Specific binding of Ulex europaeus agglutinin I lectin to sarcolemma of distal myopathy with rimmed vacuole formation

Ulex europaeus agglutinin I (UEA I) binding was studied in 83 patients with various neuromuscular disorders. UEA I labelled endomysial capillaries and endothelial cells of perimysial blood vessels in all the examined muscles. There was no UEA I binding to muscle fibres except for all (9) cases of distal myopathy with rimmed vacuole formation (DMRV), 1 of 5 cases of inclusion body myositis and 1 of 36 cases of inflammatory myopathies. The UEA I binding was completely eliminated by preincubation of UEA I solution with L-fucose. Using electron microscopy, the UEA I binding was localized to sarcolemma and intrasarco-plasmic membranous organelles other than mitochondria. Myosatellite cells were not labelled. These findings revealed the existence of fucosylated proteins or lipids in a subset of skeletal muscles suffering from DMRV. Biochemical identification of the fucosylated substance and further detailed study on subcellular localization of UEA I binding may yield important clues to the unknown pathogenesis of DMRV.     

Multivariate evaluation of prognostic determinants for renal cell carcinomas which are metastatic at initial diagnosis

To clarify the relative importance of clinicopathological factors potentially affecting the survival of individuals initially diagnosed as having metastatic renal cell carcinoma (RCC), univariate and multivariate analyses using Cox's proportional hazards model were performed for 111 RCC patients who were admitted to four hospitals in Nagoya, Japan, between 1978 and 1993. Survival time was calculated from the date of diagnosis to the date of death or the end of May, 1995. Nineteen factors (17 clinically applicable before treatment and 2 histological in nature) were included for assessment. Univariate analysis revealed that 10 of the total 19 factors were significantly associated with patient survival. Multivariate analysis found 7 factors to be statistically significant determinants. Survival was further evaluated by categorizing the patients into three groups according to the number of the 7 factors. These groups showed clearly different survivals (log-rank test, p < 0.0001), confirming the importance of the 7 factors as definite determinants. They should therefore prove to be of advantage for classifying metastatic RCC patients when designing clinical prospective studies of immunotherapy and chemotherapy.     

Desensitization of the GABAA receptor shifts the dynamic range of retinal horizontal cells due to light and dark adaptation

The effects of the GABAergic pathway on the dynamic range of the light response of cone-driven horizontal cells (HCs) in the carp retina were investigated using conventional intracellular recordings and computer simulations. The amplitude of the HC responses to repetitive test flashes was altered by background illumination in control Ringer's solution, but was not changed following the application of picrotoxin or bicuculline, which suggests that GABAA receptors mediate the subsequent change in light response. This phenomenon was simulated by introducing the desensitization mechanism of the GABAA receptor into a cone-HC network model. These results suggest that desensitization of the GABAA receptor shifts the dynamic range of the HCs due to light and dark adaptation.     

Combined surgery for coronary artery disease and thoracic aortic disease

Combined surgery in 6 cases who had coronary artery disease and thoracic aortic disease simultaneously was analyzed. Case # 1 had ascending aortic replacement under deep hypothermic circulatory arrest because of iatrogenic aortic dissection caused by aortic clamp during the routine coronary artery bypass grafting (CABG). Case # 2 had DeBakey type II chronic dissection. Case # 3 had type I aortic dissection 4 years after the initial CABG. Both case # 2 and # 3 had ascending aortic replacement under retrograde cerebral perfusion along with CABG. Transverse aortic replacement was performed in case # 4, # 5 and # 6 under selective cerebral perfusion along with CABG. Case # 4 was associated with ascending-transverse aortic aneurysm. Case # 5 had aortitis syndrome complicated with severe coronary ostial stenosis and cervical branch stenosis. Case # 6 also had aortitis syndrome, severe coronary ostial stenosis, heavily calcified ascending-transverse aorta, and mitral and aortic regurgitation. This case had mitral and aortic valve replacement additionally. Case # 2 died of low cardiac output syndrome and multi-organ failure postoperatively. Case # 4 did not recover from profound shock that followed the preoperative acute myocardial infarction. The problems of low cardiac output syndrome caused by long interval of ischemic cardiac arrest, and also the problems of proximal anastomotic site of saphenous vein grafts were discussed.     

