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K Hamada

Publications and source records attributed to K Hamada.

At least 19 recordsLinked to original sources

Perioperative real-time monitoring of indocyanine green clearance by pulse spectrophotometry predicts remnant liver functional reserve in resection of hepatocellular carcinoma.

BACKGROUND: There is no standard method for predicting remnant liver functional reserve after hepatectomy or for monitoring it in real time. METHODS: Indocyanine green (ICG) clearance (K) was measured non-invasively and instantaneously using pulse spectrophotometry before surgery, during inflow occlusion and after hepatectomy in 75 patients who underwent anatomical liver resection for hepatocellular carcinoma (HCC). RESULTS: Eight patients (11 per cent) suffered liver failure and one (1 per cent) died in hospital. An estimated remnant K value of 0.090 per min was the cut-off value for liver failure. In a logistic regression model, the estimated remnant K (0.090 per min; P = 0.022) and age (65 years; P = 0.025) were significant predictors of postoperative liver failure. There was a correlation between the estimated and measured post-hepatectomy K, and between the inflow occlusion K and measured post-hepatectomy K (P < 0.001). The cut-off value of less than 0.090 per min for the estimated remnant K resulted in 88 per cent sensitivity and 82 per cent specificity for predicting liver failure. CONCLUSION: Perioperative real-time monitoring of ICG-K is useful for evaluating the remnant liver functional reserve before, during and after liver resection for HCC. The estimated remnant K is a significant predictor of liver failure.

Aged↗

Inhibitory autocrine factors produced by the mesenchyme-derived hair follicle dermal papilla may be a key to male pattern baldness.

BACKGROUND: Androgenetic alopecia, or male pattern baldness, is a common, progressive disorder where large, terminal scalp hairs are gradually replaced by smaller hairs in precise patterns until only tiny vellus hairs remain. This balding can cause a marked reduction in the quality of life. Although these changes are driven by androgens, most molecular mechanisms are unknown, limiting available treatments. The mesenchyme-derived dermal papilla at the base of the mainly epithelial hair follicle controls the type of hair produced and is probably the site through which androgens act on follicle cells by altering the regulatory paracrine factors produced by dermal papilla cells. During changes in hair size the relationship between the hair and dermal papilla size remains constant, with alterations in both dermal papilla volume and cell number. This suggests that alterations within the dermal papilla itself play a key role in altering hair size in response to androgens. Cultured dermal papilla cells offer a useful model system to investigate this as they promote new hair growth in vivo, retain characteristics in vitro which reflect their parent follicle's response to androgens in vivo and secrete mitogenic factors for dermal papilla cells and keratinocytes. OBJECTIVES: To investigate whether cultured dermal papilla cells from balding follicles secrete altered amounts/types of mitogenic factors for dermal papilla cells than those from larger, normal follicles. We also aimed to determine whether rodent cells would recognize mitogenic signals from human cells in vitro and whether factors produced by balding dermal papilla cells could alter the start of a new mouse hair cycle in vivo. METHODS: Dermal papilla cells were cultured from normal, balding and almost clinically normal areas of balding scalps and their ability to produce mitogenic factors compared using both human and rat whisker dermal papilla cells as in vitro targets and mouse hair growth in vivo. RESULTS: Normal scalp cells produced soluble factors which stimulated the growth of both human scalp and rat whisker dermal papilla cells in vitro, demonstrating dose-responsive mitogenic capability across species. Although balding cells stimulated some growth, this was much reduced and they also secreted inhibitory factor(s). Balding cell media also delayed new hair growth when injected into mice. CONCLUSIONS: Human balding dermal papilla cells secrete inhibitory factors which affect the growth of both human and rodent dermal papilla cells and factors which delay the onset of anagen in mice in vivo. These inhibitory factor(s) probably cause the formation of smaller dermal papillae and smaller hairs in male pattern baldness. Identification of such factor(s) could lead to novel therapeutic approaches.

Alopecia↗

Comparison of nutrient removal efficiency between pre- and post-denitrification wastewater treatments.

