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Biomedical subjects

H Handa

Publications and source records attributed to H Handa.

At least 343 records · Page 19Linked to original sources

Generation of functional clonal cell lines from human bone marrow stroma.

Five clonal human bone marrow stromal cell lines were isolated from the adherent cell populations in long-term liquid cultures after transfection with the recombinant plasmid pSV3gpt. All the cell-line feeder layers and their conditioned media stimulated the proliferation of committed granulomonocytic stem cells (CFUc) from human bone marrow. The size and number of early erythroid stem cell (BFUe)-derived colonies were significantly increased when in the presence of 10% conditioned medium from the cell lines. Furthermore, a substantial number of mixed colonies with erythroid components were observed in the cultures in the presence of erythropoietin and conditioned medium. These findings suggest that the human bone marrow stromal cell lines obtained after transfection with pSV3gpt may be extremely useful in identifying the hematopoietic factors derived from the hematopoietic microenvironment and in analyzing their mechanism of action.

Bone Marrow↗

Tentorial cavernous angioma with calcification in a neonate.

A cavernous angioma of the tentorium cerebelli, first disclosed by perinatal serial ultrasonographic studies, was extirpated totally without remarkable neurological deficit in a neonate. The tumor was accompanied by a calcified expansive hematoma in the posterior fossa. To our knowledge, this is the first case not only of cavernous angioma treated surgically and verified histologically in a neonate, but also of a calcified hematoma revealed on a conventional skull x-ray film at birth. This case suggests the possibility of hemorrhage from intracranial cavernous angioma early in life, even prenatally, and emphasizes the necessity for early diagnosis and early treatment of intracranial cavernous angiomas.

Adult↗

Immunoregulatory role in gamma interferon production by a T cell growth factor-dependent experimental malignant glioma-specific cytotoxic T lymphocyte clone.

The authors have established a murine malignant glioma-specific cytotoxic T lymphocyte clone (G-CTLL 1) by T cell growth factor (TCGF) using 203-glioma (a methylcholanthrene-induced ependymoblastoma of C57BL/6 mouse origin). The cloned cells were found to release a large amount of gamma interferon (IFN) in response to glioma-associated antigen-specific stimulation. The authors have investigated whether the IFN produced can contribute to killing the target cells. Adding anti-mouse gamma IFN antibody to the mixed clone-target cell culture inhibited IFN production by the cloned cells but the toxicity of the cells was minimally diminished. Therefore, it is suggested that the endogenous gamma IFN produced by the TCGF-dependent cloned cytotoxic T lymphocyte line does not have direct cytotoxic action on the target cells. Furthermore, IFN production as well as cytotoxicity was blocked by anti-Lyt-2 monoclonal antibody in the absence of complement. This suggests that IFN plays a role in the process of antigen recognition of target cells because the Lyt-2 molecule is involved in an antigen-specific function on the cytotoxic T lymphocyte receptor. The role of TCGF in gamma IFN production was also investigated. The spontaneous production of gamma IFN by the cloned cells paralleled the amounts of exogenous TCGF added to the cultures, but TCGF had no synergistic effect on IFN production in the presence of mitogen or tumor antigen. Accordingly, it is possible that TCGF stimulates the cloned cells to proliferate, causing IFN release.

Animals↗

[Brain stem auditory evoked potentials for assessment of isolated fourth ventricle in three patients].

