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Biomedical subjects

N Kawai

Publications and source records attributed to N Kawai.

At least 91 records · Page 5Linked to original sources
PubMed2000

Radioimmunoassay for hypocretin-2.

OBJECTIVE: To develop radioimmunoassay for hypocretin-2 (Hcrt-2). And search for its presence in certain rat tissues. METHODS: Anti-Hcrt-2 serum has been raised in New Zealand white rabbits immunized with a conjugate of synthetic Hcrt-2 with bovine serum albumin. Radioiodination of Hcrt-2 was performed by chloramine T method, followed by purification of radoiodinated material on Sephadex G-25 column. RESULTS: The obtained antibody did not cross react with hypocretin-2, hypothalamic hormones, pituitary hormones, neuropeptides or gut hormones. The assay was performed with a double antibody system. Hcrt-2 was extracted from the tissues with acid acetone. The dilution curve of acid acetone extracts of rat hypothalamus in the radioimmunoassay system was parallel to the standard curve. The recovery of tissue Hcrt-2 was about 85 % and the intra-assay and inter-assay variation were 5.6 % and 8.0 %, respectively. Hcrt-2 was found in the hypothalamus, cerebrum, brain stem and testes. CONCLUSIONS: The obtained data suggest that the assay system developed is suitable to measure Hcrt-2 in tissues and that Hcrt-2 is mainly found in the hypothalamus.

Animals↗
PubMed2000

[Long-term results of TIPS].

The long-term results of transjugular intrahepatic portosystemic shunt(TIPS) were analyzed in 48 patients between February 1992 and December 1998, for treatment of esophageal varices and ascites caused by portal hypertension. The procedure was successful in 42 patients. Portal vein pressure was reduced from 29 mmHg +/- 7.9 to 19 mmHg +/- 7.3 immediately after TIPS and to 17 mmHg +/- 6.5 one year later. Varices were controlled in 82% (23/28) of patients after one year and in 78% (7/9) of patients after five years. Ascites disappeared or decreased in 79% (11/14) after one year. Primary shunt patency was 12%, with a secondary patency rate of 79% after five years. The overall incidence of new or worsened encephalopathy was 31% (13/42). Long-term follow-up showed one-, three-, and five-year survival rates of 82%, 68%, and 59%, respectively. TIPS is an effective means of lowering portal hypertension, and it controls varices and ascites with little risk of hepatic encephalopathy.

Adult↗
PubMed2000

[Therapeutic effect of TAE in patients with hepatocellular carcinoma using color Doppler imaging with intravenous ultrasound contrast agent].

We evaluated the therapeutic effect of TAE in 9 nodules with hepatocellular carcinoma (HCC) using color Doppler flow imaging with an intravenous ultrasound contrast agent. The intratumoral color signal enhancement that was detected in 7 nodules resulted in complete disappearance after TAE. The other 2 nodules without color signal enhancement showed well-differentiated HCC with fatty degeneration on histological study. The intratumoral enhancement noted in dynamic MRI in 7 of the 9 nodules resulted in complete disappearance after TAE. Color Doppler flow imaging with an intravenous contrast agent is a promising method for assessing the therapeutic effect of TAE.

Aged↗
PubMed2000

Induction of cyclooxygenase-2 in rat gastric mucosa by rebamipide, a mucoprotective agent.

Recent studies indicate an expression of mitogen-inducible cyclooxygenase (COX-2) in gastric mucosa. Rebamipide, a mucoprotective agent enhances prostaglandin (PG) synthesis. The present study was designed to clarify the mechanism for rebamipide-induced mucosal protection. Male Sprague-Dawley rats were administered 5, 15, or 50 mg/kg/day rebamipide for 14 days. The expression of constitutive cyclooxygenase (COX-1) and COX-2 in gastric mucosa was determined using Western blot analysis. Another series of rats was used to examine 1) the levels of PGE(2) in stomach with and without pretreatment with a COX-2 inhibitor; 2) the protective action of rebamipide against gastric damage caused by 0.6 N HCl; and 3) the effects of a COX-2 inhibitor on rebamipide-induced gastric mucosal protection. COX-2 expression was enhanced, whereas COX-1 expression did not change significantly in the gastric mucosa of rats after treatment with rebamipide. The gastric mucosal PGE(2) was higher in the rebamipide groups than in the vehicle-treated group. Rebamipide also suppressed gastric damage induced by HCl in a dose-dependent manner. A COX-2 inhibitor blocked the rebamipide-induced increase in mucosal PGE(2), and mucosal protection induced by rebamipide. The results indicate that rebamipide induces COX-2 expression, increases PGE(2) levels, and enhances gastric mucosal defense in a COX-2-dependent manner. Thus, COX-2 has an important role in the effects of rebamipide on gastric mucosal protection.

