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Biomedical subjects

T Komiyama

Publications and source records attributed to T Komiyama.

At least 73 records · Page 4Linked to original sources
PubMed1996

Elevation of serum levels of matrix metalloproteinase-2 and -3 as new predictors of recurrence in patients with urothelial carcinoma.

BACKGROUND: The relationship between serum levels of matrix metalloproteinase-2 (MMP-2) and MMP-3 and recurrence in patients with urothelial carcinoma after complete resection was studied to determine whether the enzymes could be a new predictor of recurrence. METHODS: Serum levels of MMP-2 and MMP-3 in 146 healthy controls, 52 patients with superficial (noninvasive) and 35 patients with advanced (invasive or metastatic) bladder carcinoma, and 30 patients with advanced upper urothelial carcinoma (renal pelvis and ureter) were measured by a one-step sandwich enzyme assay. RESULTS: Among the 53 patients with advanced urothelial carcinoma who underwent complete resection, the 1- and 3-year disease free survival rates of patients with elevated serum levels of either or both of the enzymes were 51% and 19%, respectively, whereas those of patients with normal serum levels of these enzymes were much higher, 86% and 79%, respectively (P < 0.005). In pT2N0M0 and pT3N0M0 patients who underwent complete resection, the recurrence rate in those with preoperative elevated serum levels of either or both of the enzymes was significantly higher than that in patients with normal levels (75% vs. 8%; P < 0.001). The 1- and 3-year disease free survival rates of pT2N0M0 and pT3N0M0 patients with elevated serum levels of either or both of the enzymes were 55% and 21%, respectively, which was significantly lower than that of patients with normal levels (92%; P < 0.001). CONCLUSIONS: The results of this study indicate that the elevation of serum levels of either MMP-2 or MMP-3 or both could be new predictors of recurrence in patients with advanced urothelial carcinoma after complete resection.

Adult↗
PubMed1996

Prognostic significance of circulating matrix metalloproteinase-2 to tissue inhibitor of metalloproteinases-2 ratio in recurrence of urothelial cancer after complete resection.

The relationship between the serum matrix metalloproteinase-2 (MMP-2):tissue inhibitor of metalloproteinases-2 (TIMP-2) ratio and disease recurrence was examined in 53 urothelial cancer patients with muscular invasion or with lymph node metastasis who underwent complete resection. The mean MMP-2:TIMP-2 ratio in 31 patients with recurrence was significantly higher than that in 22 patients without recurrence (P < 0.05). Disease-free survival of patients with high MMP-2:TIMP-2 ratios was extremely poor compared with that of patients with lower ratios (P < 0.01). Cox's multivariate analysis suggests that the serum MMP-2:TIMP-2 ratio would be a new independent prognostic indicator of urothelial cancer recurrence.

Female↗
PubMed1996

Soleus H-reflex depression induced by ballistic voluntary arm movement in human.

A biomechanical and neurophysiological analysis of anticipatory postural adjustments associated with the early phase of a voluntary arm movement was carried out in normal human subjects. Arm elevation, performed at maximal velocity, was studied with unilateral arm movement in freely and counterbalanced (suspended in a safety harness) standing humans. The ground reaction force of both legs, tangential acceleration of the shank and electromyographic activity (EMG) of the anterior deltoid (AD), biceps femoris (BF) and soleus (Sol) muscles were recorded. Sol H-reflexes of both legs were also elicited. To examine how the Ia inhibitory and presynaptic inhibitory pathways are related to anticipatory postural adjustments, additional Sol H-reflexes were elicited using the classical conditioning-test technique (time interval 2 and 15 ms, respectively). In this study, we systematically described biomechanical and EMG phenomena that precede and follow the onset of voluntary arm movements. Prior to and during the arm movement (i.e. AD activation), a sequence of EMG modifications occurred in ipsilateral BF and Sol muscles. Those modifications preceding BF activation included silent phases in Sol EMG and depression of Sol H-reflexes. By comparing EMG modifications with depressions of the Sol H-reflex, we conclude that Ia and presynaptic inhibitory pathways do not play a specific role in those Sol H-reflex depressions. Moreover, because Sol H-reflex depression occurs in both freely standing and counterbalanced postures, anticipatory postural adjustment appear to be preprogrammed in the central nervous systems unrelated to peripheral neural mechanisms. Since changes of EMG activities of ipsilateral BF and Sol appeared simultaneously and Sol H-reflex depressions were dependent on EMG activities of ipsilateral BF, control commands to anticipatory postural adjustment would excite BF and inhibit Sol.

