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Biomedical subjects

M Tanaka

Publications and source records attributed to M Tanaka.

At least 37 records · Page 2Linked to original sources

Aleukaemic leukaemia cutis as an initial manifestation of myeloid/NK cell precursor acute leukaemia.

Aleukaemic leukaemia cutis is a rare condition characterized by infiltration of leukaemic cells into the skin before they appear in the peripheral blood. We report a case of an aleukaemic leukaemia cutis, which had a history of exposure to atomic bomb radiation. A 57-year-old Japanese woman initially presented with a 20-week history of multiple red papules and plaques mainly over the trunk. Histological examination revealed the infiltration of atypical monocytic cells in the dermis, but no leukaemic cells were detected in the peripheral blood. Twenty-three weeks after the appearance of the eruption, leukaemic cells were detected in the peripheral blood for the first time. The results of immunohistochemistry of the skin biopsy specimen and flow cytometry of the peripheral blood indicated the rare phenotype of myeloid/NK cell precursor acute leukaemia. This is the first case report of myeloid/NK cell precursor acute leukaemia presenting as aleukaemic leukaemia cutis in the English literature, and awareness of this clinical presentation may be important to reach the correct diagnosis.

Fatal Outcome↗

Expression of granulysin in polymyositis and inclusion-body myositis.

BACKGROUND: Granulysin, a recently defined cytolytic molecule, is expressed in cytotoxic T cells and natural killer cells in a similar way to perforin, which is reported to have a major role in the pathogenesis of polymyositis and inclusion-body myositis (IBM). OBJECTIVE: To clarify the role of granulysin in polymyositis and IBM. METHODS: The expression of granulysin and perforin was examined by double staining with CD8, CD4 and CD56 in endomysial infiltrating cells and autoinvasive cells in muscle biopsy specimens of 17 patients with polymyositis (6 steroid resistant and 11 steroid responsive) and of 7 patients with IBM. RESULTS: Similar to perforin, granulysin was expressed in CD8, CD4 or CD56 cells in patients with polymyositis and IBM. The ratio of cells double positive for granulysin and CD8 to all CD8 cells at endomysial sites was notably higher in steroid-resistant polymyositis than in steroid-responsive polymyositis and IBM. CONCLUSION: Granulysin expression in CD8 cells seems to be correlated with steroid resistance in polymyositis.

Antigens, Differentiation, T-Lymphocyte↗

Effect of prenatal exposure to bisphenol A on the serum testosterone concentration of rats at birth.

In the rat, testosterone (T) in the neonatal period plays an important role in sexual differentiation and there is a serum T surge in male rats 2 hours after birth. Pregnant female rats were exposed to various doses of bisphenol A (BPA) from gestational day 1 (GD1) through 2 hours after parturition. About half of the BPA-exposed and control dams were subjected to cesarean section on GD22. The male fetuses on GD22 were immediately sacrificed and blood was collected. The other half of the BPA-treated and control dams delivered at GD23 (parturition day). The male pups were sacrificed 2 hours after birth. Serum T concentration was determined by radioimmunoassay (RIA). The BPA concentration in the fetal serum on GD22 increased inversely to the T levels in the serum. The T concentration in the pups' serum 2 hours after birth decreased inversely to the BPA concentration in the serum. However, there were no differences in the serum T concentration among the various doses of BPA. These results suggest that exposure to BPA in utero inhibits the T surge in the neonatal period and we speculate that exposure to BPA in utero disrupts the endocrine environment in the neonatal male.

Animals↗

A single base insertion of the 4-alpha-galactosyltransferase gene led to the deficiency of Gb3 biosynthesis.

cDNAs for alpha 1,4 galactosyltransferase (A4GALT) have been isolated. To explore the molecular basis of the p phenotype in Japanese donors, we analyzed the A4GALT gene sequences of normal and p phenotype samples. The coding region in the A4GALT gene for DNA sequencing was amplified by PCR amplification. A4GALT expression vectors for individual were constructed by PCR amplification of the coding region using primers and subsequent subcloning into an expression vector. The expression of Gb3/CD77 antigen on the cell surface was evaluated by flow cytometry and by immunochemical techniques. All individuals with the p phenotype were found to have a single base insertion (A4GALT/insC) at the same nucleotide position. Neither the transfectant cells with a mutant gene (A4GALT/insC) of donor origin or those with a synthesized mutant gene (A4GALT/insC-Mu) expressed Gb3 antigen indicating that the presence of A4GALT/insC diminished the A4GALT enzyme activity. In addition, an allele-specific PCR (ASP) system was developed in which of the p phenotype with A4GALT/insC can be unambiguously discriminated from normal donors. Based on the finding that a single base insertion (A4GALT/insC) diminishes A4GALT activity, an ASP assay was developed to detect individuals with this particular p phenotype.