Alanine↗
PubMed1999

Protective role of nitric oxide synthase against ischemia-reperfusion injury in guinea pig myocardial mitochondria.

In guinea-pig myocardial mitochondria preparation, lowering the Ca2+ concentration or pH level in the perfusate rapidly elevated the fura-2 Ca2+ signal ([Ca2+]m). Pretreatment with 10(-4) M L-Arg inhibited the rapid [Ca2+]m influx, whereas administration of 10(-4) M L-NAME did not, suggesting some association between nitric oxide (NO*) synthase (NOS) activation and Ca2+ kinetics in mitochondria. Immunoblotting analysis showed that endothelial (e)-NOS was present in mitochondria, but not inducible (i)-NOS or brain (b)-NOS. Electron microscopy observations revealed that the e-NOS antibody-reactive site in the mitochondria was the inner cristae. The production of reactive oxygen species and NO* in isolated mitochondria was detected by the spin trapping technique with electron paramagnetic resonance (EPR) spectrometry. Pretreatment with 10(-5) M S-nitroso-N-acetyl-DL-penicillamine (SNAP) and 10(-5) M 3-[2-Hydroxy-1-(1-methylethyl)-2-nitrosohydrazino]-1-propananin e (NOC 5), which spontaneously generate NO*, completely inhibited the [Ca2+]m uptake. In addition, N-morpholino sydnonimine hydrochloride (SIN-1) (10(-5) M), which simultaneously generates NO* as well as *O2- and peroxynitrite anion (ONOO-), inhibited the increase in [Ca2+]m. ONOO- (3 x 10(-4) M) itself also inhibited this increase. Pretreatment with the *O2(-)-scavenger manganese superoxide dismutase or catalase (200 units/ml) completely inhibited the increase in [Ca2+]m caused by lowering of either the Ca2+ concentration or the pH in the perfusate. These results suggested that the formation of reactive oxygen species promoted the [Ca2+]m influx. The agents that inhibited the [Ca2+]m influx improved contractility even in Langendorff preparations after ischemia. Based on these findings, we concluded that e-NOS exists in mitochondria and that NO* may play an important protective role in reperfusion cardiac injury after ischemia, by inhibiting the Ca2+ influx into mitochondria which are otherwise damaged by *O2-.

Animals↗
PubMed1999

A relationship between urine specific gravity and hyponatremia in hospitalized schizophrenic patients.

The relationship between urine specific gravity (USG) and the incidence of polydipsia/hyponatremia in hospitalized schizophrenic patients was examined. On the basis of five independent USG values, we identified 49% (35 out of 72) of male and 22% (8 out of 37) of female patients with hyposthenuria (mean USG < or = 1.008). Review of 2 years of records of routine laboratory examinations identified 12 males with hyponatremia, 11 males with borderline hyponatremia, and 49 males with normal values; among female patients, only one patient with hyponatremia and three patients with borderline values were identified. A significantly lower mean USG (1.003 +/- 0.001) for the male patients with hyponatremia compared with the male patients with normal serum sodium data (1.011 +/- 0.005) was observed. All of the male patients with hyponatremia, as well as 18 of the 49 male patients with normal serum sodium values, exhibited hyposthenuria. The USG values of all the patients with hyponatremia were consistently quite low (< or = 1.005), whereas 14 of the 18 normonatremia/hyposthenuria patients had normal USG values (i.e. > or = 1.009) in at least one of five determinations; the mean USG values for most (16 of 18) of the normonatremia/hyposthenuria patients ranged from 1.006 to 1.008. Thus, many hospitalized schizophrenic patients exhibit hyposthenuria of varying degrees, but consistently low USG values are most suggestive of the risk of polydipsia/hyponatremia.

