Surgical experience in patients with Marfan's syndrome and cardiovascular disease

10 patients with Marfan's syndrome and cardiovascular disease were operated at Tohoku University Hospital from 1971 to 1988. Surgery included composite valve graft replacement of ascending aortic aneurysm with aortic regurgitation in 5 patients and prosthetic mitral valve replacement in three patients; two had resection of aneurysm with Dacron tube replacement. Operative mortality was 10%. Two late death occurred (22%). It was suggested that regular follow-up examination is important in these patients to detect new lesions and to evaluate known lesion.     

Development of thick wall 2.25Cr-1MoNiNb steel forgings for steam generators of fast breeder reactors

The large and thick forgings made of 2.25Cr-1MoNiNb steel are required for vessel material of steam generator (SG) of the fast breeder reactor SNR 300.In order to study the feasibility of 2.25Cr-1MoNiNb steel heavy section forging, chemical composition, melting practice and ingot making, hot working and heat treatment conditions were investigated. The following recommendations were derived: (1) 0.04% C, 0.10% ΔNb, (2) application of electro-slag remelting process, (3) grain refining by hot working, (4) two-step austenitizing at 1020°C.Based on these recommendations, the actual products such as hollow cylinders with maximum 290 mm thickness, solid bars with 420 mm diameter and forged plates with maximum 185 mm thickness could be supplied for application in the helical coiled SG of the SNR 300. Statistical analysis of the products showed the sufficient and isotropic material properties, which fulfill the requirements of the basic safety rules.     

A possible mechanism for hyperthermic radiosensitization mediated through hyperthermic lability of Ku subunits in DNA-dependent protein kinase

DNA-dependent protein kinase (DNA-PK), composed of p470 catalytic subunit and p85/p70 heterodimer of Ku autoantigen, is considered a critical enzyme in DNA double-strand break repair. We purified DNA-PK from human leukaemic MOLT-4 cells by successive column chromatography and separated into p470 and Ku subunits by ultracentrifugation in glycerol gradient. We studied hyperthermic stability of DNA-PK holoenzyme and its separated subunits to test a possible role of DNA-PK in hyperthermic radiosensitization. DNA-PK was found to lose its activity rapidly at hyperthermic 44 degrees C, and further, Ku subunits instead of p470 catalytic subunits were found to be sensitive to hyperthermia. These results indicate a possibility that hyperthermic radiosensitization is mediated through the heat lability of Ku subunits of DNA-PK, impairing repair of radiation-induced double-strand break of DNA.     

Gene-dose effect on carnitine transport activity in embryonic fibroblasts of JVS mice as a model of human carnitine transporter deficiency

Recently, the marked decline in renal carnitine reabsorption has been thought to account fotr the systemic carnitine deficiency in juvenile visceral steatosis (JVS) mice. We have conducted a kinetic analysis using embryonic fibroblasts derived from normal, heterozygous, and homozygous jvs mice and found that the high-affinity carnitine transporter (Km = 5.5 microM), which shows Na+ and temperature dependency and stereospecificity, is defective in homozygous jvs mice. Moreover, a gene dose-dependent decrease of carnitine transport activity, which was due to a decrease in the number of the transporter molecules, was found in heterozygous jvs mice. Similar phenomena have been observed in human primary carnitine deficiency. Therefore, JVS mice may be useful for understanding this extremely rare human hereditary disorder.     

Mast cell chymase-like protease(s) modulates Escherichia coli lipopolysaccharide-induced vasomotor dysfunction in skeletal muscle in vivo

This study investigated whether short-term exposure to Escherichia coli lipopolysaccharide (LPS) elicits vasomotor dysfunction in skeletal muscle in vivo and, if so, whether perivascular mast cell proteases partly modulate this response. With intravital microscopy, we found that suffusion of E. coli LPS on the in situ hamster spinotrapezius muscle for 60 min elicits immediate vasoconstriction followed by vasodilation. Vasoconstriction is abrogated by SK&F 108566, a selective, nonpeptide angiotensin II (AT II) subtype 1 receptor antagonist, chymostatin and soybean trypsin inhibitor. These compounds also attenuate E. coli LPS-induced vasodilation. By contrast, superoxide dismutase, catalase and indomethacin attenuate only E. coli LPS-induced vasodilation. Endothelin receptor antagonists, lisinopril, leupeptin, Bestatin and DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid are ineffective. Histochemical analysis of the spinotrapezius muscle reveals abundant perivascular mast cells with chymostatin-inhibitable chymase-like activity. Pretreatment of hamsters with compound 48/80 for 4 days curtails E. coli LPS-induced vasoconstriction and converts vasodilation to vasoconstriction. On balance, these data indicate that E. coli LPS stimulates perivascular mast cells in the in situ hamster spinotrapezius muscle to release an AT II-producing chymase-like protease(s). AT II thus produced elicits local vasoconstriction and elaborates reactive oxygen species which, in turn, generate vasodilator prostaglandins.     

Suppressed UDP-galactose: ceramide galactosyltransferase and myelin protein mRNA in twitcher mouse brain

To investigate the role of temporal processing in language lateralization, we monitored asymmetry of cerebral activation in human volunteers using positron emission tomography (PET). Subjects were scanned during passive auditory stimulation with nonverbal sounds containing rapid (40 msec) or extended (200 msec) frequency transitions. Bilateral symmetric activation was observed in the auditory cortex for slow frequency transitions. In contrast, left-biased asymmetry was observed in response to rapid frequency transitions due to reduced response of the right auditory cortex. These results provide direct evidence that auditory processing of rapid acoustic transitions is lateralized in the human brain. Such functional asymmetry in temporal processing is likely to contribute to language lateralization from the lowest levels of cortical processing.     

Juxtaglomerular cell tumor without hypertension

The diagnosis of haematological malignancies has undergone major conceptual changes in the past decade. Accurate diagnosis now depends on a combination of morphological examination, cell marker studies, and molecular biological techniques. Specialist haematopathology diagnostic services are best provided in an integrated laboratory, able to carry out the full range of techniques and staffed by pathologists and scientists with expertise in the investigation of leukaemia and lymphoma.