Augmentation and subsequent attenuation of Ca2+ current due to lipid peroxidation of the membrane caused by t-butyl hydroperoxide in the rabbit sinoatrial node.

Cellular electrophysiological effects of membrane lipid peroxidation by t-butyl hydroperoxide (TBH) were studied in the rabbit sinoatrial (SA) node. Superfusion for 1-5 min with 300 microM TBH caused an initial increase and subsequent decrease in the spontaneous firing frequency of the SA node. Voltage clamp experiments revealed that TBH initially enhanced but later blocked the Ca2+ current. Thus, membrane lipid peroxidation appears to accelerate and then suppress physiological automaticity by causing biphasic changes in the Ca2+ current.     

Antibodies to brain proteins in paraneoplastic cerebellar degeneration

A 68-year-old man had subacute cerebellar degeneration and a non-Hodgkin's lymphoma. Using an immunoblotting method, we found serum antibodies to rat cerebral 250-kd and 110-kd and cerebellar 110-kd acidic cytoplasmic proteins. The antibodies did not react unless the antigens were prepared soon after death with protease inhibitors. Two hundred fifty-kd and 110-kd proteins are minor components of soluble cytoplasmic proteins of the brain. The molecular weights differed from other soluble brain-specific proteins already characterized.     

Absence of highly homologous sequence to HTLV-I in Japanese multiple sclerosis

We tried to detect HTLV-I-related sequences in Japanese patients with multiple sclerosis with a highly sensitive method that employs the polymerase chain reaction (PCR) of genomic DNA followed by Southern blot hybridization analysis. To amplify HTLV-I sequences, we used primers for LTR, pol, gag, and env coding regions. Fourteen patients with definite MS, 14 disease controls, 12 normal controls, and 3 patients with HTLV-I-associated myelopathy (HAM) were investigated. Results of particle aggregation assay for HTLV-I antibodies were negative in serum from all subjects except for the 3 HAM patients. Neither the 14 MS patients nor the 26 controls showed the presence of any highly homologous sequences to HTLV-I. We did observe faint signals for gag, pol, and env coding regions only at low stringent hybridization in some MS patients as well as some normal controls. The nucleotide sequence analysis of the faint bands was more homologous to major histocompatibility complex molecules than the HTLV-I genome.     

Prevention of Restenosis after Coronary Angioplasty with Low-Density Lipoprotein Apheresis

Abstract: A prospective study was performed to determine whether low-density lipoprotein (LDL) apheresis, when performed only immediately before and after percutaneous transluminal coronary angioplasty (PTCA), is effective in preventing restenosis of coronary artery lesions following PTCA. Thirty-six patients with coronary heart disease (CHD) and hypercholesterolemia were divided into 2 groups. The 9 patients in the LDL group underwent LDL-apheresis 1 day before and 5 days after PTCA while the 27 patients of the control group underwent PTCA but did not undergo LDL-apheresis. Follow-up coronary angiography (CAG) was performed 4 months after PTCA. The rate of restenosis of coronary artery lesions was significantly lower in the LDL group (0%) than in the control group (30%). These findings suggest that LDL-apheresis, when performed before and after PTCA, is effective in preventing restenosis of coronary artery lesions in patients with CHD and hypercholesterolemia.     

Significance of the hepatic mitochondrial redox state in the development of posttraumatic jaundice

The effect of the hepatic energy status on the development of posttraumatic jaundice (PTJ) was studied to clarify the mechanism of PTJ. Fifty-four patients with severe torso injury who were expected to develop PTJ on admission with an average Injury Severity Score of 27 were selected for this study. They were retrospectively divided into three groups according to their maximum bilirubin concentration by day 10: group H, 12 patients with marked elevation of serum bilirubin (>8 g/dl); group L, 23 with mild bilirubinemia (2–8 g/dl); and group N, 19 with no bilirubinemia (<2 g/dl). Group H patients, in whom trauma-related shock was severe and prolonged, developed severe hyperbilirubinemia, and their arterial ketone body ratio (AKBR), which reflects the hepatic mitochondrial redox state and is closely correlated to its energy production, was significantly lower throughout the first week. In contrast, the AKBR increased to an above normal level, indicating enhanced energy production in groups N and L. The serum direct/total bilirubin was also higher in group H. The abnormal hepatic energy metabolism is considered to have reduced the excretion of conjugated bilirubin from the hepatocytes into the bile canaliculi, which is a process that has to proceed against the bilirubin concentration gradient. The subsequent diffusion of the accumulated water-soluble conjugated bilirubin in hepatocytes into the blood is thus considered to be one of the causes of PTJ.     

