HGF prevents tacrolimus (FK 506)-induced nephrotoxicity in SHR rats.
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Biomedical subjects
Publications and source records attributed to M Koga.
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A 37-year-old man was admitted to the hospital because of an abnormal shadow in the right lower field on a chest roentgenogram. The lesion was calcified and was therefore suspected to be benign. Thoracoscopic resention was performed. The pathological diagnosis was cryptococcosis of the lung. The lesion was completely resected, so no antifungal drug was given. The patient was doing well as of 12 months after the operation.
Changes in plasma endogenous ouabain-like substance (EOLS) and plasma noradrenaline, along with changes in blood pressure (BP), heart rate, and blood lactate concentration, were investigated in hypertensive individuals during strenuous exercise testing. Thirteen (4 men and 9 women) middle-aged (34-63 years, mean 50 +/- 2 years) patients with mild essential hypertension underwent graded multistage submaximal exercise testing on a cycle ergometer. The workload in each exercise test was increased depending on the individual's physical fitness until they reached 75-80% of the predicted age-adjusted maximal heart rate prescribed by the American College of Sports Medicine. Systolic (S) BP rose by 67 +/- 9 mm Hg (P < 0.001), mean (M) BP by 28 +/- 3 mm Hg (P < 0.001), diastolic (D) BP by 9 +/- 2 mm Hg (P < 0.005) and heart rate by 79 +/- 6 beats/min (P < 0.001) after submaximal graded exercise. The blood lactate concentration and plasma noradrenaline increased significantly (+3.40 +/- 0.34 mmol/l and +895 +/- 94 pg/ml respectively, P < 0.001). Although the change in EOLS was not significant, it showed a strong positive correlation with the change in plasma noradrenaline (R = 0.760, P < 0.001). These results suggest that EOLS may participate in modifying sympathetic vasoconstriction during submaximal graded exercise.
We evaluated the Björk-Shiley tilting-disc (BS) valve replacement up to the longest duration for about 12 years. The study was started in November 1982 and ended in September 1991. There were total number of 206 with 117 males and 89 females aged between 18 and 71 with a mean of 51.6. Eighty three patients had isolated aortic valve replacement (AVR), 92 had isolated mitral valve replacement (MVR), and 31 had AVR plus MVR. One hundred and fourteen spherical-disc valves were replaced in the aortic, 112 spherical and 11 monostrut in the mitral position. The mean duration of follow up was 6.5 years for a total of 1330.6 patient years (PY). Forty-one patients (3.8%/PY) died later, and 14 out of 41 died of valve-related complications. Actuarial survival rates for all, AVR, MVR and DVR at 10 years after operation were 71.2%, 73.5%, 73.9% and 55.4%, respectively. The linearized rates of thromboembolism (TE), thrombosed valve (TV), anticoagulant-related hemorrhage (ACH), prosthetic valve endocarditis (PVE), hemolysis (H), and reoperation (RO) were 1.2%/PY, 0.2%/PY, 0.7%/PY, 0.2%/PY, 0.1%/PY, and 0.2%/PY, respectively. The rates of freedom from TE, TV, ACH, PVE, H, and RO and 10 years after operation were 83.5%, 98.5%, 94.0%, 98.4%, 99.0% and 95.6%, respectively. The major causes of postoperative mortality and morbidity were TE, TV, and ACH. One hundred and fifty-six out of 161 patients showed an improvement in NYHA functional class post operatively. The surgical results of valve replacement with the BS valve was excellent and acceptable one. Intensive management with a special reference of anticoagulant therapy is necessary for a long-term management of the patients with mechanical valve replacement.
As limited studies have been done on surface morphology of Gnathostoma, adult specimens and eggs of four kinds of species in Japan were compared by scanning electron microscopy. Worms had a subglobular head-bulb which was armed with 7-10 rows of cephalic hooks. Mutidigitate cuticular spines were spaced unevenly on transverse cuticular striations on the anterior half of the body. The lengths of the spines were variable with tridentate spines longer than bidentate ones, These tridantate spines became one of the species specific characteristics. The posterior half of the bodies of G. doloresi and G. hispidum were covered densely with long unidentate spines which were gradually shorter towards the posterior ends. Ventral sides of male terminals had different shape of papillae which so called small and caudal ones in species. Eggs recovered from the uteri of female worms were covered with cuticular pits of different sizes, shapes and depths in species.
