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Biomedical subjects

Y Kaku

Publications and source records attributed to Y Kaku.

At least 55 records · Page 3Linked to original sources
PubMed1994

Novel lowly immunosuppressive antitumor fluorouridine derivative, UK-21: antitumor activity and effect on humoral immune response in mice.

Our previous studies indicated that a newly synthesized 5-fluorouridine derivative, 2',3',5'-tris-O-[N-(2-n-propyl-n-pentanoyl)glycyl]-5-fluorouridine (UK-21), revealed its antitumor activity by being converted to 5-fluorouridine (5-FUR) and showed a low level of immunological side effects. However, the bioavailability of UK-21 given orally did not seem to be good. In the present study, we focused on the antitumor and immunosuppressive activities of UK-21 given i.p. to mice. UK-21 suppressed the growth of L-1210, P388 and EL4 leukemias inoculated i.v. into corresponding syngeneic mice and both the growth of Lewis lung carcinoma transplanted s.c. and its subsequent metastasis to the lung. UK-21 showed antitumor activity at doses almost 10 times lower than those of 5-fluorouracil (5-FU). The side effects of UK-21, especially on immune functions, were examined in comparison with those of 5-FUR, 5-FU, and cyclophosphamide (CY) at doses producing comparable antitumor activity. The suppressive effect of UK-21 on IgM and IgG antibody formation in mice immunized with ovalbumin was clearly weaker than that of 5-FUR, 5-FU, and CY. The suppressive effect of UK-21 on thymus weight was markedly weaker than that of 5-FU and CY. The reduction of WBC counts induced by UK-21 was also lower than that produced by any other agent. The results reported herein suggest the strong possibility of UK-21 being developed as a novel anticancer drug with cytotoxic mechanisms different from those of 5-FU. Our study also points to the chemical modification of 5-FUR as a feasible way of developing new anticancer drugs.

Analysis of Variance↗
PubMed1994

Remission of recurrent primary intracranial malignant lymphoma after high-dose intra-arterial corticosteroid administration and intra-arterial chemotherapy--case report.

A 39-year-old male presented with rapidly growing recurrent primary intracranial malignant lymphoma, manifesting as intractable headache, recent memory disturbance, and left hemiparesis during the previous month. He had received irradiation and chemotherapy for primary intracranial malignant lymphoma 15 months before admission. Signs of uncal herniation developed soon after admission. High-dose intra-arterial corticosteroid infusion followed by intra-arterial chemotherapy (etoposide and cisplatin) successfully relieved the symptoms of uncal herniation. Magnetic resonance imaging demonstrated a dramatic remission in the size of the tumor and associated mass effect. Sequential administration of corticosteroid and chemotherapy agents is a possible treatment for recurrent malignant lymphoma.

Adrenal Cortex Hormones↗
PubMed1993

Arteriovenous malformation and diaschisis.

We investigated the haemodynamic dysfunction and secondary thalamic and brainstem atrophy in 24 patients with angiographically proven cerebral arteriovenous malformations (AVM) and no clinical history of cerebral haemorrhage. Cerebral blood flow (CBF) was measured by the method using either stable Xenon or single photon emission computerized tomography (SPECT). Morphological changes in the thalamus and brainstem were evaluated by magnetic resonance imaging (MRI). Two factors are considered to influence hypoperfusion in the ipsilateral cerebral and contralateral cerebellar hemisphere and secondary atrophy of the thalamus and brainstem. One is the size of the nidus and the other is the involvement of the basal ganglia. It is presumed that continuous haemodynamic stress over a long period of time may cause irreversible histological changes in areas remote from the lesion, especially in the AVM which demonstrates involvement of the basal ganglia or a large nidus.

Adolescent↗
PubMed1993

Alterations of a 200 kDa neurofilament in the rat hippocampus after forebrain ischemia.

