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Biomedical subjects

T Kitano

Publications and source records attributed to T Kitano.

At least 19 recordsLinked to original sources

Organochlorine pesticides and polychlorinated biphenyl residues in foodstuffs and human tissues from china: status of contamination, historical trend, and human dietary exposure.

Concentrations of persistent organochlorine pesticides such as DDTs, hexachlorocyclohexanes (HCHs), chlordane compounds (CHLs), hexachlorobenzene (HCB), and polychlorinated biphenyls (PCBs), were determined in a wide variety of foodstuffs and human tissues collected from Shanghai and its vicinity in China in 2000-2001. Among the organochlorines analyzed, DDT and its metabolites were prominent compounds in most of the foodstuffs. In particular, mussels contained noticeable residues of DDTs (34,000 ng/g lipid weight), which are one to three orders greater than those reported levels in bivalves from other Asian countries. Concentrations of HCHs, CHLs, HCB, and PCBs in foodstuffs were generally low, suggesting small amounts of inputs into the environment. Temporal trends examined by comparing the results of previous studies of organochlorine levels in Chinese foodstuffs in 1970s and 1992 revealed a greater amounts of declines of DDTs and HCHs residues and the average daily intakes during the past 30 years. In contrast, very high concentrations of DDTs and HCHs were detected in human tissues from Shanghai, with the maximum values as high as 19,000 ng/g lipid weight (mean: 7,600 ng/g) and 17,000 ng/g (mean: 7,400 ng/g), respectively. Considering that foodstuffs are a main source of human exposure to contaminants, the greater concentrations of DDTs and HCHs in Chinese people might be due to past extensive usage of these compounds as agricultural pesticides. Continuous monitoring and epidemiological studies of organochlorine pesticides in humans are warranted in China. To our knowledge, this is the first report to present the residue levels of persistent organochlorine pesticides and PCBs in human tissues of China.

Aged↗

Control of ceramide-induced apoptosis by IGF-1: involvement of PI-3 kinase, caspase-3 and catalase.

Insulin-like growth factor-1 (IGF-1) inhibited N-acetylsphingosine (C2-ceramide)-induced HL-60 cell apoptosis via relieving oxidative damage. This inhibitory action of IGF-1 was blocked by a phosphatidylinositol-3 (PI-3) kinase inhibitor wortmannin and enhanced by overexpression of the p110 catalytic subunit of PI-3 kinase. Either IGF-1 pretreatment or PI-3 kinase overexpression restored ceramide-depleted catalase function, and this restoration was inhibited by wortmannin. A catalase inhibitor 3-amino-1h-1, 2, 4-triazole (ATZ) blocked the inhibitory action of IGF-1 on ceramide-induced apoptosis, whereas exogenous purified catalase enhanced it. Ceramide-activated caspase-3 was inhibited by IGF-1/PI-3 kinase and enhanced by wortmannin, while the addition of a specific caspase-3 inhibitor DMQD-CHO significantly enhanced the restoration by IGF-1 of ceramide-depleted catalase function. Moreover, IGF-1 inhibited C2-ceramide-induced decrease of mitochondrial membrane potential, and increase of cytochrome c release, caspase-3 cleavage and caspase-3 activity as judged by PhiPhiLux cleaving method. In summary, these results suggest that IGF-1/PI-3 kinase inhibited C2-ceramide-induced apoptosis due to relieving oxidative damage, which resulted from the inhibition of catalase by activated caspase-3.

Androstadienes↗

Flecainide reverses neuropathic pain and suppresses ectopic nerve discharge in rats.

We investigated effects of flecainide, a Class IC sodium channel blocker, in the rat chronic constrictive injury (CCI) and ectopic nerve discharge models. In the behavioral evaluation, 2, 6, and 12 mg/kg flecainide were intravenously given to the CCI model, and a dose-dependent analgesic effect was shown on both thermal hyperalgesia and tactile allodynia. In the electrophysiological evaluation using the ectopic nerve discharge model produced by saphenous neurectomy, i.v. administration of 2, 6, and 12 mg/kg flecainide suppressed spontaneous discharge at the peripheral nerve level in a dose-dependent fashion as with the behavioral evaluation, but flecainide did not affect nerve conduction at the dose of 12 mg/kg.