Adult↗
PubMed1999

Toxicological significance in the cleavage of esterase-beta-glucuronidase complex in liver microsomes by organophosphorus compounds.

Egasyn is an accessory protein of beta-glucuronidase (beta-G) in the liver microsomes. Liver microsomal beta-G is stabilized within the luminal site of the microsomal vesicles by complexation with egasyn which is one of the carboxylesterase isozymes. We investigated the effects of organophosphorus compounds (OPs) such as insecticides on the dissociation of egasyn-beta-glucuronidase (EG) complex. The EG complex was easily dissociated by administration of OPs, i.e. fenitrothion, EPN, phenthionate, and bis-beta-nitrophenyl phosphate (BNPP), and resulting beta-G dissociated was released into blood, leading to the rapid and transient increase of plasma beta-G level with a concomitant decrease of liver microsomal beta-G level. In a case of phenthionate treatment, less increase in plasma beta-G level was observed, as compared with those of other OPs. This may be explained by the fact that phenthionate was easily hydrolyzed by carboxylesterase. Similarly, carbamate insecticides such as carbaryl caused rapid increase of plasma beta-G level. In contrast, no significant increase of plasma beta-G level was observed when pyrethroid insecticides were administered to rats. This is due to the fact that pyrethroids such as phenthrin and allethrin were easily hydrolyzed by A-esterase as well as carboxylesterase. On the other hand, addition of OPs to the incubation mixture containing liver microsomes caused the release of beta-G from microsomes to the medium. From these in vivo and in vitro data, it is concluded that increase of the plasma beta-G level after OP administration is much more sensitive biomarker than cholinesterase inhibition to acute intoxication of OPs and carbamates.

Animals↗
PubMed1999

Involvement of cyclooxygenase-2 in proliferation and morphogenesis induced by transforming growth factor alpha in gastric epithelial cells.

Transforming growth factor alpha is one of the most potent growth factors for gastrointestinal epithelium. In this study, we examined the roles of cyclooxygenase-2 on proliferation and morphogenesis of RGM1 rat gastric epithelial cells after stimulation with transforming growth factor alpha in vitro, RGM1 cells increased expression of cyclooxygenase-2 messenger RNA 20-60 min after stimulation with transforming growth factor alpha. Transforming growth factor alpha stimulated [3H]thymidine incorporation and tubulogenesis of RGM1 cells in collagen matrix, both of which were significantly suppressed by treatment with a cyclooxygenase-2 specific inhibitor, NS-398 or cyclooxygenase-2 antisense oligonucleotide. Both of the treatment lowered prostanoid production by enzyme immunoassay. The transforming growth factor alpha-induced expression of cyclooxygenase-2 is followed by cell proliferation and development of tubular morphology of RGM1 gastric epithelial cells. Treatment with cyclooxygenase-2 inhibitor and cyclooxygenase-2 antisense oligonucleotide suppressed these responses induced by transforming growth factor alpha suggesting the involvement of cyclooxygenase-2 in proliferation and morphogenesis in gastric mucosal epithelium.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Effect of moderate hypothermia on systemic and internal jugular plasma IL-6 levels after traumatic brain injury in humans.

