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Biomedical subjects

T Hirano

Publications and source records attributed to T Hirano.

At least 55 records · Page 3Linked to original sources

Association between interleukin-18 gene polymorphism 105A/C and asthma.

BACKGROUND: IL-18 has been shown to exert anti-allergic or allergy-promoting activities, but the existence of genetic polymorphisms in the coding regions of IL-18 gene has not been demonstrated. OBJECTIVE: The aim of this study was to investigate whether polymorphism is present in the coding regions of the IL-18 gene and, if so, to further analyse the association between polymorphism and asthma in a case-control study. METHODS: We screened the coding regions of the IL-18 gene for polymorphisms by using PCRsingle-stranded conformation polymorphism and direct sequencing of PCR products, followed by analysis of the association between polymorphism and asthma. RESULTS: We identified one polymorphism (105A/C) in the coding regions. The frequency of the 105A allele was significantly higher in asthmatic patients than in controls (P<0.01; odds ratio (OR)=1.83 (1.37-2.26)). Significant linkage disequilibrium was observed between the 105A/C and -137G/C polymorphisms in the 5' flanking region of the IL-18 gene (D=0.58, P<0.0001). However, in asthmatic patients the 105A allele was not associated with either total serum IgE or IL-18 levels. CONCLUSION: The 105A/C polymorphism of the IL-18 gene may be associated with the pathogenesis of asthma.

Adolescent↗

Holmium:YAG laser-induced liquid jet dissector: a novel prototype device for dissecting organs without impairing vessels.

BACKGROUND AND OBJECTIVE: Neurosurgery has long required a method for dissecting brain tissue without damaging principal vessels and adjacent tissue, so as to prevent neurological complications after operation. In this study we fabricated such a prototype device and used it in an attempt to resect an animal liver, which, like the brain, contains many vessels. MATERIALS AND METHODS: The prototype device consisted of a jet nozzle and a suction tube. Pulsed liquid jets at 3 Hz were ejected from the nozzle by a pulsed holmium:YAG (Ho:YAG) laser at an irradiation energy of 230 mJ/pulse. The profile of the liquid jet was observed with a high-speed camera. With this device, liver dissections of anesthetized rabbits were attempted while measuring the local temperature of the target. A histological study of the incised parts was also performed. RESULTS: The liquid jet was emitted straight from the nozzle at an initial velocity of 38 m/sec. The liver parenchyma was cut with the device while preserving the tiny vessels and keeping the operative field clear. The local temperature rose to no more than 314 K (below the heat damage threshold of brain tissue). In the histological findings, there were no signs of hepatic degeneration or necrosis around the dissected margin. CONCLUSIONS: The Ho:YAG laser-induced liquid jet dissector can be applied to neurosurgical operations after incorporating some minor improvements.

Animals↗

Intraoperative thermal artery imaging of an EC-IC bypass in beagles with infrared camera with detectable wave-length band of 7-14 microm: possibilities as novel blood flow monitoring system.

OBJECTIVE: In the past, the usefulness of thermal arterial imaging during coronary bypass surgery using an infrared camera has been reported by several investigators. The goal of this study is to apply this novel imaging system for intraoperative arterial imaging, as well as to develop new utilizations for a neurosurgical procedure. MATERIALS: We have attempted real-time imaging of anastomotic and flow status in an external carotid-internal carotid artery (EC-IC) bypass surgery using a new-generation infrared camera (IRIS IV thermographic imaging system) in beagles. No contrast medium or radiation was used to obtain the images. The detectable wave-length band of the infrared lens was 7-14 microm. After completion of bypass monitoring, an additional teflon tube was inserted into a branch of the STA to inject physiological saline of different temperatures to see the changes in cortical images. RESULTS: Anastomotic and flow status were clearly visualized throughout the operation without local surface cooling, which had been an inevitable procedure in coronary imaging to make a pronounced temperature difference between artery and adjacent tissue. In addition, cortical flow territory was visualized after injection of either cold or warm physiologic saline into the artery from an additionally inserted teflon tube into a branch of STA via bypass artery. CONCLUSION: From the present experience, it is considered that infrared imaging using a detectable wave length band of 7-14 microm may be applicable to a wide variety of near surface lesions, providing a non-invasive functional angiography.

