[Wildervanck syndrome, cervico-oculo-acoustic syndrome].
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Abnormalities, Multiple↗
Biomedical subjects
M Hayashi
Publications and source records attributed to M Hayashi.
Mild renal dysfunction is associated with insulin resistance in chronic glomerulonephritis.
BACKGROUND: Insulin resistance is associated with advanced and moderate chronic renal failure (CRF). However, insulin resistance in chronic glomerulonephritis (CGN) before onset of frank renal dysfunction is not fully evaluated. We attempted to investigate the association of insulin resistance with mild renal dysfunction and with abnormal calcium homeostasis. PATIENTS AND METHODS: Eighteen young, lean non-diabetic male patients with biopsy-proven CGN (age 30 +/- 7 years, body mass index 23.0 +/- 2.5 kg/m2) were enrolled. Insulin sensitivity was estimated by the glucose infusion rate (M value) during euglycemic hyperinsulinemic clamping for 60 to 120 min. Calcium-related parameters including intracellular calcium concentrations ([Ca2+]i) in platelets were also measured. Renal function was normal or slightly impaired (serum creatinine, 1.0 +/- 0.2 mg/dl; glomerular filtration rate (GFR), 68 to 131 ml/min/1.48 m2). We divided subjects into an insulin-sensitive (IS) group (M value > 7.3 mg/kg/min, the overall mean) and an insulin-resistant (IR) group (M value < 7.3 mg/kg/min). RESULTS: During a 75 g oral glucose tolerance test, the plasma glucose concentration at 120 min after glucose loading and the immunoreactive insulin concentration at 60 min were significantly higher in the IR group. GFR was notably lower in the IR group than in the IS group (p = 0.0003), and was significantly correlated with insulin sensitivity (p < 0.02, r = 0.58). The basal [Ca2+]i was significantly higher in the IR than in the IS group (39 +/- 9 vs. 30 +/- 9 nM, p < 0.05). CONCLUSION: Mild renal dysfunction and elevated basal [Ca2+]i are associated with insulin resistance in CGN.
Adult↗
[Present state and development of the network communication system].
Information technology is a dynamic technology that has sparked the development of many new products and new services and the medical field is not an exception. We would like to introduce our new service which started in December 1999, and is called "SNCS". Connecting Laboratory and Sysmex by a dedicated network, SNCS provides services such as 'On-line QC' and 'On-line Support' to support Laboratory technicians.
Clinical Laboratory Information Systems↗
Regulation of dosage of conjugated equine estrogen is useful for add-back therapy.
In the hormonal treatment of uterine myomas, which are estrogen dependent, GnRH agonist (GnRHa) therapy has become widespread. However, the severe hypo-estrogenic state induced by the GnRHa gives rise to annoying side effects. Although the risk of these side effects may be reportedly modified when GnRHa is combined with estrogen (add-back therapy), it is difficult to target serum estradiol (E2) concentration to stay within the therapeutic window (20 approximately 50 pg/mL) by administering 0.625 mg conjugated equine estrogen (CEE)/day. Also, there is great individual variation in the circulating E2 concentration by administering the same dosage of CEE. Therefore, the use of smaller quantities of CEE in different dosages may approximate more closely to the clinical situation. This article focuses on the methods of administration of CEE combined with GnRHa for women with symptomatic uterine myomas.
Animals↗
Restorative effects of a short afternoon nap (<30 min) in the elderly on subjective mood, performance and eeg activity.
This study investigated the effects of a short afternoon nap (<30 min) in the elderly on subjective mood, performance and electroencephalograms (EEG). Ten healthy elderly persons who habitually napped in the afternoon three or more times a week participated in the present study. They participated in two experimental conditions with an interval of more than five days. In the nap condition, the participants went to bed at 13:00 hours and slept for 30 min, whereas they just had a rest while watching television in the no-nap condition. In both conditions, subjective sleepiness, fatigue, performance and EEG activities with eyes opened and closed were repeatedly measured before and after the nap or rest. The nap significantly reduced subjective sleepiness and fatigue in the afternoon. It also improved performance levels and EEG theta, alpha 1 or alpha 2 band activities with eyes opened and closed. These findings suggest that a short afternoon nap is useful for the elderly in maintaining their daytime psychological, behavioral and physiological arousal at an adequate level.