Isolated fourth ventricle is an untoward but interesting complication caused by the shunt procedure, which has been recognized since the introduction of CT scanning. Auditory brain stem evoked potentials (BAEPs) were recorded in a patient with isolated fourth ventricle for assessment of brain stem function. Case 1. A 9-year-old boy. He had undergone repair of the lumbosacral meningocele at birth, followed by shunting procedures, including repeated shunt revision, for hydrocephalus which subsequently developed. CT scanning on admission revealed typical findings of isolated fourth ventricle, while neurological examination disclosed no abnormalities. BAEPs on admission revealed normal waves both in amplitude and latency. This patient has been doing well without further shunting procedures. Case 2. A 17-year-old male was admitted with complaints of headache, diplopia, nystagmus and ataxic gait. He had a history of operation for radical removal of cerebellar astrocytoma and lateral ventriculo-peritoneal shunt at 9 years of age. CT scanning on admission revealed a typical isolated fourth ventricle, and fourth ventricle-peritoneal shunt was performed. Postoperative serial BAEPs revealed gradual improvement of brain-stem function. Clinically he has been symptom-free thereafter except for slight nystagmus. Case 3. A 2-year-old female suffering from hydrocephalus developed after neonatal intraventricular hemorrhage and ventriculitis. After repeated revision of a lateral ventriculo-peritoneal shunt, she was admitted in semicoma with vomiting and opisthotonic posture. CT study revealed an isolated fourth ventricle and preoperative BAEPs showed marked abnormalities. Although fourth ventricle-peritoneal shunt was performed, no remarkable change in BAEPs was obtained, and neurological deficit of considerable degree persisted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effector mechanisms of syngeneic anti-tumour responses in mice. II. Cytotoxic T lymphocytes mediate neutralization and rejection of radiation-induced leukaemia RL male 1 in the nude mouse system.

We demonstrated the efficacy of a long-term cultured cytotoxic T-lymphocyte line, CTLL-D4, on tumour growth inhibition using athymic nude mice as recipients. CTLL-D4, specific for a unique surface determinant on a radiation-induced leukaemia RL male 1 of BALB/c origin, was obtained from the limiting dilution culture of MLTC cells performed between spleen cells of a CB6F1-nu/+ mouse immunized in vivo and RL male 1 stimulator cells, and cultured for several months in the absence of added TCGF as described in our preceding paper (Kuribayashi, 1985). The specific inhibition of tumour growth by CTLL-D4 was demonstrated both in Winn-type neutralization assay and in systemic transfer experiments. A subcutaneous inoculation of the mixture of CTLL-D4 and RL male 1 cells resulted in the complete inhibition of tumour growth, even at the effector to tumour cell ratio of 1:1, whereas non-cytolytic D4f, which was self-Ia antigen(s)-reactive, composed entirely of Lyt-1+23- T cells and derived originally from CTLL-D4 but completely lost its cytotoxic activity during culture with the irradiated syngeneic feeder cells alone, had no inhibitory effect at all. In the adoptive transfer studies, the subcutaneously established tumours were rejected by the single i.v. transfer of 2 X 10(7) CTLL-D4 cells into CB6F1-nu/nu mice. However, D4f was ineffective again in this systemic transfer system. When the effect of CTLL-D4 cells on tumour rejection in vivo was compared to that of non-cultured spleen cells hyperimmunized with RL male 1 cells, the former exhibited more rapid rejection in nude mice after i.v. transfer than the latter did, suggesting that CTLL-D4 cells also attack the tumour cells much more effectively as effectors in vivo. Thus, it is conceivable that CTLs are mainly involved in tumour rejection in this adoptive transfer system using RL male 1 tumour cells and athymic nude mice.

Animals↗

Glandular kallikrein content in tissues of diabetic and hypertensive rats measured by enzyme immunoassay.

The contents of glandular kallikrein in the submaxillary gland and pancreas of normal, diabetic and hypertensive rats were compared using a specific enzyme immunoassay. The kallikrein levels in the submaxillary gland and pancreas of the diabetic rats were significantly lower than those of normal rats. On the other hand, the submaxillary and pancreatic levels in hypertensive rats tended to be higher than in normal rats.

Animals↗

[Clinical application of a sustained release anticancer pellet].

