Biomedical subjects

M Hara

Publications and source records attributed to M Hara.

At least 361 records · Page 20Linked to original sources

PubMed1998

A combined surgical and endovascular treatment for a case with five vertebro-basilar aneurysms and bilateral internal carotid artery occlusions.

BACKGROUND: Whereas multiple aneurysms may be found in 20% of patients in whom one aneurysm is discovered, the identification of five vertebrobasilar aneurysms is distinctly rare. We described such a case treated by surgical and endovascular method. CASE DESCRIPTION: A case of multiple aneurysms treated with combined surgical clipping and intravascular surgery is described. Five separate posterior circulation aneurysms and bilateral internal carotid artery occlusion were identified in one patient. Three of the aneurysms were treated surgically. Access to the fourth aneurysm was deemed difficult because of its location and because of the previously placed surgical clips; this aneurysm was treated by endovascular approaches that provided optimum therapy in this unusual multiple aneurysms case. CONCLUSIONS: We have described an unusual case of multiple posterior circulation aneurysms in the setting of bilateral internal carotid occlusions, treated by a combination of surgical and endovascular therapies. We will be able to provide safer treatment for such difficult cases in the future.

Adult↗

PubMed1998

Radiation-related adverse effects observed on neuro-imaging several years after radiosurgery for cerebral arteriovenous malformations.

BACKGROUND: To our knowledge, there are no reported arteriovenous malformation (AVM) series in which detailed long-term follow-up results after radiosurgery were described based on the whole patient group. METHOD: We performed a detailed long-term follow-up study of 53 patients with cerebral AVMs treated with gamma knife (GK) radiosurgery, with emphasis on radiation-related adverse effects detected on neuro-imaging after a long post-irradiation latency period (3-10 years). The post-GK follow-up period was 40-232 months excluding two mortalities, the mean being 112 and the median being 111 months. RESULTS: Three patients (5.6%) have, as yet, refused all neuro-imaging follow-up studies. Complete nidus obliteration was confirmed angiographically in 32 patients (60.4%) between 1 and 5 post-GK years. In the other 18 patients (34%), despite significant nidus shrinkage being angiographically demonstrated, complete obliteration was not achieved during a 2-7 year follow-up period. There were two mortalities, one AVM-related (massive re-bleeding during the latency period) and the other angiography-related. There were five radiation-related morbidities (9.4%), three of which-hemi-Parkinson syndrome, hemiparesis, and visual field disturbances attributable to delayed cyst formation-manifested at 5.5, 7 and 7 post-GK years, respectively. We also experienced five patients (9.4%) in whom, despite remaining asymptomatic to date, radiation-related adverse effects were seen on neuro-imaging: middle cerebral artery stenosis at 3 post-GK years in one patient; dural arteriovenous fistula at 7 post GK-years in one; delayed cyst formation in two, at 5 and 10 post-GK years; and a small cavitation at 9 post-GK years. CONCLUSION: Long-term follow-up, particularly with neuro-imaging modalities, is essential even after the "treatment goal" has been attained.

Adolescent↗

PubMed1998

Recurrence in meningeal hemangiopericytomas.

BACKGROUND: Meningeal hemangiopericytomas are more aggressive than typical meningiomas, with a high rate of recurrence and distant metastases. The question of whether a correlation exists between prognosis and histologic features remains controversial. CASE DESCRIPTION: We report two cases of recurrent meningeal hemangiopericytomas. Although local growth control of the tumor was obtained by tumor removal and irradiation in a 38-year-old male patient (Case 1) with a recurrent tentorial tumor, the tumor disseminated and metastasized extracranially within a short period after treatment, leading to rapid deterioration. Another 38-year-old female patient (Case 2) with a recurrent orbital tumor had a favorable outcome after tumor removal. The Ki-67 proliferative index using the MIB-1 monoclonal antibody increased as the tumor recurred in Case 1 (2.5%, 7.9%, and 15.7%), but did not change between primary and recurrent tumors of Case 2 (4.2%, 3.1%). Immunostaining for p53 protein in Case 1 was negative at the first resection, and became positive at the second and third resections, whereas in Case 2, it was negative in both the primary and recurrent tumors. CONCLUSIONS: Our results suggest that p53 protein accumulation with a high proliferative potential is a useful marker to estimate malignant progression in meningeal hemangiopericytomas.