Moderate hypothermia may reduce subsequent neuronal damage after traumatic brain injury. Interleukin (IL)-6 may have a role in the pathogenesis of traumatic neuronal damage or repair. Using the enzyme-linked immunological sorbent assay (ELISA), we serially measured IL-6 levels in plasma obtained from the radial artery (systemic) and internal jugular vein (regional) in 13 cerebral trauma patients who underwent hypothermia of 32-33 degrees C ranged from 4-9 days postinjury and 10 head-injured patients who were maintained at normothermic levels (36-37 degrees C). In both patient populations, surface cooling was used since even in the normothermic group, cooling was needed to maintain patient temperature in the normothermic range. All patients were mechanically ventilated after injection of midazolam and vecuronium. The administration of these agents were continued until the end of the study. Hypothermia was typically maintained for four days, however, in some cases based upon CT findings and/or intra-cranial pressure change, the duration was prolonged. No significant differences were found between the two groups in age, gender and Glasgow Coma Scale upon admission. Further, no differences were found in terms of the classification of computed tomography findings or the occurrence of pupillary abnormalities on admission. The patients in this study had not sustained either abdominal or thoracic trauma. Before inducing hypothermia, IL-6 levels in the arterial and internal jugular venous blood exceeded the normal range. Specifically, the internal jugular plasma levels were significantly higher than those in the arterial plasma. While IL-6 levels in the normothermic group did not decrease even at 4 days postinjury, the plasma cytokine levels fell at both sites sharply after moderate hypothermia. The cytokine suppression found in the hypothermic group continued even after rewarming in these patients showing an improved clinical course, but not in those whose condition worsened. In addition to these changes in cytokine levels, the Glasgow Outcome Scale at 6 months postinjury was significantly higher in the hypothermic group than in the normothermia group. Based on the above, this clinical study with its small patient sample size suggests the need for further prospective randomized studies to examine the role of cytokine suppression in the beneficial effects of moderate hypothermia in patients with traumatic brain injury.

Adolescent↗
PubMed1999

Blood-brain barrier glutamine transport during normoglycemic and hyperglycemic focal cerebral ischemia.

This study examines the effects of middle cerebral artery (MCA) occlusion in the rat on blood to brain glutamine transport, a potential marker of early endothelial cell dysfunction. It also examines whether the effects of ischemia on glutamine transport are exacerbated by hyperglycemia. In pentobarbital-anesthetized rats, 4 hours of MCA occlusion resulted in a marked decline in the influx rate constant for [14C]L-glutamine from 16.1+/-1.2 microL.g(-1).min(-1) in the contralateral hemisphere to 7.3+/-2.5 microL.g(-1).min(-1) in the ischemic core (P < 0.001). This reduction was even greater in xylazine-ketamine-anesthetized rats in which the influx decreased to 2.6+/-1.1 microL.g(-1) min(-1). This greater reduction appears related to the hyperglycemia induced by xylazine-ketamine anesthesia. Glucose injection in pentobarbital-anesthetized rats also resulted in a greater decline in [14C]L-glutamine influx in the ischemic core but had no effect on the contralateral tissue. The effects of hyperglycemia on glutamine transport in the ischemic tissue were associated with a decline in plasma volume, which may reflect either endothelial cell swelling or plugging of the microvasculature. The reduction in glutamine transport during ischemia was progressive, but even as early as 1 hour, there was a 60% and 40% decline in influx in hyperglycemic and normoglycemic rats, respectively. The fall in [14C]L-glutamine influx may reflect a dissipation of the endothelial cell [Na+] gradient. A decline in this gradient would affect many blood-brain barrier transporters with potentially deleterious effects on the ischemic brain.

Animals↗
PubMed1999

[Non-Hodgkin's lymphoma complicated by recurrent intractable generalized herpes zoster responsive to long-term acyclovir therapy].

A 34-year-old male with a history of chickenpox developed primary abdominal non-Hodgkin's lymphoma (diagnosed in August 1995). Treatment with cyclophosphamide, doxorubicin, vincristine, and prednisolone achieved a partial remission. In July 1996, the disease recurred, and the patient received chemotherapy with carboplatine, etoposide, mitoxantrone, and prednisolone, but no response was noted. Involvement of the central nervous system and meninges was diagnosed on September 12, 1997. Blast cells were detected in the peripheral blood on September 26. Based on these findings, he was diagnosed as having leukemia. On September 27, painless vesicles developed on the left gluteal region. On October 13, the patient was hospitalized because the vesicles had spread over his entire body. Pathologic examination of the roofs of the blisters showed masses of inclusion bodies. Based on this, a diagnosis of varicella-zoster infection was made. Treatment with acyclovir (750 mg/day) for seven days failed to form crusts. New vesicles developed after the drug was discontinued, but crusts formed after acyclovir therapy was resumed. He died of interstitial pneumonia on December 21. Autopsy could not be performed. Histopathologic examination of pulmonary tissue obtained by necropsy did not reveal the presence of inclusion bodies characteristic of herpes simplex or varicella-zoster infection. Varicella-zoster virus (VZV) antigen was negative by an immunochemical staining method using monoclonal antibodies against VZV. Continuous long-term administration of acyclovir has been reported to be effective for non-Hodgkin's lymphoma complicated by recurrent intractable herpes zoster.

