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Biomedical subjects

K Kishikawa

Publications and source records attributed to K Kishikawa.

At least 19 recordsLinked to original sources
PubMed2001

Enantioselective intramolecular aromatic [4 + 4] photocycloaddition in crystalline state: parameters for reactivity.

Photoreactivity of seven 9-anthryl-N-(naphthylcarbonyl)carboxamide derivatives, 1a-g, in their intramolecular [4 + 4] photocycloadditions in solid state is discussed on the basis of their single-crystal X-ray analyses. The distances (d(1) and d(2)) between the two carbon atoms to be reacted, the angles (theta(1) and theta(2)), and the torsion angle (theta(3)) between the anthracene and naphthalene rings were chosen as structural parameters for reactivity. For 1a and 1e, the first example of absolute asymmetric synthesis in [4 + 4] photocycloaddition was attained. [reaction: see text]

Journal Article↗
PubMed2001

Trapping of 1,8-biradical intermediates by molecular oxygen in photocycloaddition of naphthyl-N-(naphthylcarbonyl)carboxamides; formation of novel 1,8-epidioxides and evidence of stepwise aromatic cycloaddition.

The photocycloaddition reaction of naphthyl-N-(naphthylcarbonyl)carboxamides (1) was examined under argon and oxygen atmospheres. In addition to the [2 + 2] and [4 + 4] cycloadducts, 3 and 4, respectively, novel 1,8-epidioxides (5) were formed under oxygen atmosphere. The transient absorption at lambda max of 360 nm with the lifetime of 360 ns was observed by laser flash photolysis of 1c and was interpreted as the absorption of biradical intermediate 2. On the basis of the anti stereochemistry of 5, which was different from that of the major [4 + 4] cycloadducts, syn-4, it was deduced that equilibrium between biradical intermediates syn-2 and anti-2 would exist. Retro [2 + 2] cycloaddition of 3 was responsible for the efficient trapping of the biradical intermediate with molecular oxygen. The photocycloaddition of the anthryl derivatives, 9-anthryl-N-(methylethyl)-N-(naphthylcarbonyl)carboxamides (7), afforded the [4 + 4] cycloadducts (8) exclusively in a quantitative yield even under oxygen atmosphere. The absence of trapping with molecular oxygen was interpreted to be due to the lack of retro [4 + 4] cycloaddition of 8.

Journal Article↗
PubMed2001

Small graft for living donor liver transplantation.

OBJECTIVE: To evaluate the impact of graft size on recipients in living donor liver transplantation (LDLT) to establish a clinical guideline for the minimum requirement. SUMMARY BACKGROUND DATA: Although the minimum graft size required for LDLT has been reported to be 30% to 40% of graft volume (GV)/standard liver volume (SLV), the safety limit of the graft size was unknown. METHODS: A total of 33 cases of LDLT, excluding auxiliary transplantation, were reviewed with a minimum observation period of 4 months. The 33 patients were divided into three groups according to GV/SLV: medium-size graft group, small-size graft group, and extra-small graft group. The effect of GV/SLV on graft function, graft regeneration, and survival was evaluated. RESULTS: The overall patient survival rate was 94% at a mean follow-up of 15 months with a minimum observation period of 4 months. There were no statistically significant differences in postoperative bilirubin clearance, alanine aminotransferase, prothrombin time, and frequency of postoperative complications among the three groups. One week after transplantation, the regeneration rate (GV at 1 week/harvested GV) in the extra-small and small groups was significantly higher than that of the medium group. The graft and patient survival rates were both 100% in the extra-small group, 75% and 88% in the small group, and 90% and 95% in the medium group. CONCLUSIONS: Small-for-size grafts less than 30% of SLV can be used with careful intraoperative and postoperative management until the grafts regenerate.

Adult↗
PubMed2000

The impact of donor age on living donor liver transplantation.

BACKGROUND: The impact of the age of the donor on the outcome of living related liver transplantation is yet to be clarified. METHODS: During October 14, 1996 and December 20, 1999, 34 living related liver transplantations were performed. Of these, 26 cases were performed using the extended left lobe graft, which were classified into three groups; younger donor group (group Y, donor age < 30, n = 7), middle-aged donor group (group M, 30 < or = donor age <50, n=13), and older donor group (group O, donor age < 50, n = 6). Early allograft function and regeneration were compared between these groups. RESULTS: There was no difference in standard liver volume, and predicted or harvested graft size between the three groups. Although serum transaminase and total bilirubin levels within postoperative day 7 were not different between the groups, the prothrombin time on postoperative day 3 was significantly longer in group O than in group Y. One week after transplantation, group Y had significantly greater graft/standard liver volume ratio than group O, and greater graft volume than group M and O. One month after transplantation, however, there was no significant difference in such graft size parameters between the groups. Graft and patient survival were comparable between the three groups. CONCLUSION: Although function and regeneration of the allografts from older donors in living donor liver transplantation is worse than those of their younger counterparts, the outcome is not affected by the age of the liver.