Adult↗

PubMed1998

Galactocerebroside and not glucocerebroside or ceramide stimulate epidermal beta-glucocerebrosidase activity.

Glycosphingolipids including glucocerebroside (GluCer) and galactocerebroside (GalCer) have been recognized as bioreguratory lipids by our group and others. In addition, our recent study demonstrated that GalCer corrects dry skin conditions in humans. The processing of stratum corneum lipids, which occurs when beta-glucocerebrosidase (beta-GluCer'ase) changes GluCer to ceramide (Cer), is required to form the epidermal permeability barrier. We herein investigated the effects of GluCer, GalCer and Cer on the processing of GluCer to Cer by assaying epidermal beta-GluCer'ase in mice (155%, P < 0.01) when compared to vehicle treated controls, while neither GluCer nor Cer had this effect. Studies using inhibitors of beta-GluCer'ase or beta-galactosidase and measuring the optimum pH of the enzyme verified that GalCer specifically activated beta-GluCer'ase. We confirmed that GalCer significantly increased beta-GluCer'ase activity in the outer epidermal fraction (172%, P < 0.01) and that the activation of beta-GluCer'ase is not due to a direct activating effect of GalCer on the enzyme. Furthermore, the induction of beta-GluCer'ase activity by GalCer was also observed in cultured normal human deratinocytes (123%, P < 0.01). Finally, acylceramide content in stratum corneum was increased in mice treated with GalCer (194%, P < 0.0005). These results indicate that GalCer appears to affect the Cer construct in the stratum corneum by the activation of beta-GluCer'ase, which ultimately contribute to an enhancement of barrier formation.

Animals↗

PubMed1998

Graft rejection and recovery of host-derived hematopoiesis after allogeneic bone marrow transplantation: relation to conditioning with high dose etoposide and total body irradiation.

Engraftment failure following allogeneic bone marrow transplantation (BMT) is rare in patients with acute leukemia, after frequent conditioning with marrow-lethal chemoradiotherapy. We evaluated the efficacy of a preparatory regimen consisting of fractionated total body irradiation (TBI) (12 Gy in six fractions) and high dose etoposide (60 mg/kg) administered as an 8-h infusion for allogeneic BMT in 16 consecutive patients with acute leukemia. Although 14 patients showed complete and sustained engraftment, the remaining two patients rejected bone marrow grafts from HLA-identical sibling donors and showed subsequent recovery of host-derived hematopoiesis. Despite the limited number of patients, this observation suggests that the immunosuppressive potential of etoposide may be inferior to that of cyclophosphamide (CY) and that etoposide as an alternative to CY as an antileukemic and immunosuppressive agent in allogeneic BMT may increase the risk of graft rejection.

Acute Disease↗

PubMed1998

14q11 abnormality and trisomy 8q are not common in Japanese T-cell prolymphocytic leukemia.

We studied ten cases of Japanese T-cell prolymphocytic leukemia (T-PLL) collected over the last 9 years. Median age was 61 years with a male predominance (M:F, 8:2). The main disease features were splenomegaly, lymphadenopathy, hepatomegaly, skin lesions and serous effusions. The clinical course was progressive with a median survival of 10 months. Immunophenotyping showed that the prolymphocytes had a post-thymic phenotype (TdT-, CD1a-, CD2+, CD3+, CD5+, CD7+) with a predominant CD4+ immunophenotype. Cytogenetic analysis showed no consistent abnormalities. 14q abnormality and trisomy 8q, which are frequently seen in T-PLL of Western countries, were found in only two and zero cases, respectively. We conclude that the clinical and biological characteristics of T-PLL in Japan are almost the same as those in Western countries. However, the cytogenetic findings of T-PLL in Japan might be different.