Acyclovir↗
PubMed1999

[A neutropenic acute myeloid leukemia patient complicated with chronic otitis media due to Aspergillus niger and yeast-like fungi caused by superinfection].

There have been few reports describing otomycosis in association with compromised hosts. So we report a neutropenic acute myeloid leukemia (AML) patient complicated with otomycosis caused by superinfection. A 51-year-old male was admitted because a third relapse of AML in March 1998. Two years ago, he was diagnosed as having chronic otitis media involving the VII cranial nerve due to Pseudomonas aeruginosa coinciding with AML. Then, he had suffered from a right-sided earache and otic discharge in accord with every myelosuppression, which improved on treatment with otic administration of ofloxacin. After 1 course of induction chemotherapy, he developed a spiking fever with severe earache and otic discharge at a nadir period of WBC. Ear swab cultures yielded Aspergillus niger and yeast-like fungi. So, he was treated with intravenous administration of amphotericin B (AMPH-B): initial dose was 5 mg/day and was gradually increased to 30 mg/day. Thereafter, the otic symptoms subsided and never recurred. Subsequently, he was given another antifungal agent, itraconazole. Although induction chemotherapies resulted in failure, he did not suffer otic symptoms until his death due to cerebral bleeding in January 1999. For neutropenic patients without rapid hematological improvement, we recommend intensive antifungal therapy as the first-line of therapy for otomycosis rather than local therapy.

Acute Disease↗
PubMed1999

Osteopontin expression in prostate cancer and benign prostatic hyperplasia.

OBJECTIVES: Osteopontin (OPN), a secreted adhesive glycoprotein, has been shown to be produced in excessive amounts in a variety of experimental models of malignancy. Increased levels of OPN exist in blood from the lungs, breasts, and gastrointestinal tracts of cancer patients with metastases. However, there have been no reports on the expression of OPN in human urological malignancies. The present study investigates the presence of OPN in adenocarcinoma of the human prostate and in benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Using prostate tissue from 34 patients with primary prostate cancer, 13 patients with prostate cancer after having undergone hormonal therapy, and 12 patients with BPH, formalin-fixed paraffin sections were prepared. Specimens were obtained by needle biopsy or radical prostatectomy. Immunohistochemical staining (ABC method) was then performed. Staining was divided into either negative or positive categories. RESULTS: Positive staining of OPN was observed on cancer cells and macrophages in 52.9% of the primary prostate cancers and 14.5% of the prostate cancers after hormonal therapy. In BPH specimens, 66.7% of the cases displayed positive staining of OPN. The staining level of OPN showed no correlation with serum prostate-specific antigen, but did correlate with stage, differentiation, and Gleason's score. CONCLUSIONS: The result postulates that the expression of OPN is an indicator of cell differentiation; however, it cannot be used as a marker of malignancy in prostate cancer.

Adenocarcinoma↗
PubMed1999

Pathophysiological roles of endothelin-1 in Dahl salt-sensitive hypertension.

