Biomedical subjects
Publications and source records attributed to M Kaneko.
A new bis-quinolizidine alkaloid, xestosin A (1), possessing cis- and trans-quinolizidine nuclei, has been isolated from the Papua New Guinean sponge Xestospongia exigua. The structure was determined by spectrometric and single-crystal X-ray analyses.
This study was undertaken to clarify the role of high-energy phosphate metabolism in hydrogen peroxide-induced cardiac dysfunction using phosphorus and fluorine nuclear magnetic resonance spectroscopy. The exposure of a Langendorff-perfused heart to hydrogen peroxide (200-400 micromol/L, 8 min) provoked biphasic contractile dysfunction characterized by a transient depression of left ventricular developed pressure during the administration of hydrogen peroxide and a delayed elevation of left ventricular end-diastolic pressure after the washout of hydrogen peroxide. The initial phase of cardiac dysfunction correlated well with the accumulation of sugar phosphates (r = 0.89, p < 0.01). Furthermore, we demonstrated that glibenclamide, a potent inhibitor of the ATP-sensitive K+ channel, attenuated the initial depression of developed pressure. On the other hand, the delayed elevation of end-diastolic pressure correlated well with the total ATP depletion (r = 0.96, p < 0.01). However, ATP loss was supposed to be a mere result from the increased ATP consumption corresponding to a rise in intracellular free Ca2+ (from the control value of 315+/-23 nmol/L to 708+/-104 after the administration of hydrogen peroxide, p < 0.01), which also paralleled the elevation of end-diastolic pressure. Thus glycolytic inhibition and intracellular Ca2+ overload are independently responsible for the biphasic contractile dysfunction induced by hydrogen peroxide.
AIMS/BACKGROUND: The present investigation compared the histological features of the liver of chronic hepatitis C patients who are or are not coinfected with hepatitis G virus (HGV) to determine the histological and clinical characteristics of HGV infection. SUBJECTS AND METHODS: This study included 194 patients with chronic hepatitis C who visited our institution between 1993 and 1995. Detection of serum HGV RNA was performed by nested reverse transcription-polymerase chain reaction. Scores were assigned to indicate the severity of each of the following features on the liver biopsy of a patient: inflammatory cell infiltration in the periportal, parenchymal, and portal area; fibrous stage; lymphoid aggregates in the portal area; portal sclerotic change; perivenular fibrosis; pericellular fibrosis; bile duct damage; bridging necrosis; and irregular regeneration of hepatocytes (IR). RESULTS: HGV RNA was detected in the sera of 18 (9.3%) of the 194 patients. The histological features of the HGV RNA-positive patients show significantly more severe bile duct damage, perivenular fibrosis, pericellular fibrosis and IR than the liver of the HGV RNA-negative patients. The biochemical results in the two groups did not significantly differ. CONCLUSION: Our data suggest that chronic HGV coinfection worsens the histological features of liver disease.
We report here a patient who suffered from PCR- confirmed human herpesvirus type 6 (HHV-6) meningoencephalitis after allogeneic purified CD34+ cell transplantation from his HLA-mismatched sibling donor, even though he had been on intense prophylaxis with i.v. ganciclovir (GCV), acyclovir (ACV) and gamma-globulin containing a specific antibody against HHV-6. Serological evaluation disclosed that both the donor and recipient had IgG antibody against HHV-6 before transplantation. His blood WBC count started to transiently increase on day 10, and all blood components had decreased by day 20. He then developed a severe headache and high blood pressure, and sporadic abnormal neurological findings including nystagmus and delirium. An analysis of cerebrospinal fluid (CSF) revealed 8 cells/microl, a glucose level of 130 mg/dl and a protein level of 201 mg/dl (normal, 50 mg/dl) on day 26. At the time, HHV-6 was detected only in CSF by a PCR-based method and he was diagnosed as having meningoencephalitis due to the local reactivation of HHV-6. Although he failed to respond to high-dose therapy with ACV (60 mg/kg/day) and gamma-globulin, the DNA of this virus disappeared from the CNS upon treatment with GCV (30 mg/kg/day) combined with the intraventricular infusion of alpha-interferon. His clinical course was further complicated with meningoencephalitis due to staphylococcus epidermidis, and he died of tentorial herniation on day 79 without the recovery of blood components. This experience may indicate that intense prophylaxis to prevent reactivation of HHV-6 in the CNS is essential for the management of such profoundly immunosuppressed patients.