Adult↗

PubMed1998

Expression of p53, MDM2 protein and Ki-67 antigen in recurrent meningiomas.

Association of p53 gene abnormalities with tumor progression and prognosis of many neoplasms has been demonstrated, but little is known about the clinical significance of p53 abnormalities in meningiomas. The significance of p53 protein expression in recurrent meningiomas and its relationships with MDM2 protein and proliferation activity were investigated by analyzing 39 meningiomas immunohistochemically. p53 protein was expressed in 11 (35%) of 31 non-recurrent and 7 (88%) of 8 recurrent meningiomas. A high frequency of p53 expression was observed in recurrent meningiomas, which tended to have a high p53 positive index (p53 PI), indicating that p53 immunoreactivity may be a marker for predicting tumor recurrence. Four recurrent meningiomas with high p53 PIs were analyzed by the polymerase chain reaction-single strand conformation polymorphism method to detect p53 gene mutations, but none were found in exons 4-8 of this gene. Fifteen (71%) of 21 MDM2-positive and 3 (17%) of 18 MDM2-negative tumors expressed p53 protein, showing that MDM2 expression was more common in meningiomas with p53 expression. p53 immunoreactivity in the absence of mutation may indicate stabilization of the wild type through interaction with the MDM2 protein. The Ki-67/MIB-1 proliferation index (MIB-1 PI) correlated well with recurrence. The p53-positive tumors had a significantly higher mean MIB-1 PI than p53-negative tumors, suggesting that wild-type p53 inactivation by the MDM2 protein may be involved in controlling the proliferative activity in meningiomas. In conclusion, immunohistochemical examination for p53 protein as well as proliferative activity may help predict the malignant potential of tumor recurrence.

Adult↗

PubMed1998

Proteasome inhibitors which induce neurite outgrowth from PC12h cells cause different subcellular accumulations of multi-ubiquitin chains.

The effects of two proteasome inhibitors on neurite outgrowth from PC12h cells were investigated in terms of the mean length of the neurites and the frequency of occurrence of cells with long neurites. Benzyloxycarbonyl-leucyl-leucyl-leucinal (ZLLLal) and benzyloxycarbonyl-isoleucyl-t-butyl-glutamyl-leucinal (PSI) caused a significant elongation of PC12h cell neurites. Since ZLLLal is known to inhibit both calpain and proteasome activity, we examined the effects ofbenzyloxycarbonyl-leucyl-leucinal (ZLLal) which inhibits calpain activity to the same degree as ZLLLal, but which inhibits proteasome activity only weakly. ZLLal did not induce the significant elongation of neurites at any of the concentrations we studied. These results show that the inhibition of proteasome activity causes neurite elongation. We also quantified subcellular levels of multi-ubiquitin chains and free ubiquitin after treatments with PSI, ZLLLal and ZLLal. Treatment with ZLLal had no effects on levels of water- and urea-soluble multi-ubiquitin chains or of free ubiquitin either in the nucleus or in the cytoplasm. PSI and ZLLLal induced a large accumulation of water- and urea-soluble multi-ubiquitin chains and free ubiquitin in the nucleus. Similarly, PSI and ZLLLal increased cytoplasmic levels of urea-soluble multi-ubiquitin chains. On the contrary, PSI and ZLLLal had no effect on levels of water-soluble multi-ubiquitin chains or free ubiquitin in the cytoplasm. This is the first study to demonstrate subcellular differences in the accumulation of multi-ubiquitin chains and free ubiquitin during the neurite elongation induced by proteasome inhibitors.

Animals↗

PubMed1998

Deleted HTLV provirus in peripheral blood cells of a patient with T-cell prolymphocytic leukaemia.