The purpose of the present experiment was to study the pathophysiological roles of endothelin-1 (ET-1) in salt-sensitive hypertension with the use of Dahl salt-sensitive (DS) and salt-resistant (DR) rats. PreproET-1 mRNA expression was determined by reverse transcription-polymerase chain reaction. In the kidney, expression of preproET-1 mRNA was greater in DS rats on a normal salt diet compared with DR rats of the same age. In DS rats, the level of preproET-1 mRNA expression in kidney had a significant correlation with systolic blood pressure. The expression of preproET-1 mRNA in aorta and kidney was increased by 3-week high salt intake in DS rats but not in DR rats. Expression of preproET-1 mRNA and ET-1 levels in left ventricle was exaggerated by high salt intake in DS rats. However, there was no significant difference in plasma ET-1 levels between DS and DR rats regardless of salt intake. Pressor response curves for ET-1 in DS rats with or without high salt intake were significantly shifted to the left compared with those in DR rats. A single oral dose (3 to 10 mg/kg) of J-104132 (L-753 037), a potent, orally active mixed endothelin A and B (ET(A)/ET(B)) receptor antagonist, reduced blood pressure to normotensive levels in DS rats with high salt intake, and its action was maintained for >/=24 hours. In DS rats with normal salt intake, J-104132 (10 mg/kg) slightly but significantly decreased blood pressure. DR rats did not show obvious depressor responses to J-104132 (10 mg/kg) regardless of salt intake. These results suggest that ET-1 acts as one of the pathophysiological factors in the development and maintenance of salt-sensitive hypertension, and a mixed ET(A)/ET(B) receptor antagonist could be useful in the treatment for salt-sensitive hypertension.

Animals↗
PubMed1999

Serum free insulin-like growth factor I (IGF-I), total IGF-I, and IGF-binding protein-3 concentrations in normal children and children with growth hormone deficiency.

To evaluate the role of serum free or unbound insulin-like growth factor I (IGF-I) on bone growth, we measured serum free IGF-I levels in 354 healthy children and adults (193 males and 161 females, aged 0-40 yr) and in 21 prepubertal GH-deficient (GHD) children (complete GHD, n = 5; partial GHD, n = 16) using a recently developed immunoradiometric assay. We obtained the following results. 1) In the normal children, the serum free IGF-I levels were low in infancy (<1 yr of age; males, 0.71 +/- 0.26 microg/L, mean +/- SD; females, 1.05 +/- 0.49 microg/L), increased during puberty (males, 5.84 +/- 2.18 microg/L; females, 5.80 +/- 1.49 microg/L), and declined thereafter. 2) Free IGF-I in the serum occupied about 0.95-2.02% of the total IGF-I values, with the highest ratio occurring in infancy (males, 1.77 +/- 0.60%; females, 2.02 +/- 0.87%). 3) The SD scores of serum free IGF-I in the 21 GHD children ranged from -3.30 to 0.30, and the 5 complete GHD children had free IGF-I values more than -2 SD below those of age-matched normal subjects. 4) There was a significant correlation between the SD scores of free IGF-I and those of total IGF-I (r = 0.715; P < 0.0005) in the GHD children. 5) In the 16 partial GHD children receiving GH treatment, the serum free IGF-I levels were elevated to 209% of pretreatment levels after 1 month of GH treatment and remained high during GH therapy. The GH-induced increase in the serum free IGF-I levels was significantly higher than those of the total IGF-I and IGF binding protein-3 levels. 6) The percent increase in the serum free IGF-I level after 1 month of GH treatment showed a significant positive correlation with that of the GH-induced improvement in the percent increase in the height velocity during 1 yr of GH therapy (r = 0.526; P < 0.05). These results show that free IGF-I in the serum has an essential role in bone formation because the higher free IGF-I levels were observed when the growth rate accelerated. The measurement of serum free IGF-I may become a useful tool for both diagnosing GH deficiency and predicting growth responses to long term GH therapy.

Adolescent↗
PubMed1999

Effect of propolis extract on D-galactosamine-induced hepatic injury in rats.

The preventive effect of propolis extract on D-galactosamine-induced hepatic injury was examined in rats. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were significantly increased at 24 h after intraperitoneal injection of D-galactosamine (400 mg/kg) in the animals. Propolis extract was administered orally three times in doses of 3 or 30 mg/kg at 18 h and 1 h before and 8 h after D-galactosamine injection. The extract itself and the vehicle alone (dextran) caused no significant changes in serum AST or ALT activities. Treatment with the extract dose-dependently prevented the increases in serum AST and ALT activities induced by D-galactosamine, and significant inhibition was observed at a dose of 30 mg/kg. These results suggested that propolis extract may have an ameliorating effect on hepatic dysfunction.

Alanine Transaminase↗