Alteration in the concentration of a 200 kDa neurofilament (NF200) in the rat hippocampus after forebrain ischemia and its relationship to hippocampal neuronal death were studied with an anti-200 kDa neurofilament antibody, using immunohistochemical and immunoblotting techniques. In rats subjected to 8 min of transient forebrain ischemia, hematoxylin-eosin staining showed survival of most of the neurons in the hippocampal CA1 region at 1 day and loss of more than 75% of the neurons at 7 days after ischemia. Immunoblotting showed that the concentration of NF200 in the hippocampal homogenate tended to decrease after ischemia, to 69% of that of control at 1 day and to 60% of the control value at 7 days after 8 min of forebrain ischemia. Following 5 min of ischemia as well, the decrease in the concentration of neurofilaments in the hippocampal region preceded histological confirmation of neuronal cell death. These results suggest that degradation of neurofilament triplet proteins occurred even after ischemia of minimal duration and preceded neuronal death. Degradation of cytoskeletal proteins may play an important role in the mechanism of delayed neuronal death after cerebral ischemia.

Animals↗
PubMed1993

[Idiopathic normal pressure hydrocephalus in elderly patients: its pathophysiology and diagnosis].

We described 10 cases of idiopathic normal pressure hydrocephalus (NPH) in elderly patients who had good results after shunting. Retrospective analysis of our cases offers the following results which indicate the pathogenesis and surgical selection of idiopathic NPH. 1) Most of the patients had risk factors of ischemic cerebrovascular disease and had multiple small ischemic lesions such as lacunae. 2) Cerebrospinal fluid (CSF) pressure is below 20mmHg in all cases and its response to acetazolamide loading was suppressed or almost lost in most of cases. 3) The volume of the lateral ventricle was slightly reduced after the effective operation. 4) Some of the patients showed clinical improvement even if they had symptoms for more than 2 years before treatment. Two primary theories exist concerning the cause of NPH. One is extraventricular obstruction to CSF flow at the level of the arachnoid villi or the basal cistern. The other is periventricular white matter ischemic damage which decreases the tensile strength of the ventricular walls and leads to ventricular dilatation. Tangential periventricular shearing force due to ventricular dilatation produces the symptom of NPH. Our results support these descriptions as the causes of idiopathic NPH in elderly patients. We noticed, firstly, involvement of the ischemic risk factor. Other findings implied decreased elasticity or compliance of the brain and the loss of the autoregulatory properties of cerebral circulation which accelerate the ischemic damage to the periventricular white matter. In understanding the etiology, it is important to know the fragility of the aged brain and the mechanical and hemodynamic stress to which it is subjected.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Regeneration of the rat carotid artery after clipping injury. Part I. A morphological study.

We investigated the natural course of the morphological regeneration of the endothelium and smooth muscle of the rat carotid artery after clipping injury. Vascular damage was produced by clipping the right carotid arteries of Wistar rats. Endothelial regeneration was confirmed by the injection of Evans blue dye and the detection of factor VIII-related antigen. The volume of the smooth muscle cell layer and the luminal size were measured by computer-assisted morphometric analysis. Immediately after arterial injury, Evans blue dye freely permeated the smooth muscle layer, suggesting that complete endothelial denudation had occurred. Endothelial regrowth started within 24 hours and was fastest on the third and fourth days after injury. The endothelial injury was repaired within 5 days. The area of the smooth muscle layer did not change immediately after clipping injury, but it gradually increased within a month. The luminal area of the injured artery increased during the 3-month recovery period. These findings suggest that endothelial regrowth is completed within a week after clipping injury, whereas smooth muscle cell regrowth is slower. In addition, arteriosclerotic luminal narrowing did not occur during recovery of the rat carotid artery from clipping injury.

Animals↗
PubMed1993

Regeneration of the rat carotid artery after clipping injury. Part II. A pharmacological study.

