Circadian variation of exercise capacity in patients with Prinzmetal's variant angina: role of exercise-induced coronary arterial spasm.

Thirteen patients with Prinzmetal's variant angina performed treadmill exercise tests in the early morning and in the afternoon of the same day. The attacks with ST elevation were induced repeatedly in all 13 patients in the early morning, but in only two patients in the afternoon. Propranolol did not suppress the exercise-induced attacks in all 13 patients. Diltiazem suppressed the attacks in all 13 patients and phentolamine in eight of the nine patients. Coronary arteriograms demonstrated that spasm occluding completely or almost completely the large coronary artery supplying the area of myocardium showing ST elevation appeared during the attacks and disappeared along with the attacks after nitroglycerin administration in all four patients in whom the attacks were induced by arm exercise in the catheterization laboratory. We conclude that there is circadian variation of exercise capacity in patients with Prinzmetal's variant angina caused by coronary arterial spasm induced by exercise in the early morning but not in the afternoon.     

Structure of poly(adenosine diphosphate ribose): identification of 2''-[1''''-ribosyl-2''''-(or 3''''-)(1''''''-ribosyl)]adenosine-5'',5'''',5''''''-tris(phosphate) as a branch linkage.

Poly([14C]adenosine diphosphate ribose) was synthesized from [14C]NAD+ with calf thymus nuclei. The fraction containing poly(adenosine diphosphate ribose) eluted with 0.22--0.40 M phosphate buffer (pH 6.8) from a hydroxylapatite column, was completely hydrolyzed with venom phosphodiesterase, and was separated by DEAE-Sephadex A-25 column chromatography in 7 M urea. A new compound, which constituted 2% of the products from poly(adenosine diphosphate ribose), was found in addition to the expected products--i.e., 5'-AMP, 2'-(1'-ribosyl)adenosine-5',5'-bis(phosphate), and its derivatives. This compound was identified as 2'-[1'-ribosyl 2'-(or 3'-)(1'-ribosyl)]adenosine-5',5',5'-tris(phosphate). The existence of this compound is evidence of a branching structure of poly(adenosine diphosphate ribose), which was previously thought to be a linear molecule. The content of this compound suggests that the frequency of branching is about 1 per 20--30 adenosine diphosphate ribose residues of high molecular weight poly(adenosine diphosphate ribose).     

Hyperunstable hemoglobin Koriyama anti-Hb Gun Hill insertion of five residues in the beta chain

A new hyperunstable hemoglobin was found in a Japanese girl who had very severe, chronic hemolytic anemia. Her parents and siblings were hematologically normal. The abnormal hemoglobin comprised a very small proportion of the total hemoglobin, although it was produced almost at the same rate as normal hemoglobin. Sequencing of an abnormal peptide which was liberated from the beta chain by hydrolysis with a protease from Staphylococcus aureus V8 disclosed the tandem insertion of a five-residue segment which included the proximal histidine at beta 92(F8).     

Partial resection of atrial septal aneurysm with multiple fenestrations--a case report

Aneurysms of the interatrial septum are uncommon lesions that are often accompanied by other cardiac anomalies or systemic thrombosis. The authors report 1 case of atrial septum aneurysm that was diagnosed by two-dimensional contrast echocardiography. At surgery a membrane-like, fenestrated aneurysmal protrusion to the right atrium without thrombosis was seen. The atrial septum was closed without using an artificial patch after some of the aneurysm with fenestrations was resected.     

Promotive action of acylated ascorbate on cellular DNA synthesis and growth at low doses in contrast to inhibitory action at high doses or upon combination with hyperthermia

Effects of 6-O-palmitoyl ascorbate (ascorbate) developed to increase the antitumour activity of ascorbic acid on DNA synthesis and proliferation of Ehrlich ascites tumour cells were investigated. Treatment of the cells with the acylated ascorbate at 25–50 M for 1 h resulted in no effect on DNA synthesis, assayed by pulse incorporation of [³H]thymidine after a culture period of 20 h, but led to 49%–87% enhanced DNA synthesis after 4 days, suggesting that long-term culture is required for promotion by ascorbate to occur. At a dose as high as 75 M acylated ascorbate, however, cellular DNA synthesis was 64% inhibited after 20 h and 99% after 4 days. The results suggest that acylated ascorbate exhibits a dual action on DNA synthesis: promotion at low doses and inhibition at high doses, both of which are potentiated in a time-dependent manner. In contrast to the above-mentioned results at 37°C, acylated ascorbate at 25–75 M inhibited but did not promote DNA synthesis at 42°C whatever the culture period. Similar results were exhibited when proliferation of cells cultured for a long period was investigated. At 37°C, 50M acylated ascorbate increased the number of the cells to 3.6 times the control values after 8 days and to 1.9 times after 11 days; in contrast, a 75-M dose decreased the cell number considerably. Combination with hyperthermia (42°C) suppressed the increase and cell growth was completely inhibited at 75M.Abbreviation 6 Pam-ascorbate 6-O-palmitoyl ascorbate     

Maturational stage specific immunoglobulin heavy chain gene rearrangements, determined by D and D upstream region gene structures.