A case of carcinosarcoma of the urinary bladder in a 2-year-old girl is reported. The tumor, measuring 34 x 20 x 18 mm, was located in the peri-trigone area of the urinary bladder with polypoid features. Histologic examination revealed transitional cell carcinoma at the tumor surface with downward invasion. Concurrently, a sarcomatous area was found beneath the carcinoma, with these two different malignant components sharing on apparent transition without distinct boundaries. Sarcomatous components included immature round cells focally showing rhabdoid features. No rhabdomyomatous component was observed. Immunohistochemistry disclosed vimentin and cytokeratin-double positive cells at the transposition between carcinoma and sarcomatous components. In addition, ultrastructural analysis revealed that the epithelial cells had a distinct junctional complex, and the sarcomatous cells occasionally had a meshwork of cytoplasmic intermediate filaments, indicating bidirectional cytodifferentiation to epithelial and mesenchymal elements. The extremely young age at which this case of carcinosarcoma occurred suggests that the tumor may be of mesodermal stem cell origin.
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BACKGROUND: Eosinophils are selectively recruited into the tissues during chronic allergic inflammation. IgE is considered an initiator of the allergic reaction; however, the roles of IgE in allergic inflammation are not fully understood. OBJECTIVE: We tested the hypothesis that antigen interaction with specific IgE antibody provokes eosinophilic inflammation. METHODS: BALB/c mice were actively sensitized with ragweed extract and passively sensitized with anti-dinitrophenyl (anti-DNP) mouse IgE and challenged intraperitoneally by injecting either ragweed extract or DNP-ovalbumin (OVA). Immediate anaphylactic responses were examined by monitoring vascular permeability and by measuring histamine content in peritoneal lavage fluids. Late-phase allergic responses were examined by total cell counts and cell differentials. RESULTS: Mice sensitized and challenged with ragweed showed immediate anaphylactic responses followed by temporal increases in neutrophils at 3 to 12 hours and sustained increases in eosinophils in their peritoneal cavities after 24 hours. Double-sensitized mice (ie, sensitized actively for ragweed and passively for DNP-OVA) challenged with ragweed showed immediate anaphylactic responses and peritoneal eosinophilia at 48 hours. Double-sensitized mice challenged with DNP-OVA showed comparable immediate anaphylactic responses but no peritoneal eosinophilia. Furthermore, at 8 hours, ragweed-challenged animals recruited both eosinophils and neutrophils, but DNP-OVA-challenged animals recruited only neutrophils. Finally, after active sensitization and challenge with ragweed, mast cell-deficient mice (WBB6F1-W/W(v)) lacked the immediate response but showed comparable eosinophil accumulation as their litter mate controls (WBB6F1-+/+). CONCLUSION: Interaction of antigen with IgE antibody is insufficient to provoke eosinophilic inflammation in mice.
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Transbronchial brachytherapy for small peripheral lung cancer was developed with the use of the CT-guided bronchoscopy technique. Under CT guidance, an applicator carrying a dummy source was introduced into a lesion and stabilized. A radioactive source was then delivered through the applicator using a high dose rate remote afterloading system. For multiple radiation fractions, a marker was placed immediately under the pleura in a peripheral bronchus penetrating the lesion using the CT-guided barium marking technique. During brachytherapy, an applicator with a dummy source was inserted under fluoroscopic guidance up to the marker. A radioactive source was subsequently delivered. CT-assisted transbronchial brachytherapy allows radiation to be delivered from inside a lesion. This minimizes radiation damage to noncancerous tissue and offers distinct advantages over conventional radiation techniques.
