FK 506 prevents critical warm ischemia damage to the pig liver and improves hepatic microcirculation.
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Animals↗
Biomedical subjects
K Kawano
Publications and source records attributed to K Kawano.
[Usefulness of 5-FU high-dose continuous therapy at home in patients with recurrent gastric and colon cancer].
Recurrence of gastric cancer or colon cancer was observed in some patients who received 5-fluorouracil (5-FU) high-dose continuous Methotrexate (MTX)-Leucovorin (LV) therapy (FML therapy) previously. 5-FU high-dose 48-hours continuous therapy (5-FU therapy) as maintenance therapy for the patients was performed in the hospital and successively at home. The patients included 3 with recurrent gastric cancer and 2 with recurrent colon cancer: there were 4 males and 1 female, the mean age was 51.8 years (33-59 years). All patients had received FML therapy during the hospital stay before the maintenance chemotherapy at home. 5-FU therapy (30 mg/kg/day x 2 days/w), 30.2 courses on an average (11-40 courses), was performed through a catheter (Port-A-Cath), which was introduced into the right subclavian vein and placed under the skin, with a Baxter infusion pump. The concentration of 5-FU was 197 +/- 172-401 +/- 127 ng/ml between the 2nd and 48th hour. Adverse reaction included anorexia in 5 patients, stomatitis in 4, pigmentation in 4, leukopenia in 3, neuropathy in 2 and alopecia in 1. The therapy was effective for 10.4 months on an average (4-18 months) and the mean survival period was 12.0 months (7-18 months).
Adult↗
[A case of Jordans' anomaly].
A 35-years old female with Jordans' anomaly was reported. She had been treated for diabetes mellitus and hypertension at another hospital. She was admitted to our hospital for operation for diabetic retinopathy on July 9, 1992. Wright-Giemsa stained peripheral blood smear revealed multiple vacuoles in the cytoplasm of the granulocytes and monocytes. Histochemical studies of these vacuoles showed positive for Sudan III but negative for peroxidase, alkaline phosphatase and PAS staining. Electron microscopic examination revealed that lipid containing vacuoles had no clear membrane and were not associated with cell organelles. Laboratory findings of the serum showed hyperglycemia (FBS 188mg/dl), high HbA1c level (9.4%) and mild type IIa hyperlipidemia. Abdominal sonogram and abdominal CT showed no remarkable abnormalities except for mild fatty liver. Her elder sister and daughter had similar morphological findings in granulocytes, monocytes and lymphocytes.
Adult↗
[Lp(a) serum concentrations in diabetes mellitus].
Lp(a) has been considered as an independent risk factor for atherosclerosis, mainly for coronary heart disease. Recent epidemiologic studies have demonstrated elevation of Lp(a) serum concentration in diabetes mellitus. Atherosclerosis is the most common cause of death in diabetic patients, but there is little information available concerning the importance of Lp(a) in these patients. We investigated the relationship between Lp(a) serum concentration and the presence of chronic diabetic complications. Lp(a) was determined in 14 IDDM patients and 62 NIDDM patients. Median Lp(a) serum concentration in diabetics was 21.8 mg/dl, which was significantly higher than in nondiabetic controls described before. Glucose, HbA1c, fructosamine, total cholesterol, triglycerides, HDL-cholesterol, apolipoprotein A1, B and E were not associated with raised Lp(a) values. With increasing Lp(a) levels, higher prevalences of retinopathy and of albuminuria were observed. We conclude that in diabetic patients, Lp(a) levels are elevated compared with non-diabetic subjects, and that higher Lp(a) levels are associated with higher prevalences of retinopathy and of albuminuria.
Adult↗
[Antibodies to human T-cell lymphotropic virus type 1 in the aqueous humor of HTLV-I associated uveitis].
To elucidate the pathomechanism of human T-cell lymphotropic virus type 1 (HTLV-I) associated uveitis (HAU), we assessed antibodies to HTLV-I and IgG for paired samples of serum and aqueous humor. Seven of 10 samples from HAU patients showed antibodies to HTLV-I in the aqueous humor with antibody titer ranging from 16 to 128, and five of these samples showed significantly high antibody quotients as calculated by reference to the IgG levels in the serum and aqueous humor, hence suggesting local production of antibodies rather than their transfer from the serum. On the other hand, eight of 45 control samples from HTLV-I carriers with senile cataract but without uveitis had antibodies to HTLV-I in the aqueous humor with antibody titer ranging from 8 to 128, but none of these samples showed high antibody quotient. We conclude that, although antibodies to HTLV-I in aqueous humor were detected in those HAU and control cases which showed high antibody titer in the serum, intraocular synthesis of antibodies to HTLV-I may sometimes occur in HAU.