In 43 cases of various B-cell lineage tumors, precise gene structures of rearranged immunoglobulin heavy chain (IgH) were studied. By Southern-blot analysis of D upstream (5'D) gene of IgH, biallelic rearrangement structures, D-J or V-D-J, were determined and consequently maturational stage specific IgH rearrangement patterns were investigated. B-precursor ALL cases (especially stage IV of Nadler's criteria) have V-D-J rearranged IgH genes on both alleles. In contrast, most of the mature B-cell malignancies, excluding multiple myeloma, have IgH genotype of D-J/V-D-J. In addition, in case of D-J/V-D-J, the D gene used in D-J joining has been speculated by Southern-blot of D genes. So, these approaches for inquiring precise structures of rearranged IgH genes are supposed to provide new information of lymphocyte differentiation and leukemogenesis.     

Effects of ACNU and radiotherapy on malignant glioma

A randomized clinical study of irradiation and irradiation combined with ACNU in the treatment of malignant gliomas was performed in order to determine if there was an enhancing therapeutic effect of ACNU given in addition to radiotherapy. An effect was defined as a reduction in tumor size, changes in neurological signs and performance status within 1 month after the completion of radiotherapy, or statistically improved survival times. Seventy-seven patients from 14 neurosurgical clinics were included in this validated study group. Radiotherapy with a total dose of 5000 to 6000 rads, given in 25 to 30 subdoses, was applied to the whole brain and to a generous field surrounding the tumor. Patients who were assigned to receive chemotherapy were given ACNU intravenously once or twice during radiotherapy at a dose of 100 mg/sq m of body surface area. The response rate (more than 50% reduction of the tumor size) was 13.5% in the group treated by radiotherapy alone and 47.5% in the group with radiotherapy and ACNU. The hematological toxicity was more severe in the group treated with radiotherapy and ACNU. Other toxicity was mild and acceptable. The survival rates of patients with astrocytoma grade III and glioblastoma multiforme at 36 months after the surgery were 48.9% and 0% for radiotherapy alone and 59.0% and 16.3% for radiotherapy plus ACNU, respectively. The differences between the survival curves were not significant at the p = 0.05 level. This study has demonstrated that, although the use of ACNU during radiotherapy suppressed malignant gliomas more than radiotherapy alone, the survival time was not extended significantly. It is necessary to continue to search for an effective chemotherapeutic regimen to prolong survival of patients with malignant gliomas.     

BCAA-enriched snack improves nutritional state of cirrhosis

OBJECTIVE: A late evening snack improves the catabolic state in patients with advanced liver cirrhosis. We tested whether long-term (3 mo) late evening snacking that included a branched-chain amino acid (BCAA)-enriched nutrient mixture produces a better nutritional state and better quality of life than ordinary food in patients with hepatitis C virus-positive liver cirrhosis. METHODS: In a multicenter, randomized study, 48 patients with liver cirrhosis received late-evening supplementation with the BCAA-enriched nutrient mixture or ordinary food, such as a rice ball or bread, for 3 mo. During the study period, each patient was instructed on energy and protein intake. Blood biochemical data, nitrogen balance, respiratory quotient, and health-related quality of life (Short Form 36 questionnaire) were evaluated at baseline and at the end of the study. RESULTS: Total and late-evening energy intakes were similar in the two groups at 3 mo. Serum albumin level, nitrogen balance, and respiratory quotient were significantly improved by the BCAA mixture but not by ordinary food. The parameters of the Short Form 36 did not statistically significantly improve over 3 mo in either group. CONCLUSION: Long-term oral supplementation with a BCAA mixture is better than ordinary food in a late evening snack at improving the serum albumin level and the energy metabolism in patients with cirrhosis.     

Tumor promoters specifically and reversibly disturb development and behavior of Caenorhabditis elegans

Summary The effect of phorbol ester tumor promoters on the development and behavior of a free-living soil nematode, Caenorhabditis elegans, was studied. When young developing C. elegans were grown on E. coli-seeded agar with low concentrations (0.1 g/ml) of 12-0-tetradecanoyl-phorbol-13-acetate or phorbol-12,13-didecanoate, their growth was arrested. These tumor promoters reduced the brood size when gravid adults were treated and caused uncoordinated movement in animals treated at any stage of development. The effects of these tumor promoters on nematode development and behavior were partially reversible. The nonpromoting derivatives phorbol and 4-phorbol-12,13-didecanoate showed no effect on the animals.Abbreviations TPA 12-0-tetradecanoyl-phorbol-13-acetate - PDD phorbol-12,13-didecanoate - 4-PDD 4-phorbol-12,13-didecanoate - DMSO dimethylsulfoxide This work was supported by the IBR fund to JM