OBJECTIVES: Calcified tendinitis of the shoulder joint is a common painful condition. Resorption of the calcium deposits is one of the key events in the pathogenesis of this disease. The aim of this study was to examine whether the multinucleated giant cells that appear in this condition have osteoclast phenotypes. METHODS: Immunohistochemical and RNA in situ hybridization analysis of cathepsin K, a marker for osteoclasts, was performed in human surgical samples. RESULTS: The multinucleated cells located near the calcium deposits were positive for cathepsin K protein and mRNA. Reverse transcription-polymerase chain reaction using human cathepsin K-specific oligonucleotide primers confirmed that synthesis of cathepsin K mRNA occurs in the tissues of calcified rotator cuffs. CONCLUSION: The multinucleated giant cells which appear in the resorption area of calcium deposits in calcified tendinitis have the osteoclast phenotype.
OBJECTIVE: Numerous cytokines are expressed in lesions of synovial hyperplasia of patients with rheumatoid arthritis (RA), and their pathophysiological contributions have been the subject of speculation. These genes are regulated by the transcription factor NFkappaB which in turn is activated by tumour necrosis factor-alpha (TNF-alpha) and cytokines. In this study we examined the inhibition of the production of pro-inflammatory cytokines, adhesion molecule and matrix metalloproteinase (MMP) from synovial tissue of patients with RA by the introduction of synthetic double-stranded DNA with high affinity for the NFkappaB binding site. METHOD: NFkappaB decoy oligonucleotides (ODN) were introduced with the aid of the haemagglutinating virus of Japan (HVJ)-liposome method into synovial tissue or synovial cells derived from patients with RA. The levels of interleukin-1beta (IL-1beta), IL-6, TNF-alpha, intercellular adhesion molecule-1 (ICAM-1) and MMP-1 were determined by means of enzyme-linked immunosorbent assay (ELISA) and Northern blotting analysis. A cell counting kit was used to study the effect of NFkappaB decoy ODN on synovial cell proliferation. RESULTS: The production of these mediators was significantly inhibited by the introduction of NFkappaB decoy ODN compared with the effect of scrambled decoy ODN. Transfection of NFkappaB decoy ODN resulted in a significant inhibition of synovial cell proliferation as compared with that of scrambled decoy ODN. CONCLUSION: The results demonstrated in this study suggest the potential usefulness of NFkappaB decoy ODN for gene therapy of inflammatory synovitis of RA.
The purpose of this study was to investigate the effects of an endothelin-receptor antagonist TAK-044 on functional defects and metabolic derangement in myocardial ischemia/reperfusion injury. We sequentially measured high-energy phosphate metabolites and intracellular pH by phosphorus magnetic resonance spectroscopy during 35-min global ischemia followed by 60-min reperfusion in Langendorff-perfused rat hearts. TAK-044 (initial loading by 3 mg/kg followed by perfusion with 100 nM solution) was administered in two different ways: before ischemia or immediately after reperfusion. In addition, we investigated the effects of TAK-044 on functional defects and metabolic alterations induced by hydrogen peroxide (200 microM, 30 min). The recoveries of left ventricular developed pressure after reperfusion in TAK-044 groups (51 +/-12% in TAK-I, 61 +/- 12% in TAK-R) were better than in control (10 +/- 5% in control; p < 0.01). Increases in left ventricular end-diastolic pressure (LVEDP) in TAK-044 groups (22 +/- 5 mm Hg in TAK-I, 24 +/- 5 mm Hg in TAK-R) were less than in control (38 +/- 3 mm Hg; p < 0.01). Adenosine triphosphate (ATP) (33 +/- 5% in TAK-I, 28 +/- 4% in TAK-R) in TAK-044 groups were higher than in control (13 +/- 3%; p < 0.01). The creatine phosphokinase (CPK) release during reperfusion in TAK-044 groups (3.3 +/- 1.5 IU/g wet wt/60 min in TAK-I, 3.5 +/- 2.5 IU/g wet wt/60 min in TAK-R) were lower than in control (13.8 +/- 3.9 IU/g wet wt/60 min; p < 0.05). In contrast, TAK-044 did not attenuate the myocardial injury induced by hydrogen peroxide. TAK-044, even if administered simultaneous with coronary reperfusion, attenuated myocardial ischemia/ reperfusion injury. The energy-preservative effect of TAK-044 could be associated with the good functional recovery in ischemia/reperfused rat hearts.
