Suppressive effect of ascorbic acid on the mutagenesis induced by the bystander effect through mitochondrial function.

Here, we focused on suppressive effect of ascorbic acid (AsA) on changes in mitochondrial function and mutagenesis by the radiation- induced bystander effect (RIBE). In mammalian cell lines, medium transfer assay was performed and conditioned medium including secreted factors after X-irradiation were examined to detect the RIBE. We found that the membrane potential and increased levels of superoxide radical (O2(-)) in mitochondria were modulated in cells treated with conditioned medium from irradiated cells. The result of the present study also demonstrated that increases in reactive oxygen species (ROS) levels led to the induction of gene mutations. Interestingly, the modulations in mitochondria, in addition to mutation inductions by RIBE, were completely suppressed by treatment with AsA in cells treated with conditioned medium. These results suggest that mutagenesis, which may have resulted from secreted factors involving the RIBE, may be induced by ROS that are localized in mitochondria and may be relieved by AsA.

Comprehensive diagnosis of growth rates of the ablative Rayleigh-Taylor instability.

The growth rate of the ablative Rayleigh-Taylor instability is approximated by gamma = square root[kg/(1 + kL)] - beta km/rho(a), where k is the perturbation wave number, g the gravity, L the density scale length, m the mass ablation rate, and rho(a) the peak target density. The coefficient beta was evaluated for the first time by measuring all quantities of this formula except for L, which was taken from the simulation. Although the experimental value of beta = 1.2+/-0.7 at short perturbation wavelengths is in reasonably good agreement with the theoretical prediction of beta = 1.7, it is found to be larger than the prediction at long wavelengths.

A new top-loading venous bag provides vacuum-assisted venous drainage.

A new venous bag has been developed, prototyped, and tested. The new bag has its inlet, outlet purge, and infusion tubes extending upward from the top of the bag, and are threaded through, bonded to, and sealed within a flat rigid top plate. This design allows the bag to be hung from its top plate by its tubes. It also allows the bag to be: 1) dropped into or removed from its holder, as is done with existing hard-shell reservoirs so that its weight pulls it into the holder without the need for eyelets and hooks and 2) placed closer to the floor so that gravity drainage is facilitated. The V-Bag (VB) is easily sealed within an accompanying rigid housing. Once sealed, vacuum applied to the housing is transmitted across the flexible walls of the bag to the venous blood. Thus, vacuum-assisted venous drainage (VAVD) is obtained as it is with a hard-shell reservoir, but without any contact of air with the blood. Bench tests, using a circuit that simulated the venous side of the cardiopulmonary bypass (CPB) circuit, showed that applying suction to the housing increased venous flow, and the fractional increase in flow was not a function of the venous cannula, but of the level of vacuum applied. In the gravity drainage mode, the bubble counts at the outlet of the V-Bag compared to two other bags were lower at any pumping condition. When used in the VAVD mode, bubble counts were two orders of magnitude lower than when using kinetically assisted venous drainage (KAVD) with a centrifugal pump. Results obtained with the VB suggest its clinical usefulness.

Regional fat deposition in the legs is useful as a presumptive marker of antiatherogenesity in Japanese.

To examine the pathological role of regional fat deposition in development of metabolic and cardiovascular disorders, regional fat distribution was evaluated using metabolites and hormones as measures of obesity-related disorders. The subjects enrolled were 100 sex-matched inpatients, who were admitted, regardless of their body mass index values, for further examination of unusual results from periodic medical screening tests, and for examination of obesity-induced complications and treatment of obesity. Body fat distribution was analyzed using dual energy X-ray absorptiometry (DEXA). Analysis of parameters regarding fat distribution showed that gender was one of the determinants affecting correlation between fat distribution and metabolites of fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), total cholesterol (TC), or triglyceride (TG). However, regardless of gender, both leg trunk fat (L/Tr) and arm trunk fat (A/Tr) ratios negatively correlated with a total body fat (% total fat) ratio, whereas the intercept value of female regression line in L/Tr was greater than that in males, but not in A/Tr. Percentage total fat, L/Tr, and A/Tr in males correlated significantly with FPG, TC, TG, low-density lipoprotein (LDL), very low density lipoprotein (VLDL), atherogenic index (A.I.), and apoB/A1 only low density lipoprotein (LDL) was significantly correlated solely to L/Tr and A/Tr. These results indicate that regional fat distribution in males may not be a major determinant for development of metabolic disorders in obese patients. Unlike male regional fat distribution, female L/Tr correlated significantly not only with TC, TG, and LDL, but also with FPG and HbA1c, although both of the latter 2 glucose-related parameters in males showed no correlation with any parameters of fat deposition. The remaining female parameters of fasting plasma insulin, VLDL, A.I., and ApoB/A1 correlated with each of the three parameters of fat deposition, as similarly shown in males. The powerful and negative correlation was thus evident, particularly in females, between leg fat deposition and parameters of glucose and lipid metabolites. The resulting information provides a novel insight that regional fat deposition at the legs is useful as a marker for metabolic and cardiovascular disorders associated with obesity.

