Negative evidence for a proton-tunneling mechanism in the phase transition of KH2PO4-type crystals.
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Biomedical subjects
Publications and source records attributed to N Yamada.
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To assess the rationale of intraarterial (i.a.) 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea chemotherapy, distribution of 14C-labeled 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)- 3-nitrosourea in rat glioma was studied after i.a. or i.v. infusion. Immediately after infusion, the tumor located in the hemisphere of intracarotid infusion received 4.6-fold higher radioactivity than the tumor located contralaterally to intracarotid infusion and 2.8-fold higher radioactivity than i.v. infusion. The difference was kept up to 30 min after i.a. infusion. Autoradiographic observation indicated rather uniform distribution of the tracer in the central portion of i.a. infusion. However, in the periphery of i.a. infusion, distribution of the tracer was nonhomogenous. The results indicate that i.a. 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea chemotherapy is useful when the tumor has high blood flow and is located in the center of an infused area.
Artificial casein micelles were prepared by adding 30 mM calcium, 22 mM phosphate and 10 mM citrate to sodium caseinate solutions, and the content of the casein aggregates cross-linked by colloidal calcium phosphate was determined by high-performance gel chromatography on a TSK-GEL G4000SW column in the presence of 6 M urea. The content of the casein aggregates cross-linked by colloidal calcium phosphate in artificial whole casein micelles was 48% of total casein, and their relative casein composition determined by high-performance ion-exchange chromatography was 53.1% for alpha s1-casein, 15.8% for alpha s2-casein, 31.1% for beta-casein and 0% for kappa-casein. The order of cross-linking by colloidal calcium phosphate agreed with that of the ester phosphate content of casein constituents. The content of the casein aggregates cross-linked by colloidal calcium phosphate was higher in alpha s1-kappa-casein micelles than in beta-kappa-casein micelles. kappa- and gamma-caseins and dephosphorylated alpha s1-casein were not cross-linked by colloidal calcium phosphate. Although kappa-casein was not cross-linked, chemically phosphorylated kappa-casein, of which the average phosphate content was 8.5 per molecule, was cross-linked. It is concluded that caseins are cross-linked through their ester phosphate groups by colloidal calcium phosphate.
Five patients (1 female and 4 males) with cerebral infarction of 4 h to 27 months duration were studied 9 times with magnetic resonance (MR) using Gd-DTPA. Spin-echo (SE) MR images (MRI) were obtained before and after the administration of Gd-DTPA, and correlative CT scans were performed on the same day. In 2 cases, 4 h and 27 months after the ictus, there was no enhancement with Gd-DTPA. There was faint enhancement in 2 cases with cerebral infarction of about 24 h duration and obvious enhancement in all cases in the subacute stage. Compared with enhanced CT, MR using Gd-DTPA demonstrated more obvious enhancement of infarcted areas. MR enhancement using Gd-DTPA showed a gradual increase and the accumulated Gd-DTPA in infarcted areas slowly diffused to the periphery. MR enhancement with Gd-DTPA is similar to that of enhanced CT, but may be more sensitive in the detection of blood brain barrier breakdown.
We report three cases of autosomal dominant type endosteal hyperostosis which occurred in one Japanese family. A new pattern of sclerotic changes in the jaw bones is evident. In all members of the family there was a symmetrical thickening of the diaphyseal cortices of the long bones. The affected bones were only minimally widened and the epiphyses and metaphyses were spared. Endosteal sclerosis of the neurocranium was present with loss of the diploë. The sclerotic changes included enlargement and mottled sclerosis of both the maxilla and mandible, with multiple embedded teeth and odontomas. The ramus of the mandible was spared. Severe sclerosis of the jaw bones was present only in a 28-year-old woman. The 2-year-son showed only focal sclerosis in the mandible, and his grandmother had minimal changes in the skeleton.
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Hydrolysis of membrane phospholipid phosphoinositides following ibotenate stimulation of an excitatory amino acid receptor subtype has recently been demonstrated to be a receptor-mediated biochemical response. The present study examined ibotenate-stimulated phosphoinositides hydrolysis, determined as accumulation of [3H]inositol 1-phosphate, in amygdala/pyriform cortical and hippocampal slices of amygdala-kindled rats which exhibited fully developed kindled seizures on 20 consecutive days. Animals which underwent a sham operation were used as controls. Ibotenate (10(-3) M)-stimulated accumulation of [3H]inositol 1-phosphate increased significantly by 191% in the amygdala/pyriform cortex (P less than 0.01) and by 59% in the hippocampus (P less than 0.05) of the amygdala-kindled rats killed 24 h after the last seizure. One week after the last seizure, a similar magnitude of significant increase (by 171%, P less than 0.05) was maintained in the amygdala/pyriform cortex of the amygdala-kindled rats. In contrast, the increase in the hippocampus had attenuated by this time, although accumulation of [3H]inositol 1-phosphate increased significantly (P less than 0.05) when stimulated by 10(-4) M ibotenate. These results suggest that enhancement of ibotenate-stimulated phosphoinositides hydrolysis in the amygdala/pyriform cortex may be associated with the long-lasting seizure susceptibility of amygdala-kindled rats.