During a 6.5-year period from March 1978, 136 patients with brain tumors, which were diagnosed as gliomas or metastatic brain tumors during surgical operation, were treated by the application of sustained release anticancer pellets in seven institutes. Histological diagnosis disclosed that the majority of the tumors were malignant gliomas (61 cases), metastatic brain tumors (35 cases), and benign astrocytoma (17 cases). The anticancer agents (250 mg of 5FU, 1.5 mg of MMC, 250 mg of BUdR and 6,000 iu of urokinase) were sealed in a Silastic silicone tube of 6 mm in diameter, 0.25 mm in wall thickness, and 12 mm in length. The daily delivery of the drugs was (2-3)/10,000 of the original volume. This treatment was combined with surgical and irradiation therapy with or without general chemotherapy. The median survival time of patients with malignant gliomas was 545 days (18 months). The 1-year survival rate was 65.63%, and the 3-year survival rate 16.2%. On the other hand, in patients with benign astrocytomas, the median survival time was 1,500 days (4.1 years), 1-year survival rate 83.75%, and 3-year survival rate 42.84%. In those with metastatic brain tumors, the median survival time was 280 days, 1-year survival rate 43.87%, and 3-year survival rate 24.84%. The present findings revealed that the tube-type anticancer pellets cannot inhibit the growth of the brain tumors located 5 cm from the pellets.

Antineoplastic Agents↗

[Continuous monitoring of cerebral blood volume in cats using a reflectance spectrophotometer].

The importance of cerebral blood volume (CBV) as a physiological parameter has been well recognized, especially in its relation to the intracranial pressure (ICP). Although various methods have been applied to measure CBV, several problems and difficulties still remain to be settled. In the present study, noninvasive monitoring of CBV on the cortical surface was done with organ reflectance spectrophotometry. Through the cranial window, the cat brain was illuminated by the white light via optical fibers and reflected light was analized by spectrophotometer equipped with microcomputer and image-sensor (Sumitomo Elec. Co., Spectrum analyzer TS-200), which enables to estimate CBV on real time as the absorbance value at the isobestic point of the spectral curve of hemoglobin (Hb). In order to ascertain the reliability and reproducibility, the change of CBV was examined by 5% & 10% CO2 inhalation, 5% O2 inhalation and bilateral jugular vein occlusion. A linear correlation was found between PaCO2 and Hb absorbance value on CO2 inhalation. By the bilateral jugular vein occlusion, Hb increased concomitantly with ICP, while cerebral blood flow (CBF) decreased. On 5% O2 inhalation, absorbance spectral pattern of tissue Hb changed from that of oxy-Hb to deoxy-Hb without change of absorbance value at the isobestic point. Thus, the Hb absorbance value obtained by this spectrophotometer was considered to be reliable for the estimation of CBV on the cortical surface. Using this, the change of CBV was examined on the drug-induced seizure and post-decompression state after sustained intracranial hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Effect of intravenous administration of diltiazem on cerebral blood flow and brain function].

The effect of intravenous administration of diltiazem on cerebral circulation and brain function were studied in animals. Diltiazem, at a dose of 150 micrograms/kg BW, was administered intravenously over a period of 5 minutes beginning 30 minutes after ligation of the right brachiocephalic artery in 9 cats in order to investigate its effects in the acute stage of cerebral ischemia. In 5 animals, mean arterial blood pressure was recorded and blood flow in the basilar artery was measured transdurally by use of an ultrasonic Doppler flow-meter. Mean arterial blood pressure began to elevate immediately after ligation of the right brachiocephalic artery, but the degree of elevation was minimal. It began to fall during diltiazem injection and returned to the preadministration value 30 minutes after injection. Basilar artery flow decreased slightly during injection of diltiazem, but began to increase after completion of injection. The increase relative to the preadministration value was 62 +/- 31% 10 minutes after injection, 88 +/- 38% 20 minutes after, and 24 +/- 53% 30 minutes after. The short latency somatosensory evoked potentials (short latency SEP) recorded in the other 2 animals showed no noticeable change either in amplitude or latency during the same procedures. In 1 of 2 animals in which brainstem auditory evoked potentials (BAEP) were monitored, the latency of peak IV increased after ligation of the right brachiocephalic artery, and decreased 20 minutes after injection of diltiazem.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Treatment of primary empty sella with intractable headache via the transsphenoidal approach].