Adult↗
PubMed1996

Interaction of subtilisins with serpins.

Serpins are well-characterized inhibitors of the chymotrypsin family serine proteinases. We have investigated the interaction of two serpins with members of the subtilisin family, proteinases that possess a similar catalytic mechanism to the chymotrypsins, but a totally different scaffold. We demonstrate that alpha 1 proteinase inhibitor inhibits subtilisin Carlsberg and proteinase K, and alpha 1 antichymotrypsin inhibits proteinase K, but not subtilisin Carlsberg. When inhibition occurs, the rate of formation and stability of the complexes are similar to those formed between serpins and chymotrypsin family members. However, inhibition of subtilisins is characterized by large partition ratios where more than four molecules of each serpin are required to inhibit one subtilisin molecule. The partition ratio is caused by the serpins acting as substrates or inhibitors. The ratio decreases as temperature is elevated in the range 0-45 degrees C, indicating that the serpins are more efficient inhibitors at high temperature. These aspects of the subtilisin interaction are all observed during inhibition of chymotrypsin family members by serpins, indicating that serpins accomplish inhibition of these two distinct proteinase families by the same mechanism.

Amino Acid Sequence↗
PubMed1996

Pore formation on proliferating yeast Saccharomyces cerevisiae cell buds by HM-1 killer toxin.

The cytocidal effect of HM-1 produced by Hansenula mrakii on yeast Saccharomyces cerevisiae cells was studied. The HM-1 strongly inhibited the growth of S. cerevisiae cells at a low concentration (IC50: 2.1 x 10(-8) M) by reducing the number of viable cells. The killer action of HM-1 was most efficient when cells were actively proliferating. Cells in a resting state were resistant, but they became HM-1-sensitive after about 90 min of culturing at 30 degrees C, concomitantly with the increment of budding index. In association with the reduction of viable cell number, ultraviolet light-absorbing cellular components were discharged from sensitive cells. HM-1 molecules appear to bind to susceptible cells rather loosely since cells incubated with HM-1 were able to proliferate after having been washed. By phase-contrast light microscopy and scanning electron microscopy, discharge of cell material was observed at the budding portions of HM-1-treated cells. Addition of sorbitol to make the culture medium isotonic partially reduced the cell death induced by HM-1. These results suggest that HM-1 acts on the budding region of proliferating yeast cells, resulting in pore formation, leakage of cell material and eventual cell death.

Cell Division↗
PubMed1996

[Hemodynamic study for the assessment of atherosclerotic occlusive disease].

Of all modalities used for the assessment of the severity of ischemic limbs none has proved to be more simple, reliable and reproducible than Doppler ultrasonography. The critical level that endangers the leg in patients with arteriosclerosis obliterans will be defined around 0.3 of ankle brahcial index by Doppler pressure measurement. Concerning the evaluation of the severity of intermittent claudication Doppler study may provide some standards to predict the state of muscle ischemia after exercise from the value measured at resting state. Near infrared spectroscopy is capable of direct continuous monitoring for the change of the state of oxygenated haemoglobin and deoxygenated one in the ischemic calf muscle during exercise. NIRS can be a new modality to asses the muscle ischemia during exercise in ASO patients. The objective diagnostic techniques should be reproducible, capable of intrinsic standardization, easily employed, relatively rapid to perform, adaptable to current recording equipment, and applicable to studies during and after exercise.