Adult↗
PubMed2000

Domino liver transplantation from a living related donor.

BACKGROUND: Although domino liver transplantations (OLT) from cadaveric donors have been performed in about 50 cases since 1995, only one case in the Japanese literature has been reported on a domino OLT from a living related donor. The difficulties of the later surgery lie in the small size of the graft volume and the short length of the vascular cuffs in the graft. METHODS: The left lobe graft was procured from a 43-year-old younger brother of a familial amyloidotic polyneuropathy (FAP) patient. Next, the left lobe graft (510 g, 44% of the estimated standard liver volume of the FAP patient) was implanted into the 48-year-old female FAP patient. At surgery for the FAP patient, a sufficient length of the vascular cuffs was secured by an extended left lobe resection, although the right lobe graft was able to maintain sufficient vascular cuffs. The right lobe graft (720 g, 54% of the recipient's estimated standard liver volume) was then implanted in the 43-year-old male patient with liver cirrhosis and hepatocellular carcinoma (stage IV-A). RESULTS: The two recipients were discharged from the hospital 1 month after OLT. At 7 months after OLT, they are both doing well and the domino recipient is free of any tumor recurrence. CONCLUSION: A domino OLT from the living related donor can therefore be done safely when careful attention is paid to the graft volume and the length of the vascular cuffs for anastomosis.

Amyloid Neuropathies↗
PubMed1999

Phosphatidic acid is a potent and selective inhibitor of protein phosphatase 1 and an inhibitor of ceramide-mediated responses.

In the present study, we report that phosphatidic acid (PA) functions as a novel, potent, and selective inhibitor of protein phosphatase 1 (PP1). The catalytic subunit of PP1alpha was inhibited by PA dose-dependently in a noncompetitive manner with a K(i) value of 80 nM. The inhibition by PA was specific to PP1 as PA failed to inhibit protein phosphatase 2A (PP2A) or PP2B. Furthermore, PA was the most effective and potent inhibitor of PP1 compared with other phospholipids. Because we recently showed that ceramides activated PP1, we next examined the effects of PA on ceramide stimulation of PP1. PA inhibited both basal and ceramide-stimulated PP1 activities, and ceramide showed potent and stereoselective activation of PP1 in the presence of PA. Next, the effects of PA on ceramide-induced responses were examined. Molt-4 cells took up PA dose- and time-dependently such that by 1 and 3 h, uptake of PA was 0.37 and 0. 65% of total PA added, respectively. PA at 30 microM and calyculin A at 10 nM (an inhibitor of PP1 and PP2A at low concentrations), but not okadaic acid at 10 nM (a PP2A inhibitor at low concentrations) prevented poly(ADP-ribose) polymerase proteolysis induced by C(6)-ceramide. Moreover, the combination of PA with okadaic acid prevented retinoblastoma gene product dephosphorylation induced by C(6)-ceramide. These data suggest that PA functions as a specific regulator of PP1 and may reverse or counteract those effects of ceramide that are mediated by PP1, such as apoptosis and retinoblastoma gene product dephosphorylation.

Animals↗
PubMed1999

Long chain ceramides activate protein phosphatase-1 and protein phosphatase-2A. Activation is stereospecific and regulated by phosphatidic acid.

The search for potential targets for ceramide action led to the identification of ceramide-activated protein phosphatases, which include protein phosphatase-2A (PP2A) and protein phosphatase-1 (PP1) with roles in regulating apoptosis and cell growth. Thus far, in vitro studies on ceramide-activated protein phosphatases have been restricted to the use of short chain ceramides, limiting the extent of mechanistic insight. In this study, we show that the long chain D-erythro-C18-ceramide activated PP2A (AB'C trimer), PP2Ac (catalytic subunit of PP2A), and PP1gammac and -alphac (catalytic subunits of PP1gamma and -1alpha isoforms, respectively) 2-6-fold in the presence of dodecane, a lipid-solubilizing agent, with 50% maximal activation achieved at approximately 10 microM D-erythro-C18-ceramide. The diastereoisomers of D-erythroC18-ceramide, D-threo-, and L-threo-C18-ceramide, as well as the enantiomeric L-erythro-C18-ceramide, did not activate PP1 or PP2A, but they inhibited PP1 and PP2A activity. The addition of phosphatidic acid decreased the basal activity of PP1c but also increased the stimulation by D-erythro-C18-ceramide from 1.8- to 2. 8-fold and decreased the EC50 of D-erythro-C18-ceramide to 4.45 microM. The addition of 150 mM KCl decreased the basal activity of PP1 and the dose of D-erythro-C18-ceramide necessary to activate PP1c (EC50 = 6.25 microM) and increased the ceramide responsiveness up to 10-17-fold. These studies disclose stereospecific activation of PP1 and PP2A by long chain natural ceramides under near physiologic ionic strengths in vitro. The implications of these studies for mechanisms of ceramide action are discussed.

