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Biomedical subjects

T Kitagawa

Publications and source records attributed to T Kitagawa.

At least 91 records · Page 5Linked to original sources

Direct intraoperative measurements of aortic and pulmonary blood flows in patients with severe pulmonary artery hypertension.

BACKGROUND: Evaluate the significance of direct intraoperative measurements of aortic and pulmonary blood flows by electromagnetic flowmeter as an absolute decision basis for operability in patients with ventricular septal defect/complete atrioventricular septal defect and severe pulmonary artery hypertension. METHODS EXPERIMENTAL DESIGN: Prospective study. SETTING: Institutional practice. PATIENTS: Eight patients with marginal operability based on preoperative Doppler echocardiography and cardiac catheterization (pulmonary-to-systemic flow ratio=1.1-2.3, pulmonary-to-systemic resistance ratio=0.34-0.91, and pulmonary vascular resistance=4.6-18.2 units x m2) underwent direct intraoperative measurements of aortic and pulmonary blood flows by electromagnetic flowmeter. Operation would be performed according to the results of direct intraoperative measurements in every patient. RESULTS: Aortic flow by direct intraoperative measurements ranged from 0.9 to 3.2 L/min/m2, and pulmonary blood flow from 4.1 to 8.4 L/min/m2. Pulmonary-to-aortic flow ratio was calculated at 2.1-6.6. Pulmonary vascular resistance ranged from 2.6 to 7.7 units x m2. We assessed that all patients still had operability, and performed corrective operations. Postoperative courses corresponded with the data from the direct intraoperative measurements. CONCLUSIONS: When some clinical findings, particularly Doppler echocardiographic findings, of these patients are slightly in favor of reversibility of pulmonary vascular disease despite discrepant data of preoperative cardiac catheterization under a tight control of carbon dioxide tension, we recommend that direct intraoperative measurement of aortic and pulmonary blood flows is especially useful in decision making for the operability of patients with severe pulmonary artery hypertension.

Aorta↗

[An autopsied case of progressive spinal muscular atrophy showing tremor and choreiform movement].

A 42-year-old man without family history of neurologic disease developed muscle weakness, and wasting associated with tremor and choreiform movement. He died at age 75 with 33 years of total duration of illness. Autopsy revealed neuronal loss and gliosis in the anterior horns of the spinal cord, hypoglossal nuclei, caudate nuclei, putamen, globus pallidus, and substantia nigra. Bunina bodies or Lewy bodies were not seen. Several similar cases with motor neuron disease, dementia and parkinsonism have been reported in the literature. However, this pattern of chronic spinal neostriato-pallido-nigral degeneration has not been reported.

Aged↗

UV resonance Raman studies of alpha-nitrosyl hemoglobin derivatives: relation between the alpha 1-beta 2 subunit interface interactions and the Fe-histidine bonding of alpha heme.

Human alpha-nitrosyl beta-deoxy hemoglobin A, alpha(NO)beta(deoxy), is considered to have a T (tense) structure with the low O(2) affinity extreme and the Fe-histidine (His87) (Fe-His) bond of alpha heme cleaved. The Fe-His bonding of alpha heme and the intersubunit interactions at the alpha 1-beta 2 contact of alpha(NO)-Hbs have been examined under various conditions with EPR and UV resonance Raman (UVRR) spectra excited at 235 nm, respectively. NOHb at pH 6.7 gave the UVRR spectrum of the R structure, but in the presence of inositol-hexakis-phosphate (IHP) for which the Fe-His bond of the alpha heme is broken, UVRR bands of Trp residues behaved half-T-like while Tyr bands remained R-like. The half-ligated nitrosylHb, alpha(NO)beta(deoxy), in the presence of IHP at pH 5.6, gave T-like UVRR spectra for both Tyr and Trp, but binding of CO to its beta heme (alpha(NO)beta(CO)) changed the UVRR spectrum to half-T-like. Binding of NO to its beta heme (NOHb) changed the UVRR spectrum to 70% T-type for Trp but almost R-type for Tyr. When the pH was raised to 8.2 in the presence of IHP, the UVRR spectrum of NOHb was the same as that of COHb. EPR spectra of these Hbs indicated that the Fe-His bond of alpha(NO) heme is partially cleaved. On the other hand, the UVRR spectra of alpha(NO)beta(deoxy) in the absence of IHP at pH 8.8 showed the T-like UVRR spectrum, but the EPR spectrum indicated that 40-50% of the Fe-His bond of alpha hemes was intact. Therefore, it became evident that there is a qualitative correlation between the cleavage of the Fe-His bond of alpha heme and T-like contact of Trp-beta 37. We note that the behaviors of Tyr and Trp residues at the alpha 1-beta 2 interface are not synchronous. It is likely that the behaviors of Tyr residues are controlled by the ligation of beta heme through His-beta 92(F8)-->Val-beta 98(FG5)-->Asp-beta 99(G1 )-->Tyr-alpha 42(C7) or Tyr-beta 145(HC2).