A shortage of organic substances (COD) may cause problems for biological nutrient removal, that is, lower influent COD concentration leads to lower nutrient removal rates. Biological phosphorus removal and denitrification are reactions in which COD is indispensable. As for biological simultaneous nitrogen and phosphorus removal systems, a competition problem of COD utilisation between polyphosphate accumulating organisms (PAOs) and non-polyphosphate-accumulating denitrifiers is not avoided. From the viewpoint of effective utilisation of limited influent COD, denitrifying phosphorus-removing organisms (DN-PAOs) can be effective. In this study, DN-PAOs activities in modified UCT (pre-denitrification process) and DEPHANOX (post-denitrification process) wastewater treatments were compared. In conclusion, the post-denitrification systems can use influent COD more effectively and have higher nutrient removal efficiencies than the conventional pre-denitrification systems.

Aerobiosis↗

Esophageal candidiasis as a side effect of inhaled fluticasone propionate dry powder: recovery by switching over to hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP).

BACKGROUND: Esophageal candidiasis is one of the local side effects of inhaled corticosteroid treatment, and it is difficult to prevent this condition. Our previous report indicated that the prevalence of esophageal candidiasis among patients treated with inhaled fluticasone propionate dry powder (FP-dp) reached up to 37% in Japanese patients. Although a reduction in the daily dose of inhaled FP-dp can eliminate this infection, it may lead to asthma not being well-controlled in these patients. OBJECTIVE: The aim of this study was to estimate whether switching to an equal daily dose of inhaled hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP), the oropharyngeal deposition of which is very low, can eliminate the infection without deterioration of asthma. METHODS: A total of 10 stable asthmatic patients with esophageal candidiasis, induced by inhaled FP-dp treatment (400 or 800 microg/ day), were enrolled in this study. A second upper GI endoscopy was performed, more than 1 month but less than 3 months after switching to an equal dose of inhaled HFA-BDP with a tube spacer device, Duopacer. The patients' medications were not changed during the study. RESULTS: Esophageal candidiasis was eliminated in 9 of the 10 patients. The degree of candidiasis reduced in another patient. The forced expiratory volume in 1 sec (FEV1.0) did not worsen during the study. CONCLUSION: Switching from FP-dp to HFA-BDP with Duopacer is useful in preventing esophageal candidiasis.

Administration, Inhalation↗

Progression and prognosis in pure autonomic failure (PAF): comparison with multiple system atrophy.

OBJECTIVE: To clarify the progression of autonomic symptoms and functional deterioration in pure autonomic failure (PAF), particularly in comparison with multiple system atrophy (MSA). METHODS: The investigation involved eight patients with PAF (M/F = 7/1; mean age at onset, 57 years) and 22 with probable MSA matched for age at onset (M/F = 14/8; onset 56 years). Subjects were followed up for neurological symptoms, activities of daily living, and autonomic function for more than seven years. Autonomic functional tests were carried out. RESULTS: In PAF, fainting or sudomotor dysfunction occurred first, followed by constipation and syncope. Urinary dysfunction developed late, and respiratory dysfunction was not evident. This clinical course contrasted sharply with that in MSA, where early urinary dysfunction usually proceeded to sudomotor dysfunction or orthostatic hypotension (p = 0.004), followed by respiratory dysfunction (p = 0.0004). Results of pharmacological tests also distinguished PAF from MSA. Progression and prognosis in patients with PAF did not worsen, unlike the steady progressive autonomic dysfunction in MSA (p < 0.0001, p < 0.0001, p = 0.0009, and p = 0.003, for progression to modified Rankin scale grade III, IV, V, and death, respectively). CONCLUSIONS: The time course and pattern of progression of autonomic failure differed significantly between PAF and MSA. Patients with PAF had slower functional deterioration and a better prognosis.

Activities of Daily Living↗

[Successful treatment of bronchial mucoepidermoid carcinoma by bronchoplasty].

A 63-year-old man who was pointed out abnormal shadow on chest X-ray admitted to our hospital. Chest computed tomography (CT) showed a tumor originated from right upper bronchus and grew into right main bronchus. The tumor was diagnosed as mucoepidermoid carcinoma by bronchoscopic biopsy. Fluorodeoxyglucose positron emission tomography (FDG-PET) showed abnormal uptake localized at the tumor. The standardized uptake values of the tumor 60 minutes after injection were 2.86, and 120 minutes after injection, it increased to 3.97. Right upper lobectomy with bronchoplasty by deep wedge resection of right main bronchus at the orifice of right upper bronchus and lymphadenectomy was performed. Pathological diagnosis was high-grade mucoepidermoid carcinoma without lymph nodes metastasis which was compatible with FDG-PET. Postoperative course was uneventful.