We describe the first case of T-cell prolymphocytic leukaemia (T-PLL) in which the peripheral blood cells contained a human T-lymphotropic virus (HTLV) related tax sequence. Serum screening tests for anti-HTLV-I/II antibodies were negative. Polymerase chain reaction disclosed the presence of an HTLV-I tax sequence in the peripheral blood. Other sets of oligonucleotide primers for HTLV-I gag, pol, env and the long terminal repeat regions and for the HTLV-II pol region were negative in the DNA of the cells. Although patients with T-PLL have been reported to be seronegative for HTLV-I, our findings point to the possibility that HTLV-I infection might be involved in the aetiology of at least some cases of T-PLL and that there may be alternative mechanisms involved in HTLV-associated leukaemogenesis.

Base Sequence↗

PubMed1998

Dramatic effect of ethosuximide on epileptic negative myoclonus: implications for the neurophysiological mechanism.

Epileptic negative myoclonus (ENM) is a recently defined epileptic seizure type seen in various epileptic syndromes. Although the long-term prognosis appears to be favorable, the treatment of localization-related epilepsy (LRE) with ENM in childhood is sometimes difficult due to the apparently pharmaco-resistant nature of ENM. We evaluated the effects of antiepileptic drugs (AEDs) in 10 patients with ENM. Carbamazepine was administered to eight patients, none of whom improved. Responses to clonazepam and valproic acid were unpredictable, whereas ethosuximide (ESM) achieved complete control of ENM in all six cases treated with this drug as adjunctive therapy. The pharmacological responses of ENM to CBZ and ESM were quite similar to those of absence seizures. According to the SPECT and ictal EEG findings in addition to the pharmacological responses from this study, we favor to postulate that ENM is produced by a direct inhibitory action on the motor cortex resulting in the interruption of voluntary muscle contraction as generated by sharp-slow wave complexes, compatible with the mechanism considered to underlie absence seizures. ENM are refractory to treatment and persisting if the wrong AEDs, such as PHT or CBZ, are selected at the diagnosis of LRE. We recommended a trial of ESM when ENM develops during the clinical course of LRE regardless of etiology.

Adolescent↗

PubMed1998

Delayed cyst formation after radiosurgery for cerebral arteriovenous malformation: two case reports.

Two patients who underwent gamma knife radiosurgery for ruptured cerebral arteriovenous malformations (AVM) developed cystic lesions at 78 and 111 months after undergoing treatment. Both patients presented initially with intracerebral hemorrhage. In one patient, the cystic lesion was discovered during routine follow-up imaging and clinical examination revealed homonymous hemianopsia; the second patient presented with seizure and the lesion was identified more than 9 years after radiosurgery. One patient underwent resection of the nidus and histologic analysis of the resected specimen showed vessels in various stages of obliteration. The present paper discusses the possible mechanism for the delayed development of cystic lesions, and the possibility that radiation-induced vascular changes may continue in a nidus even when angiography shows complete obliteration of the nidus.

Adult↗

PubMed1998

Correlation between intracranial pressure (ICP) and changes in CT images of cerebral hemorrhage.

The relationship between intracranial pressure and CT images was investigated in 80 cases of cerebral hemorrhage that occurred between 1984 and 1990. In traumatic intracerebral hematoma, positive correlation was found between intracranial pressure and both shift of midline structures and volume of hematoma except in the occipital lobe or at the base of the frontal lobe. In nontraumatic intracerebral hematoma, increased intracranial pressure was found to correlate with changes in the configuration of the lateral ventricles, intraventricular hemorrhage, and compression of the basal cisterns and cortical sulci. No correlation between intracranial pressure and hematoma volume was observed, most likely due to the number of elderly patients in the subject population. In nontraumatic subarachnoid hemorrhage, positive correlation existed between increased intracranial pressure and intraventricular hemorrhage as well as Evans' ratio calculated using repeat CT images that were obtained due to disturbances in cerebrospinal fluid circulation. These results suggest that the degree by which intracranial pressure increases in patients with cerebral hemorrhage can be estimated by the changes in CT images.

Adolescent↗

PubMed1998

Relationship of apolipoprotein E phenotypes to serum lipid and lipoprotein levels in Japanese schoolchildren.