Electrophysiological studies of rat substantia nigra neurons in an in vitro slice preparation after middle cerebral artery occlusion

We studied sequential changes in electrophysiological profiles of the ipsilateral substantia nigra neurons in an in vitro slice preparation obtained from the middle cerebral artery-occluded rats. Histological examination revealed marked atrophy and neurodegeneration in the ipsilateral substantia nigra pars reticulata at 14 days after middle cerebral artery occlusion. Compared with the control group, there was no significant change in electrical membrane properties and synaptic responses of substantia nigra pars reticulata neurons examined at one to two weeks after middle cerebral artery occlusion. On the other hand, there was a significant increase in the input resistance and spontaneous firing rate of substantia nigra pars compacta neurons at 13-16 days after middle cerebral artery occlusion. Furthermore, inhibitory postsynaptic potentials evoked by stimulation of the subthalamus in substantia nigra pars compacta neurons was suppressed at five to eight days after middle cerebral artery occlusion. At the same time excitatory postsynaptic potentials evoked by the subthalamic stimulation was increased. Bath application of bicuculline methiodide (50 microM), a GABA(A) receptor antagonist, significantly increased the firing rate of substantia nigra pars compacta neurons from intact rats. These results strongly suggest that changes in electrophysiological responses observed in substantia nigra pars compacta neurons is caused by degeneration of GABAergic afferents from the substantia nigra pars reticulata following middle cerebral artery occlusion. While previous studies indirectly suggested that hyperexcitation due to deafferentation from the neostriatum may be a major underlying mechanism in delayed degeneration of substantia nigra pars reticulata neurons after middle cerebral artery occlusion, the present electrophysiological experiments provide evidence of hyperexcitation in substantia nigra pars compacta neurons but not in pars reticulata neurons at the chronic phase of striatal infarction.     

Effect of resin monomer composition on toothbrush wear resistance

BACKGROUND: The study was carried out to evaluate the correlation between blood-retinal barrier (BRB) permeability and the progression of diabetic retinopathy (DR), defined by development of "need for photocoagulation", over a 7-year period by means of vitreous fluorometry (VF). METHODS: Forty type 2 diabetic patients with minimal or no retinopathy, aged 40-65 years (mean 53.9 + 7.3 years), were followed up prospectively for 7 years. Investigations including standard ophthalmological examination, fundus photography, fluorescein angiography and VF were performed at entry and 1, 4, 5 and 7 years later. Only one eye per patient was included in the study. Need for photocoagulation was based on Early Treatment Diabetic Retinopathy Study protocols and decided by the attending ophthalmologist. RESULTS: After 7 years of follow-up a total of 22 of the 40 eyes had received photocoagulation. The eyes that needed photocoagulation were those that had higher VF values at the entry of the study and showed higher rates of deterioration (initial values 5.1 + 1.9 vs 2.8 + 1.5 x 10(-6) min-1, P < 0.001; annual increase in leakage for the first year, 1.5 + 0.8 vs 0.5 + 1.0 x 10(-6) min-1, P < 0.001,). The eyes that did not need photocoagulation during the 7 years of follow-up showed stable VF readings (-0.1 + 1.2 x 10(-6) min-1, difference between initial values and 7 years later). CONCLUSIONS: Abnormally high VF values and their rapid increase over time are good indicators of progression and worsening of the retinopathy in diabetes type 2.     

Trehalose 6-phosphate production with energy coupling fermentation by yeast cells

Protein phosphorylation/dephosphorylation on tyrosine residues are regulated by tyrosine kinases/phosphatases. The tyrosine phosphatase SH-PTP2 (PTP1D, PTP2C) interacts physically through its SH2 domain with phosphorylated epidermal growth factor receptor (EGFR). In KB cells, an oral epidermoid carcinoma, high epidermal growth factor (EGF) concentrations (10-9, 10-8 and 10-7 M) downregulate its receptor for the duration of the incubation with EGF. Thus, it was hypothesized that in KB cells, SH-PTP2 expression would also be downregulated by high EGF concentrations. This hypothesis was investigated by incubating the KB cells with increasing concentrations of EGF (0, 10-11, 10-10, 10-9, 10-8, 10-7 M) and by evaluating the expression of SH-PTP2 protein under these conditions. This study showed that EGF 10-7 and 10-8 M significantly decreased SH-PTP2 protein expression compared to controls. EGF 10-10 and 10-11 M did not change the expression of SH-PTP2 protein. We conclude that high EGF concentrations downregulate the expression of SH-PTP2 protein.     

Effect of UFT on treatment of urological cancer--effect of UFT on treatment of invasive bladder cancer and advanced prostate cancer. Ibaraki Urological Cancer Chemotherapy Study Group

