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Use of a nonpulsatile pump is one of the most interesting approaches in the development of artificial hearts. A centrifugal pump without a seal around the rotating part was evaluated in five goats. The size of the pump is 8.4 cm x phi 7.0 cm, including an electric motor. A polypropylene impeller with four fins on the top of a column in which a magnetic ring is embedded spins by coupling with a rotating magnet outside the housing. In the goats, the pump was placed paracorporeally to provide total left heart bypass at a flow rate of 4.6-7.6 L/min, and activated clotting time was controlled at 200-300 sec by continuous heparin infusion. Although the first three goats died within 3 days due to bleeding, embolism, and a jammed impeller, respectively, a pump could be driven for 14 days in the fourth goat, and another pump with a rotational control feedback system ran for 32 days in the fifth goat. Plasma free hemoglobin levels were 13.8 +/- 4.3 mg/dl and 9.5 +/- 2.5 mg/dl, and platelet counts were 53.8 +/- 24.7 x 10(4)/mm3 and 62.0 +/- 22.0 x 10(4)/mm3 after 12 hours and 7 days pumping, respectively. No thrombus was observed in the blood chamber in the last two cases. In conclusion, this pump has possibilities as a nonpulsatile pump for long-term use.

The authors developed a novel hybrid system for long-term respiratory support with extracorporeal placental oxygenation. In this system, the patient's blood is oxygenated with O2 saturated artificial blood across the villous membrane during passage through the fetal circuit of the placenta, which is placed in a specially constructed artificial uterus. Human term placentas were obtained immediately after vaginal delivery and used for the experiments. The gas transfer performance of the current apparatus was 60 ml/min for O2 and 40 ml/min for CO2 at a blood flow rate of 1.0 L/min. From these results (and the assured blood compatibility of the placenta), the authors conclude that this system will become one of the most promising modalities for prolonged extracorporeal oxygenation.

In a previous article, a left ventricular assist system (LVAS) with a percutaneous transseptal cannulation technique for easy application was described. This system was safe and efficient (maximum output greater than 3 L/min) and fitted between the intraaortic balloon pumping and LVAS with thoracotomy. But technical skill for placement was slightly complicated. The cannulation system has been improved. In the new system, the inlet cannula is initially used as a sheath introducer and is quickly inserted into the left atrium after transseptal puncture. The new inlet cannula is made of polyvinyl chloride (TM100, Toyobo, Co., Ltd., Osaka, Japan), which has excellent antithrombogenicity and low friction using a polyester plasticizer. The distal part is designed to be flexible with a spiral wire for easy manipulation. A sealing hub was installed to prevent bleeding at the proximal The simplicity and safety of the new system were examined in chronic animal experiments. The inlet cannula was placed into the left atrium within a few seconds after transseptal puncture. During 20 days of activation, there were no episodes of systemic or pulmonary embolism, although no anticoagulant was used. Under fluoroscopy, there was no thrombus formation around the cannula at removal. On the 14th day after removal, the puncture site of the septum had healed. This system is ready for clinical use and shows promise of satisfactory safety and manageability.

5-fluorouracil (5-FU) was orally administered before surgical operation to two groups of patients, one treated at 300 mg for 7 days and the other treated at 400 mg for 5 days, to examine the change of TSIR in gastric patients. Tumor tissue, lymph node and normal lesions were collected from removed specimens immediately frozen. As a result, there were no differences in FdUMP volumes of various tissues between 300 mg and 400 mg groups. TSIR tended to be higher in the order of normal tissue, lymph node and tumor lesions. TSIR was significantly higher in 400 mg group than 300 mg group. We believe that further studies on TSIR will provide a useful information as to various studies, including efficacy reinforcement by combination therapy, problems in resistance, histological efficacy and sensitivity tests.

