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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 163 records · Page 9Linked to original sources

[Endoscopic extirpation for benign breast tumor].

Endoscopic extirpation using a fine endoscope and related devices via the extramammary approach (mainly the transaxillary approach) has been applied for benign breast tumors since 1997 in the Second Department of Surgery, Kyushu University. The operative procedures, morbidity, and mortality are presented here. We have treated 37 patients with a mean age of 27.6 years, whose tumors had been diagnosed as benign; average tumor diameter was 3.6 cm. Seven patients had multiple tumors, including 4 with bilateral lesions. The transaxillary approach was chosen in 35 patients and the inframammary approach, which was a procedure in the early phase, was chosen in the remaining 2 patients. Patients with benign tumors can thus avoid direct incision on the breast by endoscopic extirpation via the extramammary approach. We recommend this procedure as a new option instead of direct excisional biopsy for benign breast tumors.

Adult↗

Histochemical correlates of (15)O-water-perfusable tissue fraction in experimental canine studies of old myocardial infarction.

UNLABELLED: A method has been proposed to quantitate the myocardial water-perfusable tissue fraction (PTF) in the area of hypoperfused asynergic segments using (15)O-water (H2(15)O) and PET. This study investigated the histochemical correlates of PTF (and perfusable tissue index, PTI) in a canine model of old myocardial infarction. METHODS: Myocardial infarction was produced in 12 mongrel dogs, and PET was performed 1 mo later, providing quantitative parametric images of PTF, regional myocardial blood flow (MBF), and extravascular density from H2(15)O, (15)O-carbon monoxide, and transmission datasets. At the end of scanning, the myocardium was sectioned, and the PET images were compared directly with the corresponding myocardial sections. RESULTS: The distribution of tissue necrosis identified by histochemical staining corresponded well with the defect in PTF but not in MBF. PTF agreed with the equilibrium images of myocardial H2(15)O distribution, obtained after injection of a large bolus of H2(15)O. The defect surface area identified on PTF agreed well quantitatively with the morphometric estimates of the surface area of myocardial infarction. PTI agreed with the absolute proportion of histochemically defined normal myocardium (0.87 +/- 0.09 and 0.83 +/- 0.08, respectively; P < 0.01). Both PTF and PTI decreased significantly in segments of myocardial infarction and showed a significant difference between the transmural and nontransmural myocardial infarction. CONCLUSION: The absolute mass and proportion of histochemically defined noninfarcted tissue may be quantitated with PTF and PTI in the area of myocardial infarction segments.

Animals↗

[The genetic diagnosis of hematopoietic malignancy by polymerase chain reaction method].

Since 1994, chimeric gene test for major-BCR/ABL, minor-BCR/ABL, AML1/MTG8, PML/RARa, DEK/CAN, CBFb/MYH11, MLL/LTG9, E2A/PBX1, TEL/AML1, and MLL/LTG4 by reverse transcription-nested-polymerase chain reaction (RT-nested-PCR) have been routinely performed in our laboratory. The frequently requested tests were those for major-BCR/ABL, minor-BCR/ABL, AML1/MTG8, PML1/RARa, and TEL/AML1 chimeric genes, being the test for major-BCR/ABL the most frequent one, accounting for more than 50% of the total orders. By the high sensitivity for minimal residual disease(MRD) detection, these methods are extremely useful for the therapeutic control of chemotherapy and bone marrow transplantation, as well as for prediction of prognosis. However, in the most cases a well-controlled monitoring could not be obtained, due to the 6-months interval between the tests, the minimal interval allowed by the insurance. The following points should be carefully observed. (1) The setting site of the primer can affect the sensitivity and the specificity of the test; (2) For the detection of chimeric genes with multiple translocation breakpoints, a genetic DNA sequencing is necessary to confirm them; (3) In patients receiving chemotherapy or bone marrow transplantation, that show extremely low blood cell counts, false-negative tests dependent on the quality of the extracted RNA and the low volume of DNA, should be avoided by careful managements. For improvements of the MRD detection tests, the quantification of the expression levels of chimeric gene and WT1 mRNA is necessary.

Hematologic Neoplasms↗

[A case of tuberculous aneurysm of the aorta].