Two cases of primary empty sella with intractable headache were treated via the transsphenoidal approach. One patient was a fifty-three-year-old female with right upper nasal quadrantanopsia and intractable retrobulbar pain and the other was fourty-six-year-old female with continuous retrobulbar pain with a history of transient right temporal hemianopsia. Both cases were diagnosed by metrizamide CT cisternography. They had normal endocrinological functions. They did not respond to drug therapy and were treated surgically. In each case, the dura mater of the floor of the sella was elevated with lyophilized human dura mater and bone fragments obtained during the procedure. In the former case, significant improvement of visual field defect was not obtained but the retrobulbar pain disappeared completely after the operation. In the latter case which had intractable headache for six months, the symptom disappeared just after the operation. Until now, retroorbital pain has not recurred in both cases for several months. Primary empty sella has been considered to be a benign condition except in some cases with CSF rhinorrhea or with visual disturbance. Headache which is often accompanied to primary empty sella has rarely been treated surgically because it is difficult to know whether the headache is related to the empty sella or not. Another reason may be that there is few available data concerning to the efficacy of surgical treatment. Headache caused by stretching of the dura of the floor of the sella is usually frontal or retrobulbar, continuous, profound and intractable.(ABSTRACT TRUNCATED AT 250 WORDS)

Empty Sella Syndrome↗

[Analysis of 53 ruptured middle cerebral artery aneurysms].

In spite of a recent remarkable progress in operative results of ruptured middle cerebral artery aneurysms, a mortality rate of 2-8% appears to be unavoidable. In the present study, 53 ruptured MCA aneurysms were retrospectively analyzed to determine causative factors of unfortunate outcome (fair, poor and dead). Surgical results of 53 ruptured MCA aneurysms are shown in Table 1, where the outcome was unfortunate in 7 cases (17%). Intracerebral hematoma was responsible for 4 cases, two of which were fatal and postoperative vasospasm for 3 cases. There were 13 cases with intracerebral hematomas (25%) ranging from 21 mm to 68 mm in diameter. Although hematomas less than 40 mm in diameter localized in temporal or frontal subcortical areas and yielded no neurological deficits, those more than 60mm extended to the caudate nucleus or thalamus through the internal capsule and led to deep coma (Table 2, Fig. 1). Intracerebral hematoma with the diameter between 50 to 60 mm seems to be critical in regard to postoperative outcome. Repeated rupture caused intracerebral hematoma (50%) more frequently than single rupture (21%) and aneurysm with intracerebral hematoma was liable to bleed (27%), resulting in acute deterioration of neurological conditions by marked enlargement of the hematoma (Fig. 2). Accordingly it is essential for the cases with intracerebral hematoma to prevent rerupture. Subarachnoid hemorrhage and symptomatic vasospasm were observed less frequently in hematoma group than in non-hematoma group. However, prophylactic treatment of vasospasm is important even in the cases with intracerebral hematoma since more than half of them suffer from relatively thicker subarachnoid clot.

Adult↗

[Estrogen-induced pituitary tumors--in relation to the changes in the pituitary gland after estrogen withdrawal].

Pituitary tumors were induced in female rats of Wistar strain by administration of estradiol valerate (E2) and the effect of estrogen withdrawal on E2-induced tumors were studied to elucidate the nature of the induced tumors. Ten mg of E2 was administered to 100 rats intraperitoneally once every 2 weeks, totally four times. Experimental animals were sacrificed at 1 week before, 2, 6, 10, and 14 weeks after stopping injection of E2. The incidence of pituitary tumor and hyperplasia (Table 1). Pituitary glands in each animals were examined and were classified into three groups, namely pituitary tumor, hyperplasia, and normal gland according to histological findings. The incidence of pituitary tumors was highest in rats sacrificed 6 weeks after E2 withdrawal. Pituitary tumors became less frequent and hyperplasias and normal glands became more frequent in rats sacrificed thereafter. Pituitary weight (Table 2, Fig. 1) Irrespective of timing of sacrifice, the weight of pituitary gland (mean +/- SE) was 134 +/- 70 mg in the group which were judged as having a pituitary tumor, 38 +/- 17 mg in the hyperplasia group, and 17 +/- 5 mg in the normal group, respectively. Pituitary weight of control rats were 12 +/- 3 mg. The tumor group had a significantly heavier pituitary weight than hyperplasia and normal groups (p less than 0.01). In each group, there was no significant difference of pituitary weights between animals sacrificed at different intervals after E2 withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