We have devised a new method, termed alternate synchronous driving (ASD), to wean patients from a left ventricular assist system (LVAS) to a pressure assist intraaortic balloon pump (IABP). We have built a new drive unit, VCT200, to apply ASD easily and automatically. After IABP insertion in the final weaning stage, this method drives the LVAS and IABP alternately, with electrocardiogram (ECG) synchronization. The pumping ratio of IABP increases while that of LVAS decreases according to recovery of natural heart function. In in vitro studies, ASD was effective when bypass flow (BF) was less than 50% of total flow (TF) (TF:BF + cardiac output [CO]), and its advantages increased under lower BF conditions. Mean aortic pressure (mAP) and CO increased 10 mmHg and 15%, respectively, with this method (IABP:LVAS = 1:1) when BF was 30% of TF. During in vivo studies, mAP increased 75.7 +/- 6.7 mmHg to 80.1 +/- 3.6 mmHg (p less than 0.001), and the CO increased from 3.1 +/- 0.5 L/min to 3.3 +/- 0.5 L/min (p less than 0.001), while the endocardial viability ratio (DPTI/TTI) increased 20-30%. This method was used in a 62-year-old man in which LVAS was applied after ventricular aneurysmectomy, BF was reduced from 2.2 L/min to 1.1 L/min by using ASD without any change in systemic perfusion. This reduction of BF could not be achieved with LVAS alone. From these data, this system could wean patients from LVAS and then switch to IABP smoothly, easily, and automatically, without hemodynamic instability.

A novel method of long-term ECMO was designed and evaluated experimentally. Special features of this ECMO method include: 1. using a pneumatic diaphragm type VAD with excellent blood compatibility as a pump system; 2. using a newly developed, high performance, compact oxygenator, with a novel gas exchange membrane in which micropores are blind at the blood contacting surface; 3. regional anticoagulation within the ECMO circuit with short-acting protease inhibitor FUT-175; and 4. right heart bypass with direct cannulation through a thoracotomy. Four goats implanted with a VAD between the right atrium and the pulmonary artery underwent ECMO by interposing a compact oxygenator in the return cannula for as long as 14 days. Blood clotting was regulated with continuous infusion of FUT-175 from the inflow cannula of the ECMO circuit. In this system, 2 to 4 L/min of bypass flow, 80 to 120 ml/min of O2, and 40 to 80 ml/min of CO2 gas exchange were obtained. Serum leakage in the oxygenator did not occur, and various blood chemical and hematologic parameters were maintained within the normal range. Regional anticoagulant therapy was successfully achieved with a significant difference of activated clotting time between the blood samples from the systemic circulation and those from the ECMO circuit. These results indicate that this method overcomes several problems with ECMO, and has the capacity for long-term respiratory assistance.

The authors verified the excellent antithrombogenicity of a blood-liquid interface (BLI) and introduced an oxygenator based on the principle of gas exchange across direct BLI. In a newly developed oxygenator, three layers of liquid flowed horizontally, contacting one another: O2 saturated silicone oil on the top, O2 saturated fluorcarbon at the bottom, and blood in the middle. Gas exchange was carried out across both direct BLIs. This system provided excellent antithrombogenicity as well as good gas exchange. The results indicate that this method will become a promising modality for prolonged extracorporeal oxygenation.

An electrohydraulic total artificial heart (EHTAH) system, consisting of a separately placed actuator and blood pumps with good anatomic fit, was designed. In the actuator is a brushless DC motor sandwiched between two metal bellows or two pusher-plate pumps connected with the blood pumps by polyvinylchloride tubes. A roller-screw system coupled with the bellows is used for alternative pumping, and silicone oil transmits the action. The pumps are elliptical, and the right pump has a flatter and longer shape than the left to fit the extremely short distance between the right atrium and the sternum. To evaluate in vivo performance, the pumps were implanted as a pneumatic system in a calf weighing 53 kg and three goats weighing 54-55 kg. The pump fit well in the animals, and the calf survived for 111 days, and one goat was alive for 8 days. The EHTAH system could provide an output of 6 L/min with pusher-plate pumps as oil chambers on in vitro evaluation. This system could become one of the most suitable approaches for a totally implantable system.