Action Potentials↗

Binding rate constant of Tc-99m DTPA galactosyl human serum albumin measured by quantitative dynamic SPECT--clinical evaluation as a total and regional liver function test.

To evaluate the clinical utility of a new method with dynamic single photon emission computed tomography (SPECT) and scatter and attenuation compensation to estimate both total and regional liver function quantitatively. Five controls, 20 patients with chronic liver disease, and 2 patients with Budd-Chiari syndrome were studied. Dynamic liver SPECT data were acquired during 20 minutes after injection of Technetium (Tc)-99m diethylenetriaminepentaacetic acid (DTPA) galactosyl human serum albumin (GSA) with scatter and attenuation compensation. The binding rate constant of Tc-99m GSA (Ku) was derived quantitatively from the Patlak plot based on kinetic models for GSA receptor binding. The mean Ku was obtained by dividing the Ku value (total Ku) by the liver volume. Both total and mean Ku were significantly lower in patients with chronic liver disease than in controls (302 +/- 112 vs. 523 +/- 78 ml/min; p < 0.001, 0.26 +/- 0.11 vs. 0.43 +/- 0.03 ml/min/cm3; p < 0.001). In the patient group, both total and mean Ku were significantly correlated with the results of conventional liver function tests and the histological severity of chronic liver disease. In 2 patients with Budd-Chiari syndrome, the mean Ku was lower in the right lobe, where the hepatic veins were occluded, than in the left lobe, where draining veins were patent. In conclusion, this method is a reliable diagnostic technique for estimating total and regional liver function.

Adult↗

Neutrophilia and granulocyte colony-stimulating factor levels after cardiopulmonary bypass.

PURPOSE: The precise mechanism of neutrophilia after cardiac surgery is unknown. Granulocyte colony stimulating factor (G-CSF) can increase the number of leukocytes. The purpose of this study was to evaluate the relationship between serum G-CSF levels and peripheral blood leukocyte counts after cardiac surgery. METHODS: We prospectively studied 10 patients undergoing cardiac surgery (coronary artery bypass grafting) using cardiopulmonary bypass (CPB). Plasma G-CSF levels and neutrophil count were measured before induction of anaesthesia, at the end of surgery, and on the first postoperative day. These changes were compared with those in patients undergoing non-cardiac major surgery (control group). RESULTS: At the end of surgery, G-CSF levels increased (P < 0.01) in both groups, but were higher in the control than in the cardiac group (3,250 +/- 690 vs 194 +/- 29.5 pg ml(-1), respectively, mean +/- SEM, P < 0.01). On the first postoperative day, G-CSF levels were still high in both groups, and were still higher in the control (710 +/- 179 vs 122 +/- 19.9, respectively, P < 0.01). However, neutrophilia was greater in the cardiac group than in the control. G-CSF response correlated positively with neutrophilia in the control group (r = 0.656, P < 0.05) but not in the cardiac group. CONCLUSIONS: Our results indicate that changes in leukocyte count following cardiac surgery are unique to patients undergoing CPB. G-CSF plays an important role as the mediator of neutrophilia after non-cardiac surgery, but not after cardiac surgery with CPB.

Aged↗

Constituents and pH changes in protein rich hyaluronan solution affect the biotribological properties of artificial articular joints.