Animals↗

Amidated fish ghrelin: purification, cDNA cloning in the Japanese eel and its biological activity.

We purified ghrelin from stomach extracts of a teleost fish, the Japanese eel (Anguilla japonica) and found that it contained an amide structure at the C-terminal end. Two molecular forms of ghrelin with 21 amino acids were identified by cDNA and mass spectrometric analyses: eel ghrelin-21, GSS(O-n-octanoyl)FLSPSQRPQGKDKKPP RV-amide and eel ghrelin-21-C10, GSS(O-n-decanoyl) FLSPSQRPQGKDKKPPRV-amide. Northern blot and RT-PCR analyses revealed high gene expression in the stomach. Low levels of expression were found only in the brain, intestines, kidney and head kidney by RT-PCR analysis. Eel ghrelin-21 increased plasma growth hormone (GH) concentrations in rats after intravenous injection; the potency was similar to that of rat ghrelin. We also examined the effect of eel ghrelin on the secretion of GH and prolactin (PRL) from organ-cultured tilapia pituitary. Eel ghrelin-21 at a dose of 0.1 nM stimulated the release of GH and PRL, indicating that ghrelin acts directly on the pituitary. The present study revealed that ghrelin is present in fish stomach and has the ability to stimulate the secretion of GH from fish pituitary. A novel regulatory pathway of GH secretion by gastric ghrelin seems to be conserved from fish to human.

Amino Acid Sequence↗

Dual mode of cortisol action on GH/IGF-I/IGF binding proteins in the tilapia, Oreochromis mossambicus.

Glucocorticoids are known to impede somatic growth in a wide range of vertebrates. In order to clarify the mechanisms through which they may act in an advanced teleost fish, we examined the effects of cortisol administration on the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF-binding protein (IGFBP) system in the tilapia (Oreochromis mossambicus). In a short-term experiment, fish were injected intraperitoneally with cortisol (2 or 10 microg/g), and killed at 2, 4, 8 and 24 h after the injection. In a longer-term experiment, fish were killed 24 and 48 h after cortisol injection (2, 10 and 50 microg/g). Cortisol at doses of 2 and 10 microg/g significantly increased IGFBPs of four different sizes (24, 28, 30, and 32 kDa) in the plasma within 2 h without altering plasma levels of IGF-I or GH. On the other hand, cortisol at doses of 10 and 50 microg/g significantly reduced plasma IGF-I levels after 24 and 48 h. IGF-I mRNA levels in the liver were also significantly reduced by cortisol at doses of 10 and 50 microg/g after 48 h, suggesting that a decrease in plasma IGF-I levels is mediated through the attenuation of IGF-I gene expression in the liver. In contrast, no significant change was observed in plasma or pituitary contents of GH at any time point examined, which would appear to indicate that cortisol reduces IGF sensitivity to GH (GH-resistance). These results clearly indicate that cortisol induces a rapid increase in plasma IGFBPs and a more delayed decrease in IGF-I production. The dual mode of cortisol action may contribute to the inhibitory influence of cortisol on somatic growth in teleosts.

Animals↗

A case of acute renal failure due to rhabdomyolysis, associated with non-autoimmune fulminant type 1B diabetes mellitus.

A 38-year-old man developed severe diabetic ketoacidosis complicated with rhabdomyolysis and acute renal failure after presenting hyperglycemic symptoms for 4 days. Initial investigation showed significant hyperglycemia (blood glucose level 1,593 mg/dl) with a relatively low level of HbA1c (7.0%) and a high pancreatic enzyme concentration without any signs of pancreatitis. Diabetes-related antibodies were absent except for the anti-glutamic acid decarboxylase antibody, which disappeared later on. Pancreatic biopsy examination showed the lack of insulin-secreting cells, without insulitis. These findings were almost consistent with non-autoimmune fulminant type 1B diabetes. The patient remained dependent on dialysis for 1 month, then his renal function recovered. In patients with this type of diabetes, the onset of overt diabetes, frequently accompanied with severe diabetic ketoacidosis, is rapid, hence, early detection, quick diagnosis and immediate treatment of this novel type of diabetes are important in the rescue of these patients.