Chronic experiments of the electrohydraulic ventricular assist system with a linear motor actuator were performed in two goats weighing 54 kg and 56 kg, and the system was used for more than 30 days. The actuator was designed to be fixed on the goat's back with a saddle. The pump was connected between the left atrium and descending aorta and placed paracorporeally on the chest wall. Linear action of an actuator bellows was delivered by silicone oil in a U-shaped polyvinylchloride tube to activate the pump. The maximum output in the 56 kg goat was 5.0 L/min. Goats could stand and sit freely. The first goat with a pusher-plate type pump died on the fifth day because of thromboembolism, but the second goat with a diaphragm type pump survived for 42 days. Blood chemistries remained within normal limits. Pump control was easy in both the duty-control mode and the stroke-control mode. With the automatic negative pressure control (ANPC) to prevent atrial wall sucking, the left atrial pressure was kept within +/- 10 mmHg, although left atrial pressure sometimes went below -80 mmHg without ANPC. Considering reliability, automaticity, and portability, the electrohydraulic ventricular assist system has become another choice for a practical, electrically driven ventricular assist system.

The purpose of this study is to clarify physiologic reactions to an immediate switch of flow pattern from pulsatile to nonpulsatile. A pulsatile ventricular assist device (VAD) was implanted in four 40-64 kg goats. Blood was drawn from the left atrium and ventricle and expelled into the aorta. After 2 weeks the VAD was quickly replaced by a centrifugal pump, MD-10 (Iwaki Pump, Tokyo, Japan), 760 g in weight and phi 70 mm x 84 mm in size, set on the back, without anesthesia. A 100% nonpulsatile bypass flow was immediately obtained, and the pump was set to maintain the same mean aortic pressure as before the switch; central venous pressure, cardiac output, systemic vascular resistance, oxygen consumption, blood lactate, plasma adrenalin, noradrenalin, renin activity, angiotensin II, and aldosterone were measured. Behavior of the goats did not change, and fluid infusion and higher cardiac outputs were not required. Most of the parameters did not deviate from control levels after the switch. In conclusion, a mammal immediately accommodates well to nonpulsatile flow.

In order to obtain satisfactory smoothness and sharpness in images as regards the sublimation-type thermal dye transfer printer, the following problems are discussed to be compensated. (1) Unevenness of optical density in main scanning direction (2) Drop of voltage depending on the number of driven heating elements (3) Thermal effect due to adjacent heating elements or preceding lines (4) Time lag at heating-on and off We estimated the thermal influence of the above problems by numerical computations. As for the experiments, we compensated the energy applied to the heating elements. As a result, we have obtained good smoothness and sharpness in images.

The relationship between L-tryptophan uptake and tryptophan 2,3-dioxygenase activity in hepatocytes was examined and compared with the change of hepatic L-leucine, L-phenylalanine, and L-tyrosine uptakes using isolated hepatocytes of rats in which the oxygenase was induced with L-tryptophan or hydrocortisone. In L-tryptophan- or hydrocortisone-treated rat hepatocytes, the rate of L-tryptophan uptake into hepatocytes via the saturable high-affinity transport component significantly increased but the hepatic uptake rate of L-leucine did not change at all. In hydrocortisone-treated rat hepatocytes, a little stimulated hepatic uptake of L-phenylalanine or L-tyrosine was observed. In the stimulated hepatic uptake of L-tryptophan via the high-affinity transport component, the Km value did not change but the Vmax value increased. Liver plasma membranes prepared from rats treated with L-tryptophan or hydrocortisone showed the same binding rate of L-tryptophan to the membranes as those from control rats. In addition, hepatic L-tryptophan uptake via the high-affinity transport component correlated well with hepatic tryptophan 2,3-dioxygenase activity (r = 0.787). The present results indicate that the uptake of L-tryptophan into hepatocytes via a transport system which works under physiological conditions is closely related to hepatic tryptophan 2,3-dioxygenase activity.