Tumor uptake rates, concentrations in mitochondrial fraction (containing lysosome) of liver and tumors, avid accumulations in connective tissue (especially inflammatory tissue) and binding substances in these tissues for 46Sc3+ and 51Cr3+ were essentially similar to those for 67Ga3+, 111In3+, 169Yb3+, 167Tm3+, 95Zr4+ and 181Hf4+. However, the main binding substance of 46Sc3+ and 51Cr3+ in tumor and liver was the acid mucopolysaccharide (as described concerning 95Zr and 181Hf) whose molecular weight exceeded 40,000, although the main binding substance of 67Ga3+, 111In3+, 169Yb3+ and 167Tm3+ was the acid mucopolysaccharide with a molecular weight of about 10,000.
It has been reported that apomorphine-induced stereotypy is sensitized after a chronic intermittent administration of haloperidol (HPD), but not after a chronic continuous exposure to haloperidol-decanoate (HPD-D). The present study was undertaken to investigate changes in the D2 dopamine and muscarinic receptors in the rat striatum after the administration of HPD intermittently and HPD-D continuously. The number of striatal [3H]spiperone binding sites increased significantly after HPD-D, but did not change after HPD. Neither the number of [3H](-)QNB binding sites nor carbachol-stimulated phosphoinositide hydrolysis changed after either HPD or HPD-D. These results indicate that the increase in striatal D2 receptors in rats administered HPD-D represents behavioral and biochemical tolerance, and that neither the D2 dopamine receptor supersensitivity nor muscarinic receptor hyposensitivity underlies sensitization of apomorphine-induced stereotypy.
The kinetics of apolipoprotein (apo) B-100 in particles containing apo E (B,E particles) or lacking apo E (B particles) were studied in Watanabe heritable hyperlipidemic (WHHL) rabbits deficient in low density lipoprotein (LDL) receptors, and compared with those of normal rabbits after injection of radioiodinated very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and LDL. In both groups results of kinetic modeling were consistent with the hypothesis that all apo B enters the plasma in VLDL, mainly as B,E particles, followed by delipidation and partial conversion to IDL and LDL, with concomitant conversion of some B,E particles to B particles. In WHHL rabbits, production of VLDL apo B was reduced by 40%, but LDL production was increased threefold. Defective removal of B,E and B particles in all three lipoprotein classes, coupled with preserved processes of delipidation, can account for the observed increases in the concentration of apo B (threefold in VLDL, fivefold in IDL, and twenty-twofold in LDL) in WHHL rabbits.
Local hyperthermia by 13.56-MHz radiofrequency (RF) capacitive heating was evaluated in 16 patients with malignant brain tumors. Intracranial heating during operation was performed in 4 patients. RF applicators with a cooling system were placed on the cerebral convexity and medial brain surface with the tumor between them. RF power was controlled to maintain the brain temperatures under 40 degrees C. Under this condition, the highest temperature of each tumor varied from 44 to 49 degrees C. After heating for about 60 minutes, 2 tumors showed regression on computed tomographic (CT) scans. Extracranial heating was performed in 12 patients with cerebral glioblastoma. RF applicators were placed on the lateral sides of the scalp and applied to diametrically opposite sides of the tumor. To avoid the influence of the skull on RF conduction, we performed a bilateral craniectomy slightly larger than the applicator at the initial operation. Heating was performed for approximately 60 minutes at each session and was repeated twice a week for a total of 4 to 10 times in combination with radiation and ACNU chemotherapy. No anesthetic agent was used during heating. Brain temperatures were maintained under 42 degrees C. The scalp under the applicators remained at 28-35 degrees C during heating, and no heat injury of the scalp was observed after repeated heating. The highest temperatures of the tumor or cavity after tumor removal were 45-46 degrees C in 3 cases, 43-44 degrees C in 3 cases, 42-43 degrees C in 4 cases, and 40-41 degrees C in 2 cases, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Plasma concentrations of the major metabolites of 450191-S, a new sleep inducer which is a 1H-1,2,4-triazolyl benzophenone derivative, were determined in rats. Under the HPLC conditions employed, several major metabolites were detected in plasma, and thus the plasma concentration-time profiles for these metabolites were checked in rats in various states. When the animals were pretreated with high doses of 450191-S (200 or 600 mg/kg for 5 or 3 days, respectively) to induce hepatic drug-metabolizing enzymes, plasma concentrations of the metabolites after oral administration of a dose of 200 mg/kg of 450191-S decreased markedly depending on the induced enzyme activity. Pretreatment of rats with phenobarbital also caused decreased plasma levels of metabolites, which were almost the same as those in 450191-S-pretreatment. On the other hand, administration of beta-naphthoflavone to rats led to higher plasma levels of metabolites, and slower elimination compared with those in the control and 450191-S- or phenobarbital-pretreated rats. These results indicate that plasma levels of metabolites are regulated by the drug-metabolizing enzymes in the liver. It also suggests the participation of some specific forms of cytochrome P-450 in the biotransformation of 450191-S and its metabolites.
