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Biomedical subjects

S Kasai

Publications and source records attributed to S Kasai.

At least 127 records · Page 7Linked to original sources

The importance of cellular adhesion for mesangial cell proliferation in serum sickness nephritis of the rat: a co-culture study of glomerular macrophages and mesangial cells.

The role of cell-cell contact on activating mesangial cell proliferation by nephritic macrophage was investigated. Nephritic glomerular macrophages were obtained from serum sickness nephritis (SSN) rat kidneys at 14 days after the cessation of sensitization, when proliferating cells were most increased in the glomeruli in the course of the SSN. The effect of the nephritic macrophages on mesangial cell proliferation was greater than that of control by co-culture allowing cellular contact. However, nephritic macrophages did not enhance mesangial cell proliferation by co-culture without direct contact even though the nephritic macrophages were activated with lipopolysaccharides. Conditioned medium from co-culture of the nephritic macrophages and mesangial cells did not enhance mesangial cell proliferation. Anti-intercellular adhesion molecules (ICAM)-1 antibody inhibited mesangial cell proliferation by direct co-culture dose-dependently. From these results, cellular contact was important for stimulation of mesangial cell proliferation by macrophages and ICAM-1 participated in these interactions.

Animals↗

Is the biological artificial liver clinically applicable? A historic review of biological artificial liver support systems.

Hemoperfusion, hemodiafiltration, plasma exchange, and extracorporeal liver perfusion have already been adopted to treat patients with acute and chronic hepatic failure. However, the survival rate of patients with acute hepatic failure remains at approximately 30% and has not improved as expected. Current advances in biotechnology have opened the way for the development of a biological artificial liver, which is called the hybrid artificial liver because it consists of both biological and artificial materials. Isolated hepatocytes have been investigated for use in various types of hybrid artificial liver. In addition, the role of biomatrices, microcarriers, and the microencapsulation technique has been studied with respect to long-term maintenance of hepatocellular function and development of high-density culture systems for hepatocytes. Before clinical application of hybrid artificial liver support systems becomes possible, many problems have to be resolved, including large-scale preparation and long-term preservation of biomaterials, high-density and stable immobilization of biomaterials on artificial materials, control of immunological hazards, biocompatibility, safe transportation and sterilization of biomaterials, and the high cost. We review the history of biological artificial livers and discuss their future role.

Animals↗

Specificity of riboflavin molecular groups for riboflavin binding to rat small intestinal brush border membrane.

The binding of riboflavin to rat small intestinal brush border membrane at equilibrium was formerly shown to have a saturable, specific component, prevailing at the intraluminal physiological concentrations of the vitamin. In this study, the specificity of riboflavin binding to rat small intestinal brush border vesicles was further investigated using structural analogues of riboflavin. The vesicles, prepared by Ca(2+)-precipitation, were incubated at 25 degrees C, for 20 min, in the presence of [3H]-riboflavin at physiological intraluminal concentrations for rat, and each analogue, at appropriate concentrations. Three groups of analogues were used, that were derived from the riboflavin molecule by modifying one of the following positions: the ribityl side chain, position 3, and position 8 of the isoalloxazine moiety. Group specificity was assessed by determining the inhibition potency of each analogue on the saturable component of riboflavin binding to the vesicles. Inhibition constants were calculated, according to Dixon, for lumiflavin, lumichrome, and for analogues substituted at position 8. Specific riboflavin binding was inhibited competitively by most of the analogues used. Substitutions at the ribityl side chain or at position 3 of the isoalloxazine moiety reduced the inhibition power. Substitutions at position 8 enhanced the inhibition power in direct proportion to the bulk of the substituents. We conclude that the ribityl side-chain and the NH group at position 3 are essential for recognition by the specific binding sites, whereas the methyl group at position 8 is important but not essential. The analogues that bind to specific membrane sites for riboflavin share specificity requirements with many riboflavin binding proteins, and are also good substrates for the intracellular phosphorylating enzyme flavokinase. Thus, the riboflavin-binding component in the membrane is likely to be a protein with high specificity. Cellular internalization of the membrane bound vitamin is probably achieved by phosphorylation of the vitamin bound to the inner side of the membrane.