We evaluated the limits of recovery of decompensated hearts experimentally and clinically and studied the problems of applying a left ventricular assist device (LVAD). In the chronic experiments, 16 adult goats were studied as follows: Group I consisted of seven with left ventricular infarction in a 70-80% area of the free wall induced by the multiple-ligation method; Group II, three with infarcted areas larger than 80% of the free wall; Group III, three with a 30 min anoxic arrest, and Group IV, a 45-min anoxic arrest. An LVAD was applied in all goats, and a right ventricular assist device was applied simultaneously for two goats in Group IV. Clinically, 21 patients receiving treatment with an LVAD from December 1982 to September 1988 in our center were examined. No goat in Groups II and IV could be weaned from the LVAD. Thus, the severity of artificial heart failure in Groups I and III was considered to be the limit for accomplishing restoration. In successfully-weaned cases, both in experimental and clinical settings, periods of LVAD therapy with or without IABP were less than two weeks, which was thought to be the upper time limits for LVAD application. All but one successfully-weaned patients were alive in the experiment, while clinically many patients died of multiple organ failures regardless of the results of the LVAD assistance. Analysis of data suggested that the difference was caused by the durations of the LVAD applications and weanings, the degree of right ventricular failure, the doses of catecholamine used, and the systemic care afforded, especially during tracheal intubation.

Recent studies have shown that the presence of accessory or multiple corpora lutea (CL) and increased progesterone (P4) concentrations reduced early embryonic mortality in cattle. The objective of this study was to evaluate the effect of equine chorionic gonadotropin (eCG) treatment on the number of CL, the P4 concentrations, and pregnancy rates after embryo transfer (ET). Holstein heifers (n = 120) from 7 dairy farms received an intravaginal progesterone-releasing device (CIDR; InterAg, Hamilton, New Zealand) and 2 mg IM of estradiol benzoate (EB; Gynandol®; Sankyo, Tokyo, Japan) at random stages of the estrous cycle. After 7 to 9 days, CIDRs were removed and 15 mg of prostaglandin F2α (PG; Pronalgon®; Pfizer Japan, Nagoya, Japan) were administered, followed by 100 µg IM GnRH (Conceral®; Takeda Pharmaceutical Co., Ltd., Osaka, Japan) 2 days later (Day 0). The heifers were placed at random into 3 groups for eCG treatment. The eCG was not administered in a control group (n = 53); heifers in other 2 groups received 1000 IU eCG (Peamex®; Sankyo, Japan) IM at the time (0 h group, n = 37) or 48 h before (48 h group, n = 30) PG injection/CIDR removal. On Day 7, heifers were examined by ultrasonography (Aloka SSD500; Aloka, Tokyo, Japan) for number of CL; heifers with at least one functional CL received an in vivo-derived frozen–thawed embryo by direct transfer. At the same time, a blood sample was collected to determine P4 concentration. Pregnancy rates were determined on Days 30 and 60 by ultrasonography and rectal palpation, respectively. The data were analyzed by ANOVA and means were compared with Fisher's PLSD. Proportional data were analyzed by the chi-square test. P4 concentrations (mean ± SD) on Day 7 were 1.8 ± 1.0, 5.6 ± 3.3, and 2.2 ± 1.1 ng mL−1 for the control, 48 h, and 0 h groups, respectively (48 h vs. control and 0 h; P < 0.001). The number of CL on Day 7 were 1.1 ± 0.4, 2.5 ± 1.4, and 1.8 ± 0.9 for the control, 48 h, and 0 h groups, respectively (control vs. 48 h and 0 h, and 48 h vs. 0 h; P < 0.01). Pregnancy rates did not differ between 0 and 48 h groups but both were higher than in the control group (Table 1). Results suggest that the estrus synchronization protocol with administration of eCG at the time of CIDR removal or 48 h earlier significantly increased the number of CL and the P4 concentration, and improved pregnancy rates in Holstein heifers after ET. Table 1.Pregnancy rates of Holstein heifers synchronized with CIDR and PG and treated with eCG

