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Biomedical subjects

J Handa

Publications and source records attributed to J Handa.

At least 37 records · Page 2Linked to original sources
PubMed1997

Altered expression of src tyrosine kinase after axotomy.

Although most peripheral neurons show regenerative changes after axotomy, neurons of some nuclei show degenerative changes. To study the mechanisms responsible for such differences in neuronal reactions after axotomy, we investigated the changes of pp60c-src and phosphotyrosine (pTyr) in the dorsal motor nucleus of the vagus nerve and the hypoglossal nucleus after transection of each nerve in adult rats using immunohistochemistry. Polyclonal antibody against pp60v-src stained the cytoplasm of neurons homogeneously in both the severed and non-severed sides of the vagal and hypoglossal nuclei from days 1 to 56 after axotomy. On the other hand, the monoclonal antibody against pp60v-src (mAb327, which recognizes src homology 3 region in pp60src as an epitope) showed different immunoreactivities. No pp60c-src immunoreactivity was observed in neurons in either the vagal and hypoglossal nuclei of the non-severed side between days 1 and 56, whereas in the severed side of the hypoglossal nucleus intense pp60c-src immunoreactivity was observed along the plasma membrane of neurons from days 5 to 28 after axotomy. In contrast, in the severed side of the vagal nucleus pp60c-src immunoreactivity appeared along the plasma membrane of neurons on day 5 and remained until day 7. Conformational changes accompanying the activation of pp60c-src are suggested to cause differences in immunoreactivities of these antibodies. The expression (or activation) of pp60c-src in the neurons was stronger and longer lasting in the hypoglossal nucleus, which regenerates successfully after axotomy, than in the dorsal motor nucleus of the vagus nerve, which undergoes necrobiotic reaction. These results indicate that pp60c-src plays an important role in regeneration after axotomy.

Animals↗
PubMed1997

p53 accumulation and apoptosis in embolized meningiomas.

Preoperative embolization of meningiomas is performed to decrease blood loss at surgery. While it is also expected to reduce tumor recurrence by producing necrosis at the site of dural attachment, very little has been described about what happens to the non-necrotic tumor cells. We investigated how the proliferative activities of meningiomas were modified after embolization. In nine meningiomas which were embolized preoperatively, proliferative potentials and expression of cell cycle inhibitors were assessed immunohistochemically using MIB-1, anti-53 (DO-1 and DO-7), and anti-p21 (WAF1/CIP1) monoclonal antibodies. To determine whether a cell underwent apoptotic death besides necrosis, we applied the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling method. Results were compared with control meningiomas without embolization. MIB-1 positive cells often gathered in perinecrotic areas, although the mean MIB-1 staining index of the embolized meningiomas was not significantly different from the control. p53 and its downstream effector p21 accumulated mainly in the perinecrotic areas in eight of the nine embolized meningiomas. Apoptosis was also observed in the concomitant areas. Double staining for both MIB-1 and p21 frequently showed positive cells for both antibodies. The accumulation of MIB-1 positive cells in the embolized meningiomas may not be a sign of fast growth or malignancy, but it may implicate arrest of cell cycle by the p21. This study indicates that embolized meningiomas exhibit not only necrosis but also apoptosis and cell cycle arrest. The latter effects appear to be at least partly p53 dependent.

Adult↗
PubMed1997

Early treatment of posterior retinopathy of prematurity: a controlled trial.

OBJECTIVE: The purpose of the study is to assess the possible benefits of early laser treatment for posterior retinopathy of prematurity (ROP) and to provide data concerning the natural history of posterior ROP. DESIGN: The study design was a prospective, multicenter, randomized trial. PARTICIPANTS: A total of 19 infants with prethreshold posterior ROP were studied. INTERVENTION: Randomization to immediate indirect laser photocoagulation or observation, with application of laser photocoagulation for those control eyes reaching threshold disease, was performed. MAIN OUTCOME MEASURES: Patients were assessed at 3 months and the anatomic outcome recorded along with any adverse treatment effects. RESULTS: An unfavorable structural outcome developed in 3 (16%) of 19 early treatment eyes compared with 3 (18%) of 17 for those treated only if threshold disease was reached. Of the 17 control eyes, 15 (88%) reached threshold disease. Progression to threshold occurred within 1 week in all but two eyes. All 12 control eyes with posterior ROP and any amount of extraretinal fibrovascular proliferation progressed to threshold disease. CONCLUSIONS: Although the number of patients studied is too small to reach statistical significance, the likelihood of a favorable outcome for eyes with prethreshold posterior ROP treated immediately with laser photocoagulation is comparable to that obtained by withholding treatment until threshold disease is reached. There is a high probability of progression from prethreshold to threshold disease, usually within 1 week or less.