Animals↗

Method for quantifying the contribution of overlying tissue to rat liver 31P-NMR spectra using the surface-coil technique.

A method for quantitatively analyzing the overlying tissue contribution to the in vivo 31P-NMR spectra from rat liver observed by the surface-coil technique is presented. The peak area of beta-ATP obtained either through the abdominal wall or directly from the liver was compared before and after occlusion of the portal vein or infusion of fructose. The phosphocreatine (PCr) signal is a characteristic signature of the 31P spectrum of muscle, and did not differ before and after portal vein occlusion or fructose infusion. After 30 min of occlusion, the beta-ATP obtained through the abdominal wall decreased to 25% of its initial value and that taken directly from the liver almost disappeared. Accordingly, the overlying tissue contribution to the in vivo liver spectra could be quantitatively assessed from the post-occlusion reduction of the beta-ATP peak in the spectra. The recovery of the beta-ATP concentration 10 min after fructose infusion should also reflect the augmentation of ATP synthesis in the liver. The difference of 25% in beta-ATP concentration between the spectra obtained through the abdominal wall and those directly from the liver following fructose infusion showed the overlying tissue contribution. We demonstrated that this contribution was 25% for the liver spectra obtained through the abdominal wall and 75% of the components in the spectra originated from the rat liver in our surface-coil measurements.

Adenosine Triphosphate↗

Laparoscopic cholecystectomy from fundus downward.

Laparoscopic cholecystectomy from fundus downward (LCFD) is desirable when exposure of the cystic duct is difficult and hazardous. First the cystic duct and artery are exposed and clipped, and the artery is divided. Then removal of the gallbladder is started from fundus downward. After the gallbladder is dissected from the liver bed, the cystic duct is double clipped and divided. This approach affords better visualization of the cystic duct and common duct with less chance of common duct injury. Twenty-eight LCFDs were performed without complications, immediate or late. LCFD appears to be a safe procedure and does not compromise the retrograde method.

Adult↗

The immunostimulant OK-432 enhances liver regeneration after 90% hepatectomy in rats.

The effect of reticuloendothelial system activation on liver regeneration after 90% hepatectomy was investigated. OK-432, a killed streptococcal preparation that increases reticuloendothelial system activity, was administered to rats before 90% partial hepatectomy. Pretreated rats showed marked improvement in long-term survival: 87% (18 of 23) survived beyond 42 hr, compared with only 44.2% (24 of 52) of controls (p < 0.05). Survival was determined by means of life-table analysis and regeneration response by means of bromodeoxyuridine labeling index of hepatic DNA. OK-432 pretreatment had significantly increased bromodeoxyuridine labeling index 18, 24, and 42 hr after partial hepatectomy (p < 0.05). The results indicate that reticuloendothelial system activation by OK-432 before 90% partial hepatectomy enhances liver regeneration and improves survival, but these factors may not be related. The improved survival may be because of less infection in macrophage-stimulated animals or more rapid clearance of hypotension-causing vasoactive compounds.

Adjuvants, Immunologic↗

Large-scale cryopreservation of isolated dog hepatocytes.

This study aimed to develop methods for the large-scale preparation of hepatocytes from large animal livers and for the mass cryopreservation of isolated hepatocytes. Isolated hepatocytes were obtained from Beagle dogs weighing around 10 kg by collagenase digestion plus preperfusion with the Ca2+ chelator ethylene glycol bis N,N'-tetraacetic acid. The cell yield was 2.1 +/- 0.45 x 10(10)/liver with 90% viability by the trypan blue dye exclusion test, and the estimated cell yield was 72 +/- 13%. The optimal conditions were large-scale cryopreservation of dog hepatocytes were (i) a freezing rate of 1-10 degrees C/min, (ii) a dimethyl sulfoxide (Me2SO) concentration of 20% (final concentration: 10%), (iii) a cell density that did not exceed 10(8)/ml, and (iv) rapid thawing in a 37 degrees C water bath. The viability of preserved hepatocytes was 75 +/- 3.0% and the estimated recovery rate was approximately 50%. Preserved hepatocytes showed 20-50% of the metabolic activity of fresh cells, as assessed by ammonia and fructose loading tests, ATP content, and [14C]leucine uptake. Following culture after thawing, the morphological normalization of preserved cells was confirmed by light and electron microscopy.

