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Biomedical subjects

H Kikuchi

Publications and source records attributed to H Kikuchi.

At least 739 records · Page 41Linked to original sources

A new antitumor antibiotic, FR-900482. IV. Hematological toxicity in mice.

The new antibiotic FR-900482 (4-formyl-6,9-dihydroxy-14-oxa-1,11-diazatetracyclo-[7.4.1.02,7. O10,12]tetradeca-2,4,6-triene-8-ylmethyl carbamate) possesses an antitumor activity equal to or greater than that of mitomycin C (MMC). The hematotoxicity of equivalent effective doses of the two compounds was compared in mice. A single iv injection of either compound similarly decreased the number of white blood cells (WBC) in the peripheral blood, whereas FR-900482 had no effect on the number of platelets (PTL). Both drugs slightly reduced the number of red blood cells (RBC). The effect of FR-900482 on the bone marrow cells (BMC) measured by cfu in spleen and cfu in culture was weaker than that of MMC. The results suggest that FR-900482 is a promising antitumor agent both in efficacy and safety.

Animals↗

[A molecular basis for multidrug-resistance and reversal of resistance with human malignant cells].

Development of cellular resistance to multiple types of anticancer agents has been recognized as one of the major obstacles for the effective cancer chemotherapy. Increased expression of mdr 1 mRNA seems to be a common mechanism for multidrug resistance (MDR) in human malignant cells. The product of the mdr 1 gene is P-glycoprotein. The predicted membrane orientation of the protein and homology with bacterial active transport proteins, and capability of the protein to bind hydrophobic anticancer agents are consistent with the function of P-glycoprotein as an energy-dependent efflux pump responsible for MDR phenotype. Most of the hydrophobic agents which overcome MDR are cationic and amphipathic. These agents interact with certain polar lipids and inhibit also the binding of hydrophobic anticancer agents with P-glycoprotein. They might directly bind to the binding site of anticancer agents on P-glycoprotein and competitively inhibit the binding of anticancer agents. Alternatively, they might bind to polar lipids of membrane vesicles and indirectly inhibit the binding ability of the protein to anticancer agents by perturbing the membrane function.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Genetic mechanisms of tumor-specific loss of 11p DNA sequences in Wilms tumor.

Wilms tumor, a common childhood renal tumor, occurs in both a heritable and a nonheritable form. The heritable form may occasionally be attributed to a chromosome deletion at 11p13, and tumors from patients with normal constitutional chromosomes often show deletion or rearrangement of 11p13. It has been suggested that a germinal or somatic mutation may occur on one chromosome 11 and predispose to Wilms tumor and that a subsequent somatic genetic event on the normal homologue at 11p13 may permit tumor development. To study the frequency and mechanism of such tumor-specific genetic events, we have examined the karyotype and chromosome 11 genotype of normal and tumor tissues from 13 childhood renal tumor patients with different histologic tumor types and associated clinical conditions. Tumors of eight of the 12 Wilms tumor patients, including all viable tumors examined directly, show molecular evidence of loss of 11p DNA sequences by somatic recombination (four cases), chromosome loss (two cases), and recombination (two cases) or chromosome loss and duplication. One malignant rhabdoid tumor in a patient heterozygous for multiple 11p markers did not show any tumor-specific 11p alteration. These findings confirm the critical role of 11p sequences in Wilms tumor development and reveal that mitotic recombination may be the most frequent mechanism by which tumors develop.

Child↗

[Measurement of energy expenditure in the acute stage of head injury (Part I)].

Oxygen consumption (VO2), carbon dioxide production (VCO2), resting metabolic expenditure (RME), RME of that expected for an uninjured resting person of equivalent age, sex, and body surface area (RME%), nitrogen balance, and protein calorie contribution (PCC) were measured in 8 patients with head injury. Metabolic measurements were carried out with the technique of indirect calorimetry from onsets to 14th day. Mean values of VO2 and VCO2 were 298 ml/min, 236 ml/min respectively on admission and those decreased gradually. Mean values of RME%, nitrogen balance, and PCC were 130.6%, -14.5 gm/day, and 17.3% respectively on admission. And those three values significantly decreased on 14th day in those 8 patients. From those facts, it was implied that hypermetabolism and hypercatabolism existed, and measurement of energy expenditure was indispensable to supply enough calorie maintaining body weight and immunocompetence in the acute stage of head injury.

Acute Disease↗

[Evaluation of regional cortical blood flow by thermal diffusion using a Peltier stack].

