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Biomedical subjects

K Ohara

Publications and source records attributed to K Ohara.

At least 19 recordsLinked to original sources
PubMed1996

Polymorphisms of dopamine D2-like (D2, D3, and D4) receptors in schizophrenia.

The result of most association studies and linkage analyses have suggested a negative association between schizophrenia and D2-like (D2, D3, and D4) receptor polymorphisms. Although the polymorphisms of the D2-like receptor in themselves may not account for the etiology of schizophrenia, they can contribute to the severity of the symptoms. Thus, we studied the associations between the polymorphisms and their combinations, and the vulnerability of schizophrenics. Fragments of the D2-like receptor genes were amplified by means of the polymerase chain reaction, and the polymorphisms were identified by the restriction fragment length polymorphism and single-stranded conformation polymorphism methods. There were no statistically significant differences in the polymorphisms and their combinations between schizophrenics and controls. Schizophrenics with D4E1(A1/A2), which contains 2 and 1 tandem repeats of a 12-base-pair sequence in exon 1, had a lower total positive symptom score before medication than schizophrenics with D4E1(A1/A1). There was no association between the polymorphisms and negative symptoms.

Adult↗
PubMed1996

Effect of Prograf (FK506) on spermatogenesis in rats.

Prograf (FK506) was given to male mature rats in a daily subcutaneous dose of 1 or 3 mg/kg/day for 2 weeks to investigate its effect on spermatogenesis. Prograf dose-dependently sperm counts and motility, but did not affect testosterone level in the serum of rats. Histopathologically, there were no abnormal changes in the testis, seminal vesicle or prostate in any rats dosed with Prograf, but intra-ductal eosinophilic globules, probably degeneration of the sperm cells, were observed in the epididymis of the 3 mg/kg/day group. Sperm counts and motility returned to the control levels after stopping of the drug. The results indicate that Prograf decreased sperm counts and motility through direct action on the sperm in the epididymis, but not the production of sperm in the testis. Cyclosporine A (CsA) was used as the reference drug in the present study. Thirty mg/kg/day of CsA also decreased sperm counts and motility, and stopping of the drug led to the recovery of these changes. The males dosed with Prograf for 2 weeks were mated with non-dosed females to investigate its effect on the fertility potential of the males. Prograf did not affect copulation or fertility index, but a decrease in the number of live fetuses associated with implantation loss was observed in the 3 mg/kg/day group. The changes were considered to be due to the decrease of sperm counts and motility, although 1 mg/kg/day of Prograf, 5-10 times the clinical dose, did not affect any fertility parameters including implantation index.

Animals↗
PubMed1996

Daily rhythm of serum melatonin in patients with dementia of the degenerate type.

The daily rhythm in serum melatonin levels was measured in patients with dementia of the degenerate type (Alzheimer's disease, Pick's disease and senile dementia of the Alzheimer type) by radioimmunoassay. Thirteen patients (age: 69.0 +/- 8.0 years, mean +/- S.D.) were studied. All patients were hospitalized at the time of the study and had a history of sleep-wake disturbances, nocturnal wandering and/or delirium. We also studied 13 age-matched healthy control subjects (control group 1), ten young adults (control group 2), and nine hospitalized patients without dementia (control group 3). Two subjects in the control groups showed no measurable changes in melatonin level throughout the day, while the other 30 control subjects exhibited a clear daily rhythm with the peak concentration occurring during the night. On the other hand, four out of the 13 patients with dementia did not show any melatonin rhythm. Two of the demented patients who did not exhibit melatonin rhythm displayed clinical symptoms of rhythm disorders. One out of the nine patients with melatonin rhythm presented with clinical symptoms, such as delirium and sleep-wake disturbance. Our results suggest that the probability of absent melatonin rhythm is higher in demented patients compared with subjects without dementia. However, a lack of melatonin rhythm is not always associated with symptomatic rhythm disorders. Since the melatonin rhythm reflects that of the suprachiasmatic nucleus, it follows that the SCN function of the patients having a history of rhythm disorders was not always severely damaged.

Aged↗
PubMed1996

Impact of biological clearance on tumor radioresponsiveness.