Acute Kidney Injury↗

[Re-dissection of aortic root without gelatin-resorcin-formalin (GRF) glue effect one year after aortic repair].

A 58-year-old man, who had undergone emergency graft replacement of ascending and total aortic arch using gelatin-resorcin-formalin (GRF) glue 1 year before, complained of progressive shortness of breath. Ultrasound cardiography revealed severe aortic regurgitation and dissecting aneurysm of aortic root. He underwent composite graft replacement with the aid of the right axillary artery perfusion and deep hypothermic circulatory arrest. The redissected brownish intima was identified in the area of noncoronary cusp. There was no special finding in the subsequent histopathological examination. The use of GRF glue for reconstructing the dissected aortic root is associated with a certain amount of risk of aortic wall redissection. Therefore, care should be taken to ensure proper use of GRF glue.

Aortic Dissection↗

[Thoracoscopic segmentectomy of the left upper division in a patient with endobronchial hamartoma; report of a case].

A 71-year-old man was admitted to our hospital for treatment of an endobronchial tumor. Although he was asymptomatic and chest radiography showed no tumor shadow, bronchoscopic findings demonstrated an endobronchial tumor with a villous surface occluding the bronchus of the left upper division. Endobronchial resection was abandoned because we could not directly observe the cervix with a bronchoscope. In addition, because we could not diagnose the tumor histologically as benign by biopsy specimens, we elected to perform a segmentectomy of the left upper division. To reduce surgical stress, the operation was carried out using thoracoscopy. The tumor was finally diagnosed as endobronchial chondromatous hamartoma. The patient's postoperative course was uneventful. When endobronchial resection is not feasible, a less invasive surgical approach and method should be taken in patients with suspected endobronchial hamartoma.

Aged↗

Phosphorylated tyrosine-containing proteins in primary lung cancer correlates with proliferation and prognosis.

To determine the usefulness of tyrosine phosphorylation in evaluating biological characteristics, we attempted to evaluate the relationship between the amount of phosphorylated tyrosine-containing proteins and clinicopathological factors, cell proliferation and outcome in non-small cell lung cancer. To evaluate phosphorylated tyrosine-containing proteins we used 96 surgically resected materials of non-small cell lung cancer and normal peripheral lung, while immunohistochemical evaluation was performed. Cell proliferating ability was evaluated using the labelling index of proliferating cell nuclear antigen-positive nuclear staining cells. There were statistically significant differences between the expression levels of phosphorylated tyrosine-containing proteins of normal and cancerous tissues (P<0.0001). Evaluations based on clinicopathological factors apart from histopathological differentiation, showed no statistically significant differences of phosphorylated tyrosine-containing proteins expression. However, phosphorylated tyrosine-containing proteins correlated with cell proliferation activity evaluated (P((Low, High))<0.0001; P((Low, Int)) <0.0001; P((Int, High))<0.0001). Furthermore, non-small cell lung cancer cases with high expression and intermediate expression of phosphorylated tyrosine-containing proteins had a significantly shorter disease-free postoperative survival than those with low expression of phosphorylated tyrosine-containing proteins using log-rank analysis (P((Low, Int)) <0.0028; P((Low, High))=0.0002). Furthermore, phosphorylated tyrosine-containing proteins expression level statistically contributed to disease-free survival in Cox's proportional hazard model. Therefore, phosphorylated tyrosine-containing proteins in non-small cell lung cancer tissues seem to reflect its biological malignancy, and this evaluation may be valuable for constructing the most appropriate therapeutic strategy.

Aged↗

Isolation and characterization of a homologue of mammalian prolactin-releasing peptide from the tilapia brain and its effect on prolactin release from the tilapia pituitary.