Antigens, Tumor-Associated, Carbohydrate↗

[Acute aortic regurgitation by spontaneous rupture of a fibrous strand in fenestrated aortic valve; report of a case].

Although fenestration of the aortic valve cusps is a common anatomic finding, it rarely causes aortic regurgitation. We describe acute aortic regurgitation by spontaneous rupture of a fibrous strand in fenestrated aortic valve. A 65-year-old man was referred with sudden onset of dyspnea and cough. He diagnosed acute heart failure due to severe aortic valve regurgitation. After medical therapy, the aortic valve replacement was performed. Operative findings reviewed that a fibrous strand in the fenestrated non-coronary cusp was ruptured, which caused severe aortic regurgitation. Pathological examination showed the myxomatous degeneration. The postoperative course was uneventful, and the patient was discharged on postoperative day 11 with good health.

Aged↗

International transmission of uncompressed endoscopic surgery images via superfast broadband Internet connections.

BACKGROUND: Although telecommunication is increasing in popularity, poor-quality images sent through a narrowband network limit its use in the medical field. METHODS: Kyushu University Hospital in Japan and four hospitals in Korea were linked via superfast broadband Internet connection. The digital video transfer system, which can transmit digital videos without loss of image quality, was used, and the bandwidth was 30 Mbps per line. RESULTS: Of the 16 teleconferences conducted, 6 demonstrated real-time endoscopic surgery. In addition to the surgical images, preoperative diagnostic images, images of the operating room, and images of the staff in the conference room were transmitted to facilitate discussion. The network remained stable, and the sound delay was restricted to less than 0.3 s. In the other 10 teleconferences, recorded video images were used for discussion. CONCLUSIONS: The authors have established a high-quality, practical teleconference system that is economical and easy to use in clinical practice. This system shows promise for remote education beyond geographic borders.

Cholecystectomy, Laparoscopic↗

Gli1, downregulated in colorectal cancers, inhibits proliferation of colon cancer cells involving Wnt signalling activation.

BACKGROUND: Early events in the progression of 90% of sporadic colorectal cancers depend on constitutive activation of Wnt signalling. Recent data also indicate a close association between the Hedgehog (Hh) and Wnt pathways in colonic epithelial cell differentiation. AIMS: To investigate whether expression of Gli1, a transactivator of Hh signalling, can suppress Wnt signalling and inhibit proliferation of human colorectal cancer cells. METHODS: Gli1 and nuclear beta-catenin expression were examined in a series of 40 human colorectal cancers by immunohistochemistry. We quantified Gli1 and nuclear beta-catenin staining as markers of Hh and Wnt pathway activation, respectively. Two human colon cancer cell lines, SW480 and HCT116, with mutations in APC and beta-catenin, respectively, were used. The effects of Gli1 overexpression on Wnt transcriptional activity, beta-catenin subcellular distribution, and proliferation in these cells were analysed. RESULTS: Nuclear accumulation of beta-catenin and the Gli1 staining level were inversely associated in the 40 human colorectal cancers. Wnt transcriptional activity was reduced in Gli1 transfected cells. These effects were observed even in Gli1 transfected cells cotransfected with mutated beta-catenin. Furthermore, nuclear accumulation of beta-catenin was diminished compared with that in empty vector transfected cells, and downregulated transcription of c-Myc was observed in Gli1 transfected cells. Proliferation of Gli1 transfected cells was also significantly suppressed compared with that in empty vector transfected cells. CONCLUSIONS: Our data suggest that Gli1 plays an inhibitory role in the development of colorectal cancer involving Wnt signalling, even in cases with the stabilising mutation of beta-catenin.

Carrier Proteins↗

Laparoscopically assisted distal gastrectomy with standard radical lymph node dissection for gastric cancer.