Investigations of the prevalence of larval gnathostomes in fresh water fishes were carried out at the southeastern Yangtze Valley, People's Republic of China, in the periods of October 1989 and November 1990. Fishes were collected from Shanghai, Chenchiang, Nanching, Chiuchiang and Nanchang districts in 1989. Additional sampling in Shanghai district was done at Kunshan, Tien-shanfu, Chingpu and Nanhui. Species of fishes collected were Channa argus (110), Siniperca chuatsi (24) and Silurus asotus (2). Muscle tissue of the fishes was dissected into small pieces, sliced and then examined under a dissecting microscope. The viscera were pooled by species in groups of 4 or 5 individuals, homogenized, and were then digested overnight in artificial gastric-juice at 37 degrees C. Four encysted larvae were recovered from the muscle tissue of four C. argus. Thirty-four larvae were obtained from digestion of viscera. A total of 38 larvae were recovered. Eighteen of 38 larvae were examined morphologically and they were able to be divided into three types by their body length; 5 early third-stage larvae (0.58-0.86 mm), 12 third-stage larvae (1.12-2.61 mm), and one advanced third-stage larva of 4.86 mm. Light and scanning electron microscopy revealed that the former two types had characteristics of Gnathostoma hispidum and the last one had those of G. spinigerum. In 1990, we investigated fish near Hongtze-hu and Tai-hu lakes. A total of 553 fishes belonging to 12 genera and 12 species were examined. Seventeen larvae were recovered from the viscera of G. argus and Monopterus albus. These larvae were identified as G. hispidum.
We report on 2 sibs with desquamative interstitial pneumonia. The female died at age 1 7/12 years despite use of prednisolone and methylprednisolone, while the male, now age 3 years. is alive with oxygen support. The occurrence of desquamative interstitial pneumonia in sibs born to normal parents suggests that in some cases the disease is an autosomal-recessive trait.
To examine the biological role of fibroblast growth factor receptor 1 (FGFR1) oligomerization for its signal transduction, we construct an expression vector encoding a FGFR1-beta-galactosidase fusion protein. This vector is designed to fuse the 3'-portion of FGFR1 to beta-galactosidase. Transfection of this vector into FGFR-negative rat L6 myoblast cells results in ligand-independent inhibition of differentiation into myocytes, suggesting that FGFR1 within this fusion protein is constitutively activated. This can be confirmed by demonstrating that this fusion protein exhibits the tyrosine kinase activity and phospholipase C gamma 1 is tyrosine-phosphorylated even in the absence of ligand stimuli. Since the transfected cells also exhibit the enzyme activity of beta-galactosidase which is known to be active only in a tetramer form, this constitutive activation can be elicited by tetramerization of FGFR1. Furthermore, deletion of a region corresponding to C terminal 10 amino acids important for tetramerization of beta-galactosidase from this expression vector abolishes the constitutively active nature of FGFR1 with simultaneous loss of beta-galactosidase activity. Transfection of non-deleted expression vector into NIH3T3 cells results in acquisition of focus-forming activity while a deleted form of expression vector fails to show this activity even in the presence of basic FGF. These results would suggest that tetramerization of FGFR1 can produce a constitutively active form responsible for transformation of NIH3T3 cells.
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Hepatitis B virus (HBV), with a G-to-a point mutation at nucleotide 83 in the precore region (mutant HBV83), accounts for most cases of hepatitis B e antigen (HBeAg)-defective HBV. However, it is still not clear how mutant HBV83 is associated with HBe seroconversion. Twenty-six HBeAg-positive patients with chronic hepatitis B who received oral prednisolone (30 mg/day) for 3 weeks were studied to clarify the prevalence of mutant HBV83 during the treatment using polymerase chain reaction with a restriction fragment length polymorphism assay. Twelve (46%) patients seroconverted to anti-HBe 1 year after treatment, whereas 14 (54%) did not. The proportion of mutant HBV83 to whole HBV remained unchanged in both groups during an acute exacerbation induced by withdrawal of corticosteroids. Among 12 anti-HBe-seroconverted patients, five (56%) of nine patients with only wild-type HBV at baseline developed detectable levels of mutant HBV83 while all three patients with a mixed viral population of wild-type HBV and mutant HBV83 at baseline developed a higher proportion of mutant HBV83 one year after treatment. In contrast, these changes were observed in only one (14%) of seven who failed to seroconvert. The results indicate that a flare-up of hepatitis precedes emergence or selection of mutant HBV83, followed by HBe seroconversion in patients with chronic hepatitis B.
We used deuterium magnetic resonance imaging (2H MRI) to visualize water movement in the rabbit eye. Dynamic 2H MRI was obtained every 3.5 min at 2 tesla by FLASH pulse sequence (TR, 300 ms; TE, 10 ms; alpha = 90 degrees) with a slice thickness of 10 mm using a surface coil (4 cm in diameter). After topical administration (0.2 ml D2O), only the aqueous chamber was imaged, and the signals decreased mono-exponentially. The flow rate was 0.113/min, in agreement with that already reported. After intravenous administration of deuterated saline (3 ml/kg), the aqueous chamber became visible first during imaging, then by the vitreous body. The signals around the lens were only faintly detected. Thus, deuterium MRI was determined to be useful for visualizing water movement in the eye.