Carboxyhemoglobin↗

The structure and unusual pH dependence of plastocyanin from the fern Dryopteris crassirhizoma. The protonation of an active site histidine is hindered by pi-pi interactions.

Spectroscopic properties, amino acid sequence, electron transfer kinetics, and crystal structures of the oxidized (at 1.7 A resolution) and reduced form (at 1.8 A resolution) of a novel plastocyanin from the fern Dryopteris crassirhizoma are presented. Kinetic studies show that the reduced form of Dryopteris plastocyanin remains redox-active at low pH, under conditions where the oxidation of the reduced form of other plastocyanins is inhibited by the protonation of a solvent-exposed active site residue, His87 (equivalent to His90 in Dryopteris plastocyanin). The x-ray crystal structure analysis of Dryopteris plastocyanin reveals pi-pi stacking between Phe12 and His90, suggesting that the active site is uniquely protected against inactivation. Like higher plant plastocyanins, Dryopteris plastocyanin has an acidic patch, but this patch is located closer to the solvent-exposed active site His residue, and the total number of acidic residues is smaller. In the reactions of Dryopteris plastocyanin with inorganic redox reagents, the acidic patch (the "remote" site) and the hydrophobic patch surrounding His90 (the "adjacent" site) are equally efficient for electron transfer. These results indicate the significance of the lack of protonation at the active site of Dryopteris plastocyanin, the equivalence of the two electron transfer sites in this protein, and a possibility of obtaining a novel insight into the photosynthetic electron transfer system of the first vascular plant fern, including its molecular evolutionary aspects. This is the first report on the characterization of plastocyanin and the first three-dimensional protein structure from fern plant.

Amino Acid Sequence↗

Quaternary structure sensitive tyrosine residues in human hemoglobin: UV resonance raman studies of mutants at alpha140, beta35, and beta145 tyrosine.