BACKGROUND: Laparoscopically assisted distal gastrectomy (LADG) with limited lymph node dissection (D1+alpha) has been used to treat a subset of patients with early gastric cancer. Technical advances have expanded indications for LADG to more advanced gastric cancers. However, little data are available on the feasibility or advantages of LADG with standard radical D2 lymph node dissection for patients with gastric cancer. METHODS: This study reviewed the clinical features of 37 patients who underwent LADG with D2 lymph node dissection for preoperatively diagnosed gastric carcinoma, then compared the results with the features of 31 patients who underwent conventional open distal gastrectomy (ODG) with D2 lymph node dissection. RESULTS: The laparoscopic procedure was not converted to laparotomy in any patient. There was no operative mortality and no serious morbidity among the patients who underwent LADG with D2 lymph node dissection. As compared with the ODG group, the LADG group had less operative blood loss (p < 0.001), earlier recovery of bowel activity (p = 0.012), and a shorter duration of fever after surgery (p = 0.015), despite the longer operation time (p = 0.007). CONCLUSIONS: According to this study, LADG with D2 lymph node dissection is feasible and provides several advantages similar to those of limited lymph node dissection (D1+alpha). Depending on surgeons' technical proficiency, LADG can be used with standard radical lymph node dissection for patients with gastric cancers.

Carcinoma↗

A new congenital form of X-linked autophagic vacuolar myopathy.

In a new family with X-linked congenital autophagic vacuolar myopathy (AVM), seven affected boys presented with congenital hypotonia, dyspnea, and dysphagia with delayed motor milestones. Muscle pathology revealed autophagic vacuoles with sarcolemmal features, multilayered basal lamina with marked sarcolemmal deposition of C5-9 membrane attack complex and calcium, histologically indistinguishable from childhood-onset X-linked myopathy with excessive autophagy (XMEA). Haplotype analysis suggests that this new AVM and XMEA may be allelic despite different clinical presentations.

Antigens, Protozoan↗

High temperature ferromagnetism in GaAs-based heterostructures with Mn delta doping.

We show that suitably designed magnetic semiconductor heterostructures consisting of Mn delta (delta)-doped GaAs and p-type AlGaAs layers, in which the locally high concentration of magnetic moments of Mn atoms are controllably overlapped with the two-dimensional hole gas wave function, realized remarkably high ferromagnetic transition temperatures (T(C)). A significant reduction of compensative Mn interstitials by varying the growth sequence of the structures followed by low-temperature annealing led to high T(C) up to 250 K. The heterostructure with high T(C) exhibited peculiar anomalous Hall effect behavior, whose sign depends on temperature.

Journal Article↗

Water adsorption on a p(2x2)-Ni(111)-O surface studied by surface x-ray diffraction and infrared reflection absorption spectroscopy at 25 and 140 K.

The adsorption of water molecules on an oxygen-predosed p(2x2)-Ni(111)-O surface was studied by surface x-ray diffraction and infrared reflection absorption spectroscopy (IRAS) at temperature of 25 and 140 K. Precise structures including adsorbed water, predosed oxygen, and substrate nickel atoms at these two temperatures were determined by x-ray structural analysis. It was found that water molecules adsorb on oxygen additive sites, forming a hydrogen bond at 25 K. A predosed 2x2 oxygen atom appears to accommodate one, two, or three water molecules at positions relating to threefold rotation symmetry. When the surface temperature was raised to 140 K, water molecules appear at an atop site of Ni. The distance between Ni and the oxygen atoms of a monomer water molecule was found to be 0.2241(22) nm. The adsorbed water molecule induces buckling and a lateral shift of the substrate nickel. The IRAS results provided evidence regarding the existence of two distinct adsorption sites. Water molecules in the low-temperature phase exhibit bands from both hydrogen-bonded nuOD and free OD stretchings, while those in the high-temperature phase lie flat with a molecular plane parallel to the surface.

Journal Article↗

Baroreflex control of heart rate during and after propofol infusion in humans.

BACKGROUND: This study was designed to determine cardiovagal baroreflex gain during propofol infusion and to characterize its recovery profile using the pharmacological and spontaneous sequence methods in 13 healthy volunteers without cardiovascular or autonomic disorders. METHODS: After an 8- to 10-h fast and no premedication, measurements of RR intervals obtained from the electrocardiogram and non-invasive beat-to-beat systolic blood pressure (SP) were made at conscious baseline, at 60 and 120 min after induction of general anaesthesia using propofol, and at 20, 60, 120 and 180 min after emergence from anaesthesia. During propofol anaesthesia, ventilation was mechanically controlled to maintain normocapnia and calculated propofol concentration was adjusted by a TCI system at 5 microg ml(-1). Baroreflex responses were triggered by bolus i.v. injections of phenylephrine and nitroprusside to alter SP by 15-30 mm Hg. The linear portions of the baroreflex curves relating RR intervals and SP by least-square regression analysis were determined to obtain pharmacological gains. In addition, spontaneous sequence baroreflex gains were calculated from spontaneously fluctuating SP and RR intervals. RESULTS: Baseline pressor and depressor test gains before propofol anaesthesia were 29.1 (SD 14.9) and 12.5 (7.8) ms mm Hg(-1), respectively. They were significantly depressed by 65-73% during propofol infusions. Similarly, baseline up- and down-sequence baroreflex gains were 33.8 (28.9) and 27.3 (19.8) ms mm Hg(-1), respectively, and were significantly depressed by 71-87% during propofol anaesthesia. Pressor test and up-sequence baroreflex gains returned to the baseline values 20 min after emergence from propofol anaesthesia, but depressor test and down-sequence baroreflex gains did not recover until 60 min after emergence. CONCLUSIONS: We conclude that heart rate responses to both lowering and elevating blood pressure were depressed by propofol anaesthesia, and 60 min was required for their full recovery after discontinuation of propofol infusion.