Adult↗
Intrahepatic neutrophil accumulation in ischemia/reperfusion injury of pig liver.
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Animals↗
[Thoracic solitary neurenteric cyst--case report].
A 61-year-old man presented with repeated back pain and progressive anesthesia of both lower limbs. MR images and myelography showed an intradural, extramedullary tumor at the Th8-9 level. Surgery revealed a thin membrane containing xanthochromic cerebrospinal fluid behind the spinal cord. Microscopically, the excised lesions contained columnar epithelium with goblet cells. Spinal neurenteric cysts are a rare anomaly, especially solitary cysts located in the thoracic spine. The neurenteric canal transiently develops in the lumbosacral region during the 3rd week of gestation. Thus, it is difficult to claim that the neurenteric cyst in our case originated in a remnant of the neurenteric canal. As Bentley and Smith (1960) suggested, thoracic solitary neurenteric cysts may develop from a remnant of adhesion between ectoderm and endoderm during the 3rd week of gestation as a result of splitting of the notochord.
Humans↗
[A case of idiopathic chylothorax--successful pleurodesis with OK-432].
A 73-year-old woman was referred to our hospital because of left pleural effusion. Chyle was obtained by thoracocentesis. Because there was no organic lesion to cause chylothorax, idiopathic chylothorax was diagnosed. Her condition improved by chest-tube drainage and pleurodesis with intrapleural injection of OK-432. We report a rare case of idiopathic chylothorax and conclude that pleurodesis with intrapleural injection of OK432 is very useful for the treatment of idiopathic chylothorax.
Aged↗
Inverse-dynamics model eye movement control by Purkinje cells in the cerebellum.
Many lines of evidence suggest that the cerebellum is involved in motor control. But what features of these movements are encoded by cerebellar neurons? For slow-tracking eye movements, the activity of Purkinje cells in the ventral paraflocculus of the cerebellum is known to be correlated with eye velocity and acceleration. Here we show that the complex temporal pattern of the firing frequency that occurs during the ocular following response elicited by movements of a large visual scene can be reconstructed by an inverse-dynamics representation, which uses the position, velocity and acceleration of eye movements. Further analysis reveals that the velocity and acceleration components can provide appropriate dynamic drive signals to ocular motor neurons, whereas the position component often has the wrong polarity. We conclude that these Purkinje cells primarily contribute dynamic command signals.
Action Potentials↗
Water-soluble chymotrypsin specific inhibitors containing arginine.
In an attempt to develop water-soluble, potent inhibitors for chymotrypsin, structurally rigid dipeptides containing arginine were designed and synthesized. The dipeptide H-D-Arg-Phe-NHBzl inhibited chymotrypsin very strongly (Ki = 5.9 microM). The dipeptide with the inverse sequence, H-D-Phe-Arg-NHBzl, was also a moderate inhibitor for chymotrypsin with Ki of 240 microM. In spite of the presence of arginine in these dipeptides, they inhibited trypsin only weakly, indicating that they are highly specific for chymotrypsin. High resolution 1H-NMR (400-MHz) indicated that these dipeptides can make a strong intramolecular hydrophobic interaction between Arg-beta, gamma, delta-methylenes and Phe-phenyl, producing a rigid hydrophobic core which interacts with the chymotrypsin S2 site. Since these dipeptides are easily soluble in water, they are regarded as the sophisticated and effective inhibitors for chymotrypsin.
Amino Acid Sequence↗
Transmembrane calcium influx associated with von Willebrand factor binding to GP Ib in the initiation of shear-induced platelet aggregation.
