Further studies on the resolution of human mercapt- and nonmercaptalbumin and on human serum albumin in the elderly by high-performance liquid chromatography

High-performance liquid chromatographic (HPLC) analysis of human serum albumin (HSA) on Asahipak GS-520 showed at least two peaks, the principal component corresponding to human mercaptalbumin (HMA) and the secondary one to nonmercaptalbumin (HNA). HPLC analysis of HSA on Asahipak ES-520 N showed three peaks, the principal component corresponding to HMA, the secondary one to HNA having mixed disulfide with cysteine or glutathione and the tertiary one to HNA oxidized higher than mixed disulfide. Two kinds of rapid HPLC for the resolution of HSA into HMA and HNA were developed by the present authors. Using these HPLC, the present authors found a significant decrease in the fraction of HMA in the elderly.     

Effectiveness of nilvadipine in two cases of chronic schizophrenia

Abstract Nilvadipine is a calcium channel inhibitor used commonly for the treatment of cerebrovascular insufficiency. We observed two patients with schizophrenia whose psychiatric symptoms and tardive dyskinesia improved after the addition of nilvadipine to their antipsychotic drug regimen. The total score of the brief psychiatric rating scale (BPRS) in case 1 fell from 56 to 42 after 8 weeks on nilvadipine; while that of case 2 fell from 44 to 32. The total score of the abnormal involuntary movement scale (AIMS) in case 2 decreased from 12 to 7. No adverse effects occurred during treatment. Nilvadipine may thus offer a new approach to the adjunctive treatment of schizophrenia.     

Water structure in modified bovine plasma albumin (BPA*) gel and bovine mercaptalbumin solution† 1 H-n.m.r. studies

Bovine plasma albumin Fr. V (BPA) has been known to contain small amounts of proteolytic enzyme. Wilson & Foster (1971) found a very limited and specific cleavage of BPA catalyzed by the enzyme with BPA in the F-form near pH 3.8, resulting in the formation of partially hydrolyzed BPA (BPA*). BPA* had a tendency to form a transparent gel at pD 4.0 (pD range of the F-form) above 8%, though proteolytic enzyme-free bovine mercaptalbumin (BMA) was in a transparent solution at pD 4.0 even at 12%. Water structures of the F-form of BMA in the solution state and of BPA* in the gel state were studied by measuring ¹ H-n.m.r. spectra, spin-lattice relaxation time (T₁) and cross relaxation time (T_IS) between irradiated and observed protons. Protein concentration-dependent changes of T₁ of water protons indicated that the amount of hydrated water of BPA* in the gel state is far greater than that of the F-form of BMA in the solution state. T_IS values from protein protons to water protons also indicated a large amount of hydration of BPA*, strong interaction between water and BPA* and rapid exchange between bound and bulk water in the gel state.     

An early gallstone clearance following repeat piezoelectric lithotripsy

Piezoelectric extracorporeal litotripsy was performed in 128 symptomatic patients with radiolucent gall-bladder stones to assess the significance of disintegration in fragment clearance. Up to 10 repeat lithotripsy sessions were scheduled to achieve a fragment target size of <3 mm. Fragmentation assessed by the size of the largest fragments after the last session was graded into three classes. I: sludge-like disintegration, 18%; II: <3 mm (mean ± s.d., 1.7 ± 0.5 mm), 56%; and III: < 3 mm (3.3 ± 0.6), 26%. All patients were initially subjected to lithotripsy alone. Bile acid dissolution therapy was started only when ultrasonography failed to show the evidence of decrease in the <3 mm fragments during a 1 month follow up. Finally, 69 patients (54%) were treated by lithotripsy alone, and the remaining 59 received additional dissolution therapy at a mean period of 2.5 months after the initial lithotripsy. The rate of complete clearance in class I, II and III patients was 91, 42 and 10% at 6 months and 100, 68 and 49% at 18 months, respectively. Significant differences were noted between the three fragmentation grades (I vs II, III, P <0.0001; II vs III, P <0.02). The patients with complete clearance within 6 months were seen only in those treated by lithotripsy alone, while the majority (87%) of patients with complete clearance during the later period were seen in those treated by additional dissolution therapy. We conclude that a high degree of fragmentation appears to lead stones to an earlier period clearance, and reduce the need for dissolution therapy.     

Single-nucleotide polymorphisms in the 17β-hydroxysteroid dehydrogenase genes might predict the risk of side-effects of estramustine phosphate sodium in prostate cancer patients

BACKGROUND: Estramustine phosphate sodium (EMP) frequently causes side-effects such as gastrointestinal discomfort, nausea, and edema in extremities. We analyzed single nucleotide polymorphisms (SNP) in the 17beta-hydroxysteroid dehydrogenase (HSD17B) genes, which are involved in the metabolism of EMP, to predict the risk of EMP side-effects in prostate cancer patients. METHODS: We performed genotyping of SNP in the HSD17B genes of 44 Japanese patients with newly diagnosed prostate cancer. The association of SNP and individual EMP side-effects was evaluated. RESULTS: Peripheral edema occurred more frequently in patients with C/C genotype of IMS-JST123219 than in those with C/G genotype (OR: 5.47, 95% CI: 1.27-23.64). Haplotype analysis showed that appetite loss was associated with the G allele of IMS-JST123219 and the T allele of IMS-JST123218 (OR: 9.13, 95% CI: 1.15-72.76). CONCLUSIONS: These preliminary data demonstrated that analyses of SNP in the HSD17B genes might predict the occurrence of side-effects from EMP.     