Arteriosclerosis Obliterans↗
PubMed1996

[Benzodiazepine receptor and cerebral blood flow in early Alzheimer's disease--SPECT study using 123I-iomazenil and 123I-IMP].

This study was designed to investigate benzodiazepine receptors (BZR) and cerebral blood flow (CBF) in patients with early Alzheimer's disease. Imaging of BZR and measurement of CBF were performed by SPECT using 123I-Iomazenil (IMZ) and 123I-IMP respectively, in seven patients with early Alzheimer's disease and five patients with unilateral left cerebral infarction as controls. The values for the normal cerebral hemisphere (ratio to the contralateral cerebellum) in patients with cerebral infarction were adopted as control values. In patients with Alzheimer's disease, the CBF (ratio to cerebellum) decreased significantly in the frontal cortex and the parietal cortex compared with the control values. There was no significant difference in late IMZ SPECT counts (ratio to cerebellum) and washout (the ratio of late-to-early IMZ SPECT counts) between patients with Alzheimer's disease and the controls. However, the late IMZ SPECT counts and washout decreased in one patient with moderate dementia. There was a significant correlation between the severity of dementia and the late IMZ SPECT counts in the temporal cortex and the parietal cortex. These results suggest that benzodiazepine binding sites are relatively well preserved in patients with early Alzheimer's disease, and reduction of the CBF is caused by neuronal dysfunction rather than by neuronal loss. IMZ SPECT study is useful and necessary for clarifying the pathophysiological state in Alzheimer's disease.

Aged↗
PubMed1996

[A quantitative study of regional cerebral blood flow in patients with dementia of Alzheimer type using single photon emission computed tomography--clinical application of the IMP autoradiographic method (IMP ARG method)].

We quantitatively measured regional cerebral blood flow (rCBF) in 37 patients with dementia of Alzheimer type (DAT) to investigate the clinical utilities of the N-isopropyl-p-[123I]iodoamphetamine autoradiographic method (IMP ARG method) that is a quantitative method more simplified and less invasive for IMP-SPECT developed by Iida et al. A given standard input function and a given value of distribution volume (Vd) used for the rCBF measurement of this method were calculated from the dynamic study by six normal volunteers. Mean values [SD] of rCBF (ml/ 100 g/min) in the Cerebral Cortex were 49.0 [6.0] in the controls (n = 20), 42.6 [5.9] in mild DAT group (n = 14), 36.7 [5.5] in moderate DAT group (n = 12), and 26.4 [7.5] in severe DAT group (n = 11), respectively. These values were significantly different between each neighboring group. Moreover, the correlations between the score by the Hasegawa dementia scale (HDS-R) and each rCBF were significant in the temporal, parietal, and frontal cortex. These findings suggest that the rCBF measurement in IMP-SPECT using this method is useful for the diagnosis of the clinical severity in patients with DAT.

Aged↗
PubMed1996

An objective evaluation of muscle oxygen content in claudicants receiving drug therapy.

The effects of medical treatment with a prostaglandin I2 analog (beraprost sodium) were evaluated in 19 of 120 cases studied with near-infrared spectroscopy (NIRS) from January 1993 to September 1994. The relative changes in oxygenated (Oxy) and deoxygenated (Deo) hemoglobin (Hb) in the calf muscle were measured during a treadmill walking test and the subsequent recovery period. After medical treatment in these 19 cases, recovery time of OxyHb decreased in 10 cases, increased in 7 cases and remained unchanged in two cases. Pressure studies did not facilitate the assessment of changes in the severity of claudication. Our results demonstrate that NIRS can provide objective information regarding the effects of medical therapy in claudicants.

Aged↗
PubMed1995

Structure and activity of HYI killer toxin from Hansenula saturnus.