Recent studies noted the contribution of alpha42Tyr to the T-R-dependent UV resonance Raman (UVRR) spectral changes of HbA [Nagai, M., et al. (1996) J. Mol. Struct. 379, 65-75; Huang, S., et al. (1997) Biochemistry 36, 6197-6206], but the observed UVRR changes of the Tyr residue cannot be fully interpreted with alpha42Tyr alone. To identify the remaining contributions, the 235 nm-excited UVRR spectra of Tyr mutant Hbs at alpha140, beta35, and beta145 were investigated here. The Fe-His stretching mode demonstrated that all of these mutant Hbs take the T structure in the deoxy form under these experimental conditions. The UVRR change of the Trp residue of these mutants upon the T-R transition was the same as that in HbA, indicating that the T-R-dependent UVRR change of beta37Trp is not due to stacking with Tyr residues but is due to the formation or destruction of a hydrogen bond. The recombinant Hbs beta35Tyr --> Phe and beta35Tyr --> Thr both exhibited UVRR spectra identical with that of HbA, meaning that beta35Tyr is not responsible. In the spectra of des(beta146His,beta145Tyr)Hb with inositol hexaphosphate, the frequency shift of the Tyr RR bands was the same as that in HbA but the intensity enhancement in the CO form was small, suggesting that beta145Tyr contributes to a part of the intensity change, but scarcely relates to the frequency shift. In the spectra of Hb Rouen (alpha140Tyr --> His), the frequency shifts of bands at 1617 (Y8a) and 1177 (Y9a) cm-1 following ligation were half of those in HbA, while the intensity enhancement was not detected. This result means that alpha140Tyr is responsible for both the frequency shift and the intensity changes. It is suggested that the frequency shift of the Tyr RR bands upon the T --> R transition is due to changes in the hydrogen bonding state of alpha42- and alpha140Tyr and that the intensity enhancement is due to changes in the environment of the penultimate Tyr in both alpha and beta subunits (alpha140 and beta145). These alterations in the vibrational spectra clearly demonstrate which tyrosine residues are involved in the T-R transition as a result of modification of their local environments.

Amino Acid Substitution↗

Oxidation of Benzyl Alcohol with Cu(II) and Zn(II) Complexes of the Phenoxyl Radical as a Model of the Reaction of Galactose Oxidase.

Profound insights into the catalytic mechanism of galactose oxidase (GO) are offered by new models of the active form of the metalloenzyme. The important role of the Cu(II) center in the oxidation of benzyl alcohol to benzaldehyde by the Cu(II)-phenoxyl radical complex of ligand 1 has been revealed by comparison with the reactivity of the corresponding Zn(II)-phenoxyl radical complex; py=2-pyridyl.

Journal Article↗

Failure to detect genetic alteration of the mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) gene in hepatocellular carcinomas in Japan.

The mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) suppresses cell growth through binding to the insulin-like growth factor 2 (IGF2) and latent complex of the transforming growth factor-beta (TGF-beta). Recently, it was reported in the United States that loss of heterozygosity (LOH) and mutations in exons 27, 28, and 31 of the M6P/IGF2R gene are frequent in hepatocellular carcinomas (HCCs) and adenomas. In view of the possible importance of this finding, especially for differential diagnosis of small hepatic lesions, we analyzed 43 primary HCCs, 2 adenomatous hyperplasias (AHs), and 3 regenerative nodules (RNs) developing in 42 Japanese patients in Japan for LOH using the polymorphic locus and for mutations by both single strand conformation polymorphism (SSCP) and direct sequencing methods. In the LOH study, 21 out of 22 informative HCCs and all of the informative AHs and RNs showed no allelic loss. In mutational studies of exons 27, 28, and 31, no mutations were detected either by SSCP or direct sequencing analysis in any of the 48 lesions. Thus inactivation of the M6P/IGF2R gene because of genetic alteration does not appear to be essential for hepatocarcinogenesis in Japan.

Adenoma↗

Co-expression of E-cadherin and alpha-catenin molecules in colorectal cancer.

Immunohistochemical staining for epithelial (E)-cadherin and alpha-catenin was performed using frozen sections taken from fresh operative specimens, by the avidin-biotin-peroxidase complex method. Tumors were classified into three types according to the expression modality. Cancer cells with expression at the cell-cell boundaries were defined as normal; when the expression was positive, but not concentrated at the cell-cell boundaries, they were defined as cytoplasmic; and when the tumor showed no staining, they were defined as lost. The relationship between these three expression types and the clinicopathological features of colorectal cancer was investigated. In all 50 normal mucosa samples, E-cadherin and alpha-catenin were coexpressed normally. The expression type of E-cadherin and alpha-catenin was normal in 11 and 13 of the cancer tissue specimens, respectively, cytoplasmic in 26 and 29, respectively, and lost in 13 and 8, respectively. Cytoplasmic or lost expression was observed in cancer demonstrating an advanced clinical stage (E-cadherin, P = 0.0065; alpha-catenin, P = 0.0069), advanced tumor penetration (P = 0.0003, P = 0.0001), undifferentiated tumor histology (P = 0.0196, P = 0.0343), widespread lymph node involvement (P = 0.0204, P = 0.0340), and liver metastasis (P = 0.0063, P = 0.0299). In conclusion, the expression type of E-cadherin is significantly correlated to that of alpha-catenin, and the loss of their expression indicates the metastatic potentiality of colorectal cancer.