Bronchi↗

Midkine promoter-driven suicide gene expression and -mediated adenovirus replication produced cytotoxic effects to immortalised and tumour cells.

We examined possible application of a regulatory region of midkine (MK) gene, which is frequently upregulated in a number of human tumours but not in normal cells, to cancer gene therapy. We examined transcriptional activity of the MK genomic fragments in paired cell lines, immortalized cells and their parental normal fibroblasts, and found that the MK fragments activated a fused reporter or a suicide gene preferentially in the immortalized cells. Recombinant adenoviruses (Ad), in which the MK fragment was inserted upstream to the E1A gene (AdMK), replicated preferentially in the immortalized cells and were cytotoxie to them. Human hepatocellular carcinoma cells were significantly susceptible to AdMK compared with human normal fibroblasts in vitro and the replication of AdMK was less than that of wild-type Ad in the infected fibroblasts. Hepatocellular carcinoma cells infected with AdMK did not form tumours in immunocompromised mice and intratumoural injection of AdMK into the hepatocellular carcinoma developed in mice retarded the subsequent tumour growth. Expression of E1A and necrosis of tumours were detected in AdMK-injected but not control Ad-injected cases. The MK promoter-driven suicide gene therapy and -mediated replicative Ad can thereby produce cytotoxic effects to immortalized and tumour cells with minimal damage to normal cells.

Adenoviridae↗

Red blood cells regulate eosinophil chemotaxis by scavenging RANTES secreted from endothelial cells.

BACKGROUND: Eosinophils play a critical role in the pathogenesis of allergic diseases. CC chemokines, such as regulated on activation, normal, T cell expressed, and secreted (RANTES), are key regulators of eosinophil locomotion. Although eosinophils migrate from the bloodstream into tissues, mechanisms that generate a chemogradient across the endothelium remain to be fully elucidated. OBJECTIVE: We first examined the polar secretion of RANTES by endothelial cells. We also studied the functional scavenging effect of red blood cells (RBCs) on RANTES secreted into the intravascular side. METHODS AND RESULTS: Endothelial cells were cultured in a transwell chamber with a membrane pore size of 0.45, 3.0, and 8.0 microm and stimulated with TNF-alpha, IL-1beta, or IFN-gamma from the apical or basolateral side for 16 h. The measurement of RANTES in the supernatant was performed by ELISA. We did not see any difference in the amount of RANTES secreted from the cytokine-stimulated endothelium between inner (intravascular side) and outer (extravascular side) wells separated by the 8.0-microm membrane, although apical polarization was observed with the 0.45-microm membrane. The addition of RBCs (hemoglobin (Hb): 0.5-15 g/dL) to the apical supernatant of TNF-alpha-stimulated endothelial cells reduced the RANTES level in a concentration-dependent manner. The treatment of supernatant on the intravascular side with RBCs significantly enhanced the migration of eosinophils. CONCLUSION: RBCs possess a scavenging effect on intravascular RANTES, and thereby regulate transendothelial migration of eosinophils. Our findings suggest a new role of RBCs in allergic inflammation.

Cell Line↗

Multiple regional 1H-MR spectroscopy in multiple system atrophy: NAA/Cr reduction in pontine base as a valuable diagnostic marker.

