resistance adaptation to a hot environment. Survival time (ST) at an ambient temperature (Ta) of 42.5 degrees C was determined without appreciable thermal damage. Rats with the longest ST were sibmated over 30 generations and designated FOK. The ST, evaporative water loss, and body water economy increased rapidly during the first 10-15 generations, followed by a more gradual increase. The FOK rat resisted a Ta of 42.5 degrees C for > 5 h; this ability was hereditary. Body size progressively decreased during the early generations. The ST was longer (P < 0.01) and evaporative water loss was significantly higher (P < 0.01) in the FOK rat compared with three other strains. Tail lengths in the FOK rat were slightly shorter than those of three controls (P < 0.01). The heat loss system in the FOK rat may depend on the ability to mobilize and evaporate body fluids efficiently. FOK rats can be used for phenotypic comparisons with other strains, as well as in molecular genetic studies on thermoregulation, osmoregulation, and resistance adaptation to heat using recombinant inbred and recombinant congenic lines.

Acclimatization↗
PubMed1993

Toxicity of polyoxyethylene hydrogenated castor oil 60 (HCO-60) in experimental animals.

HCO-60, a polyoxyethylene castor oil derivative, is used as a solubilizer in the injectable formulations of lipophilic agents. This study was performed to examine the toxicity of HCO-60 in various experimental animals including dogs, monkeys, rabbits, guinea pigs and rats. With 1.25 or 2.5 mg/kg of HCO-60 injected i.v. to dogs, blood pressure decreased, flush, swelling and itching appeared after injection, and with 10 mg/kg of HCO-60 there was additionally a decrease of spontaneous motility. In the two higher dose groups, these symptoms paralleled an increase of histamine levels. Since degranulation was observed after injection in the mast cells of the skin, but not in the liver of dogs, the histamine in the plasma was considered to be released from the mast cells of the skin. Pretreatment with diphenhydramine, a H1-receptor antagonist, suppressed the decrease of blood pressure induced by HCO-60. These findings show that the toxicity of HCO-60 is associated with histamine release from the mast cells. No symptoms occurred in monkeys, rabbits, guinea pigs or rats with 50 or 100 mg/kg of i.v. of HCO-60, and there was no change in plasma histamine levels. This study demonstrated that the toxicity of HCO-60 is species specific to dogs among the animals tested.

Animals↗
PubMed1993

[Evaluation of the viscoelasticity of the human carotid wall by ultrasonography].

The purpose of this study is to evaluate non-invasively the viscoelastisity of the human carotid wall by ultrasonographic techniques. After mathematical fundamental experimentation using a rubber tube as a vessel wall model, we observed viscoelastic changes in the carotid wall in normal cases in relation to aging and in treated and non-treated cases with hypertension. An amplified single rectangular mechanical impulse with a 0.5 msec duration was applied to the carotid wall percutaneously by using Wilcoxon's vibrator. We converted B-mode images at one point of the carotid wall to ultrasonic variant M-mode images, and damped oscillation waves were thus obtained. The ultrasonic variant M-mode method, which was developed in our department to detect small vibrations of the vocal cord, was used to observe fine impulse excitations of the carotid wall. This ultrasonographic method (variant M-mode) shows the amount of reflected echoes, which are changed to electrical potentials at one point of the carotid wall. Yerzley Resilience (Y.R.) and resonance frequency (R.F.), as well as the Q-value of resonance, (Q.V.) were measured from these damped oscillation waves. It is widely known that Y.R. shows the degree of viscosity of the carotid wall while R.F. and Q.V. show the stiffness of the carotid wall indirectly. A Y.R. of 100% means complete elasticity with lower viscosity and damping degree. When Y.R. comes close to 0%, both viscosity and damping and degree increase. The carotid wall becomes stiffer in proportion to R.F. and Q.V. The following results were obtained: 1) Y.R., R.F. and Q.V. increased with aging. 2) In non-treated cases with hypertention, Y.R. was significantly, while R.F. and Q.V. tended to be, higher than in normal cases of the same generation. 3) In treated cases with hypertention, Y.R., R.F. and Q.V. had a tendency to be lower than in non-treated cases. In conclusion, non-invasive evaluation of carotid wall viscoelastisity appears to be feasible, and further investigation is warranted for applying this ultrasonographic technique to the field of head and neck vessel surgery.

Adult↗
PubMed1993

Explant culture of human lens epithelial cells from senile cataract patients.

Human lens epithelial cells (HLECs) with lens capsules were cultured to investigate the morphology and outgrowth potential of the cultured cells. Anterior lens capsules obtained during cataract surgery were placed cell side down in a medium in culture wells. Cultivation was successful with 24 of 36 specimens from senile cataract patients. The HLECs grew beyond the capsular edge from the third to fifth day after the beginning of cultivation, and extended actively to the periphery of the culture well. The cells had extended 2.5 mm beyond the capsular edge by the second week and 3.8 mm by the fourth week, but outgrowth then stopped. The cells near the capsular edge displayed elongated shapes during the earlier period of cultivation, but subsequently formed small polygons. The cells in the middle of the zone of outgrowth appeared as polygons, and were surrounded by large, irregularly-shaped cells. This study showed that HLECs from senile cataract patients have a limited but definitive outgrowth potential under explant culture conditions.

Aged↗
PubMed1993

Effects of pretreatment with mydriatics on intraocular penetration of 0.1% pranoprofen.

The mechanism by which an increase in the intraocular concentration of topically applied 0.1% pranoprofen (PPF) is induced by pretreatment with Mydrin P (0.5% tropicamide and 0.5% phenylephrine) was studied in rabbit eyes. In separate experiments, solutions of each of the various ingredients contained in Mydrin P ophthalmic solution were applied 60 minutes prior to instillation of PPF. Ninety minutes after PPF instillation, its concentration in the cornea, aqueous humor and iris-ciliary body were measured by high performance liquid chromatography. PPF concentration was not increased by pretreatment with benzalkonium chloride, chlorobutanol or tropicamide, but was increased by pretreatment with phenylephrine (PHE). After the latter, the PPF concentration was 2 to 3 times higher than that obtained without Mydrin P. It is noteworthy that the concentration of PHE in the aqueous humor also was found to be increased about 3 times in the presence of PPF. The lipophilicity of PPF, judged by the octanol/buffer partition coefficient, was increased when mixed with PHE. These findings indicate that the increase in intraocular PPF concentration after pretreatment with Mydrin P was caused by PHE. This may be attributable to the enhancement of corneal permeability to PPF resulting from formation of an ion-pair complex between the anionic PPF and the cationic PHE.

Animals↗
PubMed1993

Long-term survivors after salvage surgery combined with radiotherapy for recurrence of stage IV main hepatic duct cancer--report of two cases.

Main hepatic duct cancer is notorious for its poor prognosis and frequent locoregional failure of therapy even after curative resection. In this paper, two cases of recurrent carcinoma of the stage IVA main hepatic duct are presented. One patient had local failure 13 years after curative resection of the tumor and the other had regional failure 18 months after combination treatment with non-curative resection and intra-operative radiation therapy. Recurrent tumors were successfully treated with combined resection and postoperative radiation therapy or with combined intra-operative radiation therapy and postoperative radiation therapy. The patients are well 16.9 and 6.3 years, respectively, after primary tumor resection. We briefly review a number of other reports of salvage treatment in patients with recurrent carcinoma of the main hepatic ducts and discuss the results with particular reference to the advantage of salvage therapy for the main hepatic duct cancer.

Adenocarcinoma↗