We found that the binding of multimeric vWF to GP Ib under a shear force of 108 dynes/cm2 resulted in the transmembrane flux of Ca2+ ions with a two- to three-fold increase in their intracellular concentration ([Ca2+]i). The blockage of this event, obtained by inhibiting the vWF-GP Ib interaction, suppressed aggregation. In contrast, the blockage of vWF binding to GP IIb-IIIa, as well as the prevention of activation caused by increased intracellular cAMP levels, inhibited aggregation but had no significant effect on [Ca2+]i increase. A monomeric recombinant fragment of vWF containing the GP Ib-binding domain of the molecule (residues 445-733) prevented all effects mediated by multimeric vWF but, by itself, failed to support the increase in [Ca2+]i and aggregation. These results suggest that the binding of multimeric vWF to GP Ib initiates platelets aggregation induced by high shear stress by mediating a transmembrane flux of Ca2+ ions, perhaps through a receptor-dependent calcium channel. The increase in [Ca2+]i may act as an intracellular message and cause the activation of GP IIb-IIIa; the latter receptor then binds vWF and mediates irreversible aggregation.
Biological Transport↗
Copper-metallothionein distribution in the liver of Long-Evans cinnamon rats: studies on immunohistochemical staining, metal determination, gel filtration and electron spin resonance spectroscopy.
Distribution of metallothionein (MT) and copper ion (Cu) in the liver of LEC (Long-Evans Cinnamon) rats was investigated to examine the relationship between Cu-MT induction and the development of hepatitis followed by hepatocellular carcinomas. Immunohistochemical studies on MT in the liver of LEC rats indicated that MT is accumulated in nuclei and cytosols. Both MT and Cu, estimated by radioimmunoassay and flameless atomic absorption spectrometry, respectively, in subcellular fractions of the liver were found to be concentrated highest in cytosols, followed by nuclei, mitochondria and microsomal fractions. Gel-filtration (Sephadex G-75) studies demonstrated that MT is induced as the Cu-MT form. Furthermore, the Cu-MT fragment purified by the gel-filtration contains the Cu(I)-MT form, as demonstrated by ESR (electron spin resonance) measurements at 77K. These results will be important for understanding the development of hepatitis in LEC rats.
Animals↗
[Trend of clinical pathology tests and the effective usage for diagnosis].
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Clinical Laboratory Techniques↗
Identification of the adsorbing site of lysozyme onto the hydroxyapatite surface using hydrogen exchange and 1H NMR.
The lysozyme-hydroxyapatite interaction was studied by measuring individual hydrogen-deuterium (H-D) exchange rates of amide protons. The H-D exchange reaction was initiated by transferring the lysozyme adsorbed on hydroxyapatite powder from H2O into D2O. After various H-D exchange time periods (pH 7.0, 25 degrees C), the complex was dissociated and the remaining hydrogen label was determined by 2D NMR analysis. The H-D exchange rate of amide protons of residues 9, 11, 13, and 83 was slowed in the hydroxyapatite-lysozyme complex compared with free lysozyme. Residues 9, 11 and 13 positioned at the back of the active site would be the location of the binding site.
Adsorption↗
Prolonged normothermic ischaemia of human cirrhotic liver during hepatectomy: a preliminary report.
To evaluate the tolerance of the cirrhotic liver to extended warm ischaemia, 47 patients with cirrhosis who underwent liver resection over a 4-year period were studied retrospectively. Three groups of patients were identified. In group 1 (14 patients) liver resection was performed under conditions of portal triad occlusion ranging from 50 to 75 (mean 57.1) min. Group 2 (12 patients) was treated with portal occlusion for a period ranging from 30 to 42 (mean 33.1) min. Group 3 comprised 21 patients who underwent hepatectomy using conventional techniques. Mean blood loss was significantly reduced by portal triad occlusion (819 ml in group 1, 523 ml in group 2) compared with the conventional technique (1652 ml in group 3) (P < 0.05, group 1 versus group 3; P < 0.01, group 2 versus group 3). Hospital death occurred in three of the 21 patients in group 3 but in no patient who underwent portal triad occlusion. The morbidity rate was lower in the two occlusion groups (four of 26 patients) than in group 3 (six of 21). Bilirubin metabolism was substantially better after surgery in the occlusion groups (P < 0.05, groups 1 and 2 versus group 3 at day 14). Although the serum levels of transaminases were significantly raised until day 3 in patients undergoing long-term occlusion, the cirrhotic liver withstood the ischaemia-reperfusion insult, as assessed by changes in hepatic microcirculation, lipid peroxidation and the morphology of hepatic sinusoids. It is concluded that prolonged ischaemia during liver resection can be sustained in patients with cirrhosis and without high-risk factors.