A new bladder allows kinetic venous augmentation with a roller pump.

Augmented venous drainage improves venous return during minimally invasive cardiac surgery. Two systems to augment drainage are common: in one, a centrifugal pump draws blood from the venous site and pumps it into a venous reservoir. In the other, suction is applied directly to a hard-shell venous reservoir. Both systems overcome the high resistance of the venous cannula when gravity alone is insufficient to provide adequate drainage. Both systems also have shortcomings: in the first approach, the centrifugal pump head can entrap large bubbles, reducing flow and requiring pump stoppage to remove them. Air from the venous line also can be broken up by the centrifugal pump into small bubbles that can pass through the pump head. The direct suction system in the second approach cannot use a closed-bag reservoir, and has the potential to introduce air into the arterial line. We have developed a new venous augmentation system for a closed venous reservoir that provides excellent suction control without the potential to introduce air into the arterial line. Our system replaces the centrifugal pump of the first approach with a roller pump controlled by the Better-Bladder, a new device with FDA 510(k) clearance for long-term pumping. The Better-Bladder is a length of medical tubing, processed to form a thin-walled, enlarged bladder that is sealed within a clear rigid housing. It acts as an in-line reservoir that provides compliance in the venous line and a noninvasive means to measure blood pressure at the pump inlet. The bladder housing can maintain a negative pressure set by the user that controls the degree of gravity drainage. Tests have shown that the Better-Bladder allows for safe, smooth pump control using a roller pump in the venous line.

Longitudinal study of the dietary selenium intake of exclusively breast-fed infants during early lactation in Korea and Japan.

213 samples of human breast milk were collected from 51 healthy Korean women. Selenium content of the samples was determined by atomic absorption spectrometry with hydride generation. The selenium content of Korean milk decreased with increase of days after birth: The arithmetic mean of selenium content was higher in colostrum (< 4 days) 34 micrograms/kg (SD +/- 11, n = 44) than in transitional milk 21 micrograms/kg (SD +/- 8, n = 78) or in mature milk (> 10 days) 13 micrograms/kg (SD +/- 6, n = 91). The daily dietary selenium intake of 0-1 month aged Korean infants fed on breast milk is estimated to be around 10 micrograms per day (3 micrograms/kg body weight) regardless of days postpartum, resulting from the calculation of our selenium data and daily milk intake during early lactation. The same result on selenium intake for Japanese newborns, as well as Korean infants, is also estimated to be around 10 micrograms per day (3 micrograms/kg body weight) regardless of days postpartum.

An improved bladder for pump control during ECMO procedures.

A new inline reservoir called the Better-Bladder, now FDA-cleared for long term use, overcomes some disadvantages of the silicone bladder and bladder box used in extracorporeal membrane oxygenation circuits. The Better-Bladder provides compliance in the venous line and allows for noninvasive pressure measurements. Both features are useful for controlling pump speed as a function of venous line pressure. Bench tests showed that the Better-Bladder measures pressure noninvasively within +/- 4% of invasive (i.e., liquid contacting) pressure measurements in a range from -200 to +500 mmHg and at temperatures from 10 degrees C to 37 degrees C. After 60 days, the error in noninvasive pressure measurement with the Better-Bladder was less than +/- 3%. The Better-Bladder withstood pressurization to 1700 mmHg for ten days without leaking or failing in other ways. The advantages of the Better Bladder, along with its accuracy and durability, suggest its use for short and long term pumping applications.

Quantitation of taurine and selenium levels in human milk and estimated intake of taurine by breast-fed infants during the early periods of lactation.

With these results we report the following: Taurine levels in human milk decreased slightly during the early lactation period. The concentration of taurine (406 +/- 174 nmol/ml) in colostrum was significantly higher than that (335 +/- 115 nmol/ml) in mature milk. Selenium content of human milk also decreased slightly during the early lactation period. The content of selenium (28.6 +/- 19.6 ng/ml) in colostrum was significantly higher than that (1 5.1 +/- 5.9 ng/ml) in mature milk. A correlation was not found between the taurine and selenium content of human milk. The intake of taurine and selenium by breast-fed infants progressively increased with days postpartum. These results were due to the significant increase in milk intake by infants. It is suggested that the taurine and selenium levels in colostrum are more concentrated than those in mature milk. However, the absolute intake of taurine and selenium by infants are higher in mature milk.