Effect of solvents on the thermal isomerization of 1 alpha-hydroxyprevitamin D3 diacetate to 1 alpha-hydroxyvitamin D3 diacetate

The thermal conversion of 1 alpha-hydroxyprevitamin D3 (1 alpha-OH-previtamin D3) diacetate to 1 alpha-hydroxyvitamin D3 (1 alpha-OH-vitamin D3) diacetate was investigated in five solvents. The fraction of 1 alpha-OH-vitamin D3 diacetate was calculated from the HPLC peak areas (UV detection) of 1 alpha-OH-previtamin D3 diacetate and 1 alpha-OH-vitamin D3 diacetate. When 1 alpha-OH-previtamin D3 diacetate was dissolved in ethanol, benzene, toluene, isopropyl ether, or n-hexane, and heated at 60 degrees C, the yield of 1 alpha-OH-vitamin D3 diacetate increased during the first 4 h, and reached an equilibrium level after 8.5 h. Differences in the ratio of 1 alpha-OH-previtamin D3 diacetate to 1 alpha-OH-vitamin D3 diacetate at thermal equilibrium, and in the rate of the thermal isomerization were observed among these five solvents. Molecular mechanics (MM) calculations were performed in order to estimate solvent effects on conformation for 1 alpha-OH-previtamin D3 diacetate and 1 alpha-OH-vitamin D3 diacetate. The solvent effect was treated by specifying a dielectric constant representative of each of the three solvents: ethanol (polar), n-hexane (nonpolar), and benzene (aromatic). The dielectric constants used were 24.3 for ethanol, 1.5 for n-hexane, and 2.3 for benzene. It is suggested that the conformation of 1 alpha-OH-vitamin D3 diacetate is stabilized in polar solvent. However, the order of conformational stability when solvent effects are included in the calculations is: ethanol greater than benzene greater than n-hexane. This order does not follow the experimental results. The proton NMR chemical shifts of 1 alpha-OH-vitamin D3 diacetate are different in deuterated n-hexane, ethanol, and benzene. The downfield shift of the C-6 vinyl proton of 1 alpha-OH-vitamin D3 diacetate, when compared to the chemical shift in benzene, is 0.15 and 0.11 ppm relative to the chemical shift in n-hexane and ethanol, respectively, and that of the C-7 proton was 0.30 and 0.33 ppm, respectively. No significant proton shift of 1 alpha-OH-previtamin D3 diacetate is recorded in these three solvents. To account for the increased ratio of 1 alpha-OH-vitamin D3 diacetate to 1 alpha-OH-previtamin D3 diacetate ratio in benzene, we suggest that 1 alpha-OH-vitamin D3 diacetate may be stabilized via specific solute-solvent interactions in benzene.     

Fluctuating PEEP (F–PEEP) versus conventional PEEP in dogs with asymmetrical lung injury

Fluctuating PEEP (F-PEEP) is a newly developed PEEP in which end-expiratory pressure (EEP) is periodically changed within a certain range. In a dog model with unilateral lung injury induced by the introduction of hydrochloric acid, F-PEEP in which the EEP was periodically changed from 0.5 to 1.5 kPa at periods of 6 min, and conventional PEEP (C-PEEP) with an optimized EEP of 1.0 kPa, were each applied for 30 min. F-PEEP produced a significantly greater improvement of PaO2 and intrapulmonary shunt (QS/QT) than C-PEEP, and at the low EEP phase, the greatest improvement accompanied by an increased dynamic compliance and a large cardiac output was obtained. These results suggest that F-PEEP provides a useful mode of artificial ventilation for the treatment of unilateral lung injury.     

Blocking effect of 1389-S on the sodium current in isolated guinea-pig ventricular myocytes

Under whole cell patch conditions, 1389-S blocked the INa in guinea-pig ventricular myocytes under steady state conditions (Kdrest = 30 microM, Kdi = 2.4 microM) with a shift of the inactivation curve to the hyperpolarizing direction. Both brief and long conditioning pulses could produce a use-dependent block of 1389-S. These results suggest that 1389-S had a higher affinity to the inactivated than to the rested state under steady state conditions and had a higher affinity to the activated state during train pulses as well as to the inactivated state, making channels unavailable for conduction upon activation.     

Meaning in measurement of bone mineral content as preoperative evaluation of aged patients

Recently, mean span of life has been prolonged, and extensive operations are performed on aged patients. However, there are cases which have a difference between their chronological and actual ages. Bone mineral content (BMC) decreases with age and the decrease in BMC might suggest deterioration of immunological competence as observed in osteoporosis. Whether BMC can be an index for evaluation of geriatric patients' actual age from the aspect of immunological competence was investigated. Subjects were 54 cases aged more than 60. Twenty-one healthy young males and females were enrolled as the control group. Quantitative CT is used for assessment of BMC. The value obtained by dividing BMC by the standard BMC of the same age and sex, was defined as BMC index. BMC indices of normal BMC group were more than 0.8 and those of decreased BMC group were less than 0.8. Some immunological markers were investigated. Lymphocyte subset OKT3+ was reduced and juvenile lymphocytes expressed by OKT6+ and OKT3+-(OKT4+ + OKT8+) increased (corrected). Increased in juvenile lymphocyte and decrease in lymphocyte blast transformation and competence of generating interleukin 2 were observed in decreased BMC group. BMC is useful as preoperative evaluation for geriatric operative cases and patients of BMC index below 0.8 need to be paid attention to postoperative infection.