Adult↗
Chymotrypsin inhibitory conformation of dipeptides constructed by side chain-side chain hydrophobic interactions.
A complete series of configurational isomers (L-L, L-D, D-L and D-D) of a dipeptide Leu-Phe benzyl ester have been synthesized and assayed for chymotrypsin. In the conformational analysis by 400 MHz 1H NMR, the L-D and D-L isomers, but not the L-L and D-D isomers, showed fairly large upfield shifts (0.2-0.4 ppm) of Leu-beta CH2 and gamma CH proton signals, indicating the presence of shielding effects from the benzene ring. In addition to distinct signal splitting of Phe-beta CH2, the NOE enhancement observed between Leu-delta CH3 and Phe-phenyl groups revealed that these groups are in close proximity. These data indicated that L-D and D-L isomers form a hydrophobic core between side chains of adjacent Leu and Phe residues. When the dipeptides were examined for inhibition of chymotrypsin using Ac-Tyr-OEt as a substrate, the L-L isomer showed no inhibition, itself becoming a substrate. However, the other three isomers inhibited chymotrypsin in a competitive manner, and the D-L isomer was strongest with Ki of 2.2 x 10(-5) M. It was found that the D-L isomer was only slowly hydrolysed but the L(or D)-D isomer was not. H-D-Phe-L-Leu-OBzl with the inverse sequence of H-D-Leu-L-Phe-OBzl inhibited chymotrypsin more strongly (Ki = 6.3 x 10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Chymotrypsin↗
The effect of a prostaglandin I2 analogue (OP-41483) on energy metabolism in liver preservation and its relation to lipid peroxidative reperfusion injury in rats.
The effect of the stable prostacyclin (PGI2) analogue OP-41483 (OP) on liver preservation was investigated in the rat liver transplant model. In a 1-week survival study, 33 orthotopic liver transplants were performed using Wistar rats. In group A, untreated livers were stored with modified UW (mUW) solution at 4 degrees C. In group B, livers from OP-pretreated donors (2 micrograms/kg, i.v.) were stored with mUW solution containing OP (1 microgram/ml) at 4 degrees C. After 24 h storage, the donor grafts in each group were transplanted to untreated recipients. OP treatment (group B) significantly improved 1-week survival (62.5%, 10/16, P < 0.01 versus group A; 11.8%, 2/17). For the measurement of adenine nucleotides and lipid peroxidation (malondialdehyde, MDA) in liver tissue before preservation, after preservation, and 3 h after transplantation, 20 rat livers in groups A and B were studied. In both groups, the levels of adenosine triphosphate (ATP) declined 6 h after cold preservation, but this degradation of ATP was significantly halted at the level of adenosine monophosphate (AMP) in the OP-treated livers after 24 h of storage. However, OP treatment showed no significant difference in the degree of ATP recovery after transplantation. On the other hand, OP treatment resulted in suppression of the increase in MDA levels and histological amelioration of microcirculatory disturbance 3 h after transplantation. Our data suggested that the combined use of the stable PGI2 analog (OP-41483) and UW solution is beneficial in liver preservation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenine Nucleotides↗
Role of Purkinje cells in the ventral paraflocculus in short-latency ocular following responses.
We describe the simple-spike activity of Purkinje cells (P cells) in the ventral paraflocculus (VPFL) of behaving monkeys in association with movements of the visual scene that evoke short-latency ocular following responses. One group of P cells discharged maximally for downward motion, and the other for motion toward the side of the recording. The onset of the simple-spike response was measured in relation to the onset of ocular following in 24 P cells. The majority of P cells (79%) led by 1-9 ms. At the site of each recording, electrical stimuli (single negative pulses, 1.5-45 microA; 0.2 ms in width) were applied and 60% (18/30) of the sites elicited eye movements in the preferred direction of the P cells. The latency of the single-pulse-evoked response in the ipsilateral eye ranged from 8.6 to 10.9 ms. These data suggest that the P cells in the VPFL play a role in ocular following; some discharge early enough to generate the very earliest eye movements.
Action Potentials↗