Disease Progression↗
PubMed1997

[Mitochondrial redox change in gerbil hippocampus before and after transient ischemia].

To investigate the basis of neuronal vulnerability we studied mitochondrial redox changes in gerbil hippocampus before and after 5 minutes forebrain ischemia. The brain was frozen by in situ funnel freezing method, and grinned off coronally until exposure of hippocampus. Relative value of regional redox ratio (NAD+/NADH) was obtained from fluorescence signals of intrinsic fluorochromes, i.e., NADH (PN) and flavoproteins (Fp), using a high resolution fluorometer. We calculated a modified redox ratio MRR = FP/(Fp + PN). Each point is displayed in gray scales ranged 16 degrees corresponding to the MRR value of the point; black represents a low MRR value (reduced) and white represents a high value (oxidized). Pyramidal cell layers and the granule cell layers were seen as linear areas of high MRR. The stratum radiatum and stratum orience of the CA 1 subfield showed low MRR compared with other hippocampal regions. During ischemic period, MRR in all subfield of hippocampus had decreased but the decrease was more severe in CA 1 region than in another. Just after recirculation, MRR decreased transiently in dentate and CA 3 areas but was fully recovered in all hippocampal areas with the exception of CA 1 region, where the MRR decreased again 12 hours after recirculation. These results suggest that CA 1 area suffers more pronounced hyoxic condition (state V) than other less vulnerable regions during 5 minutes ischemia. The irreversible reduction of MRR in CA 1 area may result from continuing mitochondrial dysfunction, and this may cause lasting energy shortage in CA 1 neurons that eventually results in slowly progressive cell death.

Animals↗
PubMed1997

[Localization of the pyramidal tract in the internal capsule: relationship between CT classification of thalamic hemorrhage and motor weakness].

To better understand the pyramidal tract of the internal capsule, we evaluated the relationship between the localization of thalamic hemorrhage and motor weakness. On an axial CT scan at the level of the pineal body, two lines were drawn as follows: line-a between the lateral edge of the anterior horn and the lateral edge of the trigone, line-b vertical to the sagittal line and passing the midpoint of the third ventricle. The location of the hematoma was classified into three types according to localization of the center of the hematoma and lateral extension beyond line-a as follows: type A (anterior), type P (posterior) and type PL (postero-lateral). Discrepancy of motor weakness between upper extremities and lower extremities was higher in patients with hematoma of type P and type PL (p < 0.05) than in those with hematoma of type A. Improvement of motor weakness on discharge was higher in patients with type P (p < 0.01) than in those with type A. We concluded that most of the pyramidal tract fibers were located in the third quarter of the posterior limb of the internal capsule but a small number of pyramidal tract fibers were located in the anterior two-thirds of it. A greater number of cortico-spinal fibers to the upper extremities than to the lower extremities occupy the third quarter of the posterior limb of the internal capsule.

Adult↗
PubMed1996

Potential doubling time and tumour doubling time in meningiomas and neurinomas.

Cell kinetic study plays an important role in treatment planning of brain tumour patients. MIB-1 antibody has recently become available, which detects Ki-67 antigen even in the formalin-fixed paraffin-embedded specimens. We performed MIB-1 immunostaining in 50 meningiomas and 50 neurinomas, and estimated the cell cycle time (tc) and potential doubling time (Tpot) from MIB-1 staining index (MIB-1 SI) and mitotic index (MI). MIB-1 SI logarithmically correlated with MI in both meningiomas and neurinomas. The tc and the Tpot were expressed as a function of the mitosis time (tm), while the tm is known to be around one hour and not exceeding two hours. When the tm was assumed to be one hour, the average tcs of meningiomas and neurinomas were 6.53 +/- 3.56 days and 7.67 +/- 3.27 days, respectively. The Tpots were 447 X (MIB-1 SI)-1.29 X tm in meningiomas, and 490 X (MIB-1 SI)-0.98 X tm in neurinomas. The tumour doubling times (Tds) were calculated from serial imaging studies in 22 neurinomas and 15 meningiomas. The Tds were formulated as 794 X (MIB-1 SI)-0.83 in meningiomas and 1380 X (MIB-1 SI)-0.97 in neurinomas. Most of the Tds correlated well with the Tpots in meningiomas and neurinomas, and exceeded values of the Tpot when the tm is assumed to be one hour, although a few tumours showed unexpectedly longer Tds. The Tpot and the to estimated from MIB-1 SI and MI are clinically useful parameters for predicting the growth potential of meningiomas and neurinomas where no other simple methods are available.