We reported a rare case of tuberculous aneurysm of the aorta managed successfully with urgent surgical therapy. A 35-year-old woman was admitted to our hospital complaining of fatigue and hemoptysis. Laboratory tests showed severe anemia, slight liver dysfunction, elevated level of C-reactive protein, and negative syphilis serologies. The chest roentgenogram revealed widening of right upper mediastinum, two nodular shadows in right middle lobe, and left-sided infiltration shadow with pleural effusion. The pleural effusion was bloody and its level of adenosine deaminase was normal. Culture of pleural effusion specimen remained negative. A computed tomography scans of the chest revealed an aortic aneurysm on the aortic hiatus. Rapid increase in pleural effusion was followed by hemothorax a few hours later. After operation, she received antituberculosis therapy. Histopathologically, the resected lung showed inflammatory process including granulation of giant cells and epithelioid cells. The specimens of the aortic aneurysm revealed rupture of whole layer of aortic wall and inflammatory cell infiltrations. These findings suggested that the case to be a tuberculous aneurysm of the aorta. Therefore, we diagnosed the case as the rupture of tuberculous aneurysm of the aorta.

Adult↗

Deafness genes.

The pathophysiology of sensorineural hearing impairment, which is a common clinical disorder, remains yet to be determined. For prelingual hearing loss, epidemiological data show that 1 neonate in 1,000 is born with severe to profound hearing loss, and in half of that number the loss is inherited. Some genes responsible for sensorineural hearing impairment have been cloned during the last several years, and the underlying mechanisms causing hearing impairment have begun to be clarified with the advent of recent developments in molecular genetics. Cases of non-syndromic deafness are classified by the mode of inheritance (DFNA, dominant; DFNB, recessive; DFN, X-linked), with the loci being numbered in the order of discovery. To date, 31 autosomal dominant, 28 autosomal recessive, and 6 X-linked non-syndromic sensorineural hearing impairment loci have been mapped, and 17genes have been cloned (Hereditary Hearing Loss Homepage, http://danallab-www.uia.ac.be.dnalab/hhh/). We have identified mutations in four of those 17 deafness genes in Japanese families. Clinical and genetic findings of the above disorders are reviewed.

Adolescent↗

Effects of Particle Size and Cholesterol Content on the Partition Coefficients of Chlorpromazine and Triflupromazine between Phosphatidylcholine-Cholesterol Bilayers of Unilamellar Vesicles and Water Studied by Second-Derivative Spectrophotometry.

Phosphatidylcholine(PC)-cholesterol (0-30 mol%) unilamellar vesicles of several sizes (20-600 nm) were prepared in buffer (pH 7.4) solutions by sonication or extrusion methods. The vesicle size was measured by a dynamic light-scattering method. Absorption spectra of chlorpromazine (CPZ) and triflupromazine (TFZ) in the presence of these vesicles showed a bathochromic shift according to the increase in vesicle concentration, but the counterbalance of the baseline was incomplete due to the intensive light scattering by the vesicles; thus, no isosbestic point could be observed. In the second-derivative spectra, the residual background signal effects were eliminated and three derivative isosbestic points were clearly observed for both drugs. The derivative intensity change (DeltaD) induced by the addition of the vesicles was measured at the lambda(max) of each drug. From the relationship between the DeltaD value and the lipid concentration, the partition coefficients (K(p)) of CPZ and TFZ between these vesicles and water (buffer) were calculated. The results revealed that the vesicle size (20-600 nm) and preparation method do not affect the K(p) values, and although the incorporation of cholesterol into the PC bilayers induces a decrease of the K(p) values, the vesicle size also did not affect the K(p) values in vesicles of the same cholesterol content. Copyright 1999 Academic Press.

Journal Article↗

Characterization of the human dihydropyrimidinase-related protein 2 (DRP-2) gene.

The genes within the dihydropyrimidinase-related protein (DRP) family, were originally identified in humans by their homology to dihydropyrimidinase (DHP). Four members of this gene family, DRP-1, -2, -3 and -4, are expressed mainly in the fetal and neonatal brains of mammals and chickens, and have been implicated as intracellular signal transducers in the development of the nervous system. We isolated the human DRP-2 gene, and determined its transcriptional start site and exon/intron organization. The gene spanned more than 62 kb, and contained 14 exons with lengths ranging from 62 bp to 2606 bp. The transcriptional start site was determined by an RNase protection assay and 5' rapid amplification of cDNA ends (RACE), and a highly GC-rich promoter was identified that contained possible regulatory elements such as a TATA box, CAAT box and three GC boxes. Comparison of the phase and position of intron insertions within the human DRP-2 gene with those within DRP-1, DHP and two Caenorhabditis elegans DRP/DHP homologs, indicated that DRPs are more conserved in their exon/intron organization than DHP.