PURPOSE: To determine the capacity of biological clearance in tumor regression following radiotherapy by using metastatic brain tumors as a clinical model in which mechanical clearance is negligible. METHODS AND MATERIALS: Thirty-eight tumors (19 nonsmall cell lung cancer, 11 small cell lung cancer, and 8 nonlung cancer) in 23 patients were followed with computed tomography (CT) scans over 3 months or more following initiation of radiotherapy, with doses ranging between 34 and 66 Gy. The tumor regression rate (RR; mm3/day), which represented the capacity of biological clearance, was calculated for each CT observation period. The complete response (CR) rate was calculated. The relationship between RR and tumor diameter was determined with regression analysis in conjunction with the pattern of contrast enhancement and the type of primary disease. The change of the RR also was examined. RESULTS: The CR rate was 60.5% for the total group; it was lower for ring-enhanced tumors (41.7%) than diffusely enhanced tumors (69.2%), which included mostly small cell lung cancer metastases. The RR correlated significantly with the tumor diameter (D), with a regression curve of exponential function (RR = 0.035 *D2.5). The RR varied widely and was rather large until 40 days following initiation of radiotherapy, especially for the subgroups of diffusely enhanced tumors and the small cell lung cancer tumors, and became rather constant thereafter. CONCLUSION: A tumor diameter exponent in the regression curve of smaller than 3.0 indicates that the larger the tumor volume is, the smaller the capacity of biological clearance. The capacity of biological clearance also is dependent on vascularity and cellularity of the tumor components expressed by the pattern of contrast enhancement.

Adult↗
PubMed1996

The genes encoding the 5HT1D alpha and 5HT1D beta receptors are unchanged in patients with panic disorder.

To determine the serotonergic function in panic disorder, sequencing of the genes encoding the 5HT1D alpha and 5HT1D beta receptors was carried out. The genes for the 5HT1D alpha and 5HT1D beta receptors were amplified by polymerase chain reaction and sequenced by the dideoxy method. Some patients have both nucleotides C and T at position 1080 in 5HT1D alpha receptor gene; however, both of them code the same amino acid, asparagine. The 5HT1D beta receptor gene had a substitution from GCA276 to GCG276, not only panic disorder but also in controls; however, this substitution does not change the corresponding amino acid, alanine92.

Adolescent↗
PubMed1996

Preoperative radiotherapy and surgery for advanced thymoma with invasion to the great vessels.

From 1983 to 1994, 12 advanced thymomas with invasion to the great vessels were initially treated by irradiation (mean dose, 18.3 Gy) and subsequent surgical resection. In nine patients, complete resection was possible by concomitant resection of the surrounding tissues, mainly pericardium and/or brachiocephalic vein. Histologically, all tumors showed prominent fibrosis. Ten patients also received postoperative radiotherapy (mean dose, 42.3 Gy). Tumor-related deaths occurred in only two patients; one who did not receive postoperative irradiation 21 months and one who had viable cells at the surgical margin 10 months after operation. However, there were also 2 patients who died of respiratory failure due to operation and/or irradiation, one 45 days and the other 7 years after the treatment. Preoperative radiotherapy could facilitate complete resection of the advanced thymomas. The prognosis of the patients treated with preoperative radiotherapy seemed fair if followed by adequate resection and subsequent irradiation.

Adult↗
PubMed1996

Intact 5-HT2A receptor exons and the adjoining intron regions in schizophrenia.

Genes that regulate serotonergic (5-HT) systems may underlie the etiology of schizophrenia. In this study the gene encoding the 5-HT2A receptor in schizophrenics and healthy controls was examined. First, we sequenced all exons and the flanking introns of the 5-HT2A receptor gene in 10 schizophrenics and 10 controls. The substitution of C for T at position 102 in exon, which had been reported by Warren et al. (1993), was confirmed. Restriction fragment length polymorphism (RFLP) analysis revealed no association between polymorphism and schizophrenia. There was no association between the polymorphism and subdiagnosis, family history, age of onset, amounts of antipsychotics, or positive and negative symptoms before or after medication. Other polymorphisms in the gene were screened in 100 schizophrenics by the single-strand conformation polymorphism method, but none was found. Our results suggest that an abnormality in the 5-HT2A receptor gene in schizophrenia is unlikely.

Adult↗
PubMed1996

A new surgical technique for postaxial polydactyly of the foot.

A new technique for the treatment of the most common type of postaxial polysyndactyly of the foot is presented. The technique employs four local flaps and a skin graft from the pedal area. The outermost skeletal elements and nail tissue were excised, while the fourth interdigital commissure was deepened. This differs from historical techniques of desyndactylization in the hand that have been applied to surgery in the foot. The new technique is characterized by minimal waste of tissue from the outermost toe with preservation of the dominant fifth toe.

Abnormalities, Multiple↗
PubMed1996

Acral lentiginous melanoma (including in situ melanoma) arising in association with naevocellular naevi.