The distribution of apolipoprotein (apo) E phenotypes was investigated in Japanese schoolchildren and an attempt was made to determine whether the apoE phenotypes influence the serum levels of lipid and lipoprotein. The subjects were 289 children from a junior high school (145 M, 144 F, aged 12-13 y). The E3/3 phenotype was demonstrated in 69.9%, E4/3 in 18.7%, E2/3 in 9.0%, E4/2 in 1.4%, E4/4 in 0.7% and E5/4 in 0.3%. E2/2 was not detected. Serum levels of total cholesterol and low-density lipoprotein-cholesterol were progressively lower in the phenotypes E4/3, E3/3 and E2/3. The serum level of high-density lipoprotein-cholesterol showed a progressive increase in the same order. In conclusion, Japanese schoolchildren with E4/3 already had an atherogenic serum lipid profile.

Adolescent↗

PubMed1998

Control of the unidirectional topological orientation of a cross-linked complex composed of the bacterial photosynthetic reaction center and horse heart cytochrome c reconstituted into proteoliposomes.

Control of the unidirectional topological orientation was achieved for a cross-linked complex composed of the bacterial photosynthetic reaction center and horse heart cytochrome c (RC/cyt c) reconstituted into proteoliposomes. Using the method of Ueno et al. [Ueno et al. (1995) Mater. Sci. Eng. C3, 1-6], we prepared RC/cyt c by conjugating cyt c to the H-subunit of RC of Rhodobacter sphaeroides R-26 using a bifunctional cross-linking reagent, N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP), as previously reported. The freeze-thaw method was used to incorporate RC/cyt c into liposomes that contained dipalmitoyl-L-alpha-phosphatidylcholine and dipalmitoyl-L-alpha-phosphatidylglycerol (1:9). The topological orientation of RC/cyt c in the proteoliposomes was determined using three methods: (i) release of the cyt c moiety from the proteoliposomes by cleaving the disulfide bond in the linker residue, (ii) electron transfer from free cyt c outside the proteoliposomes to the RC moiety, and (iii) photo-induced membrane potential of RC- and RC/cyt c-reconstituted proteoliposomes. The results indicated that about 90% of the RC/cyt c in proteoliposomes was oriented with the H-subunit exposed on the outside of the liposomes, whereas only about 60% of the RC in proteoliposomes had this orientation. Thus, we successfully controlled the unidirectional topological orientation of the RC moiety in liposomes using the RC/cyt c complex.

Animals↗

PubMed1998

A polymorphism of angiotensinogen gene codon 174 and coronary artery disease in Japanese subjects.

The relationship between coronary artery disease (CAD) and polymorphisms of genes encoding angiotensinogen (AGT) and angiotensin converting enzyme (ACE) was analyzed in Japanese subjects. One hundred and four patients with CAD and 170 healthy subjects were enrolled in the study. CAD was defined as having a luminal diameter stenosis > or =50% in at least one of three major coronary arteries by coronary angiography. The genotypes (determined by polymerase chain reaction) of AGT gene codon 174 were not significantly associated with CAD in the total study population. However, the frequency of T/T homozygotes of AGT codon 174 was significantly higher in CAD patients compared to controls in each of three subgroups: 1) body mass index (BMI) below the median value of 24.1 kg/m2; 2) not more than two CAD risk factors out of five (hypercholesterolemia, hypertension, diabetes mellitus, smoking, and family history of CAD); and 3) the ACE I/I genotype. The M/M genotype of AGT codon 235 was negatively associated, and the ACE D/D genotype was positively associated, with CAD in the total study population. Our results indicate that the T/T genotype of AGT codon 174 may be a risk factor for CAD in Japanese individuals with low BMI, lesser CAD risk factors, or ACE I/I genotype.

Aged↗

PubMed1998

Relationship between fat distribution and lipid and apolipoprotein profiles in young teenagers.