Cations↗
PubMed1998

Purification and characterization of ceramide-activated protein phosphatases.

Ceramide has emerged as a potential regulator of diverse cellular functions, and a few direct targets have been identified for its action including protein kinases and phosphatases. In this study, we have purified the predominant ceramide-activated protein phosphatase (CAPP) from rat brain. Utilizing a novel chromatographic approach, CAPP was purified to near homogeneity using hydrophobic interaction chromatography on phenyl Sepharose followed by anion-exchange chromatography on MonoQ. The purified protein was composed of three major bands on SDS-polyacrylamide gel electrophoresis which comigrated with the three subunits of heterotrimeric PP2A. Immunologic studies further identified CAPP to be composed predominantly of heterotrimeric AB'C and ABalphaC as well as heterodimeric PP2A (AC), where C is the catalytic subunit, and A and B are regulatory subunits. These results were also supported by the coelution of CAPP with trimeric and dimeric PP2A on size-exclusion chromatography. These studies provide a convenient and efficient method for the isolation of trimeric and dimeric PP2A, and they allow the biochemical investigation of CAPP.

Animals↗
PubMed1998

Cutaneous responsiveness of lumbar spinal dorsal horn neurons is reduced by general anesthesia, an effect dependent in part on GABAA mechanisms.

Extracellular activity was recorded from single spinal dorsal horn neurons in both chronic cat and acute rat models. This was done to define the effects of anesthesia on the processing of sensory information elicited by nonnoxious tactile stimulation of peripheral receptive fields (RFs). In the chronic cat model, baseline data were obtained in physiologically intact, awake, drug-free animals before anesthetic administration (halothane 1.0-2.0%). This made it possible to compare and contrast activity of each cell in the drug-free and anesthetized state. Halothane effects were confirmed in the acute rat model (anesthetized, spinally transected, and in some cases decerebrate). In addition, the gamma-aminobutyic acid-A (GABAA)-receptor antagonist picrotoxin (2 mg/kg) was administered intravenously to verify that the observed halothane effect on spinal dorsal horn neurons was mediated by an interaction with GABAA-receptor systems. Halothane effects on three separate measures of response to nonnoxious tactile stimuli were observed in the chronic cat model. Halothane produced a significant, dose-dependent reduction in the low-threshold RF area of the neurons studied. Halothane also caused a significant reduction in neuronal response to RF brushing (dynamic stimulus) and to maintained contact with the RF (static stimulus). A dose dependency was not observed with these latter two effects. Neurons with a predominant rapidly adapting response seemed to be less susceptible to halothane suppression than slowly adapting cells. In the acute rat model an increase in halothane caused a reduction in neuronal response similar to that seen in the cat. The intravenous administration of 2 mg/kg of picrotoxin by itself caused no significant change in RF size or response to brushing. However, the same amount of picrotoxin did cause a 50% reversal of the halothane-induced reduction in RF size without causing a significant change in the halothane effect on response to RF brushing. In contrast to work recently reported in a chronic sheep model, halothane causes a significant reduction in spinal dorsal horn neuronal response to tactile stimulation of peripheral RFs. This effect is caused by, in part, but not exclusively, to GABAA-neurotransmitter systems. However, the relative influence of GABAA systems may vary with the nature of the stimulus.

Action Potentials↗
PubMed1996

Thromboxane A2 in preservation-reperfusion injury: the effect of thromboxane A2 synthetase inhibitor.