This study investigated the natural course of functional recovery of the vascular endothelium and smooth muscle after clipping injury of the rat carotid artery. Vascular injury was induced by clipping the right carotid arteries of Wistar rats. The contractile response to KCl, serotonin (5-hydroxytryptamine), and norepinephrine was decreased immediately after arterial injury. The response to KCl and serotonin recovered within 8 weeks, whereas the response to norepinephrine recovered after 12 weeks. Endothelium-dependent relaxation also disappeared immediately after clipping injury, but the recovery of relaxation in response to acetylcholine and adenosine triphosphate was observed within 1 week. Four weeks after clipping injury, higher doses of acetylcholine induced slight arterial contraction. These findings suggest that the recovery of smooth muscle contractility was slower than the process of endothelial regeneration in the rat carotid artery after clipping injury. Endothelium-dependent relaxation recovered within only a week, although the characteristics of the arterial cholinergic receptors may have changed in the chronic recovery stage.

Acetylcholine↗
PubMed1992

Immune status of children on continuous ambulatory peritoneal dialysis.

Immunological parameters including serum IgG, IgA and IgM, lymphocyte phenotypes (CD3, CD4, CD8, HLA-DR+CD3-), natural killer cell activity and lymphocyte proliferation with phytohaemagglutinin were assessed in 10 children on continuous ambulatory peritoneal dialysis (CAPD) and 10 control subjects. Live vaccines were injected into 6 of the 10 children on CAPD (4 had a combined measles-mumps-rubella vaccine and the other 2 mumps vaccine). Serum antibody titres to these viruses were measured before and after vaccination. The serum IgG level was statistically lower in the CAPD group than in the control group (P less than 0.01), but there was no difference in the percentage of HLA-DR+CD3- cells and in the ratio of CD4 to CD8 between the two groups. There were no differences in the other parameters between the two groups. All of the 6 vaccinated children seroconverted, and serious side effects were not noted. Our results suggest that children on CAPD have no significant immune impairment.

Adolescent↗
PubMed1992

Anomalous binding of [3H]N-methyl-quinuclidinyl benzilate methyl chloride to human lymphocyte muscarinic receptors.

Using the muscarinic cholinergic ligand [3H]N-methyl quinuclidinyl benzilate methyl chloride ([3H]NM-QNB), we demonstrated that intact, viable human lymphocytes possess specific muscarinic binding sites. Equilibrium binding studies show that muscarinic acetylcholine receptor are divided into two subtype; high affinity (Ms) and low affinity types (Mw) for the ligand.

Adult↗
PubMed1992

Human erythropoietin in children undergoing continuous ambulatory peritoneal dialysis.

The effect of intravenous recombinant human erythropoietin (rHuEPO) by two different dosage regimes was evaluated in 12 anemic children on continuous ambulatory peritoneal dialysis (CAPD). Eight patients (group A) were treated once a week at a mean dose of 89 U/kg for 24 weeks. The other four patients (group B) were treated three times a week at a mean dose of 260 U/kg for 8 weeks, and then once a week at a mean dose of 88 U/kg for the next 16 weeks. In group A, the hematocrit (Ht) increased gradually and significantly from 19.9 +/- 2.1% to 28.7 +/- 1.5% at the 24th week, while in group B, it rapidly increased from 17.9 +/- 2.5% to 30.2 +/- 4.3% at the 8th week, and thereafter was maintained at a level of approximately 30%. However, there was no significant difference in the Ht between the two groups. In two of the four patients in group B, blood pressure increased from 136/87 mmHg to 168/102 mmHg and from 106/70 mmHg to 132/92 mmHg, at the 4th and the 8th weeks respectively, related to a rapid rise of the Ht. Neither antibody to rHuEPO nor other sides effect were evident. Gradual improvement of anemia by once-a-week intravenous administration of rHuEPO is advantageous for the quality of life in children on CAPD.

Adolescent↗
PubMed1992

Superselective intra-arterial infusion of papaverine for the treatment of cerebral vasospasm after subarachnoid hemorrhage.