Amidohydrolases↗

A point mutation in a plasma membrane Ca(2+)-ATPase gene causes deafness in Wriggle Mouse Sagami.

The spontaneous mutant, Wriggle Mouse Sagami (wri), is thought to be a model of hereditary hearing losses in humans. Here we report that the plasma membrane Ca(2+)-ATPase type 2 (PMCA2) gene is mutated in the wri mouse. A G-to-A transition was detected in wri, changing Glu-to-Lys within a conserved transmembrane domain. Mutation of PMCA2 was previously reported in deafwaddler (dfw) mutants; however, the sites of the wri and dfw mutations differ. Immunohistochemical analysis demonstrated that PMCA2 labeling in stereocilia of the cochlea was absent in the wri mutant, suggesting that PMCA2 is crucially involved in the physiology of the auditory system.

Animals↗

Preirradiation evaluation and technical assessment of involved-field radiotherapy using computed tomographic (CT) simulation and neoadjuvant chemotherapy for intracranial germinoma.

PURPOSE: To investigate the importance of preirradiation mental and endocrinological evaluation, and the effectiveness of involved-field radiotherapy following neoadjuvant chemotherapy. METHODS AND MATERIALS: Following etoposide and cisplatin with or without ifosfamide, 13 patients with nondisseminated disease received involved-field irradiation of 24 Gy in 12 fractions within 3 weeks and 2 patients with disseminated germinoma received 24 Gy craniospinal irradiation (CSI). CT simulation was used to cover the tumor bed. RESULTS: Full-scale intelligence quotient (IQ) tests given at the time of the initial radiotherapy showed less than 90 in 7 of 11 patients who had tumors involving the neurohypophyseal region, but the 4 patients who had solitary pineal tumors showed higher scores. Panhypopituitarism was observed in 9 patients with tumors involving the neurohypophyseal region. All patients are alive without disease, with a median follow-up period of 40 months. No in-field relapse was noted after the involved-field radiotherapy. One patient experienced a recurrence outside of the planning target volume. CONCLUSION: Decline of neurocognitive and endocrine functions were often seen in patients with tumors involving the hypophyseal region, but not in patients with solitary pineal germinoma before radiotherapy. Involved-field radiotherapy using 24 Gy is effective with the help of CT simulation and neoadjuvant chemotherapy.

Adolescent↗

Interaction between CD45-AP and protein-tyrosine kinases involved in T cell receptor signaling.

CD45-AP associates specifically with CD45, a protein-tyrosine phosphatase essential for antigen receptor-mediated signal transduction. CD45 modulates the activity of Src family protein-tyrosine kinases involved at the onset of antigen receptor-mediated signaling by dephosphorylating their regulatory tyrosyl residues. We have shown that lymphocyte responses to antigen receptor stimulation are impaired in CD45-AP-null mice. To examine the possibility that CD45-AP coordinates the interaction between CD45 and its substrates, we investigated the associations of CD45-AP with several protein-tyrosine kinases. Endogenous CD45-AP coimmunoprecipitated with Lck and ZAP-70 in both CD45-positive T cells and their CD45-negative variants after stimulation by antigen receptor ligation. Concomitantly, CD45 coimmunoprecipitated with Lck and ZAP-70 after T cell receptor-mediated stimulation of CD45-positive cells. Recombinant CD45-AP exhibited specific binding to Lck and ZAP-70 protein-tyrosine kinases, but not to Fyn or Csk, in lysates of both CD45-positive and -negative T cells. Specific interactions were demonstrated between the respective recombinant proteins as well. These results demonstrate that CD45-AP associates directly and selectively with Lck and ZAP-70 in response to T cell receptor-mediated stimulation. The associations of CD45-AP with Lck and ZAP-70 may mediate the functional interactions of these kinases with CD45 during antigen receptor stimulation.

Animals↗

A single myosin head moves along an actin filament with regular steps of 5.3 nanometres.

Actomyosin, a complex of actin filaments and myosin motor proteins, is responsible for force generation during muscle contraction. To resolve the individual mechanical events of force generation by actomyosin, we have developed a new instrument with which we can capture and directly manipulate individual myosin subfragment-1 molecules using a scanning probe. Single subfragment-1 molecules can be visualized by using a fluorescent label. The data that we obtain using this technique are consistent with myosin moving along an actin filament with single mechanical steps of approximately 5.3 nanometres; groups of two to five rapid steps in succession often produce displacements of 11 to 30 nanometres. This multiple stepping is produced by a single myosin head during just one biochemical cycle of ATP hydrolysis.