In this study, we evaluated the effects of ALDH2, CYP1A1, and CYP2E1 genetic polymorphisms and smoking and drinking habits on the toluene metabolism. The study subjects were 92 male workers who handle toluene in a printing factory, an electrical parts factory, and a painting workplace in Japan. Their exposure levels to toluene were monitored using the diffusion-type sampler. Benzyl alcohol concentrations in their blood and hippuric acid (HA) and creatinine concentrations in their urine at the end of a workshift were determined. The genotype of ALDH2 was classified into the homozygous genotype of a normal ALDH2 gene (NN), the homozygous genotype of an inactive ALDH2 gene (DD), and the heterozygous genotype of normal and inactive ALDH2 genes (ND). The genetic polymorphism of CYP1A1 and CYP2E1 were also determined by restriction fragment length polymorphism (RFLP). A strong correlation between the personal exposure level and the urinary HA concentration was observed. Regression lines were calculated after being divided by the five factors, i.e., ALDH2, CYP1A1, CYP2E1, smoking, and drinking. The HA formation from toluene was significantly (p < 0.001) different among the genotypes of ALDH2. The slopes of the regression lines decreased from NN to ND to DD in this order. The benzyl alcohol concentration in the blood of the DD group was significantly higher than that found in the NN and ND groups. This result demonstrates that ALDH2 polymorphism affects the oxidation of benzyl alcohol to benzoic acid. The toluene metabolism was also affected by CYP1A1 polymorphism. The slope for the Ile/Ile (the predominant homozygous allele) group was significantly lower than that for the Ile/Val (the heterozygous allele) and Val/Val (the rare homozygous allele) group after correction for creatinine. A drinking habit significantly (p < 0.05) reduced urinary HA concentration in the NN group. A smoking habit also significantly (p < 0.05) reduced urinary uncorrected HA concentration in both the NN and ND groups. In a multiple regression analysis, ALDH2 and the drinking habit were significantly (p < 0.01) associated with HA excretion after toluene exposure with and without correction for creatinine, and the corrected HA concentration was also significantly (p < 0.01) increased in the Ile/Val and Val/Val group of CYP1A1. The smoking habit reduced the corrected HA concentration (p < 0.05); however, the polymorphism in the 5'-flanking region of CYP2E1 did not affect HA appearance in urine.
The vulva of the nematode Caenorhabditis elegans develops from the three vulval precursor cells (VPCs) that are induced by a signal from the gonadal anchor cell. This signal is thought to be mediated by a receptor tyrosine kinase (RTK) in the VPCs to a downstream signal transduction pathway. A mitogen-activated protein kinase kinase (MAPKK) has been found to be one of the major components of an RTK pathway in other organisms. We expressed a wild type and an activated cDNA of Dsor1, a Drosophila MAPKK, in each of the three vulvaless mutants lin-3, let-23 and lin-45. The expression of an activated from of Dsor1 in each of the mutants effectively induced a normal, functional vulva, that is, suppressed the vulvaless phenotype. The wild type Dsor1 also suppressed albeit less effectively. These results suggest that a MAPKK is involved in the vulval induction of C. elegans.
Androgen-induced growth factor (AIGF) is essential for the androgen-induced autocrine growth of a mouse mammary Shionogi carcinoma cell line (SC-3 cells). Because glucocorticoid and estrogen have been observed to weakly stimulate DNA synthesis in SC-3 cells, the expression of AIGF mRNA after stimulation with various concentrations of androgen, glucocorticoid, or estrogen was examined by Northern blot analysis. Testosterone, dexamethasone, and estradiol-17 beta (E2) induced AIGF mRNA expression, although the maximum AIGF mRNA expression levels induced by dexamethasone or E2 were lower than that by testosterone. Yet, diethylstilbestrol showed no induction, suggesting that the effect of E2 could be mediated through the androgen receptor. The induction levels of AIGF mRNA by each steroid hormone were correlated positively with hormone-induced DNA synthesis. In addition, the DNA synthesis induced by each steroid hormone was almost completely inhibited by AIGF antisense oligonucleotides, indicating that AIGF is an obligatory component in not only the androgen- but also the glucocorticoid-inducible autocrine loop in SC-3 cells.