Affect↗
MEKK3 directly regulates MEK5 activity as part of the big mitogen-activated protein kinase 1 (BMK1) signaling pathway.
Big mitogen-activated protein (MAP) kinase (BMK1), also known as ERK5, is a member of the MAP kinase family whose cellular activity is elevated in response to growth factors, oxidative stress, and hyperosmolar conditions. Previous studies have identified MEK5 as a cellular kinase directly regulating BMK1 activity; however, signaling molecules that directly regulate MEK5 activity have not yet been defined. Through utilization of a yeast two-hybrid screen, we have identified MEKK3 as a molecule that physically interacts with MEK5. This interaction appears to take place in mammalian cells as evidenced by the fact that cellular MEK5 and MEKK3 co-immunoprecipitate. In addition, we show that a dominant active form of MEKK3 stimulates BMK1 activity through MEK5. Moreover, we demonstrate that MEKK3 activity is required for growth factor mediated cellular activation of endogenous BMK1. Taken together, these results identify MEKK3 as a kinase that regulates the activity of MEK5 and BMK1 during growth factor-induced cellular stimulation.
Animals↗
[Acute pulmonary thromboembolism].
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Acute Disease↗
The behavior of calpain-generated N- and C-terminal fragments of talin in integrin-mediated signaling pathways.
Our previous results showed that the binding of an adhesive ligand to integrin alphaIIbbeta(3) on the surface of platelets triggers the activation of calpain and the limited proteolysis of talin by calpain. To explore the physiological significance of the calpain-mediated cleavage of talin, we analyzed the behavior of the calpain-generated fragments of talin (N-terminal 47 kDa and C-terminal 190 kDa) during platelet activation by biochemical and immunoelectron microscopic studies. Intact talin and micro-calpain translocate from the Triton X-100-soluble fraction to the insoluble fraction upon platelet stimulation by thrombin, and the limited proteolysis of talin occurs in the Triton X-100-insoluble fraction, the cytoskeletal fraction. The fully autolyzed 76-kDa micro-calpain (active form) is found predominantly in the Triton X-100-insoluble fraction in stimulated platelets. While the N-terminal 47-kDa fragment remains in the Triton X-100-insoluble fraction, the C-terminal 190-kDa fragment is released into the Triton X-100-soluble fraction in a time-dependent manner. Immunoelectron microscopic observations revealed that the 47-kDa fragment locates on the submembrane zone just beneath the plasma membrane, including the open canalicular systems, while most of the 190-kDa fragment exists diffusely in the cytoplasm in thrombin-stimulated platelets. These findings suggest that calpain may contribute to the reorganization of the cytoskeleton in an integrin-mediated signaling pathway through the redistribution of the functional domain of talin.
Amino Acid Sequence↗
Physiological mechanism for enhancement of paracellular drug transport.
We examined the action mechanisms of enhancers that improve paracellular drug transport. For sodium caprate (C10), the increase in the intracellular calcium level was considered to induce the contraction of calmodulin-dependent actin filaments, followed by dilation of the paracellular pathway. Although decanoylcarnitine (DC) also increased the intracellular calcium level, the action was independent of calmodulin and thus, the action mechanism of acylcarnitines was considered to differ from that of C10. Other acylcarnitines, lauroylcarnitine (LC) and palmitoylcarnitine (PC) and organic acids, tartaric acid (TA) and citric acid (CA) decreased the intracellular ATP level and the intracellular pH. From these results, it was considered that one of the action mechanism of acylcarnitines and organic acids is that the intracellular acidosis increases the calcium level through the decrease in ATP levels, followed by opening the tight junction. Membrane dysfunction which was expected from the above mechanism was assessed by the transport function of electrolytes. Membrane conductance, which was increased by C10, LC and PC, returned to the control value during a 3- to 6-h recovery period. On the other hand, Cl(-) ion secretion, which was obtained from short-circuit current (I(sc)), was decreased by these enhancers, but was normalized by C10 but not by LC and PC. Accordingly, C10 can be considered a safer enhancer than acylcarnitines.