Adolescent↗
PubMed1996

Acute focal cerebral ischemia in rats studied by diffusion-weighted magnetic resonance imaging--an experimental study.

BACKGROUND: Temporary occlusion of the cerebral artery is occasionally repeated during neurosurgical operations, but the safety of such a procedure remains to be studied further. METHOD: We studied early changes and reversibility of focal cerebral ischemia and the cumulative effects of repeated ischemic insults in rats using magnetic resonance imaging (MRI). RESULTS: Diffusion-weighted magnetic resonance images (DWI) and determination of signal intensity ratio (SIR) proved to be a valuable measure of studying early changes and reversibility of transient focal cerebral ischemia and cumulative adverse effects of repeated ischemic insults. DWIs showed marked intensity changes shortly after focal cerebral ischemia, while T2-weighted images failed to show hyperintensities until 2.5 hours after the onset of permanent ischemia. The critical period of ischemia in this model was 60 minutes. However, 20 minutes ischemia, when repeated twice with 60 minutes reperfusion in between, showed irreversible damage. CONCLUSION: Repeated insults of focal regional cerebral ischemia may cause irreversible tissue damage even if each ischemic period is less than the critical one.

Animals↗
PubMed1996

Comparative study of regional cerebral blood flow values measured by Xe CT and Xe SPECT.

The regional cerebral blood flow (rBCF) values measured by stable xenon-enhanced computed tomography (Xe XT) and by radioactive xenon-133 single photon emission computed tomography (Xe SPECT) were compared in 16 patients with cerebral infarct. On the non-lesion side Xe SPECT recorded 10.7% higher rCBF values than Xe CT in the anterior cerebral artery territory, while Xe CT recorded 9.6% higher values than Xe SPECT in the middle cerebral artery territory. These differences were not statistically significant. Although the rCBF values were almost the same, no correlation was found between the two methods in the posterior cerebral artery territory and the basal ganglia. Only hemispheric CBF on the non-lesion side showed the same value and a good correlation between the Xe CT and the Xe SPECT. There was a good correlation in the hemispheric CBF values on the lesion side, too. The difference of rCBF between the non-lesion side and the lesion side was expressed smaller in the Xe SPECT than in the Xe CT. This is in agreement with the previous reports that Xe SPECT overestimates the flow in the low flow areas. The higher rCBF values in the anterior cerebral artery territory measured by the Xe SPECT was ascribed to the artifact from the radioactivities in the inhalation mask and the air passages as reported previously. In conclusion, there is no good correlation between the rCBF values measured by the Xe CT and by the Xe SPECT. Only hemispheric CBF shows a good correlation between the two methods.

Adult↗
PubMed1996

Solitary plasmacytoma of the skull vault--case report.

A 55-year-old female presented with a rare solitary plasmacytoma restricted to the skull vault without systemic myelomatosis. She had a 9-month history of a slowly growing soft mass in the right temporal region. Neuroradiological examination revealed a skull defect and an extradural tumor. The whole layer of the skull was destroyed by the tumor, but the dura was not involved. The tumor was totally removed, and postoperative radiotherapy was given. Follow-up examination after 2 years showed she was free from local recurrence or evidence of systemic involvement. Complete surgical resection with adjuvant radiation therapy is the treatment of choice. Although the prognosis is good, regular lifelong examinations for myelomatosis are required.

Carotid Artery, External↗
PubMed1996

Clinical significance of Ki-67 staining index in acoustic neurinoma.