Adenosine Triphosphate↗

Riboflavin uptake by rat small intestinal brush border membrane vesicles: a dual mechanism involving specific membrane binding.

The first step of riboflavin absorption was studied by determining the uptake of the vitamin by rat small intestinal brush border membrane vesicles. Vesicles were incubated at 25 degrees C in the presence of [3H]-riboflavin at concentrations within the physiological intraluminal range for rat. The time course of [3H]-riboflavin uptake was unaffected by Na+ or K+ gradients. The 5 sec uptake rate plotted as a function of the initial concentration of [3H]-riboflavin in the medium (0.125 to 7.5 microM) revealed the presence of a dual mechanism, with a saturable component (apparent kinetic constants: 0.12 microM for Km and 0.36 pmol.mg-1 protein x 5 sec-1 for Jmax) prevailing at low concentrations (< 2 microM), and a nonsaturable component prevailing at higher concentrations. The presence of a carrier-mediated system for riboflavin was validated by countertransport experiments. At equilibrium, uptake was almost completely accounted for by membrane binding, whereas at earlier times the transport component accounted for about 30% of total uptake. The plot of [3H]-riboflavin binding at equilibrium as a function of its concentration in the medium was quite similar to that of the 5 sec uptake rate in both intact and osmotically shocked vesicles and demonstrated the occurrence of a saturable component: binding constants were 0.07 (Kd in microM), 0.54 (Bmax in pmol.mg-1 protein), and 0.11 (Kd), 1.13 (Bmax), respectively, indicating the existence of specific riboflavin binding sites. The specificity of riboflavin binding to the membrane was confirmed by preliminary studies with structural analogues. Specific binding could represent the first step of a specific riboflavin entry mechanism in enterocytes.

Animals↗

Ultrastructural alteration of glomerular anionic sites in nephrotic patients.

The relationship of glomerular anionic sites to proteinuria was examined ultrastructurally in human nephrotic syndrome. The anionic sites were analysed morphometrically in patients with minimal-change nephrotic syndrome (MCNS, 11 patients) and in other glomerulonephritides complicated with nephrotic syndrome (4 patients) by the high-iron diamine-thiocarbohydrazide-silver proteinate method. The anionic sites in MCNS patients in remission (7 patients) were normal. In contrast, the anionic sites in nephrotic patients with MCNS (4 patients) and the other glomerulonephritides were decreased in number. Moreover, smaller and irregularly distributed anionic sites or the greater loss of them from the paramesangial region were observed in the nephrotic patients. The loss of glomerular anionic sites may induce structural alteration of the glomerular basement membrane and mesangial matrix. The loss and structural abnormalities of glomerular anionic sites in nephrotic patients may be one of the mechanisms responsible for massive proteinuria.

Adolescent↗

Cord dorsum potentials suppressed by low power laser irradiation on a peripheral nerve in the cat.

The effects of low-power helium-neon laser irradiation on the cord dorsum potentials (CDP) evoked by electrical nerve stimulation of a distal portion of exposed sural nerve were observed in unanesthetized decerebrate cats. These evoked CDP were significantly suppressed (25.6 +/- 2.5%, p less than 0.01) during low-power laser irradiation. It is suggested that the analgesic effects of low power laser irradiation is based on the decrease of ascending signals from the spinal cord to the higher central nervous system. The suppressive effect of low power laser irradiation upon the impulse transmission of nerve fibers is discussed.

Analgesia↗

Encapsulated hepatocyte transplantation for the treatment of D-galactosamine-induced acute hepatic failure in rats.