The effects of dichloroacetate on liver damage and circulating fuels in rats exposed to carbon tetrachloride

Abstract It has been known that carbon tetrachloride-induced liver damage in starved rats is ameliorated simply by restoration of feeding. An analogue of dichloroacetate has been reported to ameliorate carbon tetrachloride-induced liver damage, and dichloroacetate has been shown to have a variety of effects on fuel metabolism. We investigated simultaneously the effects of dichloroacetate on liver damage and on circulating fuels in rats exposed to carbon tetrachloride. The effects of carbon tetrachloride varied with the rat's condition. In starved rats, the liver damage was more severe, and serum ketone body concentration decreased. In non-starved rats, the liver damage was not as severe and the serum ketone body concentration increased. The administration of dichloroacetate ameliorated liver damage both in starved and in non-starved rats given carbon tetrachloride: the administration of dichloroacetate protected from the liver damage particularly in starved rats. There were associated changes in the concentractions of circulating fuels. When the pyruvate-lowering effect of dichloroacetate was diminished in carbon tetrachloride-injected, starved rats, the alanine aminotransferase-lowering effect of dichloroacetate was also diminished. We propose that dichloroacetate's effect on fuel metabolism may produce a hepato-protective effect.     

Circular dichroic and 1 H-NMR studies on the aged form of bovine plasma albumin

Bovine plasma albumin (BPA) has 17 disulfide bonds and approximately one SH group at Cys-34 which catalyzes the intramolecular SH, S-S exchange reaction in the alkaline region at low ionic strength, resulting in the formation of the aged form (A-form). 1) Fractions of α-helix (f_α) and β-form (f_β) of iodoacetamide-blocked non-aged BPA (IA-BPA) at pH 6.5 (the N-form) and 9.0 (the B-form) in the absence of added salt were 0.70, 0.12 and 0.62, 0.18, respectively (Era et al. (1990)). However, there were no changes in f_α and f_β of the iodoacetamide-blocked A-form (IA-A-form) over the pH range from 5.5 to 9.1 in the absence of added salt or in 0.10 m KCl(f_α～ 0.60, f_β～ 0.20), indicating that the secondary structure of the IA-A-form might be similar to that of non-aged IA-BPA at pH 9.0 (B-form) in the absence of added salt, that is, the frozen B-form, stabilized covalently by the repairing of disulfide bonds. 2) The rigidity of the A- and IA-A-forms, as monitored by cross-relaxation times between irradiated and observed protein protons, was similar to or slightly higher than that of non-aged IA-BPA or BMA. However, spin-echo ¹H-NMR spectra indicated that side chains of the IA-A-form, such as ?-CH₂ of Lys, -CH₃, in the absence of added salt are more mobile than those of non-aged IA-BPA. 3) The ratio of the hydrodynamic volume of the A-form to that of non-aged BPA at pH5.5 was approximately 1.1.     

A Case of Bronchial Fibroma Associated with Subsegmental Atelectasis

A case of polypoid endobronchial fibroma which led to subsegmentalatelectasis in a 45-year-old male is reported. The diagnosiswas made pre-operatively by roentgenographic examination, bronchoscopyand biopsy. A lobectomy of the right middle lobe was performed.The polypoid tumor occupied the lumen of the subsegmental bronchusof the right middle lobe and had a stalk. Histologically, thetumor was composed mostly of collagen bundles with scant spindle-shapedfibroblastic cells and a myxomatous component. There was neithercellular atypia nor mitotic figures nor infiltration of smallround cells. The diagnosis was pulmonary fibroma of the endobronchialtype. To date, 66 cases of pulmonary fibroma have been reportedin the English literature since 1880; 21 of these were polypoidendobronchial fibroma. Only five cases of polypoid endobronchialfibroma including this case have been reported in the Japaneseliterature.     

Long-term effects of bone marrow transplantation for inborn errors of metabolism: A study of four patients with lysosomal storage diseases

Long-term effects of bone marrow transplantation (BMT) were evaluated in patients with I-cell disease, metachromatic leukodystrophy (MLD), Maroteaux-Lamy syndrome or Hunter syndrome (mild form). Donors were human leukocyte antigen (HLA)-matched siblings, and the follow-up periods were 24–71 months after BMT. The enzyme activities were increased in leukocytes, plasma or liver tissues compared with pre-BMT levels. A patient with I-cell disease acquired development of 4–8 month old infants and showed no further progression in cardiac dysfunctions. A patient with MLD showed a decelerated disease progression and an improved peripheral neuropathy, but progressive brain atrophy was not prevented. Patients with Maroteaux-Lamy syndrome or Hunter syndrome showed improvements in hepatomegaly, joint contractures, short stature and tight skin, and this greatly increased their quality of life. These results indicated that the long-term therapeutic effects achieved by BMT were subject to multiple factors including biochemical improvements, a reversibility of affected tissues, or advanced states of disease and central nervous system impairments in inborn errors of metabolism.     

Para-Aortic Nodal Irradiation in the Treatment of Carcinoma of the Uterine Cervix: A Report of 22 Cases

Twenty-two patients with previously untreated carcinoma of theuterine cervix were treated by para-aortic nodal irradiationfor the macroscopical metas-tases found at the operation withor without pathological confirmation, at the National CancerCenter Hospital from 1962 to 1980. The irradiation was givenwith 6 MeV X rays. Total doses ranged from 42 to 99 with anaverage of 69 in Time Dose Fractionation factors. All of thepatients died of the tumor within 42 months. The initial siteof relapse was intrapelvic for two patients, extrapelvic for18, and both intra- and extrapelvic for two. Of 12 patientsupon whom autopsies were performed, only one of the patientswho had multiple metastatic tumors of less than i cm in maximumdiameter had the tumor controlled in the irradiated region.