Re-epithelialization is an essential process for repair of gastric mucosal injury and ulcer healing. Previous studies have shown that H. pylori vacuolating cytotoxin (VacA) inhibits gastric epithelial cell proliferation and interferes with EGF-activated signal transduction. Several members of the Rho subfamily of GTPbinding proteins, including Rat-1 and Rho, regulate a signal transduction pathway linking growth factor receptors to the formation of actin stress fibers and focal adhesion which are essential for cell migration. The aims of this study were to determine: a) the effect of H. pylori VacA cytotoxin on levels of Rho and Rac-1 proteins, and ADP-ribosylation levels of Rho in gastric epithelial cells and b) the effect of VacA on reepitbelialization in a wounded gastric cells monolayer model. Methods: VacA purified from H. pylori 60190 or a corresponding VacA-negative preparation from 1-1. pylori 60190-vl (an isogenic mutant strain in which VacA gene has been disrupted) were used. Rat gastric epithelial cells (RGM1) were incubated with either medium only (DMEM/F-12 with 5% FBS), medium containing VacA or medium containing the VacA-negative preparation for 24 and 48 hours. Standard excisional wounds (30 ram) were made in gastric epithelial cells monolayers with a razor blade and treated with H. pylori VacA or VacA-negative preparation as above. Studies: A) Rho and Rac-1 proteins levels by Western blot analysis, B) Rho ribosylation levels by ADPribosylation assay using [32p] NAD with C3 exoenzyme. C) Localization of Rac-1 after immunostaining and D) Actin microfilament assembly using a video image system. Results: VacA (but not a VacA-negative prep) significantly inhibited RGM1 cell migration by 25% (p < 0.03), reduced Rac1 expression by 65% (p < 0.04) and reduced C3-mediated ADP-ribosylation of Rho by 21% (p < 0.03). VacA cytotoxin (but not the VacA-negative prep) inhibited assembly of actin stress fibers and reduced Rac-1 expression in migrating epithelial cells. C_onclusions: H. pylori VacA significantly: 1) inhibits re-epithelialization of wounded gastric epithelial monolayers, 2) reduces Rac-1 expression, 3) affects Rho -ribosylation and 4) interferes with actin filament assembly. These data provide molecular mechanisms for H. pylori cytotoxin interference with re-epithelialization.

Drug naive rat hippocampal slices were incubated in artificial cerebrospinal fluid (ACSF) containing 20 nM clonazepam, a concentration approximating those measured in the cerebrospinal fluid (CSF) of rats treated with high doses of clonazepam which resulted in behavioral hyperexcitability and convulsions upon withdrawal. In the slice, epileptiform activity began within 2 h of incubation in clonazepam. This activity was enhanced upon drug withdrawal. Measured intracellulary, the long-lasting post-spike train afterhyperpolarization was reduced in duration in drug-treated cells whereas just subthreshold antidromic or orthodromic IPSPs were not changed. As some of the hyperexcitability phenomena noted here were similar to those observed in slices taken from rats chronically administered with clonazepam, the technique of long-term in vitro exposure to substances which cause tolerance and dependence may be a useful model of drug withdrawal epilepsy.

New approaches are described for increasing the capability of forced gas convection cooling for integrated circuit chips, using an enhanced heat transfer technique and a higher gas flow velocity in a closed-cycle flow. A turbulence promoting fin with low pressure loss has been developed and enhancement of the heat transfer coefficient using gas flow velocities up to 50 m/s is examined using air and helium gas as coolants. 'By applying these techniques, the cooling capability of a package is investigated through the use of prototype equipment. Cooling of an alumina substrate (75 mm square) mounted with 25 chips (8 mm square) can be cooled up to 200 W in an air flow of 20 m/s. In helium gas convection cooling, the allowable heat dissipation increases to 300 W or more, and fan input power decreases to about one-fifth of that needed for air convection cooling. This cooling capability is equal to that of indirect water cooling.

Serial reconstruction at the EM level of cat retinal ganglion cell dendrites reveals that: (1) the microtubular array is discontinuous, (2) microtubular endings are associated with smooth endoplasmic reticulum (SER), mitochondria, and plasma membrane, (3) individual microtubules always maintain a minimum distance from other microtubules (87 nm), SER (43 nm) and plasma membrane (69 nm), and (5) individual microtubules can 'wander' independent of adjacent microtubules throughout the dendritic volume. These observations, taken with some recent biochemical and immunohistochemical data by other workers, suggest that the microtubules are surrounded by a coat of high molecular weight, microtubular-associated proteins (HMW MAPs), which effectively creates a 90 nm tube around a central microtubular core. Our results suggest that bundles of these 'MAP-tubes' may serve as a major component of the dendritic cytoskeleton in the cat ganglion cells.