OBJECTIVE: To evaluate the influence of serum lipids on auditory function. STUDY DESIGN: The study group comprised 607 men and 317 women who underwent medical examination at our hospital. Eligibility criteria included 1) age of 40 to 59 years; 2) normal ear drums; 3) no history of noise exposure or of diseases associated with hearing loss; 4) normal results of a glucose tolerance test; and 5) normal hearing or sensorineural hearing loss with a flat-form or high-tone gradual-form audiogram. We investigated the relation between the hearing level of the better-hearing ear and serum concentrations of total cholesterol, triglyceride, and high-density lipoprotein cholesterol. METHODS: For each variable, the subjects were divided into two groups--a high-level group (serum lipid concentration > or = 1 SD higher than the mean) and a low-level group (serum lipid concentration < or = 1 SD lower than the mean). Differences in hearing level between the two groups were compared according to sex with the t test. RESULTS: For total cholesterol and total triglyceride, there was no significant difference in hearing level between the high-level group and the low-level group in either sex. As for high-density lipoprotein cholesterol, hearing levels at 2,000 Hz (P < .05) and 4,000 Hz (P < .01) in the high-level group were significantly better than those in the low-level group in men. CONCLUSION: A low high-density lipoprotein cholesterol concentration is associated with hearing loss. Arteriopathy may play a role in auditory dysfunction.
OBJECTIVE AND IMPORTANCE: Tumoral calcinosis is a rare disorder of unknown origin. Tumoral calcinosis involving the spine is extremely rare. This is the first case of tumoral calcinosis localized in the dura mater of the lumbar spine. CLINICAL PRESENTATION: This 55-year-old male patient presented with tumoral calcinosis of the lumbar meninges. T1-weighted, sagittal magnetic resonance imaging scans of the lumbar spine revealed a round mass of slightly increased intensity with high-intensity margins, located posterior to the cauda equina at the L4-L5 level. The cauda equina was severely compressed anteriorly. T2-weighted scans revealed that the mass was composed of a high-intensity area with low-intensity margins. T1-weighted magnetic resonance imaging scans obtained after intravenous gadolinium administration revealed some enhancement at the margins. INTERVENTION: The mass lesion was totally resected. Three years after surgery, no recurrence was observed in follow-up magnetic resonance imaging scans. CONCLUSION: Although tumoral calcinosis is a rare cause of mass lesions of the lumbar spine, it should be considered in differential diagnoses. If the lesion can be totally resected, the prognosis should be good, similar to that for general tumoral calcinosis.
OBJECTIVE: Our purpose was to establish a new scoring method to survey monochorionic diamniotic (MD) twins during antepartum periods. STUDY DESIGN: A retrospective study was performed regarding MD twins delivered between January 1992 and July 1996. Maternal and neonatal records were assessed for the following 5 perinatal variables; birth-weight discordance, amniotic-fluid discordance, hydrops fetalis, umbilical-cord insertion, and fetal-heart-rate monitoring. Each variable was coded as normal or abnormal and then assigned an arbitrary weight of 0 if normal and 1 if abnormal, yielding a range of scores from 0 (all normal) to 5 (all abnormal). The relationships between individual variables and their combinations and the outcome of pregnancy was determined. A poor pregnancy outcome consisted of intrauterine death, neonatal death, or neurological sequelae of at least one twin. The 5-variable combination was termed as the MD-twin score. A chi-square test and logistic regression analysis were used to determine statistical significance. RESULTS: There were 59 MD pregnancies, of which 13 pregnancies resulted in a poor outcome. The single variable that most likely contributed to a poor outcome was amniotic-fluid discordance. All 35 pregnancies with an MD-twin score of < or = 2 had a good outcome. There were 14 pregnancies with a score of 3, and 21% of them had a poor outcome. All of the pregnancies with a score of > or = 4 had a poor outcome. When we chose the MD-twin score of 3 as the critical point for a poor outcome, the likelihood ratio statistics became the highest of any single variable or any combination of variables. CONCLUSION: The MD-twin score predicted poor outcomes better than did any single variable or combination of variables.