In the tilapia (Oreochromis mossambicus), as in many teleosts, prolactin (PRL) plays a major role in osmoregulation in freshwater. Recently, PRL-releasing peptides (PrRPs) have been characterized in mammals. Independently, a novel C-terminal RF (arginine-phenylalanine) amide peptide (Carrasius RF amide; C-RFa), which is structurally related to mammalian PrRPs, has been isolated from the brain of the Japanese crucian carp. The putative PrRP was purified from an acid extract of tilapia brain by affinity chromatography with antibody against synthetic C-RFa and HPLC on a reverse-phase ODS-120 column. The tilapia PrRP cDNA was subsequently cloned by polymerase chain reaction. The cDNA consists of 619 bp encoding a preprohormone of 117 amino acids. Sequence comparison of the isolated peptide and the preprohormone revealed that tilapia PrRP contains 20 amino acids and is identical to C-RFa. Incubation of the tilapia pituitary with synthetic C-RFa (100 nM) significantly stimulated the release of two forms of tilapia PRL (PRL188 and PRL177). However, the effect of C-RFa was less pronounced than the marked increase in PRL release in response to hyposmotic medium. The ability of C-RFa to stimulate PRL release appears to be specific, since C-RFa failed to stimulate growth hormone release from the pituitary in organ culture. In contrast, rat and human PrRPs had no effect on PRL release. C-RFa was equipotent with chicken GnRH in stimulating PRL release in the pituitary preincubated with estradiol 17beta. Circulating levels of PRL were significantly increased 1 h after intraperitoneal injection of 0.1 microg/g of C-RFa in female tilapia in freshwater but not in males. These results suggest that C-RFa is physiologically involved in the control of PRL secretion in tilapia.

Amino Acid Sequence↗

Statistical parametric mapping of hypoxic tissue identified by [(18)F]fluoromisonidazole and positron emission tomography following acute ischemic stroke.

Positron emission tomography (PET) and the ligand [(18)F]fluoromisonidazole ((18)F-FMISO) have been used to image hypoxic tissue in the brain following acute stroke. Existing region of interest (ROI)-based methods of analysis are time consuming and operator-dependent. We describe and validate a method of statistical parametric mapping to identify regions of increased (18)F-FMISO uptake. The (18)F-FMISO PET images were transformed into a standardized coordinate space and intensity normalized. Then t statistic maps were created using a pooled estimate of variance. Statistical inference was based on the theory of Gaussian Random Fields. We examined the homogeneity of variance in normal subjects and the influence of normalization by mean whole brain activity versus mean activity in the contralateral hemisphere. Validity of the distributional assumptions inherent in parametric analysis was tested by comparison with a non-parametric method. The results of parametric analysis were also compared with those obtained with the existing ROI-based method. Variance in uptake at each voxel in normal subjects was homogeneous and not affected by mean voxel activity or distance from the centre of the image. The method of normalization influenced results significantly. Normalization by whole brain mean activity resulted in a smaller volume of tissue being classified as hypoxic compared to normalisation by mean activity in the contralateral hemisphere. The ROI-based method was subject to interobserver variability with a coefficient of variability of 16%. The volumes of hypoxic tissue identified by parametric and nonparametric methods were highly correlated (r = 0.99). These findings suggest that using a pooled variance and contralateral hemisphere normalisation, statistical parametric mapping can be used to objectively identify regions of increased (18)F-FMISO uptake following acute stroke in individual subjects.

Acute Disease↗

A novel method of drug delivery for fibrinolysis with Ho:YAG laser-induced liquid jet.