This report describes the successful treatment of cerebral vasospasm after subarachnoid hemorrhage with superselective intra-arterial infusion of papaverine hydrochloride. Thirty-seven vascular territories in 10 patients with symptomatic vasospasm were treated according to the following protocol. Percutaneous transluminal angioplasty was performed in two steps. First, a silicone balloon was used for dilation of the internal carotid artery and the proximal portions of the middle cerebral artery. A silicone leak balloon or Tracker-18 catheter was then introduced into or just proximal to the site of vasospasm not accessible to the angioplasty balloon catheter for superselective infusion of 0.2% papaverine. Thirty-four of 37 vascular territories were successfully dilated, and eight of 10 patients showed improvement in neurological function after the procedure. There were no serious side effects due to infusion of papaverine. It is essential to infuse the papaverine just proximal to the spastic vessels in order to deliver sufficient concentration of drug, and infusion should be carried out as early as possible before the artery loses its ability to return to a normal luminal size. Superselective intraarterial infusion of papaverine is an alternative method of treatment for symptomatic vasospasm.

Adult↗
PubMed1991

Asymptomatic isolated microhaematuria: natural history of 136 children.

In a mass screening programme, 251 children with isolated microhaematuria were detected. Of these 251 children, 115 were excluded from the study because of microhaematuria secondary to a specific cause. The remaining 136 children were diagnosed as having asymptomatic isolated microhaematuria (ASH). Of these 136 children, 23 had evidence of urinary abnormalities in their family members. Red blood cell casts were evident in 31 children at their initial visit or during the follow-up period. Ten children had one or more episodes of macrohaematuria during the study. Renal biopsy was performed in 19 children because of indications of glomerular disease, and 13 of these 19 children had mild to moderate glomerulonephritis. None of these 136 children developed hypertension or renal impairment after a mean period of 7.4 years (range 6-13 years). Thirty-five children had normal urinary findings within 6 years of their initial visit, and 100 have had persistent microhaematuria without proteinuria throughout the follow-up period. The other child had microhaematuria with proteinuria greater than 1 g/m2 per day at the end of the study. This study suggests that the prognosis of ASH is good, and that renal biopsy is not indicated for children with ASH.

Adolescent↗
PubMed1991

Efficacy of once weekly erythropoietin therapy in children on continuous ambulatory peritoneal dialysis.

The efficacy of recombinant human erythropoietin (rHuEPO) on 10 anemic children undergoing continuous ambulatory peritoneal dialysis (CAPD) was evaluated. A mean dose of 93 U/kg of rHuEPO was given once a week for 24 weeks, either intravenously to 5 children or subcutaneously to the other 5. Anemia improved in all children by this therapy. The mean hemoglobin and hematocrit levels increased gradually but significantly from 6.9 g/dl and 20.2% to 9.4 g/dl and 30.1%, respectively, at the end of the study. Elevation of blood pressure or other side effects were not noted in any patient. The present study indicates that the once-a-week injection of rHuEPO by the intravenous or subcutaneous route is effective in children undergoing CAPD.

Adolescent↗
PubMed1991

The natural history of screening detected IgA glomerulonephritis in children.

The clinical course of 43 children with IgA glomerulonephritis detected by mass urine screening was followed for a mean period of 8.1 years. Histological findings were graded according to the severity of glomerular and tubulointerstitial lesions. There was no correlation in the severity of histological grade and clinical outcome between subjects with microscopic hematuria and those with microscopic hematuria and proteinuria nor between those with and without one or more episodes of macroscopic hematuria during the follow-up period. None of the 35 children with proteinuria less than or equal to 1 g/m2/day had severe histological findings or developed renal impairment. In contrast, the 8 children with proteinuria greater than 1 g/m2/day had moderate and severe histological findings. Four of these 8 children developed hypertension or renal insufficiency during the follow-up period. Our study indicates that the outcome of screening detected IgA glomerulonephritis in children correlates with the level of proteinuria and the severity of renal pathology.

Adolescent↗
PubMed1991

[Changes of muscarinic cholinergic binding by human lymphocytes with normal aging and Alzheimer's disease].