AI and AII cat retinal amacrine cells have highly varicose non-uniform, neuritic processes. Processes of both types were reconstructed via a computer system using serial electron micrographs. These reconstructions were analyzed for (a) varicosity volume, surface area, and length, (b) "neck" volume, surface area, and length, (c) number of microtubules within the varicosity, (d) number of microtubules within the "neck," and (e) volume and surface area of mitochondria and smooth endoplasmic reticulum and large smooth vesicular bodies within the processes. Correlation of these parameters revealed a linear relationship between the number of microtubules in the necks and mean neck cross-sectional area (rs = 0.780, P less than 0.001), while microtubule number within the varicosities showed no correlation with varicosity volume (rs = 0.239, P greater than 0.2). Varicosity volume did, however, correlate strongly with the summed volume of mitochondria and smooth vesicular bodies contained within the varicosity for both cell types examined. The ratio between membranous organelle volume and varicosity volume for AI amacrine processes of 1:6.97 (rs = 0.927), differed from the ratio of 1:1.80 for the AII amacrine processes (rs = 0.987). Similar relationships were observed in other nonvaricose neurites such as optic tract axons. Membranous organelles appear to contribute an additional obligatory volume to the cytosol that can be as much as seven times the organelles' direct volume. These observations suggest that both the cytoskeletal components, and the membrane organelles play a direct role in determining neurite shape.

Specimens of pure iron were fatigued in vacuum or in dry air. The plastic zone, which was identified by the surface roughening around fatigue cracks, was investigated. Under a fixed environmental condition, the plastic zone width, Δ, at a short fatigue life is larger than that at a long fatigue life and is proportional to the corrected stress amplitude. Under different environmental conditions, however, Δ at the same stress amplitude is about 3 times larger in vacuum than in dry air, though the fatigue life is longer in the former than in the latter.

A case of left-sided gallbladder with an anomaly of the intrahepatic portal vein and cholesterol polyps of the gallbladder is presented. A 23-year-old man with sudden onset of epigastric pain, fever and abdominal irritation was admitted to our hospital and an emergency celiotomy was carried out. The gallbladder lay on the left side of the round ligament, that is, it was a left-sided gallbladder. Since operative findings such as cholecystitis, gastrointestinal perforation and pancreatitis were not observed, no more procedures were done. Postoperative ultrasonography showed some interesting findings as follows: multiple echogenic nonshadowing small polypoid lesions which did not change in size and shape during a 2.5 year interval were detected and were thought to be cholesterol polyps. The tail of the gallbladder was situated on the left side of the round ligament and the motion of the gallbladder as determined by postural exchange was not floating. These findings are compatible with a left-sided gallbladder. The left branch of the portal vein did not form an umbilical portion as is usually expected and the right branch formed a cystic structure similar to a normal umbilical portion with the anterior, posterior and medial branches ramified. The round ligament arose from the cul-de-sac of the umbilical portion. Twenty-six cases of left-sided gallbladder from the Japanese literature were reviewed and discussed.

Although CDDP has been widely used for cancer chemotherapy in recent years, the problem is that it causes a renal dysfunction as a side effect. As briefly reported here, we have currently used this drug for the treatment of stomach esophageal cancers as a part of multidepartmental therapy, and obtained a finding on the therapeutic usefulness, particularly for monitoring the renal function before and after administration. The subjects were 6 patients with stomach and 11 with esophageal cancer given CDDP at the dose of 50 mg 2 courses, in principle, a single course per week. Blood transfusion was carried out in an amount of 1,000 ml before administration, 2,500 ml on the day of treatment and 1,000 ml for 3 days after administration. When the effects of CDDP on urinary BUN, Na, K, Cl, Mg, NAG, beta 2 microglobulin, Ccr and FENa levels were measured for the determination of renal functions before and after administration, NAG and beta 2 microglobulin levels were conceivably found to be useful indices.

This time, we used palatal plates with the individual palatal rugae using the plastic plate for copying the individual palatal rugae easily, and studied the influence of the pronunciation concerning the changes of the Formant frequencies with Sound Spectrograph.