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Experimental microvascular anastomosis using a glutide copolymer (lactide:glycolide, 80:20) as an external splint was undertaken in 33 rats between the carotid artery and the jugular vein. Both vessels were dissected free over a 1-cm length and cut at the cranial end of the dissected part. The carotid artery was then introduced into a glutide pipe-splint. The arterial wall was turned 180 degrees over the edge of the splint. This reflected artery wall and the glutide were covered by the freed-up jugular vein. One stitch was made around the vein, the artery, and the glutide in a manner similar to binding steel wire over a barrel. Thus, the "one-knot anastomosis" was completed. The patency rate at the anastomosed site was 100%, confirmed by angiography in 30 rats and by direct surgery in three. The time required to produce the anastomosis was between 5 and 7 minutes. Light microscopic observation showed that there was no obstruction by thrombus formation at 1 and 5 weeks after the anastomotic surgery. This technique may be clinically applicable for extracranial-intracranial bypass surgery, reconstruction of venous sinuses, and other vascular procedures.
For the development of 99mTc labeled tumor seeking agents, 273 drugs and chemicals were evaluated. Agents labeled by SnCl2-HCl method were injected to rats bearing Yoshida sarcoma. Scintigrams of the rats 2 hours after injection and the excised tumor and organs placed on a plate were taken and evaluated their affinity to the tumor. Isoniazid (INH) was found to be the most useful agent as a result of this screening study. Intensive study on 99mTc-INH was subsequently performed. Another labeling method, FeSO4-H2SO4 method, was evaluated and shown to be superior in both absolute tumor uptake and tumor to muscle ratio. Uptake of 99mTc-INH to Yoshida sarcoma occurred early after injection and maintained its level until later time. On the other hand, radioactivity in the blood and muscle decreased rapidly; that is, tumor to blood and muscle ratio showed rapid increase. Other animal tumor models, mouse bearing Ehrlich tumor or Sarcoma 180, were also used to evaluate the usefulness of 99mTc-INH. The labeled agent showed good localization in these tumors too. In conclusion 99mTc-INH might be a good tumor seeking agent and further clinical trials would be warrant.
We have reported a case of malignant lymphoma in associated with Hashimoto's disease arising in the right lobe of thyroid of a 57-year-old woman. The pre-operative aspirated biopsy was valuable for diagnosis Immuno-histochemical observations revealed the localization of anti B cell antibody in the cell surface of lymphoma cells and anti thyroglobulin antibody in intactly follicular epithelium within the lymphoma tissue. This lymphoma was diagnosed as diffuse, medium cell and B cell type. Radiation and chemotherapy were performed for multiple metastasis of liver and brain, but this case had died of DIC and diffuse hyaline membrane disease of lung.
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In order to perform the dexamethasone suppression test (DST) utilizing saliva as an alternative to serum, we developed a direct assay method for saliva cortisol by modification of a commercial assay kit for plasma cortisol. The correlation coefficient between saliva and serum cortisol levels was 0.94. Using this method, DST was performed in 124 patients consecutively admitted to one psychiatric ward. One mg of dexamethasone was given at midnight on the previous day, and saliva samples were collected every 4 h between 8 AM and midnight. When the maximum value was used for the discrimination of non-suppressors, the sensitivity, specificity, and diagnostic confidence levels for melancholia vs non-melancholia were 33.3%, 91.3%, and 77.8% at the criterion value of 0.3 microgram/dl, respectively. While the cortisol secretion rate in saliva was calculated from 5 measured values, the sensitivity, specificity, and diagnostic confidence for melancholia were respectively enhanced to 66.7%, 91.3%, and 87.5% at the criterion value of 0.06 microgram/dl/h, and 38.1%, 95.9%, and 88.9% at the criterion value of 0.12 microgram/dl/h. Even when compared to all patients with other psychiatric diagnoses, these indices maintained the rather satisfactory levels of 38.1%, 90.3%, and 44.4%, respectively. These figures are comparable to or even higher than those obtained by DST using serum cortisol, indicating that the measurement of saliva cortisol is sufficiently applicable to clinical situations.