Adult↗

Problems in histological diagnosis of cancer associated with chemo- and/or radiotherapy.

This special report discusses problems relevant to histological diagnosis of cancer after chemo- and/or radiotherapy. One of the issues relates to pitfalls, i.e. over-, under- or misdiagnosis or oversight, stemming from a lack of concern or awareness of therapeutic effects on tumors or normal tissues. Another set of questions concerns inadequacy or insufficiency in the evaluation of therapeutic effects stemming from practical difficulties. In view of the importance of this area, we should set out a comprehensive research programme with close cooperation among clinicians, pathologists and molecular biologists to overcome these problems.

Aged↗

Histological indications of a favorable prognosis with far-advanced gastric carcinomas after preoperative chemotherapy.

PURPOSE: Although preoperative chemotherapy for advanced gastric cancer is now commonly applied with favorable results, convincing evidence for life prolongation and predictive markers for a good prognosis are both lacking. We report here 5 cases that have shown a distinct positive effect of preoperative chemotherapy together with the results of a precise histological examination of materials indicating features predicting a favorable outcome. PATIENTS AND METHODS: A total of 18 patients with a far-advanced gastric carcinoma subjected to gastrectomy after FLEP (5-fluorouracil, leucovorin, etoposide, cisplatin) in the Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, could be divided into two distinct groups: 5 surviving over 5 years (group A) and 13 who died within 13 months (group B). Histological features (subtypes) of the carcinomas and chemotherapeutic effects were studied with reference to biopsy materials and resected stomachs and lymph nodes. RESULTS: In group A, 3 of 5 patients had solid-type poorly differentiated adenocarcinomas. In contrast, in group B, 9 had tubular adenocarcinomas (well or moderately differentiated) and 3 non-solid or diffuse-type poorly differentiated adenocarcinomas and there was only one solid-type tumor. In group A, remarkable therapeutic effects were apparent histologically in 4 of the 5 patients with almost complete disappearance of cancer cells from metastases in lymph nodes, whereas no such changes were evident in group B. CONCLUSION: FLEP is distinctly beneficial for certain types of advanced gastric carcinoma, especially solid-type poorly differentiated adenocarcinomas, and favorable results can be predicted, to a certain extent, on the basis of findings for the material resected after chemotherapy.

Adenocarcinoma↗

Ophthalmic artery velocimetry in normotensive and preeclamptic women with or without photophobia.

OBJECTIVE: To compare ophthalmic arterial velocimetry in normotensive and preeclamptic gravidas with and without photophobia. METHODS: Ophthalmic arteries were studied by color-flow Doppler ultrasonography in 118 normotensive pregnant women, 20 gravidas with preeclampsia and no visual symptoms, and 11 with preeclampsia, photophobia, and retinal edema. RESULTS: The ophthalmic arterial pulsatility index (PI) correlated negatively with gestational age (y = -0.01x + 1.84, r = -0.41, P<.01). Pulsatility index in preeclamptics with photophobia (0.71+/-0.17) was lowest among the three groups (P<.01) and was highest in normotensive pregnant women (1.41+/-0.21, P<.01). Mean velocity in normotensive pregnant women (0.19+/-0.05 m/second) was highest among the groups (P<.01) and was not significantly different in preeclamptic women with no visual symptoms (0.27+/-0.03 m/second) and with photophobia (0.30+/-0.02 m/second). CONCLUSION: Preeclamptic women, especially those with photophobia, have orbital vascular vasodilation or hyperperfusion, or both.