Adult↗

Renal clearance of glycolaldehyde- and methylglyoxal-modified proteins in mice is mediated by mesangial cells through a class A scavenger receptor (SR-A).

AIMS/HYPOTHESIS: Glomerular mesangial expansion is a characteristic feature of diabetic nephropathy, and the accumulation of AGE in the mesangial lesion has been implicated as one of its potential causes. However, the route for the AGE accumulation in mesangial lesions in diabetic patients is poorly established. METHODS: Glycolaldehyde-modified BSA (GA-BSA) and methylglyoxal-modified BSA (MG-BSA) were prepared as model AGE proteins, and their in vivo plasma clearance was examined in mice, and renal uptake by in vitro studies with isolated renal mesangial cells. RESULTS: Both (111)In-GA-BSA and (111)In-MG-BSA were rapidly cleared from the circulation mainly by both the liver and kidney. Immunohistochemical studies with an anti-GA-BSA antibody demonstrated that intravenously injected GA-BSA accumulated in mesangial cells, suggesting that such cells play an important role in the renal clearance of circulating AGE proteins. Binding experiments at 4 degrees C using mesangial cells isolated from mice showed that (125)I-GA-BSA and (125)I-MG-BSA exhibited specific and saturable binding. Upon incubation at 37 degrees C, (125)I-GA-BSA and (125)I-MG-BSA underwent endocytic degradation by these cells. The binding of the ligands to these cells was inhibited by several ligands for scavenger receptors. The endocytic degradation of GA-BSA by mesangial cells from class A scavenger receptor (SR-A) knock-out mice was reduced by 80% when compared with that of wild-type cells. The glomerular accumulation of GA-BSA after its intravenous administration was attenuated in SR-A knock-out mice, as evidenced by immunohistochemical observations. CONCLUSIONS/INTERPRETATION: These results raise the possibility that circulating AGE-modified proteins are subjected to renal clearance by mesangial cells, mainly via SR-A. This pathway may contribute to the pathogenesis of AGE-induced diabetic nephropathy.

Acetaldehyde↗

Effects of repeated maternal stress on FOS expression in the hypothalamic paraventricular nucleus of fetal rats.

The effects of repeated prenatal stress with different severity (restraint and immobilization) on Fos expression in the maternal and fetal hypothalamic paraventricular nucleus (PVN) were examined in rats. Acute stress treatment was performed for 30 min on gestational day 21, and repeated stress treatment for 30 min daily for 5 days from gestational days 17-21. In the parvocellular region of the maternal PVN, the stress-induced increases in the number of Fos-immunoreactive neurons were smaller in the repeated stress groups than the acute stress groups, indicating an adaptation of Fos expression to repeated stress. The attenuated Fos expression observed in the maternal PVN following repeated mild stress did not occur in the fetal PVN. In contrast, repeated immobilization stress caused a much smaller increase in Fos expression in the fetal PVN than did acute immobilization stress. The reduced Fos expression in the fetal PVN following repeated severe stress was thought to be due to cell death, since the fetal PVN in the chronic immobilization group revealed a reduction in the total number of cells and an increase in the number of apoptotic cells. In the female but not male fetuses, repeated restraint stress induced a significant increase in the number of apoptotic cells in the PVN. These findings suggest that the fetal PVN shows no adaptation of Fos expression to repeated maternal stress, but great vulnerability to cell death, including apoptosis. In addition, stress-induced apoptosis may more easily occur in the fetal PVN in females than males.

Acute Disease↗

Long-term results of tacrolimus therapy for renal transplantation in patients with diabetic nephropathy in Japan.

