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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 127 records · Page 7Linked to original sources
PubMed2000

The relationship between technical parameters of external beam radiation therapy and complications for localized prostate cancer.

BACKGROUND: This study was performed to review retrospectively the clinical course of chronic rectal bleeding as a complication of external beam radiation therapy for localized prostate cancer and to analyze the relationship between technical parameters of radiation therapy and the complications. METHODS: Seventy-one patients with stages A2, B and C were treated with local-field radiotherapy (total dose 52.5-66 Gy, daily dose 2.0-3.28 Gy, field area 30-81 cm2, number of fields 3-15 ports, planning simulations X-ray or CT-based) between 1989 and 1998 at three institutions. The protocols were consistent during this same period at these institutions. RESULTS: Multivariate analysis revealed pretreatment PSA and Gleason sum to be statistically significant predictors of 5 year prostatic specific antigen (PSA) relapse-free rates in a median follow-up period of 42 months (range 12-119 months). The significant risk factors for higher grading of acute morbidity were a biological equivalent dose, alpha/beta = 10(BED10) > or =65 Gy, dose per fraction > or =3.0 Gy, field area > or =42 cm2, fewer ports and X-ray planning simulation. However, no parameter was associated with higher grading of late morbidity. Eleven patients (15.4%) experienced a late GI complication: grade 1 (4.2%), grade 2 (9.8%), grade 3 (1.4%). The median time to occurrence of rectal bleeding was 12 months after radiotherapy and the mean duration of morbidity was 11 months. CONCLUSIONS: Higher total dose and dose per fraction, larger field area, fewer ports and X-ray simulation increased the grades of acute morbidity. A majority of chronic rectal bleedings were transient and responded to conservative treatment.

Aged↗
PubMed2000

Substrate specificity of bovine cathepsin B and its inhibition by CA074, based on crystal structure refinement of the complex.

The crystal structure of the bovine spleen cathepsin B (BSCB)-CA074 complex was refined to R = 0.152 using X-ray diffraction data up to 2.18 A resolution. BSCB is characterized by an extra Cys148-Cys252 disulfide bridge, as compared with rat and human CBs. Although the crystal structures of these enzymes showed similar overall folding, a difference was observed in the occluding loop, a structural element specific only to CB. Comparison of the torsion angles indicated the different flexibilities of their loop structures. The oxirane C6 atom of CA074 was covalently bonded to the Cys29 S(gamma) atom (C3-S(gamma)=1.81 A), where the S-configuration was transformed to the R-form. Concerning the oxirane carbon atom that participates in the covalent bonding with the Cys residue, an acceptable rule has been proposed. The substrate specificities at the Sn (n = 1-3) and Sn' (n=1 and 2) subsites of CB, together with the interaction features as to CA074, have been discussed in comparison with the crystal structure of the papain-CA028 (a CA074-related inhibitor) complex.

Amino Acid Sequence↗
PubMed2000

Phylogenetic analysis of psychrophilic bacteria isolated from the Japan Trench, including a description of the deep-sea species Psychrobacter pacificensis sp. nov.

Phylogenetic positions of psychrophilic bacteria isolated from the Japan Trench were determined by sequencing analysis of PCR-amplified bacterial small subunit (16S) rRNA genes. Between surface and deep-sea psychrophiles, distinct positions clearly differed within the gamma-Proteobacteria. In phylogenetic analysis using neighbour-joining, maximum-parsimony and maximum-likelihood, strains from surface seawater were inferred to be located in the Halomonas aquamarina-meridiana clade within the family Halomonadaceae. Strains from deep seawater (5000-6000 m), however, formed a novel monophyletic clade within the Moraxella-Psychrobacter branch in the family Moraxellaceae, showing separation from terrestrial and Antarctic relatives. These deep-sea strains were also discriminated from other known Psychrobacter species in phenotype, e.g. limited growth in the absence of NaCl (optimum at about 3% NaCl), positive urease activity, acid production from xylose and arabinose, and the presence of multiple fimbriae. DNA relatedness values among six deep-sea strains were > 85% in DNA-DNA hybridization experiments and > 98% in aligned 16S rDNA sequences. From this evidence, a new species, Psychrobacter pacificensis, is proposed for these deep-sea psychrophiles; the type strain of Psychrobacter pacificensis is strain NIBH P2K6T (= IFO 16270T). Occurrence of psychrobacters in cold Japan Trench deep seawater and at the Antarctic sea surface suggests that deep-sea bacterial habitation and evolution have been mediated by global deep-ocean circulation linked to the sinking of cooled seawater in polar regions.