Two of the problems inherent in the treatment of cerebral emboli are the narrow therapeutic time window and the severe side effects of fibrinolytic drugs. Thus, it is necessary to develop a new method of removing a cerebral thrombus more rapidly and with smaller quantities of fibrinolytics. The behaviour of a bubble formed by holmium (Ho):YAG laser irradiation in a capillary tube filled with pure water was observed at various stand-off distances (L; distance between the end of optical fibre and the capillary exit). Subsequently, a liquid-jet generator was created by insertion of an optical fibre (core diameter: 0.6 mm) into a catheter (6 Fr) filled with pure water, and a pulsed Ho:YAG laser (pulse duration time=350 micros, laser energy=230 mJ/pulse) was used to irradiate the optical fibre. The maximum penetration depth, into a gelatin artificial thrombus, of a liquid jet generated with this device was measured for various stand-off distances. Additionally, the phenomenon and the pressure around the catheter exit were captured via shadowgraph and PVDF needle hydrophone, respectively. The laser-induced bubble in the capillary tube grew rapidly in the direction of propagation and generated a liquid jet. The maximum penetration depth of this liquid jet into an artificial thrombus increased in proportion to L and reached a maximum value (9 mm) when L was around 13 mm. A shock wave whose overpressure at a point 4 mm away from the catheter exit exceeded 12 MPa was captured by shadowgraph. It was concluded that Ho:YAG laser irradiation within a water-filled catheter caused liquid jet formation, which could penetrate straight into an artificial thrombus. Hence, this jet is expected to promote fibrinolysis by means of injecting fibrinolytics deeply into the thrombus. After resolving some problems, this system will be applied to an endovascular therapy for cerebral embolisms in the near future.

Catheterization↗

Tyrosine 759 of the cytokine receptor gp130 is involved in Listeria monocytogenes susceptibility.

Interleukin-6 family cytokines have been implicated in adaptive and innate immunity, hematopoiesis, and inflammation. This cytokine family shares a signal-transducing receptor subunit called gp130. gp130(F759/F759) knockin mice carry a point mutation at the SHP2-binding site of gp130 due to the replacement of tyrosine-759 (Y759 for human gp130) with phenylalanine (F). To explore the effect of this point mutation on the host response to bacterial infection, gp130(F759/F759) knockin mice were infected with Listeria monocytogenes. gp130(F759/F759) knockin mice began to die at 3 to 4 days post infection (p.i.) and showed higher mortality than did controls. Listeria titers at 3 days p.i. in the peritoneal cavity, spleen, and liver were significantly higher in gp130(F759/F759)knockin mice than in controls. Nitric oxide production, upregulation of the mRNA levels of a variety of cytokines, and listericidal activity in gp130(F759/F759) macrophages were unchanged. However, gp130(F759/F759) knockin mice displayed significantly lower levels of interferon (IFN)gamma in serum and in the culture supernatant from peritoneal exudate cells and splenocytes, in response to Listeria infection. These results suggest that the Y759 point mutation in gp130 attenuates the early phase of defense against Listeria infection, possibly owing to insufficient elevation of IFNgamma levels, and thus gp130 is a possible candidate gene for Listeria susceptibility.

Animals↗

A new deletion mutation in bovine Claudin-16 (CL-16) deficiency and diagnosis.

Bovine claudin-16/paracellin-1 (CL-16/PCLN-1) deficiency is an autosomal recessive disorder caused by a 37-kb deletion mutation containing the first four exons of the CL-16 gene, which leads to the absence of the CL-16 transcript (type-1 mutation). A PCR-based DNA test for the CL-16 mutation (type-1) was used to screen a herd of Wagyu cattle. A recent report suggested that affected cattle can be bred by dams diagnosed as normal, suggesting the presence of a new mutation in the CL-16 locus. We identified the new mutation as a 56-kb deletion containing exon-1 to -4 and 21-bp of exon-5 of CL-16, and refer to this as a type-2 mutation. A DNA test for specific for this mutation was then established.

Animals↗

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and CADASIL-like disorders in Japan.

We reviewed 12 patients from 11 Japanese families diagnosed as having CADASIL from 1998 to 2001. The age of onset of focal neurologic deficits ranged from 38 to 71 years (mean: 50.4 +/- 9.8 years). Japanese CADASIL patients rarely had migraine and frequently presented with symptoms of dementia at diagnosis. Notch3 mutations were concentrated in exons 3, 4, and 5. Cysteine was replaced by another amino acid or vice versa in the majority of Japanese CADASIL patients. However, in 2 families, the mutations were not related to cysteine. In the prospective study, 2030 patients with stroke were hospitalized in 6 hospitals with stroke units in the Kumamoto district from 1999 to 2001. Among them, 14 patients fulfilled the criteria of being less than 60 years of age, showing lacunar strokes and/or TIA, presence of a family history, and no risk factors of stroke. One of these 14 patients was diagnosed as having CADASIL by DNA analysis. However, if hyperlipidemia was excluded from the list, 16 patients fulfilled the criteria and 2 patients were diagnosed as having CADASIL by DNA analysis. It was suspected that the incidence of CADASIL is not so rare in Japan. There were some families with CADASIL-like features, but without Notch3 mutations or GOM, suggesting the need for genetic analysis in the future.