OBJECTIVE: We performed (1)H-MR spectroscopy ((1)H-MRS) on multiple brain regions to determine the metabolite pattern and diagnostic utility of (1)H-MRS in multiple system atrophy (MSA). METHODS: Examining single voxels at 3.0 T, we studied metabolic findings of the putamen, pontine base, and cerebral white matter in 24 MSA patients (predominant cerebellar ataxia (MSA-C), n = 13), parkinsonism (MSA-P), n = 11), in 11 age and duration matched Parkinson's disease patients (PD) and in 18 age matched control subjects. RESULTS: The N-acetylaspartate to creatine ratio (NAA/Cr) in MSA patients showed a significant reduction in the pontine base (p<0.0001) and putamen (p = 0.02) compared with controls. NAA/Cr in cerebral white matter also tended to decline in long standing cases. NAA/Cr reduction in the pontine base was prominent in both MSA-P (p<0.0001) and MSA-C (p<0.0001), and putaminal NAA/Cr reduction was significant in MSA-P (p = 0.009). It was also significant in patients who were in an early phase of their disease, and in those who showed no ataxic symptoms or parkinsonism, or did not show any MRI abnormality of the "hot cross bun" sign or hyperintense putaminal rims. NAA/Cr in MSA-P patients was significantly reduced in the pontine base (p = 0.001) and putamen (p = 0.002) compared with PD patients. The combined (1)H-MRS in the putamen and pontine base served to distinguish patients with MSA-P from PD more clearly. CONCLUSIONS: (1)H-MRS showed widespread neuronal and axonal involvement in MSA. The NAA/Cr reduction in the pontine base proved highly informative in the early diagnosis of MSA prior to MRI changes and even before any clinical manifestation of symptoms.

Aspartic Acid↗

Mutations in the ST7/RAY1/HELG locus rarely occur in primary colorectal, gastric, and hepatocellular carcinomas.

Human cancers frequently show a loss of heterozygosity on chromosome 7q31, which indicates the existence of broad-range tumour-suppressor gene(s) at this locus. Truncating mutations in the ST7 gene at this locus are seen frequently in primary colon cancer and breast cancer cell lines. Therefore, the ST7 gene represents a novel candidate gene for the tumour suppressor at this locus. However, more recent studies have reported that ST7 mutations are infrequent or absent in primary cancer and cell lines. To ascertain the frequency of mutations of the ST7 gene in cancer cells, we examined mutations in the ST7 coding sequence in 48 colorectal, 48 gastric, and 48 hepatocellular carcinomas using polymerase chain reaction-single-strand conformational polymorphism and direct sequencing. We detected somatic mutations, which were located near the exon-intron junction in intron 8, in only three out of 144 cases. We conclude that mutations in the ST7 gene are rare in primary colorectal, gastric, and hepatocellular carcinomas.

Bacterial Proteins↗

The growth inhibitory effect of p21 adenovirus on androgen-dependent and -independent human prostate cancer cells.

OBJECTIVE: To assess the potential of p21 as a gene therapy treatment for prostate cancer, by introducing p21 into both androgen-dependent (AD) and -independent (AI) human prostate cancer cell lines via a recombinant adenoviral vector, Ad5CMV-p21, carrying human p21 cDNA. MATERIALS AND METHODS: The LNCaP, DU145 and PC-3 human prostate cancer cell lines were cultured and infected with Ad5CMV-p21. Cell growth, cell-cycle progression and tumorigenicity were then assessed by thymidine incorporation into cellular DNA, and cell number, flow cytometry, and tumour growth after inoculating the cells into nude mice. RESULTS: Growth was inhibited in Ad5CMV-p21 viral-infected AD and AI prostate cancer cells. The effects were dose-dependent, regardless of the androgen status of the cell lines. Flow cytometric analysis showed that Ad5CMV-p21 arrested cell-cycle progression at G1/S with no appreciable effect on the levels of apoptotic cells. The tumorigenicity of cancer cells infected with Ad5CMV-p21 was greatly reduced in athymic mice. CONCLUSIONS: These results suggest that Ad5CMV-p21 may be a new therapeutic agent for human prostate cancer gene therapy.

Adenoviridae↗

A novel pyrrole derivative, NS-8, suppresses the rat micturition reflex by inhibiting afferent pelvic nerve activity.