Cold Temperature↗
PubMed2000

A physiological role for adrenomedullin in rats; a potent hypotensive peptide in the hypothalamo-neurohypophysial system.

Adrenomedullin, a potent hypotensive peptide, was originally isolated from human phaeochromocytoma. Adrenomedullin immunoreactivity and gene expression are found not only in peripheral organs but also in the central nervous system. Adrenomedullin labelled cells were localised in the hypothalamus, including in the paraventricular and supraoptic nuclei, in rats. Abundant adrenomedullin-immunoreactive fibres and varicosities were found in the hypothalamo-neurohypophysial tract and the internal zone of the median eminence in colchicine-treated and hypophysectomized rats, whereas in control rats few adrenomedullin-labelled fibres were observed. We examined the effects of intracerebroventricular administration of adrenomedullin on neurosecretory cells in the paraventricular and supraoptic nuclei of rats, using immunohistochemistry for Fos protein and in situ hybridisation histochemistry for c-fos mRNA. Intracerebroventricular administration of adrenomedullin caused a marked induction of Fos-like immunoreactivity in the paraventricular nucleus and the dorsal part of the supraoptic nucleus. In the paraventricular and supraoptic nuclei, nuclear Fos-like immunoreactivity was predominantly in oxytocin-immunoreactive cells rather than vasopressin-immunoreactive cells. The induction of c-fos mRNA in the paraventricular and supraoptic nuclei was increased in a dose-related manner 30 min after intracerebroventricular administration of adrenomedullin. This induction was reduced by pre-treatment with the adrenomedullin receptor antagonist, human adrenomedullin-(22-52)-NH2. Intracerebroventricular administration of adrenomedullin also caused a marked increase in the plasma concentration of oxytocin. Extracellular recordings from magnocellular neurosecretory cells in the paraventricular nucleus revealed that putative oxytocin-secreting cells were activated by intracerebroventricular administration of adrenomedullin. These results suggest that central adrenomedullin preferentially stimulates the secretion of oxytocin by activating hypothalamic oxytocin-secreting cells and may have an important role in salt appetite and body fluid homeostasis in rats.

Adrenomedullin↗
PubMed2000

Diastolic wall stress and ANG II in cardiac hypertrophy and gene expression induced by volume overload.

We investigated the effects of diastolic wall stress (WS) and angiotensin II (ANG II) on the left ventricular (LV) hypertrophy (LVH) induced by volume overload and on the gene expression of LV adrenomedullin (AM) and atrial natriuretic peptide (ANP) in volume overload. Diastolic WS was pharmacologically manipulated with (candesartan) or without (calcium channel blocker manidipine) inhibition of ANG II type 1 receptors in aortocaval-shunted rats over 6 wk. Diastolic WS reached a plateau at 2 wk and subsequently declined regardless of further LVH. Although diastolic WS was decreased to a similar extent by both compounds, candesartan blunted LVH over 6 wk, whereas manidipine blunted LVH at 2 wk but not after 4 wk. Levels of AM and ANP gene expression increased as LVH developed but were completely suppressed by candesartan over 6 wk. ANP expression level was also attenuated by manidipine over 6 wk, whereas AM expression level was suppressed at 2 wk but not after 4 wk by manidipine. We concluded that diastolic WS and ANG II might be potent stimuli for the LVH and LV AM and ANP gene expression in volume overload and that diastolic WS could be relatively involved in the early LVH and in the gene expression of ANP rather than of AM.

Adrenomedullin↗
PubMed2000

Frequency of microsatellite instability inBreast cancer determined by high-resolution fluorescent microsatellite analysis.

In breast cancer, the rates of positivity for microsatellite instability (MSI), vary greatly in the literature. Using high-resolution fluorescent microsatellite analysis (HFRMA), we studied microsatellite alterations in 75 patients with sporadic breast cancer. In this system, several devices were prepared to improve reproducibility of polymerase chain reaction products, migration accuracy of electrophoresis, and characteristics of the detection system. Precise and objective analyses of microsatellite alterations are made feasible using HRFMA. Seven of the 75 cases were judged to be positive for MSI, the rate of positivity being 9. 3%. This rate is relatively low compared to the data in the literature. All the microsatellite changes observed in this system can be classified into two types: type A with relatively small changes in microsatellite sequences observed in limited loci and type B with drastic and widely dispersed changes. The former was thought to be connected to abnormal activity in DNA mismatch repair (MMR). Among the 7 cases, 6 (8.0%) had type A alterations, which means that the tumors may have an abnormal MMR activity. Application of precise and objective systems for microsatellite analysis is expected to be clinically useful to detect patients at high risk for cancers.