A prospective randomized joint study was conducted to evaluate the usefulness of UFT 1) as a postoperative adjuvant therapy in patients with invasive bladder cancer who had undergone curative combination therapy with operation and/or chemotherapy and/or radiation therapy, 2) as an endocrine chemotherapy in patients with newly diagnosed stage C/D prostate cancer, for a period of 3 years from January, 1992. For bladder cancer, of 36 patients with invasive bladder cancer, clinically cured by combination therapy, 20 patients were treated with UFT as an adjuvant chemotherapy over 12 months, and they were compared to 16 patients with no adjuvant therapy. After excluding 10 inappropriate patients, 12 patients in the UFT treatment group and 14 patients with no adjuvant treatment group were observed. For prostate cancer, of 29 patients with clinically stage C/D prostate cancer, 13 were treated with endocrine therapy in combination with UFT, and 16 patients were treated with endocrine therapy alone. After excluding 7 inappropriate patients, 10 patients with endocrine chemotherapy and 12 patients with hormonal therapy were observed. The non-recurrence rate, survival rate and side effects of UFT were evaluated. In the study of bladder cancer, neither a significant difference of non-recurrent rate nor of survival rate was seen between the two groups. In the study of prostate cancer, neither a significant difference of non-recurrent rate nor of survival rate was seen between the two groups. These findings suggest UFT is less useful as an adjuvant therapy for the invasive bladder cancer and as an endocrine chemotherapy for newly diagnosed advanced prostate cancer.     

JSCP Technical Committee on Laboratory Informatics; its 10th anniversary and future perspective

BACKGROUND: Recent investigation into the push-pull effect (PPE), the reduction of +Gz tolerance when preceded by less than +1 Gz, has focused on centrifuge studies to demonstrate the presence of adverse cardiovascular responses. Maneuvers found to cause the Push-Pull Effect (PPEM) have not been studied previously in U.S. Air Force (USAF) fighter aircraft. The frequency of and extent to which PPEMs are performed in fighter aircraft are unknown. METHODS: Head-up display (HUD) videotapes from F-15 and F-16 air combat training missions were reviewed for the presence of PPEMs. The frequency of engagements containing PPEMs and the magnitude of the Gz profiles were noted. RESULTS: PPEMs were found in 11 to 67%, of engagements reviewed, depending on the nature of the training mission, with an overall average of 32%. The PPEMs that were observed contained segments of less than +1 Gz, ranging on average from 0.0 to 0.5 Gz for an average of 3.5 to 5 s duration. CONCLUSIONS: PPEMs are present in air combat training missions performed by today's USAF fighter aircraft and represent an operationally significant source of risk for accidents. These findings support continued research into the physiologic response to PPE and the development of countermeasures.     

Expression, structure and chromosomal localization of the human cGMP-binding cGMP-specific phosphodiesterase PDE5A gene

1. Nicotinylalanine, an inhibitor of kynurenine metabolism, has been shown to elevate brain levels of endogenous kynurenic acid, an excitatory amino acid receptor antagonist. This study examined the potential of nicotinylalanine to influence excitotoxic damage to striatal NADPH diaphorase (NADPH-d) and gamma-aminobutyric acid (GABA)ergic neurones that are selectively lost in Huntington's disease. 2. A unilateral injection of the N-methyl-D-aspartate (NMDA) receptor agonist, quinolinic acid, into the rat striatum produced an 88% depletion of NADPH-d neurones. Intrastriatal infusion of quinolinic acid also produced a dose-dependent reduction in striatal GABA content. 3. Nicotinylalanine (2.3, 3.2, 4.6, 6.4 nmol 5 microl(-1), i.c.v.) administered with L-kynurenine (450 mg kg(-1)), a precursor of kynurenic acid, and probenecid (200 mg kg(-1)), an inhibitor of organic acid transport, 3 h before the injection of quinolinic acid (15 nmol) produced a dose-related attenuation of the quinolinic acid-induced loss of NADPH-d neurones. Nicotinylalanine (5.6 nmol 5 microl(-1)) in combination with L-kynurenine and probenecid also attenuated quinolinic acid-induced reductions in striatal GABA content. 4. Nicotinylalanine (4.6 nmol, i.c.v.), L-kynurenine alone or L-kynurenine administered with probenecid did not attenuate quinolinic acid-induced depletion of striatal NADPH-d neurones. However, combined administration of kynurenine and probenecid did prevent quinolinic acid-induced reductions in ipsilateral striatal GABA content. 5. Injection of nicotinylalanine, at doses (4.6 nmol and 5.6 nmol i.c.v.) which attenuated quinolinic acid-induced striatal neurotoxicity, when combined with L-kynurenine and probenecid produced increases in both whole brain and striatal kynurenic acid levels. Administration of L-kynurenine and probenecid without nicotinylalanine also elevated kynurenic acid, but to a lesser extent. 6. The results of this study demonstrate that nicotinylalanine has the potential to attenuate quinolinic acid-induced striatal neurotoxicity. It is suggested that nicotinylalanine exerts its effect by increasing levels of endogenous kynurenic acid in the brain. The results of this study suggest that agents which influence levels of endogenous excitatory amino acid antagonists such as kynurenic acid may be useful in preventing excitotoxic damage to neurones in the CNS.