OBJECTIVE: To investigate the suppressive effect of a newly synthesized compound, 2-amino-3-cyano-5-(2-fluorophenyl)-4-methylpyrrole (NS-8), on micturition, and its mode and sites of action in rats. MATERIALS AND METHODS: Female rats were anaesthetized with urethane, and isovolumetric bladder contractions and cystometrograms recorded. The pelvic afferent discharges from the bladder were also monitored. RESULTS: In the cystometric study, NS-8 increased the bladder capacity without affecting the maximum bladder contraction pressure, an effect unlike that of currently used anticholinergic drugs for the overactive bladder, which commonly decrease the maximum bladder contraction pressure. Intravesical and intravenous injection of NS-8 inhibited isovolumetric bladder contractions in a dose-dependent manner without affecting their amplitude, whereas intracerebroventricular injection with NS-8 had no such effect. During the urine storage phase of the cystometrogram, NS-8 decreased the discharge rate of the afferent pelvic nerve from the bladder, in association with a decrease in the increase in intravesical pressure. CONCLUSION: NS-8 suppressed the micturition reflex by decreasing afferent pelvic nerve activity. Activation of calcium-sensitive potassium channel of the bladder may be responsible for such an effect. This agent has the potential to treat patients with urinary frequency and incontinence.

Animals↗

Onset age and severity of motor impairment are associated with reduction of myocardial 123I-MIBG uptake in Parkinson's disease.

OBJECTIVES: To elucidate the factors associated with severity of cardiac sympathetic nerve involvement in idiopathic Parkinson's disease (PD). METHODS: (123)I-metaiodobenzylguanidine uptake was examined in 88 patients with PD. The ratio of the uptake in the heart (H) to that in the mediastinum (M) (the H/M ratio) was calculated and correlated with age at onset, age at examination, and disease severity and duration. Twenty five healthy people were also examined as a control. RESULTS: There was a mild but significant negative correlation between H/M ratio and age at onset (early, r = -0.33, p = 0.002; delayed, r = -0.34, p = 0.001) and between Hoehn and Yahr (H-Y) stage (early, r = -0.30, p = 0.006; delayed, r = -0.32, p = 0.003). There was no significant correlation between disease duration and H/M ratio. When patients with PD were classified into four subgroups on the basis of age at onset (> 62 or < 62 years) and disease severity (H-Y > III or H-Y < or = II), the median H/M ratio of the older and more severe group was significantly lower than that of the younger and less severe group (p = 0.005). CONCLUSION: This study suggests that late onset, high severity PD is associated with myocardial sympathetic dysfunction.

3-Iodobenzylguanidine↗

Upregulated response to chemokines in oxidative metabolism of eosinophils in asthma and allergic rhinitis.

Reactive oxygen species (ROS) from eosinophils are known to cause tissue damage in allergic inflammation. CC chemokines, especially eotaxin and regulated on activation, normal T-cell expressed and secreted (RANTES), are involved not only in chemotaxis but also in eosinophil activation, such as ROS production. It has been shown that eosinophils from allergic patients are not functionally equivalent to those from normal subjects. In the present study, the characteristics of chemokine-primed ROS production in eosinophils from allergic patients and normal controls were compared. After pretreatment with chemokines, eosinophils were stimulated with calcium ionophore A23187. ROS production by eosinophils was measured using luminol-dependent chemiluminescence. Both RANTES and eotaxin exhibited a priming effect on calcium ionophore-induced ROS production from eosinophils. Despite there being no difference in expression of CC chemokine receptor 3, the priming effect of RANTES and eotaxin was significantly enhanced in eosinophils from the patients. Interleukin-5 further enhanced the priming effect of chemokines in eosinophils from normal subjects, but not those from allergic subjects. The present results suggest an upregulated response to chemokines in eosinophils from allergic patients, and that interleukin-5 can induce a similar phenotype to that found in vivo in allergic patients.

Adolescent↗

Phenotypes and mitochondrial DNA substitutions in families with A3243G mutation.

OBJECTIVE: To clarify the relationship between mitochondrial DNA (mtDNA) sequence variations and phenotypes in patients with A3243G mutation. MATERIALS AND METHODS: We studied whole mtDNA sequences in two families with A3243G mutation and characteristic clinical features. Two brothers in Family 1 had shown thiamine deficiency and mitochondrial myopathy without central nervous system involvement. In Family 2, a 16-year-old woman showed the symptoms of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Her mother had had diabetes mellitus and died at the age of 42. The proportion of A3243G mtDNA in blood was 87 and 89% in the patients of Family 1, and 25% in the patient and less than 5% in the mother of Family 2. RESULTS: The mtDNA analysis revealed the following homoplasmic substitutions: T1520C and C12153T found only in Family 1, and A15954G found only in Family 2. These substitutions were not detected in seven other MELAS patients or in 50 controls. CONCLUSION: These substitutions might be specific to these families and could be one of the factors that modulate their clinical features together with the A3243G mutation.