Errors in flow and pressure related to the arterial filter purge line.

The purge line is a necessary component on arterial filters, although its presence may affect the amount of flow reaching the patient as well as the pump outlet pressure in the extracorporeal circuit. In-vitro and clinical studies conducted to investigate these effects with a commonly used purge line showed that at flows less than 1.5 L/min, rates for pediatric or infant patients, the purge line diverts as much as 40% of the intended pump flow away from the patient. A small diameter resistance tube connected in series with the purge line reduced purge flow such that over 80% of the pump flow reached the patient. Pressure monitored at the arterial filter port with the purge line open could be as much as 45 mmHg lower than the pressure measured with the purge line closed to the filter. Studies should be done to determine if the arterial filter purge line compromises flow to the patient, and if an additional resistance to the purge line is appropriate to reduce the flow through it.

New roller pump disposable provides safety and simplifies occlusion setting.

A new disposable insert for the arterial roller pump, the Better-Header, provides safety and functionality beyond what standard tubing provides. It automatically limits pump outlet pressure to a level determined by the user and provides a self-contained, simple means to set pump occlusion. The Better-Header consists of a Starling-like pressure relief valve connected across standard header tubing. As long as arterial line pressure at the pump outlet remains below a set limit, the valve is closed. If line pressure approaches the pressure limit, the valve opens, preventing overpressurization by shunting blood from pump outlet to inlet. The Better-Header can also be used to set occlusion by the "dynamic method" to obtain nonocclusive settings. The Better-Header was evaluated in the lab for its pressure-flow characteristics. Even when the arterial line was completely clamped at a pump flow of 7 L/min, line pressure was limited to a safe level and all circuit connections were preserved. The Better-Header has been used successfully at North Shore University Hospital in over 500 clinical cases covering a wide range of patients and procedures. In several instances, the user was alerted to high pressure situations by fluid flow through the valve and by an audible alarm, allowing rapid correction of the source of pressure. Compared to the standard setup, the Better-Header maintains outlet pressure within safe, user-settable limits, and permits consistent, nonocclusive settings with predictable retrograde flow.

A dynamic method for setting roller pumps nonocclusively reduces hemolysis and predicts retrograde flow.

In general, roller pumps are set almost occlusively despite evidence that nonocclusive settings cause less hemolysis. Almost-occlusive settings are used because of the concern that forward flow would not be accurately known if retrograde flow were allowed to occur through a nonocclusive gap. This article presents a dynamic method for setting roller pumps nonocclusively that overcomes the many difficulties of the "drop method" for setting occlusion. Studies were conducted to determine the effect of nonocclusive settings on pump flow and hemolysis generated; the results suggest that roller pumps can and should be set more nonocclusively than is the currently accepted standard to reduce pump related hemolysis without greatly affecting pump performance. The dynamic method allows retrograde flow to be easily predicted and corrected with an increase in pump speed.

[Jewish identity and immigration to Israel: an ongoing survey among the current wave of Russian immigrants]. / Identite juive et immigration en Israel: une enquete en cours sur l'actuelle vague d'immigrants russes.

PIP: "This paper aims to supply information on the factors that motivated large masses of Jews to leave the former Soviet Union and settle in Israel during the last few years. Also investigated is the relationship between Jewish identity and the decision to immigrate to Israel. Finally, the study examines the connection between immigrants' Jewish and Israeli identity and their predisposition to stay in Israel or to re-emigrate elsewhere. The findings indicate that the current Jewish emigration from the former USSR has, to a significant extent, the character of free choice, and that the decision to come to Israel is highly correlated with the respondents' commitment to their Jewishness and to the Jewish people." (EXCERPT)^ieng

Hypothalamic neuronal histamine modulates physiological responses induced by interleukin-1 beta.