Acylation↗
p53 null mutations undetected by immunohistochemical staining predict a poor outcome with early-stage non-small cell lung carcinomas.
The importance of p53 mutations in the pathogenesis of human lung carcinoma is well established, but it is still controversial whether the presence of p53 mutations or overexpression of p53 protein adversely affects an individual patient's chances of survival. The controversy may be partially due to the methodological differences in examination for p53 alterations: gene analysis or immunohistochemical staining. Furthermore, recent studies have suggested that different types of mutations of the p53 tumor suppressor gene confer different biological properties. To clarify the relationship between immunohistochemical staining and prognosis, we investigated mutations using single-strand conformation polymorphism followed by sequencing for exons 4-8 and 10 in 144 surgically treated non-small cell lung carcinoma patients with intensive clinical follow-up. Of 144 cases, 107 adenocarcinomas were examined for immunohistochemical staining with RSP53 antibody. p53 gene mutations were observed in 65 tumors (45%), including 44 missense and 21 null mutations, the latter comprising 7 nonsense mutations, 8 deletions, 2 insertions, and 4 splicing junction mutations. Presence of p53 mutations was an independent prognostic factor with a statistical trend (P = 0.14) in stage I patients but not in all cases. When examined by mutational pattern, null mutation was a significant indicator of poor outcome by multivariate analysis (P = 0.03) in stage I patients, whereas cases with missense mutations and without mutations did not differ (P = 0.76). Forty (37%) tumors demonstrated overexpression of the p53 protein but without any survival difference. Most tumors (76%) with missense mutations were immunopositive, but those with null mutations with one exception (93%) were not, and the concordance between the mutations and immunohistochemical staining was rather low at 65%. These data suggest that the type of p53 mutation is important for prediction of outcome in early-stage non-small cell lung carcinoma patients, whereas immunohistochemical staining for abnormal p53 gene products is nonpredictive. Furthermore, null mutations causing loss of function of the gene product may play more important roles than missense mutations in tumor progression.
Adenocarcinoma↗
A micronucleus assay in sea urchin embryos.
We have developed a micronucleus assay for use in sea urchin embryos. The embryos at the early blastula stage (about 256 cells) were exposed to genotoxic chemicals overnight until control embryos have reached the gastrula stage. Then all embryos were suspended in 1 M urea, dissociated by pipetting, and fixed with methanol:acetic acid (9:1). The preparations were air-dried and stained with acridine orange. The test chemicals (mitomycin C [MMC], vinblastine and 1-beta-D-arabinofuranosylcytosine [Ara C]) induced clear micronuclei dose-dependently. The maximum frequency induced with MMC was 2-3% in Clypeaster japonicus and 1-2% in Hemicentrotus pulcherrimus.
Acridine Orange↗
Synchrotron radiation study of yttria-stabilized zirconia, Zr0.758Y0.242O1.879.
The fluorite-related cubic structure of yttria-stabilized zirconia, Zr(0.75)(8)Y(0.24)(2)O(1.87)(9), has been studied by single-crystal X-ray diffraction using synchrotron radiation and by EXAFS. Two diffraction data sets obtained at X-ray energies of 512 and 10 eV below the Y K edge revealed that in the average structure Zr atoms are displaced from the origin of the space group Fm3;m along <111> by 0.19 Å, while Y atoms reside at the origin. Approximately 48% of the O atoms occupy the ideal position in the fluorite-type structure, while 43% of O atoms are displaced from the ideal position along <001> by 0.31 Å. The remaining 9% of O atoms are presumably sited at interstitial positions. Local structures around Zr and Y are investigated by combining the results of single-crystal X-ray diffraction and EXAFS studies.