It has been suggested that thromboxane A2 (TXA) plays important roles in preservation/reperfusion organ injury. In this report, we investigated the prostanoid release from the liver and the effect of a selective TXA synthetase inhibitor (E)-3-[p-(1H-imidazol-yl-methyl)-phenyl]-2-propenoic acid, OKY046) during cold preservation and after reperfusion. Rat livers were preserved in lactated Ringer's solution at 4 degrees C for 2, 4, and 6 hr and perfused with oxygenated Krebs-Henseleit buffer using recirculating perfusion system, and prostanoids were measured during cold preservation and after reperfusion. OKY046 and a novel TXA receptor antagonist [(9,11), (11,12)-Dideoxa-9a, 11a-dimethyl-methano-11,12-methano-13,14-dihydro-13-aza-14-oxo-15-cyclo pentyl-16,17,18,19,20-pentanor-15-epi-TXA, ONO3708] were added into the preservation solution and perfusate. Along with the preservation time, both the production and release of TXA was observed to increase; however, almost all the produced TXA was stored in the liver tissue. Afterwards, the stored TXA was released into perfusate in 15 min after reperfusion. OKY046 significantly decreased both the production and release of TXA. In addition, OKY046 improved the histological damage and trypan blue uptake of liver cells. Our results demonstrate that TXA, stored in the liver during preservation, might therefore be a potential trigger of reperfusion injury, and as a result, OKY046 reduces reperfusion injury by decreasing the production of TXA during preservation.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Tuberculosis following liver transplantation: report of a case and review of the literature.

We report on a 44-year-old man who developed tuberculosis 4 months after liver transplantation. The diagnosis was confirmed using a polymerase chain reaction (PCR) technique in bronchial alveolar lavage (BAL) fluid, and the patient was successfully treated by reducing his immunosuppression and administering antituberculous drugs. The patient became afebrile 20 days after starting antituberculous therapy and remains well at home. A review of the literature revealed that tuberculosis after liver transplantation is a rare complication with a reported mortality rate of as high as 40%. The mortality is highest for patients who become symptomatic within 3 months after transplantation (83% vs 0%, P < 0.01; Fisher's exact test) and for those with an interval between the initial symptom and diagnosis of more than 2 weeks (71% vs 0%, P < 0.05). Early diagnosis is, therefore, essential for successful resolution of tuberculosis after liver transplantation.

Adult↗
PubMed1996

Tolerance of the cirrhotic liver to cold ischemia: ex vivo analysis in rats.

We investigated the viability of rat cirrhotic livers preserved cold using an isolated rat liver perfusion model. Cirrhosis was induced by intravenous thioacetamide injection. Normal and cirrhotic livers were reperfused immediately or following 6 h of preservation through the portal vein with Krebs-Henseleit buffer and hyaluronic acid added. Cirrhotic livers with short cold ischemia showed higher portal venous resistance than their normal counterparts (p < 0.05), while cirrhotic livers preserved for 6 h exhibited marked elevation of the portal venous resistance as compared with their fresh counterparts or normal liver preserved cold for 6 h (p < 0.05). Similarly, the oxygen consumption of cirrhotic livers with short cold preservation was lower than that of normal livers (p < 0.05), which was further reduced by 6 h of cold preservation (p < 0.05). The bile output was not different between normal and cirrhotic livers. The sinusoidal endothelial cell function of cirrhotic livers as assessed by the clearance of hyaluronic acid was impaired even after a short period of cold ischemia. Histologically, cirrhotic livers showed severe sinusoidal endothelial cell damage, hepatocellular swelling, and marked septal edema which became more prominent by cold preservation. We conclude that the viability of the cirrhotic liver is impaired even by a short cold exposure, and that the prolongation of cold ischemia of the cirrhotic liver leads to further deterioration of the viability.

Animals↗
PubMed1996

Incidence of methicillin-resistant Staphylococcus aureus (MRSA) isolation in a skilled nursing home: a third report on the risk factors for the occurrence of MRSA infection in the elderly.

A case control study was carried out in order to evaluate the various factors which may influence the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) infections in a skilled nursing home. From April 1991 to March 1994, bacterial cultures were performed in 55 out of 102 residents in a nursing home based on various clinical aspects. We divided 102 residents into following three groups; (1) the MRSA group (n = 10), residents whose materials for bacterial culture were positive for MRSA, (2) the non-MRSA group (n = 45), residents whose specimens were negative for MRSA but positive for other bacteria, (3) the control group (n = 47), residents who did not have to undergo a bacterial culture because they were free from moderate and severe infectious diseases. Compared with the control group, the activities of daily living score and the serum albumin level were significantly lower in the MRSA group and the non-MRSA group at the beginning of the study. In contrast, the number of antibiotics used prior to the bacterial culture and the proportion of hospitalization within 6 months prior to the bacterial culture were significantly larger in the MRSA group than in either the non-MRSA group, or the control group. These results thus suggest that a low activities of daily living score, the use of many kinds of antibiotics and a recent previous hospitalization may be risk factors of MRSA infection in a nursing home environment.