Dynamic involvement of hypothalamic histamine in ingestive behavior and thermogenesis induced by interleukin-1 beta (IL-1 beta) was examined in rats. Intraperitoneal injection of 0.12 nmol/rat IL-1 beta decreased food and water intake and elevated body temperature. However, depletion of neuronal histamine induced by intraperitoneal injection of 160 mumol/rat alpha-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase (HDC), attenuated the suppressive effect of IL-1 beta on food intake, facilitated the suppressive effect on drinking, and enhanced the elevating effect on rectal temperature. Intraperitoneal injection of 0.12 nmol/rat IL-1 beta increased hypothalamic histamine turnover rate. The same dose of IL-1 beta also increased activity of HDC and histamine-N-methyltransferase (HMT). These results suggest that IL-1 beta may stimulate synthesis and release of hypothalamic histamine in presynaptic terminals by activation of HDC and facilitate degradation of extracellular histamine by activation of MHT. These changes in the dynamics of hypothalamic histamine modulate IL-1 beta-induced ingestive behavior and body temperature.

Longitudinal study on selenium content in human milk particularly during early lactation compared to that in infant formulas and cow's milk in Japan.

239 samples of human breast milk were collected from 36 healthy Japanese women. Selenium content of the samples was determined mainly by highly sensitive fluorometric analysis with 2,3-diaminonaphthalene. The highest selenium content, 247 micrograms/kg, was found on the first day postpartum. The arithmetic mean of selenium content was higher in colostrum (< 4 days) 47 micrograms/kg (SD 42, n = 116) than in transitional milk 24 micrograms/kg (SD 13, n = 87) or in mature milk (> 10 days) 10 micrograms/kg (SD 4, n = 36). Selenium content was also determined for six brands of commercial infant formula powder (32-58 micrograms/kg) based on cow's milk, seventeen brands of cow's milk (10-25 micrograms/kg) and eight brands of powered cream for cofee (9-162 micrograms/kg). The average selenium content was significant lower in the liquid formula prepared for infant lactation, 6.0 micrograms/L, than in the human colostrum and transitional milk. The dietary selenium intake of newborns fed on colostrum is estimated to be in the range of 2-12 micrograms per day.

2-deoxy-D-glucose suppresses food intake through activation of hypothalamic histamine in rats.

The aim of this experiment was to demonstrate whether brain histamine contributes to delayed suppression of food intake after administration of 2-deoxy-D-glucose (2-DG). Food intake decreased significantly for 48 h after infusion of 2-DG into the rat third cerebroventricle. This delayed decrease in food intake was abolished by depletion of neuronal histamine by intraperitoneal pretreatment with alpha-fluoromethylhistidine (160 mumol/rat), a suicide inhibitor of a histamine-synthesizing enzyme. Intracerebroventricular infusion of 24 mumol 2-DG accelerated turnover rate of hypothalamic histamine. These results indicate that the delayed feeding suppression by 2-DG is modulated through histaminergic neurons in the hypothalamus. This histaminergic response may be related, at least in part, to homeostatic control of energy metabolism in the brain.

Thermoregulation and hypothalamic histamine turnover modulated by interleukin-1 beta in rats.

To clarify the involvement of hypothalamic histamine in thermogenic response provoked by high ambient temperature, or interleukin-1 beta (IL-1 beta), changes in rectal temperature and histamine turnover were investigated. Rectal temperature was maintained normally after exposure to high ambient temperature, but elevated by IL-1 beta. In spite of these different responses of body temperature, hypothalamic histamine turnover was increased in each treatment. The results suggest that hypothalamic histaminergic neurons are activated not only peripherally by high ambient temperature, but also centrally by IL-1 beta as endogenous pyrogen.

The effects of pressure and flow on hemolysis caused by Bio-Medicus centrifugal pumps and roller pumps. Guidelines for choosing a blood pump.