Journal Article↗
Deficiency in fast repair process of potentially lethal damage induced by X-irradiation in fibroblasts derived from LEC strain rats.
The time course for the repair of PLD in LEC and WKAH rat cells irradiated at 5 Gy was examined. In the case of WKAH rat cells, the surviving fraction increased with increasing incubation times after X-irradiation. When hypertonic treatment was performed at each incubation time with 0.5 M NaCl for 20 min, increase in the surviving fractions was not shown. In contrast, no significant recovery of the surviving fraction in LEC rat cells was observed after incubation of irradiated cells with or without 0.5 M NaCl for 20 min. On dose-survival curves, hypertonic treatment with 0.5 M NaCl enhanced radiosensitivity of WKAH rat cells, but not LEC rat cells. Although the surviving fraction of the cells from backcross mice with normal radiosensitivity reduced by treatment with 0.5 M NaCl, the survival fraction was not affected in the cells from backcross mice with higher radiosensitivity by treatment with 0.5 M NaCl. When the cells were X-irradiated and incubated with or without 0.225 M NaCl, the radiosensitivities of LEC and WKAH rat cells treated with 0.225 M NaCl for 4 h were approximately two-fold higher than those of untreated cells. Treatment with caffeine also reduced the surviving fractions of both X-irradiated LEC and WKAH rat cells, compared with those of untreated cells. These results indicated that the slow repair of PLD occurred in LEC rat cells but not the fast repair of PLD.
Amino Acid Sequence↗
Role of mast cell chymase in angiotensin-induced vascular contraction of hamster cheek pouch microvessels.
We investigated the contribution of chymase-dependent conversion of angiotensin I to angiotensin II in hamster cheek pouch. To investigate the converting activities in intact tissues, angiotensin I or II was applied to microvessels of the intact cheek pouch, and the vascular contractile response was recorded. Angiotensin I or angiotensin II (20 nM) induced a rapid contraction of arterioles, irrespective of their diameter. In the presence of I mM captopril, there was no contraction in response to angiotensin I in arterioles < 25 microm in diameter, whereas contraction was still observed in larger arterioles. Chymostatin (100 microM) treatment also reduced the response to angiotensin I in arterioles > 40 microm in diameter. Treatment with 1 mM captopril and 100 microM chymostatin resulted in the loss of response to angiotensin I, but not to angiotensin II, in all arterioles. Treatment of microvessels with 100 microg/ml compound 48/80 enhanced angiotensin I-induced vascular contraction response, suggesting the significance of mast cells as a source of cheek pouch chymase.
Angiotensin I↗
Procarbazine genotoxicity in the MutaMouse; strong clastogenicity and organ-specific induction of lacZ mutations.
Procarbazine, a drug used for cancer chemotherapy, is carcinogenic in rodent bioassays. We analyzed the mutagenicity of procarbazine in various organs and the clastogenicity of the drug in hematopoietic cells of the lacZ transgenic MutaMouse. This was part of the second collaborative study of the Mammalian Mutagenesis Study Group of the Japanese Environmental Mutagen Society on the transgenic mouse mutation assay. At 50 mg kg(-1), procarbazine induced micronuclei in hematopoietic cells, but it did not increase the lacZ mutant frequency (MF) in bone marrow. It was also negative in liver, testis, spleen, kidney, and lung. Five daily administrations of 150 mg kg(-1) yielded highly positive responses in the drug's target organs for carcinogenesis (lung, bone marrow, and spleen). Lower positive responses were detected in kidney, which is a minor target organ. Liver showed only a slight increase in lacZ MF and brain showed no increase. The testis MF more than doubled which suggest that procarbazine is mutagenic to germ cells. Thus, we demonstrated that procarbazine has a strong clastogenic effect in hematopoietic cells and is mutagenic in a variety organs after high dose treatment. The induced MF was especially high in procarbazine's target organs for carcinogenesis, which supports the relevance of the transgenic mouse mutation assay for the assessment of potential genotoxins in vivo.