A potent, new muscarinic cholinergic antagonist, L-[N-methyl-3H] quinuclidinyl benzilate methyl chloride ([3H-]-NM-QNB) was used to detect functional changes of muscarinic acetylcholine receptors (mAChR) on human lymphocytes in relation to age. Using techniques developed for the study of mAChR in brain homogenate, direct binding to whole live lymphocytes was shown for [3H]-NM-QNB. We examined Group of healthy adult females (41-66 years old, N = 34) and patients with "probable" Alzheimer's disease (55-75 years old, N = 11). It was shown that mAChR on lymphocytes were divided into two subtypes; high affinity (Ms) and low affinity types (Mw) for a ligand, [3H]-NM-QNB. For the healthy controls (age range 41-66 years old, N = 31), a negative correlation (r = -0.172) was found between Kd (Ms) and age. Also the negative correlation between Bmax (Ms) and age was shown to be weak (r = -0.164). The regression equations are: Y = 11.9X + 1306.4 (Kd(Ms); N = 31) Y = -80.6X + 8296.1 (Bmax(Ms); N = 31) where, X and Y designate the age of individuals and Kd (or Bmax), respectively. Hence, for patients with Alzheimer's disease, no significant changes with age in Kd (Ms) or Bmax (Ms) were obtained. Furthermore, correlations between the stage of clinical dementia of patients and Kd (Ms), and between the staging and Bmax (Ms) were shown to be strong (p less than 0.05). Significant change (p less than 0.05) in Bmax (Ms) was recognized in lymphocytes from patients with Alzheimer's disease (N = 11), compared with age-matched controls (N = 20).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[SEP monitoring during balloon occlusion test or operation for vertebro-basilar aneurysms].

SEP (somatosensory evoked potential) monitoring was carried out on seven patients with vertebro-basilar aneurysms during balloon occlusion test, during operation, or after operation. In the patient (case 5) with basilar tip aneurysm, the amplitude of N20 remarkably decreased and this finding closely correlated with disturbed consciousness during transient balloon occlusion of the basilar artery. In another patient (case 6) with vertebral dissecting aneurysm, cerebellar retraction caused transient prolongation of N20 latency during operation. In another case, postoperative SEP monitoring revealed marked reduction of N20 amplitude in the patient (case 7) who showed disturbed consciousness and bilateral oculomotor palsy after operation for basilar aneurysms, but who showed no abnormality in postoperative ABR (auditory evoked brainstem response). The other four patients showed no neurological deterioration and no SEP change during transient balloon occlusion of the parent arteries. Because of the high rate of "false-negative" findings, it remains unclear whether SEP monitoring during surgery for vertebrobasilar aneurysms is of value to predict postoperative deficit due to brainstem ischemia. In our study, however, the changes of SEP were well correlated with neurological deterioration and/or the location of postoperative infarction. In conclusion, SEP monitoring during balloon occlusion tests or operations for vertebro-basilar aneurysms is considered to be useful in predicting ischemic complication of the brainstem caused by the occlusion of the parent artery. However other methodologies have to be developed in order to monitor the pyramidal tract and reticular activating system of the brainstem more accurately.

Adolescent↗
PubMed1991

[Changes in CSF pressure induced by acetazolamide administration test--as an indicator of shunt operation for so-called normal pressure hydrocephalus].

Lumber subarachnoid pressure was monitored via intrathecally introduced catheter in 9 patients, who showed ventricular dilatation on brain CT and were suspected of normal pressure hydrocephalus. During the pressure measurement, 500 mg of acetazolamide was rapidly injected intravenously and changes of CSF pressure were recorded. The results of the study were compared to clinical signs, brain CT findings and results of continuous pressure monitoring. The types of response of CSF pressure induced by acetazolamide administration were classified into 2 groups. In 5 cases (Group A), more than 50 percent increase of CSF pressure compared to the resting value was noted. On the contrary, in the remaining 4 cases (Group B), CSF pressure showed only slight increase (less than 25 percent or none). VP shunt was performed in 4 cases in Group A. Definite improvement of clinical symptoms was observed in all of these surgically treated cases. Correlation was found between the response to Acetazolamide administration and the appearance of B wave in the continuous spinal pressure monitoring. This study suggests that Acetazolamide test may be useful diagnostic test to select the patients for shunt operation.

Acetazolamide↗