Aged↗
PubMed1995

Halothane effects on low-threshold receptive field size of rat spinal dorsal horn neurons appear to be independent of supraspinal modulatory systems.

Recent evidence strongly supports the importance of spinal sites of action for the ability of general anesthetic agents to block response to noxious stimuli. This study was designed to examine possible spinal anesthetic effects on non-noxiously evoked activity. Three groups of rats were prepared for acute experiments in which the response of spinal dorsal horn neurons to low threshold receptive field (RF) stimulation was evaluated. In each animal in each group extracellular activity was recorded from a single spinal dorsal horn neuron. A low-threshold RF of each neuron and, at times, the sensitivity to low-threshold stimulation of multiple sites in the RF were determined under baseline conditions (light anesthesia or decerebrate). In Group 1, reversible cooling of the thoracic spinal cord in the presence of either 0.5% or 1% halothane anesthesia caused no change in RF size. However, an increase from 0.5% to 1% halothane caused a 53% decrease in RF size both in the presence and absence of a reversible cold block of the spinal cord. In Group 2, animals with spinal cords transected at the thoracic level had a similar change in low-threshold receptive field size (52%) when halothane concentrations were increased from 0.5% to 1%. Testing sensitivity within the RF areas indicated that the silenced areas at the fringe of the receptive field could still elicit activation of spinal dorsal horn neurons but at a higher threshold. In the final group of animals, decerebration and spinal cord transection allowed us to compare effects of 0.5% and 1% halothane with an anesthetic free baseline. Here, again, a dose-dependent reduction in RF area was observed although the baseline RFs were significantly smaller than those in Groups 1 and 2. These results demonstrate that the reduction in low-threshold receptive field size due to the administration of the inhalation anesthetic halothane occurs in the absence of descending modulation from supraspinal sites. This implicates the spinal dorsal horn as a potentially important site of action for general anesthetics. These results also support the spinal cord as an important tool to study the pharmacology responsible for anesthetic effects on sensory processing.

Animals↗
PubMed1995

[A survey of perioperative bronchospasm in 105 patients with reactive airway disease].

We investigated the relationship between the intra- and postoperative incidence of bronchospasm and the predisposing preoperative factors in 105 patients with reactive airway disease. (1) The incidence of bronchospasm in intra- and postoperative period was not associated with age, sex, duration of bronchial asthma, severity of disease, duration of the anesthesia and operation, or with FEV1.0%. (2) The incidence of intraoperative bronchospasm was high with general anesthesia using endotracheal intubation (8.9%), but low with general anesthesia using mask and regional anesthesia (0% and 2.2%, respectively). (3) The incidence of postoperative bronchospasm was about 20% with both general and regional anesthesia. However, the incidence of postoperative bronchospasm was higher in thoracic and abdominal surgeries than in other surgeries (39.5%:10.4%). (4) The incidences of intra- and postoperative bronchospasm increased in proportion to the proximity of the latest asthmatic attack to the operative date. (5) Prophylactic preoperative inhalation of bronchodilators was effective in the prevention of intraoperative bronchospasm, but some patients developed postoperative wheezing within a few days after the cessation of postoperative inhalation.

Adolescent↗
PubMed1995

High-dose acyclovir and intravenous immune globulin reduce the incidence of CMV disease after liver transplantation.

We attempted to prevent cytomegalovirus (CMV) disease in liver transplant (LTx) recipients by means of a combined prophylaxis regimen consisting of high-dose acyclovir (HDA) and immune globulin (IVIG). In 259 consecutive patients, HDA was given for 3 months post-LTx; recipients seronegative for CMV also received IVIG. The previous 94 patients comprised our control group; in this group, low dose acyclovir was given to prevent herpes, and prophylaxis of CMV consisted of IVIG given only to seronegative recipients of seropositive donors. The overall incidence of CMV disease was lower in the HDA group (10.8%) than in the control group (27.6%); (P < 0.001). The CMV disease rate associated with primary exposure was 26.3% in the HDA group and 83.3% in the control group (P < 0.001). The incidence of CMV disease occurring after acute rejection was 9.5% in HDA patients and 24.6% in controls (P < 0.005) The HDA protocol was associated with a trend toward a lower incidence of CMV in patients requiring OKT3 therapy (16.7% vs 29%). High-dose acyclovir/IVIG thus reduces the incidence of CMV disease in seronegative recipients after LTx and lowers the risk of CMV disease associated with therapy for rejection.

Acyclovir↗