The relationship between the coefficient of friction and pH value or protein constituents of lubricating fluid, together with viscosity, were studied within a bearing surface model for artificial joint, ultra-high molecular weight polyethylene (UHMWPE) against stainless steel (SUS), using a mechanical spectrometer. Four lubricants were tested in this study: sodium hyaluronate (HA), HA with albumin, HA with gamma-globulin, and HA with (L)alpha-dipalmitoyl phosphatidylcholine ((L)alpha-DPPC). The coefficient of friction between UHMWPE and SUS in HA with albumin or HA with gamma-globulin varied from 0.035 to 0.070 depending on angular velocity and pH. The coefficient of friction in HA or HA with (L)alpha-DPPC varied from 0.023 to 0.045 depending on angular velocity and pH. The variation in pH for HA with albumin had a large effect on the coefficient of friction at low range of angular velocity with viscosity independence. The variation in pH for HA with gamma-globulin had a large effect on the coefficient of friction with viscosity dependence at high angular velocity. The addition of (L)alpha-DPPC showed a small effect on the coefficient of friction at low angular velocity. This study confirms that the presence of albumin in the lubricant promotes pH dependence and viscosity independence of the tribological properties at low speed while the presence of globulin promotes pH and viscosity independence at low speed and promotes pH and viscosity dependence at high speed in the lubrication of UHMWPE against SUS. This study supports the clinical hypothesis that the effect of constituents and pH changes in periprosthetic fluid for the lubrication is a clue toward resolving many complications after total joint replacement.

1,2-Dipalmitoylphosphatidylcholine↗

Haplotype analysis of the human alpha2-HS glycoprotein (fetuin) gene.

Alpha2-HS glycoprotein (AHSG), which is equivalent to fetuin in other species, is a protein found in human plasma. AHSG is polymorphic with two common alleles and many variants. To examine the intragenic haplotypes and their diversity at this locus, a contiguous genomic DNA sequence (10.3 kb) was analyzed in 20 samples (40 chromosomes), and haplotypes were determined for 309 subjects. Judging from the aligned nucleotide sequences and the conserved amino acid residues comparing human and chimpanzee AHSG, it was concluded that the type 1 allele is probably older and has evolved into four major suballeles. The type 2 allele was generated from one branch of the type 1 allele. AHSG*3 and *5 variants were each found to have a single nucleotide change in exon 7, resulting in the change of an amino acid residue from Arg299 to Cys and from Asp258 to Asn, respectively. It was noted that the AHSG*3 mutation gives rise to an additional cysteine residue, which possibly affects the conformation of the protein. The AHSG gene was found to have a low mutation rate and no apparent recombination events. Furthermore, the detected substitutions were nonhomogeneously distributed at this locus. In particular, four nonsynonymous substitutions were concentrated in the carboxyl-terminal domain.

Alleles↗

Evaluation of body composition using dual-energy X-ray absorptiometry, skinfold thickness and bioelectrical impedance analysis in Japanese female college students.

We compared three methods for evaluating body composition: dual-energy X-ray absorptiometry (DXA), skinfold thickness (Skinfolds), and bioelectrical impedance analysis (BIA). Subjects were 155 healthy young college-aged Japanese females whose mean+/-SD (range) age, body height, body weight and body mass index (BMI) were 20.1+/-0.3 (19.6-21.1) y, 158.9+/-4.7 (145.4-172.6) cm, 52.0+/-6.8 (39.4-84.6) kg and 20.6+/-2.3 (16.5-32.5), respectively. Their mean skinfold thickness at the triceps and subscapular were 16.9+/-4.7 (8.0-31.0) and 16.0+/-5.7 (7.0-40.0) mm, respectively. Mean body fat mass percentages evaluated by DXA, Skinfolds and BIA were 29.6+/-5.1, 22.8+/- 5.3 and 25.8+/-4.7%, respectively. Body fat mass was 15.4+/-4.4, 12.1+/-4.5 and 13.6+/-4.5 kg, respectively. Simple correlation coefficients between the three methods for body fat mass percentages provided the following coefficients: r=0.741 for DXA vs. Skinfolds, r=0.792 for DXA vs. BIA and r=0.781 for Skinfolds vs. BIA. Simple correlation coefficients for body fat mass were as follows: r=0.898 for DXA vs. Skinfolds, r=0.927 for DXA vs. BIA and r=0.910 for Skinfolds vs. BIA (all p<0.001). There were significant differences in the values among the three methods with the Skinfolds providing the lowest body fat mass and percentage, and DXA the highest (p<0.001). They all appear to be strongly correlated for evaluating body composition: however, different cut-off values for defining obese and lean need to be defined for each method.