The correlation between various clinical parameters and MIB-1 (Ki-67) staining indices was evaluated in 58 acoustic neurinomas. The index ranged from 0.37% to 6.61% (mean 1.70%), and did not correlate with age, sex, or initial tumor volume. Sixteen of the 18 tumors removed subtotally or partially showed regrowth, and two showed a volume reduction. The 16 patients with regrowth were divided into two groups according to Ki-67 staining index, < 2.00% and > or = 2.00%. These groups had a significant difference in tumor doubling time (TDT). In addition, there was a significant logarithmic correlation between Ki-67 staining index and TDT. Ki-67 staining index can be used as an index of regrowth rate in partially or subtotally removed acoustic neurinomas. Intraoperative assessment of Ki-67 staining index may be useful for better management planning as well as the estimation of prognosis.

Adolescent↗
PubMed1996

A two-year dietary carcinogenicity study of the antiestrogen toremifene in Sprague-Dawley rats.

The carcinogenic potential of the nonsteroidal triphenylethylene antiestrogen toremifene (Fareston) was evaluated in a standard 104-week rat dietary carcinogenicity study. The doses were 0, 0.12, 1.2, 5.0 and 12 mg/kg/day and the number of animals 50/sex/dose group. The body weight gain and food consumption were monitored once weekly (study weeks 1-16) or once every four weeks thereafter (study weeks 17-104). Blood samples were taken at weeks 34, 52 and 104 and the plasma concentrations of toremifene, as well as the two main metabolites (deaminohydroxy)toremifene and N-demethyltoremifene, were measured. All doses of toremifene reduced food intake and body weight gain. Toremifene caused a significant reduction in mortality, which was mainly due to reduced incidences of pituitary tumors. This was evident in all dose groups. Drug-related decrease of mammary tumors in females (at all doses) and testicular tumors in male rats (doses > or = 1.2 mg/kg/day) were also evident. The incidence of the preneoplastic foci of basophilic hepatocytes were significantly decreased in treated female groups. Toremifene induced no preneoplastic or neoplastic lesions. Based on histopathology, no obvious toxicity could be observed. Drug-related changes were observed in the genital organs, thyroid, spleen, mammary gland, adrenal, kidney, stomach and lung. These changes were due to hormonal disturbances or as a result of reduced food consumption or reduced incidences of pituitary, mammary or testicular tumors. This study indicates that toremifene is an efficient antiestrogen in long-term treatment, is well tolerated and has no tumorigenic potential in rats.

Aging↗
PubMed1996

[Central retinal vein occlusion after embolization for spontaneous carotid cavernous sinus fistula].

A patient with spontaneous carotid-cavernous sinus fistula, who developed central retinal vein occlusion (CRVO) after interventional surgery, was reported. A 78-year-old woman was admitted with symptoms of right abducens palsy and conjunctival injection. Digital subtraction angiography (DSA) revealed bilateral carotid cavernous sinus fistulas supplied by dural branches of the carotid arteries. After embolization of the feeding arteries and the right cavernous sinus using PVA and platinum coils respectively, her symptom improved gradually. Six months after the embolization, she was readmitted because of blurred vision and abducens palsy on the left side. Engorgements of the cavernous sinuses and draining veins, and the shunt flow of the fistula were much less on DSA than those seen previously, but ophthalmologic studies showed an impending central retinal vein occlusion (CRVO) in her left eye. Prognosis of CRVO is generally poor. We discussed the mechanism of CRVO occurring after interventional surgery for CCF and the tactics for preventing it, and early detection of its development.

Aged↗
PubMed1995

Cerebral aneurysm of the distal anterior inferior cerebellar artery: case report.

A case of an extremely rare aneurysm of the distal segment of the anterior inferior cerebellar artery (AICA) is presented. A 61-year-old woman who was admitted with subarachnoid hemorrhage associated with fourth ventricular hematoma had such an aneurysm, which was successfully clipped. The literature is reviewed.

Aneurysm, Ruptured↗
PubMed1995

Transplantation of basal forebrain cells of foetal rats into the subarachnoid space: improvement of disturbance of passive avoidance memory due to injury of nucleus basalis magnocellularis.