Adolescent↗

FR226807: a potent and selective phosphodiesterase type 5 inhibitor.

We describe the pharmacological characteristics of a novel phosphodiesterase type 5 inhibitor FR226807, N-(3,4-dimethoxybenzyl)-2-[[(1R)-2-hydroxy-1-methylethyl]amino]-5-nitrobenzamide. FR226807 inhibited phosphodiesterase type 5 isolated from human platelets with an IC(50) value of 1.1 nM. FR226807 also inhibited phosphodiesterase type 6 with an IC(50) of 20 nM; however, the IC(50) value for phosphodiesterase type 6 was 18-fold higher than that for phosphodiesterase type 5. The IC(50) values of FR226807 for other phosphodiesterases (phosphodiesterase type 1, phosphodiesterase type 2, phosphodiesterase type 3, and phosphodiesterase type 4) were 1000-fold higher than that for phosphodiesterase type 5. FR226807 increased the cyclic guanosine monophosphate (cGMP) content in corpus cavernosum isolated from rabbit, an effect associated with relaxation of the muscle. FR226807 enhanced the relaxation response induced by electrical field stimulation of corpus cavernosum isolated from the rabbit. In an anesthetized dog model for the evaluation of erectile function, intravenous administration of FR226807 prolonged the time to return to 75% of maximal intracavernosal pressure after cessation of electrical stimulation of the pelvic nerve. In summary, FR226807 is a potent and highly selective phosphodiesterase type 5 inhibitor with an augmentative effect on penile erection and will be useful for the treatment of erectile dysfunction.

3',5'-Cyclic-GMP Phosphodiesterases↗

Cloning of a novel 2',5'-oligoadenylate synthetase-like molecule, Oasl5 in mice.

The 2',5'-oligoadenylate synthetase (2-5OAS) is a enzyme that catalyzes synthesis of 2',5'-oligoadenylates (2-5A) in a dsRNA-dependent manner, and known as a major component of the IFN-induced host defense mechanisms against microbial infections. Here, we report the presence of a novel 2-5OAS-like molecule, termed Oasl5, in mice. The size of Oasl5 cDNA was about 2 kb and encoded a protein consisting of 362 aa. The amino acid sequence showed 76% similarity to the mouse 2-5OAS, however, several motifs being important for the enzyme activity were not conserved. The Oasl5 mRNA was most significantly expressed in the brain, and relatively weak expression was found in other organs such as the spleen, kidney, ovary and testis. It was also expressed in embryonic stem (ES) cells. The Oasl5 mRNA expression in ES cells was elevated 5-fold after treatment with IFN and about 2-fold in the brain when stimulated with IFN inducer, polyinosinic-polycytidylic acid (poly[I:C]). In situ hybridization analysis revealed that Oasl5 is expressed in neurons in the central nervous system in adult mice. When Oasl5 was expressed in E. coli, it yielded 42 kDa protein that binds to dsRNA, but it did not show oligoadenylate synthetase activity. These findings suggest a novel function of Oasl5, which are independent of oligoadenylate synthetase activity, in the brain and developing embryos.

2',5'-Oligoadenylate Synthetase↗

Crystallization and preliminary crystallographic studies of RhoGDI in complex with the radixin FERM domain.

The Rho guanine nucleotide-dissociation inhibitor (RhoGDI) is a general regulator that forms a complex with the GDP-bound form of Rho-family GTPases and suppresses their activation. The FERM domains of ERM (ezrin/radixin/moesin) proteins bind to RhoGDI and dissociate Rho from RhoGDI. The formation of a complex between RhoGDI and the FERM domain is an important step in the regulatory cycle of Rho activation. In this study, crystals of RhoGDI complexed with the FERM domain of radixin were obtained. The crystals of the binary complex belong to the space group P2(1)2(1)2, with unit-cell parameters a = 130.9 (2), b = 151.2 (2), c = 71.2 (1) A, and contain two protein complexes in the crystallographic asymmetric unit. A 2.9 A resolution data set was collected using synchrotron radiation at SPring-8.

Animals↗