In Japan, the number of kidney transplants for the patients with diabetic nephropathy is limited because of an extreme organ shortage and poor patient and graft survival rates. We analyzed the 5-year outcomes in kidney transplant recipients treated with tacrolimus with (group 1; n = 53) and without a diagnosis of diabetic nephropathy (group 2; n = 1432). We also investigated outcomes in patients who received simultaneous pancreas and kidney transplants since 2000 (group 3; n = 15). Patients in group 1 were older than those in group 2, with a shorter duration of pretransplant dialysis (P = .0001). Five-year patient survival rates in groups 1 and 2 were 89.7% and 97.9%, respectively (P = .13), and 5-year graft survival rates were 89.6% and 94.8%, respectively (P = .44). The incidence of acute rejection within 3 months of transplantation was 28.3% in group 1 and 29.2% in group 2 (P = .98). Tacrolimus-based induction therapy was used in 13 of the 15 group 3 cases. Both kidney and pancreas grafts are surviving to date in all but one of the group 3 patients; one patient had the pancreas removed due to venous thrombosis at 7 days. It was concluded that tacrolimus-based therapy resulted in excellent 5-year outcomes in patients who had kidney transplantation because of diabetic nephropathy, despite the higher risks associated with this condition. Tacrolimus was also beneficial in association with simultaneous pancreas and kidney transplantation. These data encourage us to perform kidney transplantation in patients with diabetic nephropathy.

Adult↗

Prognosis of HTLV-I-positive renal transplant recipients.

HTLV-I is the pathogen that causes adult T-cell leukemia (ATL) and HTLV-I-associated myelopathy (HAM). The rate of disease development is low and the latency time is a few decades. However, the possible influence of immunosuppression on this disease development is unclear. The purpose of this study was to investigate the risk of development of ATL and HAM among the large number of HTLV-I-positive renal transplant recipients in western Japan. In principle immunosuppressive drugs have the possibilities to accelerate ATL development but are thought to suppress HAM development. Of 120 renal transplant recipients, 10 HTLV-I-positive recipients were reviewed, none of whom developed ATL or HAM. There are 11,896 dialysis patients in Japan and 300 dialysis patients in Okinawa who are registered with the JOTN for cadaveric renal transplant. The numbers of HTLV-I-positive patients in these groups were 97 (0.82%) and 26 (8.67%), respectively. These numbers are thought to be sufficient for an HTLV-I-positive recipient pool for HTLV-I-positive donors. Ten cases of ATL development and two of HAM development have been previously reported. Because of low number of ATL development, renal transplantation does not appear to be a contraindication for HTLV-I-positive chronic renal failure patients. In other words, kidneys from HTLV-I carriers, which include cadaveric donors, could be used for HTLV-I-positive recipients.

Adult↗

Influence of sodium benzoate on the metabolism of o-xylene in the rat.

The main metabolites of o-xylene in urine are o-methylhippuric acid, o-toluic acid, o-toluic acid glucuronide, 3,4-dimethylphenol, 3,4-dimethylphenol conjugates and o-xylylmercapturic acid. The urinary excretion of o-toluic acid, o-toluic acid conjugates and o-xylene were increased by the prior administration of sodium benzoate. Conversely, the amounts of o-methylhippuric acid, 3,4-dimethylphenol conjugates and o-xylylmercapturic acid decreased by sodium benzoate pretreatment. In addition, the urinary excretion of o-methylhippuric acid was delayed by the pretreatment. The percentages of urinary excretion of the o-xylene metabolites were substantially changed by the pretreatment with sodium benzoate. These results therefore highlight a potential interaction of an air pollutant with a food additive, an interaction that remains to be established in man.

Animals↗

Metabolism of the calmodulin antagonist DY-9760e in animals and humans.

The in vitro metabolism of the calmodulin antagonist DY-9760e was investigated using liver microsomes from humans and three other animal species and compared with the in vivo metabolism in rats after intravenous administration of DY-9760e. Seven major metabolites were produced by human liver microsomes by the following metabolic pathways: N-dealkylation, phenyl hydroxylation, O-demethylation and imidazole oxidation. These metabolites were also produced by liver microsomes from monkeys, dogs and rats; additionally, a hydroxylated derivative of the indazole moiety was produced only by rat microsomes. To identify the structures of two imidazole ring metabolites whose authentic compounds could not be obtained, Escherichia coli co-expressing human cytochrome P450 CYP3A4 and NADPH-P450 reductase was used to biosynthesize these metabolites. NMR spectra elucidated the precise structures; oxidation occurred at the imidazole ring, and the subsequent ring-opening resulted in the generation of amide and formylamine groups. Glucuronide conjugates of the hydroxylated and O-demethylated derivatives were major components in rat bile. Therefore, DY-9760e metabolites generated in vitro correspond to the aglycones of the major metabolites observed in rat bile.

Animals↗