Basal forebrain cells of foetal rats were transplanted into the subarachnoid space of adult rats harbouring a kainic acid-induced unilateral lesion in the nucleus basalis magnocellularis. Passive avoidance response tests were performed eight weeks after the transplantation, and the results were compared with those of lesioned but non-transplanted rats and of non-lesioned control rats. Although acquisition impairments did not improve, retention impairments were significantly ameliorated in the transplanted rats. Histologically, transplanted foetal neurons survived and grew very well over the cortical surface, and exhibited facilitated neuritic elongation on acetylcholinesterase staining. Choline acetyl-transferase-immunoreactive neurons were found along the needle track as well as in the subarachnoid graft tissues. The results seem to indicate that not the re-innervation from the graft to the host cortex but the diffusional supply of neurotransmitters and/or their synthetic enzymes and neurotrophic factors were responsible for improvement of memory deficits. The subarachnoid space proved to be an adequate place for growth of transplanted neuronal and glial cells for reasons of ample supply of oxygen and nutrition and of low tissue pressure.

Animals↗
PubMed1995

Meningioma: proliferating potential and clinicoradiological features.

We examined the proliferative potentials of meningiomas in 120 patients using the MIB-1 antibody against the Ki-67 antigen and compared them with the clinicoradiological features. The Ki-67 staining index (SI) did not relate to the age and sex of the patients or the location of the tumors. Asymptomatic meningiomas showed significantly lower SIs (mean +/- standard deviation [SD], 0.87 +/- 0.56%) than symptomatic meningiomas (mean +/- SD, 1.63 +/- 2.17%). We found no relation between SIs and clinical symptoms and signs in the symptomatic meningiomas. A weak correlation was found between the size of tumors and Ki-67 SIs (r = 0.21; P = 0.024). There were significant differences in SIs between calcified (mean +/- SD, 0.77 +/- 0.41%) and noncalcified tumor (mean +/- SD, 1.75 +/- 2.25%). Diffusely calcified tumors (mean +/- SD, 0.57 +/- 0.34%) showed lower SIs than focally calcified tumors (mean +/- SD, 0.92 +/- 0.41%). Lobulated tumors showed higher SIs (mean +/- SD, 2.85 +/- 3.68%) than round tumors (mean +/- SD, 1.06 +/- 0.67%). Tumors with perifocal edema or unclear borders had higher SIs than did those without such features. Signal intensities on T1-weighted magnetic resonance images had no relation to SIs, whereas low-intensity tumors on T2-weighted images, most of which presented diffuse calcification on computed tomographic scans, showed lower SIs. This study indicates that several clinicoradiological features relate to the proliferative potential of meningiomas and that they may contribute to the management of patients.

Adult↗
PubMed1995

Intra- and suprasellar germinoma mimicking a pituitary adenoma--case report.

A 25-year-old female presented with amenorrhea and bitemporal hemianopsia without diabetes insipidus due to an intra- and suprasellar dumbbell tumor. The preoperative and operative diagnosis was pituitary adenoma, but the histological diagnosis was germinoma. Differential diagnosis between germinoma and pituitary adenoma based on computed tomograms and magnetic resonance (MR) imaging features and signal intensity characteristics was difficult in this patient. An enhanced mass posterior to the normal pituitary gland on the mid-sagittal MR image normally indicates an intrasellar germinoma rather than a pituitary adenoma, but this finding was equivocal in our patient.

Adenoma↗
PubMed1995

[Pineocytoma associated with a cyst: report of a case].

We report a case of pineocytoma associated with an unusually large cyst. A 15-year-old boy was admitted with a complaint of intermittent headache. Neurological examination was normal except for bilateral papilledema. CT scan showed triventricular hydrocephalus and a large mass. A solid portion of the tumor in the pineal and retrothalamic areas was isodense, and contained massive calcification on CT. A huge cystic portion extended far into the infratentorial, supracellebellar area. On MR, the solid tumor showed isointensity on T1-WI and iso- to high intensity on T2-WI, and was enhanced by Gd-DTPA. After a ventriculo-peritoneal shunt, the tumor was partially removed through an occipital supratentorial approach. Histological examination revealed a pineocytoma with neuronal and astrocytic differentiations. Reviewing the literature, it is most unusual to find a pineocytoma associated with a huge cyst as was seen in this case.

Adolescent↗