Adult↗

Baseline blood pressure but not early computed tomography changes predicts major hemorrhage after streptokinase in acute ischemic stroke.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage is the most serious complication of thrombolytic therapy for stroke. We explored factors associated with this complication in the Australian Streptokinase Trial. METHODS: The initial CT scans (< or =4 hours after stroke) of 270 patients were reviewed retrospectively by an expert panel for early signs of ischemia and classified into the following 3 categories: no signs or < or =1/3 or >1/3 of the vascular territory. Hemorrhage on late CT scans was categorized as major or minor on the basis of location and mass effect. Stepwise, backward elimination, multivariate logistic regression analysis was used to identify risk factors for each hemorrhage category. RESULTS: Major hemorrhage occurred in 21% of streptokinase (SK) and 4% of placebo patients. Predictors of major hemorrhage were SK treatment (odds ratio [OR], 6.40; 95% CI, 2.50 to 16.36) and elevated systolic blood pressure before therapy (OR, 1.03; 95% CI, 1.01 to 1.05). Baseline systolic blood pressure >165 mm Hg in SK-treated patients resulted in a >25% risk of major secondary hemorrhage. Early ischemic CT changes, either < or =1/3 or >1/3, were not associated with major hemorrhage (OR, 1.58; 95% CI, 0.65 to 3.83; and OR, 1.11; 95% CI, 0.45 to 2.76, respectively). Minor hemorrhage occurred in 30% of the SK and 26% of the placebo group. Predictors of minor hemorrhage were male sex, severe stroke, early CT changes, and SK treatment. Ninety-one percent of patients with major hemorrhage deteriorated clinically compared with 23% with minor hemorrhage. CONCLUSIONS: SK increased the risk of both minor and major hemorrhage. Major hemorrhage was also more likely in patients with elevated baseline systolic blood pressure. However, early CT changes did not predict major hemorrhage. Results from this study highlight the importance of baseline systolic blood pressure as a potential cause of hemorrhage in patients undergoing thrombolysis.

Acute Disease↗

Immunomodulatory effects of prolactin and growth hormone in the tilapia, Oreochromis mossambicus.

To clarify the roles of prolactin (PRL) and GH in the control of the immune system, the effects of environmental salinity, hypophysectomy, and PRL and GH administration on several immune functions were examined in tilapia (Oreochromis mossambicus). Transfer from fresh water (FW) to seawater (SW) did not alter plasma levels of immunoglobulin M (IgM) and lysozyme. The superoxide anion (O(2)(-)) production in head kidney leucocytes accompanied by phagocytosis was elevated in SW-acclimated fish over the levels observed in FW fish. Hypophysectomy of the fish in FW resulted in a reduction in O(2)(-) production in leucocytes isolated from the head kidney, whereas there was no significant change in plasma levels of IgM or lysozyme. Treatment with tilapia GH and PRLs (PRL(177) and PRL(188)) enhanced O(2)(-) production in vitro in head kidney leucocytes in a dose-related manner. Extrapituitary expression of two PRLs, GH and IGF-I mRNA was detected in lymphoid tissues and cells such as head kidney, spleen, intestine and leucocytes from peripheral blood and head kidney. PRL-receptor mRNA was detected in head kidney leucocytes, and the level of expression was higher in SW-acclimated fish than that in FW fish. Treatment with PRL(177) caused higher production of O(2)(-) in the head kidney leucocytes isolated from SW tilapia than that from FW fish. In view of the fact that PRL acts antagonistically to osmoregulation in SW, its immunomodulatory actions in this euryhaline fish would appear to be independent of its osmoregulatory action.

Adaptation, Physiological↗