Two Bio-Medicus BP-50 centrifugal pumps and two roller pumps were tested simultaneously with porcine blood at 21 degrees +/- 1 degree C in four in vitro circuits to determine the effect of four combinations of flow and pressure conditions on blood damage. Flows of 300 ml/min (1/4-inch inner-diameter tubing in the roller pump) and 1775 ml/min (1/2-inch inner-diameter tubing in the roller pump) and pressure differences across the pump (delta P = outlet pressure--inlet pressure) of 215 mm Hg (n = 6) and 345 mm Hg (n = 5) were examined. The index of hemolysis (milligrams plasma hemoglobin per 100 L blood pumped) for the BP-50 pump was higher at a flow of 300 ml/min than at a flow of 1775 ml/min (p < 0.0002). At 300 ml/min, the index of hemolysis for the BP-50 pump tended to be higher at 345 mm Hg than at 215 mm Hg (mean +/- standard error of the mean, 135 +/- 22 versus 88 +/- 9, p = 0.059). At 1775 ml/min, there was no difference in the index of hemolysis for the BP-50 pump between 215 and 345 mm Hg (37 +/- 7 versus 29 +/- 5, p = 0.32). With the roller pump, the index of hemolysis was higher at a flow of 300 ml/min than at a flow of 1775 ml/min (p < 0.036), but there was no difference in the indexes of hemolysis between 215 and 345 mm Hg at 300 ml/min (60 +/- 9 versus 61 +/- 11, p = 0.93) or at 1775 ml/min (40 +/- 6 versus 36 +/- 6, p = 0.61). Comparison between the two types of pumps showed that the index of hemolysis was significantly higher for the BP-50 than for the roller pump at a flow of 300 ml/min and a delta P of 215 mm Hg (88 +/- 9 versus 60 +/- 9, p = 0.009), as well as at a flow of 300 ml/min and a delta P of 345 mm Hg (135 +/- 22 versus 61 +/- 11, p = 0.001). At a flow of 1775 ml/min, there was no difference in the index of hemolysis between the two pumps at either pressure condition.(ABSTRACT TRUNCATED AT 250 WORDS)

[Successful treatment of a pretreated elderly case of small-cell lung carcinoma with continuous five-day intravenous infusion of cisplatin plus etoposide].

A 78-year-old man was admitted to our hospital with dyspnea in June 1988, and diagnosed as having small-cell lung carcinoma by cytological findings of pleural effusion. He was treated three times with CAV (cyclophosphamide, doxorubicin, vincristine) therapy and a partial response was achieved. In March 1989, he was again admitted complaining of right dull hypochondralgia accompanied by enlargement of primary tumor in the right lower lobe of the lung and metastases to mediastinal and intraabdominal lymph nodes. Because it was an aged and recurrent case, he was treated with continuous five-day infusion of etoposide, 30 mg/m2/day and CDDP, 18.5 mg/m2/day. After the second course, subjective symptoms clearly disappeared and swelling of mediastinal and intraabdominal lymph nodes was markedly reduced on computed tomography. No severe side effects except for moderate myelosuppression, alopecia and nausea were observed. This regimen appears useful in the treatment of small-cell lung carcinoma in elderly patients.

Characterization of leukaemic basophil progenitors from chronic myelogenous leukaemia.

We describe the unique characteristics of leukaemic basophils from a patient with chronic myelogenous leukaemia (CML). The leukaemic cells were immature basophil-like blasts and expressed CD4, CD7 and HLA-DR in addition to CD13 and CD33. Both immunoglobulin and T cell receptor genes were retained in germline configurations. Interleukin-1 (IL-1) or granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as IL-3 or IL-4 enhanced the proliferation and differentiation of leukaemic cells and only basophils were generated from in vitro culture. These results suggest that basophil progenitors expressing CD4, CD7 and HLA-DR may be involved in the development of basophilic crisis of CML and that both IL-1 and GM-CSF may act on basophil progenitors as well as IL-3 or IL-4.

Bloodless testing for microporous membrane oxygenator failure: a preliminary study.

The use of a bloodless solution and high pressure to accelerate microporous membrane oxygenator (MMO) failure was investigated. It was hypothesized that albumin acts as a wetting agent, contributing to plasma leakage through the membrane, and that high MMO outlet pressure accelerates the process. Three MMO, B-Bentley BCM-40 (n = 7), M-Medtronic Maxima (n = 4), and S-Sarns 16310 (n = 7) were tested at 37 +/- 2 degrees C using three identical closed recirculating circuits and four conditions: 1) Lactated Ringer solution (LR) with MMO outlet pressure (Pmo) 750 mmHg; 2) LR + albumin (4 g/100 ml), Pmo 150 mmHg; 3) LR + albumin, Pmo 300 mmHg; and 4) LR + albumin, Pmo 750 mmHg. "Blood" flow and gas flow were maintained at 2 l/min. Failure was indicated when Na+ was detected in the effluent of the MMO exhaust gas. There were no failures without albumin in the solution. B and M showed no signs of failure under any of the test conditions at 78 hours. S failed at (mean +/- SEM) 4.9 +/- 1.0, 12.1 +/- 0.2, and 19 hours for conditions 4, 3, and 2 respectively. Preceding failure, inlet gas pressure increased more than eightfold (27 +/- 1 to 224 +/- 34 mmH2O). These preliminary results are similar to previous findings with blood and suggest that high MMO outlet pressure and the presence of albumin may promote plasma breakthrough for S. The combination may provide a basis for an accelerated bloodless test for MMO compatibility with long-term respiratory support.