Absorptiometry, Photon↗

[A case of refractory spasm of multiple coronary arteries and left internal thoracic artery graft following off-pump CABG].

A 61-year-old man with exertional angina was underwent off-pump CABG with left internal thoracic artery being constructed to his left anterior descending artery. Two hours after surgery, complete atrioventricular block developed with circulatory collapse. Emergency cardiac catheterization showed multiple coronary artery spasms and LITA graft spasm, which were refractory to intracoronary and intragraft nitroglycerin injection. So we established IABP and continuous hemofiltration (CHF) urgently. Thereafter, his hemodynamics gradually improved and spasm did not recur. His postoperative angiogram revealed no significant narrowing in coronary arteries and patent anastomosis. IABP and CHF might be one of useful procedure for refractory postoperative coronary spasm.

Angina Pectoris↗

Gene diversity of chimpanzee ABO blood group genes elucidated from exon 7 sequences.

Human and non-human primate ABO blood group genes show relatively large numbers of nucleotide differences. In this study, we determined exon 7 sequences for 10 individuals of common chimpanzee and for four individuals of bonobo to estimate nucleotide diversities among them. Sequence data showed the existence of chimpanzee specific 9-base deletion in the beginning of the exon 7 coding region. From a phylogenetic network of exon 7 sequences of ABO blood group genes for human, common chimpanzee, bonobo and gorilla, effects of parallel substitutions and/or some kinds of convergent events are inferred in the chimpanzee lineage. We also estimated nucleotide diversities for common chimpanzee and bonobo ABO blood group genes, and these values were 0.4% and 0.2%, respectively. These values are higher than that of most human genes.

ABO Blood-Group System↗

gamma-diketone peripheral neuropathy. I. Quality morphometric analyses of axonal atrophy and swelling.

Quantitative morphometric analysis was used to characterize expression of myelinated axon swelling and atrophy in rat peripheral nerve during 2,5-hexanedione (HD) intoxication. HD was administered by gavage according to different daily dosing regiments (100, 175, 250, or 400 mg/kg/day) and four proximodistal nerve regions (5th lumbar spinal nerve, proximal and distal sciatic nerve, and tibial nerve) were examined morphometrically. Morphometric determinations were made at four behavioral endpoints (unaffected, slight, moderate, and severe toxicity) and were correlated to electrophysiologic measurements of peripheral nerve function. Results show that, for all HD dose rates, onsets of behavioral neurotoxicity and nerve dysfunction were generally related to development of abundant axon atrophy. The proximodistal manifestation of atrophy was dependent upon the dosing rate; i.e., the atrophy response produced by subacute intoxication with higher daily dosing rates (250 and 400 mg/kg/day) was restricted to distal nerve regions whereas subchronic induction with lower dosing rates (100 and 175 mg/kg/day) produced abundant fiber atrophy in all proximodistal areas. In contrast to atrophy, axonal swellings constituted an inconsistent minor morphologic response, the expression of which was dependent upon subchronic dosing rates (100-250 mg/kg/day). Subacute HD administration (400 mg/kg/day) produced significant changes in neurobehavior and nerve electrophysiologic parameters in the absence of peripheral axon swelling. Thus, conditional expression of swellings suggests they are an epiphenomenon related to low-dose induction rates. Fiber atrophy, however, was numerically dominant, correlated with nerve dysfunction, and occurred at all dosing levels. These characteristics suggest atrophy is a neurotoxicologically significant feature of gamma-diketone peripheral neuropathy.

Animals↗

Effect of surfactants on human stratum corneum: electron paramagnetic resonance study.