Adult↗

Studies of bovine enterovirus structure by ultraviolet resonance Raman spectroscopy.

The structural comparison of bovine enterovirus MZ468 strain before and after the heat treatment was studied by ultraviolet resonance Raman (UVRR) spectra excited at both 235 and 251 nm. The difference between full, heated full and purified empty particles, which were expected as an in vitro model of uncoating, were demonstrated. At 235 nm excitation, the Raman bands of the capsid protein dominated in all the UVRR spectra. The UVRR spectra of the empty particles exhibited non-homogenious broadening for tryptophan W3 band and W7 Fermi doublet bands, which were characteristics of hydrophobic environment, when compared with those of the full particles. The results indicates that some Trp indole rings of the full particles were packaged inside the viral capsids and not strained by virion assembly. On the other hand, the Raman bands assigned to guanine residues of the single stranded-RNA genome were enhanced strongly in the 251-nm excited UVRR spectrum. The spectral differences between the packaged (full particles) and the unpackaged virions (heated full particles) indicates that some guanine residues had strong hydrogen bonds in the full particles.

Animals↗

Enhanced expression of glucose transporter GLUT3 in tumorigenic HeLa cell hybrids associated with tumor suppressor dysfunction.

Previous studies on human cell hybrids between HeLa and normal human fibroblasts have indicated that the tumorigenicy may be controlled by a putative tumor suppressor gene on chromosome 11. We previously demonstrated a twofold increase in glucose uptake with a reduced Km by tumorigenic HeLa cell hybrids which expressed a highly glycosylated GLUT1. In this study, we reported that a tumorigenic cell hybrid, CGL4, also expressed a glucose transporter isoform, GLUT3, that was undetectable in nontumorigenic CGL1 cells. The expression of GLUT3 together with GLUT1 of 70 kDa was also evident in three gamma-ray-induced tumorigenic clones isolated from CGL1 cells, while control nontumorigenic irradiated cells expressed 50 kDa GLUT1 alone. In accordance with this, GLUT3 mRNA was specifically expressed in tumorigenic cell hybrids. To examine the role of GLUT3, clones which stably overexpress GLUT3 were developed from both CGL1 and CGL4 cells. In these transfectants, the affinity for 2-deoxyglucose markedly increased, in parallel with the amount of expressed GLUT3 irrespective of its N-glycosylation state. These results suggest that the enhanced GLUT3 expression in HeLa cell hybrids associated with the tumorigenic phenotypes may account for the increased affinity for 2-deoxyglucose. Possible roles of the putative tumor suppressor in control of gene expression and glucose uptake is discussed.

Biological Transport↗

Mass screening for Wilson's disease: results and recommendations.

Wilson's disease is a treatable inherited disorder of copper metabolism. Established treatments include the use of oral chelating agents and the establishment of a minimum copper diet, although prognosis mainly depends on the extent of liver or nervous system damage present before treatment. Once irreversible damage has occurred, the effect of these treatments is diminished and the patient's quality of life compromised. Therefore, the establishment of a mass screening system able to detect Wilson's disease patients presymptomatically has been discussed. Recently, a monoclonal antibody specific to holoceruloplasmin has been developed. This antibody was used in a nationwide screening trial of 126,810 newborn infants, but no Wilson's disease patients were identified. However, three patients out of 24,165 were diagnosed with Wilson's disease using this specific antibody in a screening performed during the period from late infancy to elementary school. The age of 3 years is thought to be the best point for Wilson's disease mass screening. In this paper, a review of mass screening for Wilson's disease in Japan using a specific monoclonal antibody to holoceruloplasmin is presented.

Antibodies, Monoclonal↗

Stimulation of haematogenous liver metastases by ischaemia-reperfusion in rats.