Adult↗
PubMed2000

Increased plasma levels of mature adrenomedullin in chronic glomerulonephritis.

Adrenomedullin (AM) is a potent vasodilative and natriuretic peptide that is processed from its precursor as the intermediate form, AM-glycine-COOH (iAM). Subsequently, iAM is converted to the biologically active mature form, AM(1-52)-CONH(2) (mAM), by enzymatic amidation. Using immunoradiometric assays that recognize total AM (tAM) and only mAM, we determined the plasma and urinary levels of mAM and iAM in patients with chronic glomerulonephritis (CGN). The plasma mAM concentration was significantly higher in the patients than in the controls (1.8 +/- 0.1 vs. 1.3 +/- 0.1 fmol/ml, p < 0.01), whereas the plasma iAM concentration of the CGN patients did not significantly differ from that of the controls (9.4 +/- 0.5 vs. 8.9 +/- 0.5 fmol/ml). Levels of urinary mAM excretion in the patients did not statistically differ from those of the controls (1. 6 +/- 0.4 vs. 2.0 +/- 0.3 fmol/mg creatinine), whereas urinary iAM excretion was significantly lower in the CGN patients (3.7 +/- 0.7 vs. 5.6 +/- 0.8 fmol/mg creatinine, p < 0.05). Urinary excretion levels of mAM significantly correlated with those of sodium (r = 0. 47, p < 0.05), whereas those of iAM did not. In conclusion, the plasma ratio of mAM to iAM is augmented in CGN patients, and mAM appears to be involved in the regulation of sodium. Therefore, determination of the mAM in addition to the tAM concentration is essential in CGN patients.

Adolescent↗
PubMed2000

Enhanced adrenomedullin production by mechanical stretching in cultured rat cardiomyocytes.

Adrenomedullin (AM) is secreted from cultured cardiac myocytes. In this study, we examined whether mechanical stretching stimulates AM production in cardiac myocytes, and if so, whether angiotensin II (Ang II) is involved in that mechanism. Neonatal rat cardiac myocytes cultured in serum-free medium were stretched 10% or 20% on flexible silicone rubber culture dishes, and AM mRNA expression was examined by quantitative polymerase chain reaction. The AM mRNA levels in the myocytes stretched 10% and 20% for 24 hours significantly increased by 56% (P<0.05) and 88% (P<0.01), respectively, when compared with the levels in nonstretched cells. AM secretion into the medium after the myocytes were stretched 10% and 20% increased by 22% (P<0.05) and 45% (P<0.01), respectively. In nonstretched myocytes incubated with 10(-6) mol/L Ang II for 24 hours, AM mRNA and secretion increased by 86% (P<0.05) and 36% (P<0. 01), respectively. These effects of Ang II were abolished by 10(-6) mol/L CV-11974, an Ang II type I (AT(1)) receptor antagonist, but not by 10(-6) mol/L PD-123319, an Ang II type II antagonist. Stretch-induced increases of AM gene expression and secretion were significantly inhibited (P<0.05) in the presence of 10(-6) mol/L CV-11974 by 46% and 52%, respectively; however, they were not affected by 10(-6) mol/L PD-123319. These findings indicate that AM production from cardiac myocytes is augmented by mechanical stretching, partially through the AT(1) receptors, which suggests a local interaction between AM and the renin-angiotensin system in stretched cardiac myocytes.

Adrenomedullin↗
PubMed2000

Molecular dynamics simulations of bovine cathepsin B and its complex with CA074.

To promote our better understanding of the dynamic stability of the bovine cathepsin B structure, which is characterized by an extra disulfide bond at Cys148-Cys252 from the other species, and of the binding stability of CA074 (a cathepsin B-specific inhibitor), molecular dynamics (MD) simulations were performed for the enzyme and its CA074 complex, assuming a system in aqueous solution at 300 K. The MD simulation covering 400 ps indicated that the existence of a Cys148-Cys252 disulfide bond increases the conformational flexibility of the occluding loop, although the conformational stability of the overall structure is little affected. The structural characteristics of the complex elucidated by X-ray analysis were suggested to be also intrinsic and stable in the dynamic state; the hydrogen bonding/electrostatic interactions between the main and side chains of CA074 and the Sn and Sn' subsites of the enzyme were maintained throughout the MD simulation. Furthermore, the simulation made clear that the binding of CA074 significantly restricted the conformational flexibility of the substrate binding region, especially the occluding loop, of cathepsin B. Statistical analyses during the simulation suggest that the selectivity of CA074 for cathepsin B stems from the tight P1'-S1' and P2'-S2' interactions, assisted in particular by double hydrogen bonds between the carboxyl two oxygens of the CA074 C-terminus and the imidazole NH groups of His110 and His111 residues.