Acral lentiginous melanoma (ALM) occurring on the sole of the foot is the most common type of malignant melanoma in Asians, African and North American Blacks, but is relatively infrequent in Caucasians. According to the literature ALM is thought less likely to arise in a precursor naevus of any type or be associated with dysplastic naevi elsewhere on the skin. We present five cases of ALM (two invasive and three in situ cases) arising in association with pre-existing naevi on the foot in Asians and Caucasians. All patients were female, aged 35-66 years (mean = 47.8). Clinically, all five tumours demonstrated various shades of tan, brown and black, admixed with hypopigmented areas. Histologically, these melanomas showed a lentiginous character of the radial growth phase component with rare foci of pagetoid intra-epidermal spread. Invasive determal components in the form of epithelial and spindle cells were evident in two cases, with a measured depth of 1.7 and 0.85 mm, respectively. Pre-existing naevi, either dermal or junctional, were identified in all tumours. Clinical follow-up in all patients showed no evidence of recurrence or metastasis over a period of 4 months-5 years. These cases appear at variance with the general belief that ALM and ALM in situ arise de novo and rarely arise in precursor naevi. To the best of our knowledge, this is the first documented series of ALM in situ arising in association with pre-existing naevi. We conclude that ALM can arise in association with acral naevi.

Adult↗
PubMed1996

A case of cutaneous malignant fibrous histiocytoma.

A 54-year-old Japanese man with cutaneous malignant fibrous histiocytoma on the back is reported. He not only had a past history of thyroid cancer 1 year prior to the onset of the skin tumor, but also had simultaneous bladder cancer. Despite the early, wide resection, the prognosis was rapid and progressive. Histologically, the primary lesion of the skin tumor was difficult to differentiate from dermatofibrosarcoma protuberans; however, the recurrent and the metastatic lesions changed in appearance.

Fatal Outcome↗
PubMed1996

Ectopic extramammary Paget's disease affecting the upper abdomen.

We present 57-year-old man in whom ectopic extrammary Paget's disease (EMPD) affected the upper abdomen. Although the clinical appearance was suggestive of Bowen's disease or superficial basal cell epithelioma (BCE), the biopsy specimen showed EMPD histologically. Only 12 cases of ectopic EMPD have been reported (including this case). In our 20 year experience of 129 EMPD, this is the first ectopic case. Thus, the frequency of ectopic EMPD is 0.78% (one of 129) in our study. The male/female ratio in the reported 12 cases is 2: 1, nearly the same as EMPD in general (2.1: 1, in our 129 cases). The mean age of the 12 patients is 65.8 years, which is not significantly different from ordinary EMPD (66.4 years, in our 129 cases). Comparing ectopic EMPD to ordinary EMPD, clinically and histologically, we could find no difference. As they appear to be the same disease, ectopic and ordinary EMPD may share similar origins and mechanisms of occurrence. We support the hypothesis that Paget's cells originate from the remaining pluripotential germinative cells which are able to differentiate into many kinds of secreting glands.

Abdomen↗
PubMed1996

[A case of report of surgical repair of ventricular septal perforation with left ventricular free wall rupture following acute myocardial infarction in an 86-year-old woman].

An 86-year-old woman had acute anterior myocardial infarction. A doppler echocardiogram taken on the second day of onset revealed ventricular septal perforation (VSP). Cardiac catheter examination was conducted under intraaortic balloon pumping. An emergency operation was performed on the third day after the onset because of the progression of cardiac failure and an increase of the left to right shunt ratio to 63%. A pericardiotomy revealed approximately 200 ml of blood in the pericardial cavity and a rupture in the left anterior ventricular free wall. The VSP was in the anterior septum and measured approximately 10 mm in diameter. Necrotic tissues surrounding the VSP were effectively resected using an ultrasonic aspiration instrument. The defect, measuring approximately 30 mm in diameter, was closed using a Teflon felt patch and a horse pericardial patch. The patient recovered with no complications and was discharged on the 31st postoperative day. She is presently in good conditions 2 years after the surgery. Our patient was the oldest among the reported cases of surgical repair of VSP in Japan, and our repair surgery was conducted the earliest after onset among the reported surgical cases for VSP in patients at 80 years of age or older.

Aged↗
PubMed1996

[Multicystic encephalopathy with frontal lobe-originated gelastic seizure, ipsilateral oculogyric crisis, and horizontal epileptic nystagmus: an autopsy case].