The possibility of quantitative evaluation of cerebral blood flow (CBF) by thermal diffusion has been reported, when the thermal gradient was created by a Peltier stack. We already described the linear relationship between the CBF and the inverse of thermal gradient elsewhere when the CBF measured by hydrogen clearance (Hydrogen CBF) was compared to the values estimated by thermal diffusion. In this paper, the correlation of linear relationship between the thermal CBF and hydrogen CBF in each animal was first investigated. Secondary, the possibility of in vitro calibration for quantitative evaluation was discussed. Two kinds of probes were manufactured. One was treated not to leak the heat from the Peltier stack except the sensors for the experimental or intraoperative use, and the other was not treated to minimize the size of probe for the long-term use by implantation into the subdural space. When the thermal CBF was compared to hydrogen CBF in each of 3 cats, a linear relationship was obtained in each and the values showing gradient and constant of the regression line were similar in each cat. Moreover, a good linear relationship was also observed when all measurements in 3 cats were included. These results suggested that there is no difference between each animal in the relationship of thermal and hydrogen CBF when the same probe is employed. In addition, the probe can be characterized with two values, and these are gradient and constant of the linear relationship. The fact that the blood flow is proportional to the heat conductivity indicates that the heat conductivity of some material is equivalent to some CBF value in the brain tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Cerebral blood flow in subarachnoid hemorrhage: analysis in patients with poor outcomes].

Cerebral blood flow (CBF) of 6 patients with poor outcome after subarachnoid hemorrhage is analyzed. Neurological grades of these patients were grade III in 2 and grade IV in 4 patients, and subarachnoid hemorrhage on CT was diffuse and thick in all patients. Cerebral blood flow was continuously measured for 7 to 19 days by the thermal diffusion flow probe with a peltier stack which was left on the cerebral cortex at the surgery for ruptured aneurysm. Moreover, CBF studies by cold xenon CT and 133Xe inhalation methods were also performed in discussing cases. At the same time intracranial pressure was monitored. Cerebral angiography was carried out in all except for 2 patients who died due to severe cerebral vasospasm. The initial CBF value of all patients was 20 to 40 ml/100 g/min (mean value: 27 ml/100 g/min), and these were significantly low compared to normal value (50 ml/100 g/min). Moreover, these CBF was substantially decreased several days after surgery in all patients, and it was marked in 3 patients who died. From these results it was clear that the degree of vasospasm is important to determine the prognosis. One of 3 patients who died had ruptured left posterior cerebral artery aneurysm with occlusion of bilateral internal carotid arteries. In this case further decrease of CBF due to vasospasm was observed in addition to low initial CBF resulting diffuse low flow in both hemispheres although extracranial to intracranial bypass was performed. On the other hand, it was also shown that the intracranial pressure was an important factor to influence the outcomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Regional cerebral blood flow images of single photon emission computed tomography by N-isopropyl-p-[I-123] iodoamphetamine in patients with brain tumor].

Regional cerebral blood flow (r-CBF) was studied by single photon emission computed tomography (SPECT) using N-isopropyl-p-[I-123] iodoamphetamine (IMP) in order to evaluate CBF in patients with brain tumor. Total 27 studies were carried out in 20 patient, including 8 patients with meningioma, 3 with glioblastoma multiforme, 2 with oligoastrocytoma, and 7 with other intracranial tumors. All CBF images by IMP-SPECT were obtained by using a rotating gamma camera with dual heads. In the serial scans, each scan was started at 20 minutes, 2 hours and 6 hours after intravenous injection of I-123 IMP (3 mCi). The all IMP-SPECT images were compared with cerebral angiogram, X-ray CT (plain and/or enhancement), and images of Kr-81 m SPECT and Tc-99 m SPECT. In 5 patients (4 patients with meningioma and 1 with glioblastoma multiforme) this comparative study was performed before and after surgery to evaluate the r-CBF changes surrounding tumor. The abnormal lesion on X-ray-CT was identified as hot area on CBF image by IMP-SPECT in two cases with meningioma, and in 14 cases the lesion showed cold area. Totally 80% of cases showed abnormal findings on CBF images by IMP-SPECT. The cases which showed no abnormal findings on IMP-SPECT images included 1 case with meningioma which located in frontal base, 2 with small intracranial brain tumor which was smaller than 2 cm in diameter, and 1 with pituitary adenoma. On the IMP-SPECT images scanned 2 hours after injection, hot area, which was identified in two cases with meningioma on the images 20 minutes after injection, was changed into cold area.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamines↗

[Measurement of cerebral blood flow by thermal diffusion using a flow probe with a Peltier stack].