Animals↗
PubMed2000

Labyrinthine involvement and multiple perforations of the tympanic membrane in acute otitis media due to group A streptococci.

We present here three cases of acute otitis media caused by a virulent group A streptococcal infection that rapidly led to deterioration in hearing. Two of the three cases presented with severe sensorineural and mixed hearing loss with multiple tympanic membrane perforations, and the third presented with severe bilateral sensorineural hearing loss following acute otitis media involving group A streptococci. All patients were treated with systemic (piperacillin) and topical antibiotics (ofloxacin ear drops): one patient also received a systemic steroid (betamethasone). Deafness persisted in one patient but in the other two, hearing gradually recovered. Severe cytotoxicity was considered to have occurred in all patients, resulting in multiple perforations of the tympanic membrane and necrosis in the middle ear.

Adult↗
PubMed2000

Atypical aortic coarctation with resistant hypertension treated with axilloiliac artery bypass.

A 68-year-old woman was found to have atypical coarctation of the aorta, accompanied by systolic hypertension of the upper extremities despite administration of five types of antihypertensive drugs. Since the systolic hypertension was resistant to the conventional antihypertensive therapy, axilloiliac artery bypass grafting with a subcutaneous tunnel was performed to alleviate the pressure gradient. Systolic blood pressure was successfully reduced and hypertension was controlled after surgery.

Aged↗
PubMed2000

Health effects of chronic exposure to polychlorinated dibenzo-P-dioxins (PCDD), dibenzofurans (PCDF) and coplanar PCB (Co-PCB) of municipal waste incinerator workers.

A national survey of polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF) in emission gases from the municipal waste incinerators in 1997 revealed that the Nose Bika Center was heavily contaminated by PCDF. Ninety-four workers underwent a physical examination, and blood biochemistry, lymphocyte marker, and NK activity studies were carried out, along with blood dioxin measurements. Information on working history, life-style, and dietary habits was obtained by questionnaire and interview. The blood dioxin levels were as follows. The median TEQ of dioxins was 39.7 pg I-TEQ/g lipid, and the range was 13.3 to 805.8. The median 2,3,7,8-TCDD concentration was 3.9 pg TEQ/g lipid, and the range was <1 pg TEQ/g lipid (one case) to 13.4 pg TEQ/g lipid. The median TEQ of coplanar PCB was 10.8 pg I-TEQ/g lipid, and the range was 3.1 to 54.2 pg TEQ/g lipid. The congener-specific distribution was quite similar to that in soil around incinerator and waste in the factory. The relationship between dioxin concentrations and work history in the factory showed that the fluidized incinerator and fly ash treatment areas were high-risk work areas. Correlation analyses between body burden, PCDD/PCDF TEQ, Co-PCB TEQ and various laboratory data showed significant positive correlations between dioxin levels and GGT, total protein, uric acid and calcium, and a negative correlation with Fe. However, these correlations disappeared as a result of multivariate analysis adjusted for age, smoking status, and alcohol drinking. Increased NK activity and lower response to PHA stimulation remained significant even after adjusting for age. History of hyperlipidemia and allergy had significantly increased odds ratios. A study on the risk to other workers in the same type of incinerators is under way. Health effects of chronic exposure mainly to PCDF will be clarified by follow-up.

Adolescent↗
PubMed2000

[Phaeomycotic cyst caused by Phaeoacremonium parasiticum].

Phaeoacremonium parasiticum was identified as the causative agent of a phaeomycotic cyst seen just below the right knee of a 59-year-old healthy woman. She had no history of trauma. Direct KOH examination of the pus aspirated from the subcutaneous nodule revealed abundant mycelia, which were not too deeply brown in color. The nodule was surgically excised, and there was no recurrence during a half year of observation. Tissue section of the excised material revealed rather a large cavity extending from the cutis to the subcutis. The cavity had a thick wall composed of granulomatous tissues. Mycelial and yeast-like fungal elements were seen within the cavity and the granulomatous tissues. A dematiaceous fungus was cultured from both pus and the excised material. The isolates were characterized by a dark green to black colony, unbranched or infrequently branched, brownish conidiophores bearing an aculeate monophialide with a narrow funnel-shaped collarette, and slimy, hyaline, one-celled, ellipsoid to allantoid conidia.

Cysts↗