The primary structure of HYI killer toxin produced by Hansenula saturnus was determined in its reduced and pyridylethylated form, as well as the peptides resulting from protease digestion. It was found that the HYI killer toxin consisted of 87 amino acid residues and the molecular weight was calculated to be 9543 Da. It showed 87% homology with HM-1 killer toxin produced by H. mrakii, while there were multiple mutations including one amino acid deletion which, nevertheless, did not alter the strong cytocidal effect on sensitive yeasts.

Amino Acid Sequence↗
PubMed1995

Cell wall synthesis specific cytocidal effect of Hansenula mrakii toxin-1 on Saccharomyces cerevisiae.

HM-1 toxin produced by Hansenula mrakii kills sensitive Saccharomyces cerevisiae. We found that the budding cells and the cells that responded to mating factor were sensitive to HM-1 toxin. These findings indicate that the target sites of HM-1 toxin are developing buds and conjugating tubes. The in vitro activity of beta-1,3-glucan synthase solubilized and partially purified from S. cerevisiae membranes was inhibited by HM-1 toxin at a concentration (around 50 nM, 0.5 micrograms/ml) that coincided well with its minimum inhibitory concentration for the growth of yeast cells. These data indicate that the HM-1 toxin perturbs the synthesis of yeast cell walls by inhibiting the glucan synthesis occurring at a budding site or a conjugating tube, which results in cell lysis.

Cell Cycle↗
PubMed1994

Inhibition of interleukin-1 beta converting enzyme by the cowpox virus serpin CrmA. An example of cross-class inhibition.

We reported previously that human interleukin-1 beta converting enzyme (ICE) is regulated by the CrmA serpin encoded by cowpox virus. We now report the mechanism and kinetics of this unusual inhibition of a cysteine proteinase by a member of the serpin superfamily previously thought to inhibit serine proteinase only. CrmA possesses several characteristics typical of a number of inhibitory serpins. It is conformationally unstable, unfolding around 3 M urea, and stable to denaturation in 8 M urea upon complex formation with ICE. CrmA rapidly inhibits ICE with an association rate constant (kon) of 1.7 x 10(7) M-1 s-1, forming a tight complex with an equilibrium constant for inhibition (Ki) of less than 4 x 10(-12) M. These data indicate that CrmA is a potent inhibitor of ICE, consistent with the dramatic effects of CrmA on modifying host responses to virus infection. The inhibition of ICE by CrmA is an example of a "cross-class" interaction, in which a serpin inhibits a non-serine proteinase. Since CrmA possesses characteristics shared by inhibitors of serine proteinases, we presume that ICE, though it is a cysteine proteinase, has a substrate binding geometry strikingly close to that of serine proteinases. We reason that it is the substrate binding geometry, not the catalytic mechanism of a proteinase, that dictates its reactivity with protein inhibitors.

Amino Acid Sequence↗
PubMed1994

An objective assessment of intermittent claudication by near-infrared spectroscopy.

Changes in tissue oxygenation in the calf muscle were measured by near-infrared spectroscopy (NIRS) in 62 patients who complained of intermittent claudication in the calf during a treadmill test. Three distinctive patterns of oxygenated and deoxygenated haemoglobin were observed. None of the type 0 cases were severe (i.e., unable to walk for more than 5 minutes), while 37 and 82% of the type 1 and type 2 cases were severe, respectively. The mean maximum walking distance of type 1 was significantly longer than that of type 2 (179 +/- 70 m and 109 +/- 46 m, respectively; p < 0.005), while the mean ankle-brachial pressure index at rest of type 1 was not significantly different from that of type 2 (0.68 +/- 0.19 and 0.61 +/- 0.23, respectively). Our results indicate that NIRS can be used to accurately assess the severity of intermittent claudication.

Adult↗
PubMed1993

Association between severity of alcoholism and the A1 allele of the dopamine D2 receptor gene TaqI A RFLP in Japanese.