The influence of obesity and fat distribution on serum levels of lipoprotein and apolipoprotein was investigated in 294 Japanese junior high school children (12-13 years of age). Serum levels of low-density lipoprotein cholesterol (LDLC) (P = 0.013), triglycerides (TG) (P = 0.0006), and apolipoprotein B (apoB) (P = 0.003), and the apoB/A-I ratio (P = 0.005) were significantly higher and serum levels of high-density lipoprotein cholesterol (HDLC) (P = 0.00003) and apoA-1(P = 0.003) were significantly lower in obese boys than in non-obese boys. The serum levels of TG (P = 0.013) and the apoB/A-I ratio (P = 0.011) were significantly higher and the serum levels of HDLC (P = 0.004) was significantly lower in obese girls than in non-obese girls. The LDLC/apoB ratio was lower in obese girls than in non-obese girls (P = 0.03). Obesity (> or = 20% of ideal weight) was strongly correlated with the serum levels of lipids and apolipoproteins in boys; this relationship was less clear in girls. The degree of obesity and the body mass index (BMI) were more strongly correlated with serum levels of lipids and apolipoproteins in boys than in girls. In boys, atherogenic lipoproteins and apolipoproteins, such as LDLC and apoB, showed a stronger correlation with the thickness of the triceps skinfold, while in girls the anti-atherogenic lipoproteins and apolipoproteins, such as HDLC and apoA-I, showed a stronger correlation with both the triceps and the subscapular skinfold thicknesses. In girls the relationships between the BMI and the degree of obesity and the thickness of the subscapular skinfold (S) thickness were similar to the relationships between those parameters and the triceps skinfold (T) thickness. In boys, these parameters showed a stronger correlation with the subscapular skinfold thickness than with the triceps skinfold thickness. The correlation coefficients for the relationships between skinfold thickness and lipid and apolipoprotein levels were similar to the coefficients for the relationships between skinfold thicknesses and the severity of obesity and the BMI. The distribution of central-type fat accumulation, which is indicated by the thickness of the subscapular skinfold, the S/T ratio and S-T value, was inversely correlated with the HDLC level in both boys and girls. The degree of obesity was strongly correlated with the atherogenic lipoprotein profile in boys, in part because the subscapular skinfold thickness was strongly correlated with the degree of obesity and the BMI. In girls, the correlations between indices of central-type obesity and atherogenic lipid and apolipoprotein profiles were stronger than in boys. These data suggest that childhood obesity may be an early cardiovascular risk factor.

Adipose Tissue↗

PubMed1998

Paradoxically shortened QT interval after a prolonged pause.

We analyzed Holter ECG recordings in 15 patients with episodes of prolonged RR intervals > 2.5 seconds. In 13 patients, the QT interval showed a linear prolongation when RR interval was < 1.5 seconds and became relatively flat at longer RR intervals. In the remaining two patients, the QT and RR intervals were correlated within physiological range of RR intervals. However, at longer RR intervals, the QT interval was unexpectedly shortened and constant. The paradoxically shortened QT interval observed in the present 2 cases may indicate an abnormal adaptation of repolarization time to an abrupt increase in the preceding RR intervals.

Adult↗

PubMed1998

Expression of heat shock proteins in squamous cell carcinoma of the tongue: an immunohistochemical study.

Twenty-four specimens of squamous cell carcinoma of the tongue were immunostained for heat shock proteins (HSPs) to reveal differences in stainability among normal epithelium, dysplasia and carcinoma and to clarify the prognostic significance of HSPs in comparison with survival period, clinical stage, lymph node metastasis, histological grade, and p53 immunostaining. Normal epithelium was positively stained in the suprabasal layer for HSP60 and HSP70, but was negative for HSP27 and HSP90. Dysplastic lesions were positive for HSP27, HSP70 and HSP90, but stained variously for HSP60. In squamous cell carcinoma, the cytoplasm of suprabasal tumor cells was often positive for HSP27 and HSP90 (18/24, 17/24, respectively). Although HSP immunohistochemistry has revealed changes in HSP expression during tumorigenesis of squamous epithelium of the tongue, there was no correlation between HSP staining and survival period, stage, lymph node metastasis, histological grade or p53 immunostaining.

Carcinoma, Squamous Cell↗