In order to evaluate the blood flow by means of thermal diffusion, relationship between blood flow and parameters induced by thermal diffusion was investigated. Flow probe employed for measurement by thermal diffusion incorporated a Peltier stack which contained a small semiconductor and two L-shaped gold plates. These two plates were attached to both sides of the semiconductor by one side of each gold plate and the other side was surfaced with a tissue to be measured. Temperature gradient is created with current applied to the Peltier stack between two plates, one cooled and the other heated, and it is affected only by tissue blood flow. Two kinds of parameters of thermal diffusion were subjected to compare to blood flow. One was temperature gradient when the constant current was applied to the Peltier stack. The other was a current required to maintain a definite temperature gradient which was determined before hand. From the theoretical principle in thermodynamics, the correlations between blood flow and each of thermal diffusion parameters were defined by the following equations: (Formula: see text) where F is blood flow, delta V is voltage converted from temperature gradient, and Ci and Cv are constants. Each of phi v and phi i indicates the characteristics of each probe. Experimental study was carried out to confirm the above relationship using cortex of experimental animals. Under the general anesthesia, a cat was placed in prone position. After the craniotomy, dura mater was opened and a small flow probe, 10 mm in diameter, 5 mm in height and 5 g in weight, was placed on the cortex and blood flow was continuously evaluated by two parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Plasminogen activator in synovial fluid from patients with rheumatoid arthritis.

The plasminogen activator in synovial fluid from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) was analyzed on a molecular basis. The level of plasminogen activator in RA was found to be higher than in OA. The plaminogen activators of both RA and OA revealed 3 different molecular weights: 90,000, 55,000 and 33,000. RA demonstrated the 3 plasminogen activators in broadly comparable ratios, but OA had the 55,000 form dominantly. The 90,000 plasminogen activator was a tissue-type plasminogen activator, while the 55,000 and 33,000 plasminogen activators were of the urokinase-type. beta-Methasone suppressed the tissue-type plasminogen activator, and urinary trypsin inhibitor suppressed the urokinase-type plasminogen activators. When urinary trypsin inhibitor was injected clinically into the joint space of a patient with RA, the urokinase-type plasminogen inhibitor was suppressed as in the in vitro study, and the clinical signs and symptoms were markedly improved. Open trials of intraarticular injections of urinary trypsin inhibitor demonstrated improvement of the clinical signs and symptoms.

Adult↗

[Application of spinal dynamic computed tomography in the diagnosis of spinal cord arteriovenous malformations].

Seventeen cases of spinal cord arteriovenous malformation (AVM) were evaluated by use of spinal dynamic computed tomography (CT). In the intravenous injection method, contrast medium was injected bolusly into the median cubital vein. In the intraarterial injection method, contrast medium was injected slowly into the feeding artery. In both methods, lesions were demonstrated in all cases. Three-dimensional localization of the lesions were more clearly demonstrated in the intraarterial injection method. Intravenous injection method was useful in the postoperative follow-up study due to its noninvasiveness.

Adolescent↗

[Intraoperative liquid embolization of an arteriovenous malformation in the basal ganglia and thalamic region].

Total three patients with arteriovenous malformation (AVM) in basal ganglia or thalamic region were treated by intraoperative liquid embolizations. These procedures were decided because of repeated hemorrhagic episodes. In the case with AVM in the head of the caudate nucleus which was fed by several anterior perforating arteries originated from anterior cerebral artery (A1 portion) and middle cerebral artery (M1 portion), frontotemporal craniotomy was performed. After the microsurgical dissection of these feeders, one of the feeders lenticulostriate artery, was cannulated with a small-caliber polyethylene catheter, 0.6 mm in outer diameter and 0.3 mm in inner diameter. A small amount of isobutyl 2-cyanoacrylate (IBCA) was injected through the catheter. Same procedure was carried out one month later. Postoperative angiograms revealed about 90% loss of AVM. In two cases with AVM which involved almost entire thalamus, subtemporal craniotomy was done. Feeding vessels which originated from posterior communicating artery and posterior cerebral artery (PCA) were carefully dissected under the operative microscope and one of them was prepared for cannulation with small catheter. When the small amount of IBCA was injected, proximal PCA and internal carotid artery were temporarily occluded. In both cases intraoperative embolization was carried out twice. Postoperative angiograms revealed that the size of AVM was decreased to 20% in one and 40% in the other. Although temporary postoperative deterioration of neurological deficits such as hemiparesis and visual disturbance was slightly noted in all cases, no hemorrhagic episode was experienced for 6 months, 1.5 and 2 years in each after embolization.

Adult↗