The allelic association of TaqI A restriction fragment length polymorphism (RFLP) of the dopamine D2 receptor gene with alcoholism was examined in 78 Japanese alcoholics and compared with Japanese controls. A significantly higher frequency of the A1 allele (0.42) was found in 100 Japanese unscreened controls compared with those reported in white populations. Among 70 alcoholics whose severities were determined, the A1 allele was present in 77% of 43 more severe alcoholics and in 59% of 27 less severe alcoholics. The A1 allele was present significantly less frequently in the alcoholics at the age of 60 or older (42%), compared with those under the age of 60 (74%). In the subjects under the age of 60, the A1 allele was present in 83% of the 35 more severe alcoholics, being significantly more frequent than in 60% of the 35 nonalcoholic controls. All of the 7 alcoholics homozygous for the A1 allele were classified as severe. The average severity of alcoholism increased in the order A2/A2, A1/A2, and A1/A1 genotypes. These data suggest that the A1 allele is associated with severe alcoholism in the Japanese population and that the effect is related to or has a linkage disequilibrium with a genetic factor that has a small but not negligible additive effect on alcoholism.

Age Factors↗
PubMed1993

Amino acid sequences of ovomucoid third domains from 27 additional species of birds.

Ovomucoids consist of a single polypeptide chain which is composed of three tandem Kazal domains. Each Kazal domain is an actual or putative protein inhibitor of serine proteinases. Ovomucoid third domains were already isolated and sequenced from 126 species of birds (Laskowski et al., 1987, 1990). This paper adds 27 new species. A number of generalizations are made on the basis of sequences from 153 species. The residues that are in contact with the enzyme in enzyme-inhibitor complexes are strikingly hypervariable. While the primary specificity residue, P1, is the most variable; substitutions occur predominantly among aliphatic, hydrophobic residues. Consensus sequences for an avian ovomucoid third domain, for a b-type Kazal domain (i.e., a COOH terminal domain of multidomain inhibitors) and for a general Kazal domain are given. Finally, the individual new sequences are briefly discussed.

Amino Acid Sequence↗
PubMed1993

Application of carbon-11 labelled nicotine in the measurement of human cerebral blood flow and other physiological parameters.

Using positron emission tomography (PET), we measured the regional cerebral blood flow (rCBF) in five normal human subjects after intravenous injection of carbon-11 labeled (R)nicotine. The rCBF of the same subjects was measured by PET using the C15O2 inhalation steady-state method. The distribution of 11C activity in the brain after injection of 11C-(R)nicotine was almost equivalent to the CBF image obtained with the C15O2 inhalation stead-state method. The kinetics of 11C-(R)nicotine in the brain was analysed using a two-compartment model consisting of vascular and brain tissue compartments. The rCBF values obtained with 11C-(R)nicotine were higher than with C15O2 gas. The relatively long fixed distribution of 11C-(R)nicotine with a short uptake period allows stimulation studies by measurement of CBF to be performed with better photon flux and a longer imaging time than are possible with H215O.

Brain↗
PubMed1993

Distribution of 11C-(R)nicotine in human brain measured by positron emission tomography: measurement of cerebral blood flow.

We synthesized 11C-labeled (R)nicotine (11C: a positron-emitting radioisotope with a half-life of 20 min, produced in a cyclotron), and utilized it for blood flow measurement in the human brain. The positron emission tomography was employed for the data acquisition and image reconstruction. The behavior of the isotope was formulated by a mathematical model, consisting of a blood compartment and a tissue compartment, and the time-activity curve in various parts of the brain was analyzed in a computer to obtain a mathematically simulated curve which fell in consistence with both the arterial blood curve and the brain curve. The cerebral blood flow (CBF) value thus determined was compared with the value obtained by the standard C15O2 inhalation method (= H2(15)O method). The nicotine method always gave a higher value than the standard method by 27-34%. It seems that CBF determined by the 11C-(R)nicotine method is more accurate than the value determined by the standard method, because our tracer is superior as a CBF indicator to radiolabeled water.

Brain↗