OBJECTIVE: To find out whether hepatic ischaemia-reperfusion stimulates hepatic tumour metastases using a cell line of rat ascitic hepatoma (AH130). DESIGN: Prospective experimental study. SETTING: University laboratories, Japan. MATERIALS: 118 male Donryu rats. INTERVENTION: After laparotomy alone (group 1, n = 35) or laparotomy and 20-minutes ischaemia (group 2, n = 34) or laparotomy and 30-minutes ischaemia (group 3, n = 34) of the median and left hepatic lobes, the animals were given either an intraportal injection of 1 x 10(5) or an intravenous injection of 1 x 10(6) viable AH130 cells. MAIN OUTCOME MEASURES: 10 days after inoculation of tumour cells the number of nodules on the surface of the right lobe and of the median plus left lobes were separately counted for each liver. RESULTS: Irrespective of the route of tumour inoculation in group 1, there was no significant difference in the number of tumours/g liver between the right and the median plus left lobes. However, in groups 2 and 3, the number of tumours/g liver in the median plus left lobes was significantly higher than in the right lobe (p < 0.05). Furthermore, in the median plus left lobes, animals who had had 30 minutes of ischaemia had significantly more tumours than those in the other two groups (p < 0.01). CONCLUSION: Hepatic ischaemia-reperfusion may increase the risk of development of haematogenous liver metastases, by stimulating tumour cell-endothelial cell interactions.

Analysis of Variance↗

Effects of sevoflurane on regional myocardial blood flow distribution: quantification with myocardial contrast echocardiography.

BACKGROUND: Using myocardial contrast echocardiography, the authors tried to determine whether sevoflurane causes myocardial blood maldistribution in humans and dogs. METHODS: In animal experiments, 15 mongrel dogs were organized into dipyridamole (n = 6) and sevoflurane (n = 9) groups. Sonicated albumin was infused into the left main coronary artery. The peak gray level corrected for background was analyzed at the following intervals: (1) at baseline, (2) after stenosis of the left circumflex coronary artery (blood flow reduced by 40%), (3) after administration of dipyridamole (1 mg/kg given intravenously) or sevoflurane (1 minimum alveolar concentration) during stenosis, and (4) after phenylephrine during stenosis and administration of dipyridamole or sevoflurane. In human studies, nine patients undergoing coronary artery bypass grafting were studied. During partial extracorporeal circulation, the peak gray level was analyzed before and 20 min after sevoflurane (1 minimum alveolar concentration). RESULTS: In animal experiments, dipyridamole decreased significantly the inner:outer ratio of the peak gray level in the ischemic area and the ischemic:normal ratio of the peak gray level. After arterial pressure was restored with phenylephrine, neither the inner:outer ratio nor the ischemic:normal ratio improved. In contrast, after sevoflurane administration, the inner:outer ratio and the ischemic:normal ratio remained unchanged, but these increased with phenylephrine. In human studies, sevoflurane did not change the inner:outer ratio in the area supplied by the most stenotic coronary artery. CONCLUSION: These results suggest that dipyridamole, a potent coronary vasodilator, produces maldistribution of coronary blood flow in our dog models, whereas sevoflurane does not do this in animal or human studies.

Aged↗

Characteristics of Streptococcus species isolated from infectious skin diseases.

During the period from January of 1995 to June of 1998, 27 beta-hemolytic streptococci were isolated from 25 cases of infectious skin diseases including secondary infections, impetigo, phlegmone, and paronychia. The rate of beta-hemolytic streptococci among all kinds of the isolates was found to be similar during those 4 years, ranging from 3.5% to 5.6%. Staphylococcus aureus were found to coexist with beta-hemolytic streptococci in 20 (80%) out of 25 cases. beta-hemolytic streptococci were also often associated with coagulase-negative staphylococci, gram-positive rods, or other species. Twelve cases (48%) carried beta-hemolytic streptococci predominantly. Most beta-hemolytic streptococci showed high susceptibilities to all antimicrobials tested; however S. agalactiae showed no susceptibility to gentamicin. The evaluation of characteristics of Streptococcus species is very important for selecting the right antimicrobial agents and the proper term of chemotherapy.

Adolescent↗