Electron paramagnetic resonance (EPR) spectra of nitroxide spin probes are useful for studying biological membranes and chemical-membrane interactions. Recently, we established a stripping method to remove stratum corneum (SC) for this purpose. To assess this stripping method with EPR and correlate with standard methods, we quantified the irritant effects of three types of surfactants by measurements of visual score and transepidermal water loss (TEWL), SC hydration and chromametry and studied EPR spectra measurements of surfactant-treated cadaver SC (C-SC) and stripped off SC (S-SC) on patch tested sites. 5-Doxyl stearic acid was the spin label. The order parameter S obtained from the spectra of S-SC correlated with those of C-SC and TEWL values. The results suggest that this method is capable of evaluating the fluidity of SC and correlates with the above bioengineering parameters.

Adult↗

Role of c-jun expression increased by heat shock- and ceramide-activated caspase-3 in HL-60 cell apoptosis. Possible involvement of ceramide in heat shock-induced apoptosis.

Ceramide has emerged as a lipid mediator in apoptosis induced by a variety of stresses. As we previously showed that the activation of AP-1, a nuclear transcription factor was indispensable to ceramide-induced apoptosis in human leukemia HL-60 cells (Sawai, H., Okazaki, T., Yamamoto, H., Okano, H., Takeda, Y., Tashima, M., Sawada, H., Okuma, M., Ishikura, H., Umehara, H., and Domae, N. (1995) J. Biol. Chem. 270, 27326-27331), the role and mechanism of heat shock (HS)-increased c-jun expression in apoptosis was here investigated. HS increased morphological changes compatible with apoptosis in human leukemia HL-60 cells, and induced ceramide generation and sphingomyelin hydrolysis with an increase of neutral magnesium-dependent sphingomyelinase activity. When HS failed to induce apoptosis in HS-resistant HL-60 cells, ceramide generation was not detected, suggesting that ceramide was involved in downstream signals required for HS-induced apoptosis. Both HS and N-acetylsphingosine (C(2)-ceramide) increased the expression of c-jun/c-fos mRNAs with the peak 2 h after treatment. When we examined whether the inhibition of c-jun expression by its antisense oligodeoxynucleotides (AS) blocked HS- or C(2)-ceramide-induced apoptosis, AS of c-jun gene inhibited apoptotic morphological changes and DNA fragmentation whereas did not sense oligodeoxynucleotides. Moreover, a synthetic tetrapeptide, acetyl-Asp-Met-Gln-Asp-aldehyde (DMQD-CHO), which inhibited the formation of active form of caspase-3 more efficiently than those of caspase-4, -6, -7, and -8, blocked both caspase-3 like activity, c-jun expression and apoptosis induced by HS or C(2)-ceramide, although DMQD-CHO did not affect HS-induced ceramide generation. These results suggested that the ceramide was generated through sphingomyelin hydrolysis by HS-activated neutral, magnesium-dependent sphingomyelinase and that subsequent c-jun expression through activation of caspase-3 played a role in HS-induced HL-60 cell apoptosis.

Apoptosis↗

Aromatase inhibitor and 17alpha-methyltestosterone cause sex-reversal from genetical females to phenotypic males and suppression of P450 aromatase gene expression in Japanese flounder (Paralichthys olivaceus).

The sex of Japanese flounder (Paralichthys olivaceus) is easily altered by water temperature or sex steroid hormone treatment during the period of sex determination. We have previously shown that rearing the genetically female larvae at high water temperature caused the suppression of P450 aromatase (P450arom) gene expression in the gonad and phenotypic sex-reversal of the individuals to males (Kitano et al. 1999. J Mol Endocrinol 23:167-176). In the present study, we show that treatment of genetically female larvae with fadrozole (aromatase inhibitor) or 17alpha-methyltestosterone induces sex-reversal as well as suppression of P450arom gene expression. The effect of fadrozole was counteracted by co-administration of estradiol-17beta. Effective periods for fadrozole treatment to induce sex-reversal were similar to those for high water temperature treatment. RT-PCR did not detect P450arom mRNA in gonad of the sex-reversed, phenotypic males. These results indicate that sex-reversal of the genetically female larvae by aromatase inhibitor (or 17alpha-methyltestosterone) may be due to the suppression of P450arom gene expression and the resultant decrease in the amount of estrogen.