Shionogi carcinoma 115 (SC 115) has been extensively used to analyze the mechanism of androgen-dependent cancer growth. This tumor exhibits marked androgen-dependent growth in vivo and one cell line whose growth is markedly stimulated by androgen in serum-free culture condition is isolated from SC 115 tumor. This androgen-dependent growth is mediated through an induction of heparin binding growth factor termed as androgen-induced growth factor (AIGF). In addition, fibroblast growth factor receptor 1 (FGFR 1) is identified as a receptor for AIGF. The expression of FGFR 1 mRNA is up-regulated by androgen in SC 115 cells, indicating that this androgen-inducible autocrine loop is potentiated at two sites by androgen. An androgen-independent cell line is also established from this androgen-dependent SC 115 tumor. The growth of these androgen-independent cells is stimulated by AIGF, indicating that AIGF acts not only as an autocrine growth factor to androgen-dependent cells but also as a paracrine growth factor to androgen-independent cells. In addition, transfection of AIGF expression vector into androgen-dependent cells results in a facilitation of conversion from androgen-dependent to -independent phenotype. Thus, AIGF might play a role from tumor progression. These results indicate that a blockade of AIGF activity is an important therapeutic target. Actually, some compounds such as heparin and suramin are found to inhibit this androgen-induced autocrine loop. These basic observations will be discussed in relation to their possible clinical application.
We report a case of drug eruption caused by the crude drug Boi. A 41-year-old female patient had been diagnosed with chronic rheumatoid arthritis in the department of internal medicine. After ingestion of a decoction of the crude drug Boi for the alleviation of arthralgia, a slight fever developed, which was followed by systemic edematous erythema with itching. HPLC showed that the main components of the crude drug Boi are sinomenine and magnoflorine. The results of patch tests were negative for all oral drugs that the patient had been taking. Oral ingestion tests showed that the patient showed positive reactions to the as-is Boi boiling-water decoction and 1/10-volume sinomenine. Based on this, the drug eruption was judged to be caused by sinomenine. It is considered the first time that the causative component of a drug eruption was confirmed by oral ingestion tests with components of a crude drug of Kampo medicine (Sino-Japanese traditional medicine).
The expression of GHRH receptor (GHRH-R) messenger ribonucleic acid (mRNA) was studied in 22 pituitary adenomas and 2 normal anterior pituitaries. Northern blot analysis revealed that GHRH-R mRNA were expressed in all 14 GH-producing adenomas, 1 of 3 ACTH-producing adenomas, the 1 PRL-producing adenoma, 2 of 4 nonfunctioning adenomas, and the 2 normal anterior pituitaries. Their expression levels varied among GH-producing adenomas and were relatively low in GH-nonproducing adenomas. In addition to the major transcript with a molecular mass of 2.0 kilobases (kb), the transcripts were identified at 2.8 and 4.5 kb in some GH-producing adenomas. To examine the structural variations in GHRH-R mRNA in pituitary adenomas, we amplified the complementary DNA fragment encompassing the region from the third cytoplasmic loop to the sixth transmembrane domain of GHRH-R. This region was selected because this region of the G protein-coupled receptor has been known to interact with G protein. Two amplified fragments with the molecular masses of 250 and 810 base pairs were identified by the reverse transcriptase-polymerase chain reaction method. The nucleotide sequence of a smaller fragment, which was the expected size, revealed that no mutations were found in this region in 10 GH-producing adenomas examined. However, a larger fragment contained the currently unidentified insertion. Compared with the genomic DNA sequence, this insertion was found to be generated through alternative splicing. In addition, this variant form contained the premature stop codon in-frame, indicating that it encodes the truncated GHRH-R. This insertion-specific probe could hybridize with 2.8- and 4.5-kb species of GHRH-R mRNA on Northern blot analysis, and these transcripts were expressed mainly in GH-producing adenomas. Finally, study of cell transfection and cAMP measurement revealed that this truncated GHRH-R was unable to transmit GHRH signals. These results suggest that some GH-producing adenomas preferentially express the truncated GHRH-R as a nonfunctioning receptor through alternative splicing.
The let-23 receptor tyrosine kinase gene is required for vulval induction and larval survival in the nematode Caenorhabditis elegans. We carried out genetic mosaic analyses of the let-23 gene function by using the cloned let-23 and ncl-1 genes. The wild-type let-23 gene was required in a vulval precursor cell to adopt the 1 degree vulval fate in animals carrying a let-23 vulvaless or lethal chromosomal mutation. In almost all the animals, vulval precursor cells adjacent to a 1 degree fate cell were induced to the 2 degrees vulval fate regardless of the let-23 genotypes. These findings indicate that the vulval induction signal from an anchor cell induces a vulval precursor cell to adopt the 1 degree fate through LET-23, and then a 1 degree fate cell induces adjacent cells to adopt the 2 degrees fate, for which LET-23 is not required. Foci of lethality of the let-23 (mn23) mutation were found in ABal and ABplp lineages.