Animals↗
Study of a rat skin in vivo micronucleus test: data generated by mitomycin C and methyl methanesulfonate.
We have developed an in vivo micronucleus (MN) test that uses rat skin as the target organ. Sample preparation involves cold-treating the epidermis with trypsin, peeling it off with a fine forceps, treating it in hypotonic solution, and staining it with acridine orange (A.O.). We evaluated the assay using mitomycin C (MMC) and methyl methanesulfonate (MMS) as model clastogens, applying them as single and repeat treatments. Both chemicals induced a significant, dose-dependent increase in MN frequency in basal cells. One treatment per day for 3 days was optimal for MN induction.
Acridine Orange↗
Auxiliary partial orthotopic living donor liver transplantation as an aid for small-for-size grafts in larger recipients.
BACKGROUND: In countries where living donors are the only source of liver grafts, restrictions on graft size are a serious obstacle for the expansion of indications for adult recipients. To overcome this problem, auxiliary partial orthotopic liver transplants (APOLT*) was performed on the basis of the concept that the residual native liver would support the graft function until the graft had grown enough to function by itself. METHODS: APOLT as an aid for small-for-size (SFS) grafts was reviewed retrospectively to evaluate its feasibility. Between April 1995 and March 1998, 20 recipients underwent APOLT, which was indicated because of a SFS graft in 15 of them. The indication was based on the estimated graft/recipient's body weight ratio (GRWR). If the ratio was <0.8%, APOLT was performed. The other 5 patients had a graft with a GRWR >0.8% and underwent APOLT on the basis of the residual native liver supporting the graft function temporarily, 4 for supplementation of the defective enzyme in metabolic liver diseases and one for leaving the potential of the regeneration of the native liver in fulminant hepatic failure. The recipients who underwent APOLT because of a SFS graft were categorized as the SFS group, and the others were the second group. RESULTS: In the SFS group, the age of the recipients ranged from 13 to 48 (median 23). The original indications of this group were fulminant hepatic failure in 2 recipients, acute deterioration of chronic liver diseases in 3, Wilson's disease in 2, biliary atresia in 4, primary biliary cirrhosis in 3, and primary sclerosing cholangitis (PSC) in one. The actual GRWR ranged from 0.45 to 0.72 (median 0.55). The graft was implanted after resection of the left lateral segment of the native liver. Except in the first two patients, the portal vein to the residual native liver was completely transected so that all of the portal blood drained into the graft liver. This procedure was successful in 9 patients. The cause of death in the other 6 was mainly infection. The mortality rate among the recipients with signs of advanced liver failure, such as massive ascites or hepatic coma, was higher, even though APOLT was used to support the SFS graft. In the second group, in the other five recipients who underwent APOLT for other indications, one recipient with fulminant hepatic failure died of sepsis caused by the dehiscence of bilio-enteric anastomosis. CONCLUSIONS: APOLT as an aid for a SFS graft is technically viable. This procedure can thus expand the indication of living donor liver transplants for adult recipients when the native liver retains some functional capability to support the grafted liver during the immediate postoperative period.
Adolescent↗
D-aspartate is present in human retinoblastoma Y79 cells.
In mammals, D-aspartate is present in various neuroendocrine cells, being especially abundant in pinealocytes. Although D-aspartate is suggested to be involved in some neuroendocrine function, little is known about its origins as well as its physiological roles. In the present study, we found that an appreciable amount of D-aspartate (50.8 pmol/1 x 10(6) cells) is present in clonal human retinoblastoma Y79 cells. The amount of D-aspartate corresponds to 28% of that in rat pinealocytes. The D-aspartate concentration did not change with the culture duration or passage, suggesting de novo biosynthesis of it. Thus, Y79 cells may constitute a suitable experimental system for studies on the biogenesis and signal transduction of D-aspartate in mammalian cells.
Animals↗