Animals↗

Health surveillance in the population living in a methyl mercury-polluted area over a long period.

It is important to follow up on the health status of inhabitants living in the methyl mercury-polluted area surrounding Minamata City, paying particular attention to diseases not only of the central nervous system but also of other organs. We have been carrying out such concentric studies for more than 10 years. We have previously studied the cause-specific standard mortality ratios in Minamata disease patients and reported that the SMRs for liver disease and renal disease were significantly raised in male and female patients, respectively. It was also found that complications arising from diabetes could be due to the large number of old people among the autopsy cases. The next step was to clarify the actual prevalence and incidence of liver disease, renal disease, and diabetes mellitus epidemiologically among the population in this area. The aim of this study was to determine the actual prevalence of these diseases and complaints, and to investigate the contribution of various risk factors to these diseases in this area. The study was a population-based cross-sectional mass screening survey. A case-control study was designed to estimate the role of various risk factors including methyl mercury exposure for these diseases. A mass multiple health examination survey was performed in 1500 subjects aged 40 years and older in Tsunagi Town, neighboring Minamata City, every summer since 1984. Tsunagi Town is located in a methyl mercury-polluted area and there are 36.9 certified Minamata disease patients per 1000 population. Data concerning liver disease, renal disease, and diabetes mellitus were collected on the basis of urine, hematological, physical, and ultrasonographic examinations. Data on risk factors and subjective complaints were collected by interview and other measures. The prevalence of these diseases was not higher in this methyl mercury-polluted area compared with other areas in Japan, contrary to what was expected based on standard mortality ratios and pathological findings. There were no positive correlations between those diseases and methyl mercury exposure. On the other hand, the population in the polluted area had more and a greater variety of complaints than those in the nonpolluted area. It is possible that not only neurological subjective complaints but also nonspecific complaints of the population in the polluted area might be influenced by past methyl mercury exposure. This health surveillance in the population living in a methyl mercury-polluted area must be maintained in the future.

Aged↗

Thoracolithiasis.

Thoracolithiasis without any history of chest traumas or interventions is pathologically rare, with only 9 cases including our 2, reported thus far in the literature. Case 1: A 76-year-old man admitted to our hospital had an abnormal shadow in chest radiography that gradually enlarged. Serum carcinoembrionic antigen was slightly elevated during follow-up. A milky white tumor 1.5 cm in diameter with many projections was found in the thoracic cavity and removed by thoracoscopy. Histopathological examination showed the tumor to consist of fibrous tissue with fatty necrosis at the core. Case 2: A 54-year-old woman admitted to our hospital had an abnormal shadow in chest screening radiography in 1998. Transbronchial biopsy showed this shadow to be lung adenocarcinoma. A small trigonal pyramid-shaped milky white nodule 5 mm in diameter was found in the thorax during lobectomy for lung cancer. Histopathological examination showed this nodule also to consist of fibrous tissue with fatty necrosis.

Aged↗

Transsternal bilateral thoracotomy for pericardiectomy after coronary artery bypass grafting.

Surgery for constrictive pericarditis was conducted through a transsternal bilateral thoracotomy in a 45-year-old man who developed the condition 12 months after coronary artery bypass grafting with left internal thoracic artery and vein grafts. The grafts ran just beneath the sternum. To avoid injury to the bypass grafts during sternotomy and mediastinal dissection, we conducted a transsternal bilateral thoracotomy, which provided excellent exposure of the heart. Complete pericardiectomy was done safely without cardiopulmonary bypass. Constrictive pericarditis following cardiac surgery is an uncommon complication posing difficult problems for the surgeon. The presence of a patent left internal thoracic artery bypass is particularly challenging. Transsternal bilateral thoracotomy is a useful approach in patients with constrictive pericarditis in whom a median sternotomy is contraindicated.

Coronary Artery Bypass↗