Hepatitis B virus (HBV) DNA has been detected in the sera of hepatitis patients who are negative for hepatitis B surface antigen (HBsAg) by polymerase chain reaction (PCR). The purpose of the present study was to clarify the clinical characteristics of patients with chronic hepatitis C who are negative for serum HBsAg and positive for HBV DNA. The subjects included 49 patients with chronic hepatitis C who were negative for serum HBsAg and 119 blood donors who served as healthy controls. Serum samples were tested for the presence of HBV DNA by the nested PCR method. Serum HBV DNA was detected in 18 (37.7%) of the 49 chronic hepatitis C patients and in none (0%) of the 119 blood donors. Among the hepatitis C patients, HBV DNA was detected in 20.7% of those who were negative for all HBV-associated markers and in 57.1% of those who were positive for one or more HBV-associated marker. The HBV DNA-positive rate among those in each F stage did not significantly differ. The liver function parameters of the HBV DNA-positive and the HBV DNA-negative chronic hepatitis C patients did not significantly differ. These results suggest that hepatitis C virus is frequently coinfected with serum HBsAg-negative HBV, and that the incidence of HBV infection in blood donors is low. However, it is considered that HBsAg-negative HBV infection does not modify the blood biochemical features of chronic hepatitis C.
Phases of circadian locomotor activity rhythms of adult Drosophila reared in constant darkness have been shown to be set by a light stimulus delivered as early as the first-instar larval stage. This implies that a circadian clock functions continuously throughout postembryonic development. The clock genes period (per) and timeless (tim) are expressed cyclically in the larval central nervous system of Drosophila, and daily oscillations of per expression persist throughout metamorphosis in a group of cells, which gives rise to the pacemaker cells underlying locomotor activity rhythms of adults. Therefore, PER and TIM cyclings in these neurons may be responsible for the phenomenon of "larval time-memory." In the absence of any evidence for the involvement of these genes in such a developmental clock, and because circadian-pacemaker functions are underanalyzed in terms of the functions during development, the authors tested the time-memory of a fast-clock period mutant. They show that dark-reared perS mutant individuals as well as wild-type flies can be entrained as larvae and that a brief light pulse given to such entrained larvae can induce phase shifts in animals of either genotype. However, the direction and magnitude of phase shifts were different between wild type and perS, suggesting that a clock under the control of period gene participates in the regulation of developmental time-memory. The authors show that the relevant clock can be entrained by two light input pathways, one involving the phospholipase C encoded by the norpA gene, the other mediated by the blue-light receptor cryptochrome. Phase shifts of molecular oscillations during the larval stage were smaller than those measured by adult behavior, suggesting molecularly transient responses during development.
A new practical strategy has been developed for the synthesis of long-chain phosphopeptide. Both the 2-chlorobenzyloxycarbonyl (CIZ) group for Lys and methyl (Me) for phosphoamino acids remained intact, while other commonly used side-chain protecting groups were cleaved quantitatively, during the reaction using a highly acidic trifluoromethanesulfonic acid (TFMSA)-based reagent system (High TFMSA: TFMSA-TFA-m-cresol=1:9:1, v/v). Selective deprotection of the CIZ and Me group-containing protected phosphopeptide resin with the High TFMSA gave a partially protected phosphopeptide fragment suitable for thioester-mediated fragment condensation. A deprotection protocol of the 9-fluorenylmethyloxycarbonyl (Fmoc) group, which evades significant side reaction toward the protected phosphoamino acid, was also developed. These two new findings enabled us to synthesize long-chain phosphopeptide via thioester-mediated fragment condensation.