Intraperitoneal transplantation of hepatocytes encapsulated with calcium alginate gel produced a marked improvement in the survival rate (75%) of rats with D-galactosamine (D-gal)-induced acute hepatic failure (AHF) when compared to the rate of 50% in rats undergoing free hepatocyte transplantation (HCTX). The viability of encapsulated hepatocytes was still 70% at 36 h after transplantation, and a gradual improvement in the serum glutamic oxaloacetic transaminase (GOT) and total bilirubin values was observed after encapsulated HCTX. Moreover, the arterial blood ketone body ratio (AKBR) remained within the normal range for the whole period of the investigation (60 h after transplantation), and histological investigation of the liver at 36 h demonstrated only slight inflammatory cell infiltrates without hepatocellular necrosis. The phagocytic index rose immediately after encapsulated HCTX and remained high subsequently. A prostaglandin inhibitor, indomethacin, blocked the improvement in survival rate, serum GOT, and AKBR of rats with D-gal-induced AHF despite encapsulated HCTX. Furthermore, no increase in the phagocytic index was observed. Indomethacin apparently suppressed the activation of Kupffer cells by encapsulated HCTX, which then failed to improve the survival of rats with D-gal-induced acute hepatic failure. Our results indicate that the reticuloendothelial system seems to play an important role in the efficacy of encapsulated HCTX in rats with D-gal-induced AHF.

Animals↗

Recovery of the ultrastructure of jejunal absorptive cells and absorption of nutrients in starved then re-fed rats.

This study tried to find what fat level of diets would have a good effect on recovery of the ultrastructure and the digestion-absorption function of jejunal absorptive cells in rats which had been subjected to starvation. Fat-free, 5% fat, 10% fat, or 20% fat diet was given for 3 days to the starved rats, and changes in the ultrastructure of the jejunal absorptive cells were observed by transmission electron microscopy. Also, glucose and triolein absorption were studied using an in situ perfusion system. Good recovery of the ultrastructure of jejunal absorptive cells was observed in rats re-fed the 5% fat diet. Glucose absorption did not differ among the groups except in rats given the 20% fat diet. However, triolein absorption in this group was lower than that of the other groups in both the upper and lower jejunum. The best fat level for recovery of the ultrastructure and absorption of glucose and triolein in the jejunal absorptive cells was concluded to be the 5% fat diet.

Animals↗

[Ureteritis cystica diagnosed by biopsy under a ureteroscope: a case report].

We report a case diagnosed as ureteritis cystica by ureteroscopic examination. A 65-year-old female was admitted to our hospital for a thorough examination of anasarca and reduction of renal function. Computerized tomography showed atrophy in the right kidney and hydronephrosis in the left kidney. Nephrostomy was performed and antegrade pyelography showed ureteral stenosis. For the purpose of accurate diagnosis of ureteral stenosis, ureteroscopy and biopsy were performed. Histological examination revealed ureteritis cystica. Fifty-five cases including this case, reported in Japan, are herein reviewed.

Aged↗

[Hemophagocytic syndrome with high level of interferon-gamma in the advanced stage].

Serum cytokines, lymphocyte subsets of peripheral blood and natural killer cell activity were serially assayed in a 3-year-old girl with hemophagocytic syndrome. Laboratory findings showed pancytopenia, increased levels of transaminases and hyperferritinemia and proliferation of histiocytes in bone marrow and pleural effusion. The administration of prednisolone resulted in a temporary improvement followed by a further exacerbation. The patient died in spite of the treatment with VP-16 and THP-adriamycin. Serum interferon-gamma (IFN-gamma) markedly increased in active phases. TNF-alpha, IL-1 beta and GM-CSF concentrations were normal or slightly elevated. The CD4/8 ratio of peripheral lymphocytes and natural killer cell activity also fluctuated according to clinical stage. These results suggested that IFN-gamma was the most important cytokine to activate histiocytes in this case.

Child, Preschool↗

Dilazep prevents glomerulosclerosis in accelerated Masugi nephritis in the rat.

The effects of Dilazep on immunologically induced glomerular injuries were examined. Accelerated Masugi nephritis in rats produced glomerulosclerosis with proteinuria following administration of a single dose of nephrotoxic serum (NTS). When 5 mg/kg/day of Dilazep had been administered prior to the NTS injection, the proteinuria was resolved rapidly after reaching a maximum level. The glomeruli 3 months later showed significant suppression of glomerulosclerosis and lesser adhesive lesions as compared to those in control rats with Masugi nephritis. On the other hand, when Dilazep was administered from 2 weeks after the injection of NTS, the rats displayed persistent proteinuria and glomerulosclerosis at similar levels to those in the Masugi group. Dilazep appears to exert some protective effects in the early stages of glomerular injuries induced by immunological mechanisms.

Animals↗