Attacks of gelastic (laughing) seizure are usually reported as complex partial seizures of temporal lobe epilepsy and seizures associated with hypothalamic hamartomas, but are rarely reported as complex partial seizures of frontal lobe origin. We recently encountered a 29-year-old woman who had gelastic seizure attacks from age 17. She had shown severe mental retardation with cerebral palsy at 7 months, and entered precocious puberty at age 7. Attacks of gelastic seizure with ipsilateral adversive seizures, ipsilateral oculogyric crisis, and horizontal epileptic nystagmus were observed until her death at age 29. Each gelastic seizure lasted 1 to 10 minutes. Her laughing was very strong and loud. Interictal spikes were observed over the right fronto-parietal lobe, but no ictal spike was detected. The neuropathological examinations of her brain revealed no hypothalamic lesions such as hamartomas, gliosis, and distinct neuronal loss. Her brain was severely affected with multicystic encephalopathy, and the bilateral temporal lobe tissues were almost replaced by the cystic changes. The right frontal lobe and occipital lobe were not cystic. From the clinicopathological examinations, the focus of her gelastic seizure was considered to be of the right frontal origin. The hippocampus and parahippocampal gyrus are major components of the limbic system, which is involved in affective emotions. Although the right hippocampus and parahippocampal gyrus were completely lost, and those of the left hemisphere were almost completely lost, by the multicystic replacements in this case, the gelastic seizure attacks were evoked from right frontal origin. The frontal lobe may play an important role in motor expressions of laughing. The motor expressions of the loud and strong laughing may be one of the characteristic features of frontal lobe-originated gelastic seizure of this case.

Adult↗
PubMed1995

Transcriptional inhibition of insulin by FK506 and possible involvement of FK506 binding protein-12 in pancreatic beta-cell.

FK506 (tacrolimus) is a strong immunosuppressant: it has been approved as a drug for liver transplantation in Japan, the United States, and the United Kingdom. One of its main adverse effects is hyperglycemia. Thus, in this study, we investigated the mechanism and the reversibility of the hyperglycemia caused by FK506. FK506 did not affect the glucose uptake by insulin into rat strio-muscle cell line, but suppressed insulin production in rat insulinoma cells. Two-week oral administration of FK506 at 10 mg/kg/day suppressed insulin production time-dependently at the transcriptional step in pancreatic beta-cells, while glucagon content in pancreatic alpha-cells was not affected. When FK506 administration was stopped in these rats, insulin mRNA transcription and insulin production returned to normal. This recovery indicates that the adverse effect of FK506 on the pancreas is reversible. A high content of FK506 binding protein-12 (FKBP-12) in the pancreatic beta-cells was confirmed by immunostaining with anti-human FKBP-12 mAb, but the content was less in the pancreatic alpha-cells and almost negligible in the acinar cells. In contrast, a high content of calcineurin in the pancreatic alpha-cells was confirmed by using anti-calcineurin polyclonal antibody, but this content was less in the pancreatic beta-cells and not found in the acinar cells. Thus, as in the case with NF-AT in T cells, these findings point to the reduction of unidentified nuclear factors for insulin mRNA transcription caused by the binding of FK506 to FKBP-12 and a subsequent inhibition of calcineurin in the beta-cells.

Animals↗
PubMed1995

Coexistence of Pick bodies and atypical Lewy bodies in the locus ceruleus neurons of Pick's disease.

We observed abundant Pick argentophilic inclusion bodies (PBs) as well as some atypical Lewy bodies (LBs) in the locus ceruleus (LC) from a patient with Pick's disease. In addition, there were a few neurons which contained both PBs and LBs. PBs in the LC frequently appeared multiple and had lobulated or irregular shapes, though their ultrastructural elements were the same as those of the PBs appearing in the cerebral cortex, and consisted of randomly arranged smooth-surfaced straight tubules of 15 nm in diameter, mixed with a small number of long-period constricted fibrils. The ultrastructure of the LB coexisting with PB was identical with that previously reported; a dense core was surrounded by concentric layers of radially oriented 10-nm filaments and was clearly distinguishable from the PB. Immunohistochemical examination with various antibodies related to neurofibrillar pathology demonstrated that anti-tau antibodies reacted positively with both PB and the rim portion of LB in the present case; an unusual finding for LB. The anti-neurofilament 200-kDa protein stained only LBs, even when PBs and LBs coexisted in the same neuron. These findings show that two kinds of neuronal fibrillar inclusions, whose underlying cytoskeletal abnormalities are thought to be different, can coexist in the same neuron. In addition, the formation of multiple, lobulated PBs may suggest some particularity of cytoskeletal composition of the LC neurons.

Aged↗
PubMed1995

The gene encoding the 5-HT1A receptor is intact in mood disorders.

We studied the 5-HT1A receptor gene in 50 mood disorders and 50 normal volunteers. The 5-HT1A receptor gene was amplified by polymerase chain reaction and sequenced by the dideoxy method. The sequence of the 5-HT1A receptor encodes a protein of 422 amino acids, that is, one amino acid longer than the reported sequence (Kobilka et al. 1987). The DNA sequence at positions 454 to 459 is CGC GCC GCT, not CCG CGT, and the amino acids sequence at these positions is changing from proline arginine to arginine alanine alanine. These differences, however, were observed in both mood disorders and controls. One silent polymorphism, CTG to GTA at position 294, was found. These results suggest that the 5-HT1A receptor gene is intact in mood disorders.

Adult↗