Actins↗

Structural basis of inhibition of cysteine proteases by E-64 and its derivatives.

This paper focuses on the inhibitory mechanism of E-64 and its derivatives (epoxysuccinyl-based inhibitors) with some cysteine proteases, based on the binding modes observed in the x-ray crystal structures of their enzyme-inhibitor complexes. E-64 is a potent irreversible inhibitor against general cysteine proteases, and its binding modes with papain, actinidin, cathepsin L, and cathepsin K have been reviewed at the atomic level. E-64 interacts with the Sn subsites of cysteine proteases. Although the Sn-Pn (n = 1-3) interactions of the inhibitor with the main chains of the active site residues are similar in respective complexes, the significant difference is observed in the side-chain interactions of S2-P2 and S3-P3 pairs because of different residues constituting the respective subsites. E-64-c and CA074 are representative derivatives developed from E-64 as a clinical usable and a cathepsin B-specific inhibitors, respectively. In contrast with similar binding/inhibitory modes of E-64-c and E-64 for cysteine proteases, the inhibitory mechanism of cathepsin B-specific CA074 results from the binding to the Sn' subsite.

Binding Sites↗

Differential hormonal profiles of adrenomedullin and proadrenomedullin N-terminal 20 peptide in patients with heart failure and effect of treatment on their plasma levels.

BACKGROUND: Adrenomedullin (AM) is a potent vasodilatory peptide discovered in human pheochromocytoma tissue. Proadrenomedullin N-terminal 20 peptide (PAMP) processed from an AM precursor is also a novel hypotensive peptide which inhibits catecholamine secretion from sympathetic nerve endings. HYPOTHESIS: The present study sought to examine the relationships between the two peptides and other clinical parameters by measuring the plasma AM and PAMP concentrations in 98 patients with heart failure. METHODS: In all, 98 patients [65 men and 33 women, aged 58.2 +/- 11.0 years, mean +/- standard deviation (SD)] with heart failure and 26 healthy volunteers (12 men and 14 women, aged 54.1 +/- 8.6 years) were examined in this study. Heart failure was secondary to previous myocardial infarction in 58 patients, valvular disease in 28, cardiomyopathy in 9, and congenital heart disease in 3. All patients were classified into two groups of class I or II (Group 1) and class III or IV (Group 2) according to the New York Heart Association (NYHA) functional classification. RESULTS: Both plasma AM and PAMP concentrations in the patients were significantly higher than those in healthy volunteers. In addition, plasma AM and PAMP concentrations in patients in class III or IV of New York Heart Association (NYHA) classification were significantly higher than those in NYHA class I or II. The elevated plasma concentrations of these peptides in patients in NYHA class III or IV significantly decreased in response to the treatment for 7 days. There was a significant correlation between plasma AM and PAMP, though the plasma concentration of PAMP was one-fifth to one-seventh of that of AM in patients and controls. The plasma AM concentration correlated significantly with the plasma concentrations of atrial and brain natriuretic peptides, epinephrine, and right atrial pressure, whereas such a relationship was not noted for the plasma PAMP concentration. CONCLUSIONS: Judging from the difference in not only the biological actions but also the hormonal profiles between AM and PAMP, they may differentially modulate the cardiovascular system in patients with heart failure, although they are processed from the same precursor.

Adrenomedullin↗

Iodine-131 human-mouse chimeric Fab monoclonal antibody A7 guided surgery for colorectal cancer patients: a pilot study.

This study was conducted to determine the clinical usefulness of radioimmunoguided surgery (RIGS) using human-mouse chimeric Fab monoclonal antibody A7 (ch-Fab-A7) for colorectal cancer patients. Ten colorectal cancer patients were given iodine-131-labeled ch-Fab-A7 intravenously (i.v.) 2 to 7 days prior to RIGS. The RIGS was carried out using a portable gamma detecting probe (GDP). Tumor localization was identified by GDP intraoperatively in 4 of the ten patients, while liver metastasis and lymph node metastasis were identified in 2 patients and 1 patient, respectively. The GDP revealed tumor/surrounding tissue radio(gamma)count ratios of 1.5 or greater in 8 of the ten resected tumors. Although RIGS using ch-Fab-A7 is a promising tool for intraoperatively identifying the tumor localization of colorectal cancer, 125I, rather than 131I, should be used as a tracer for RIGS to enhance the accuracy of ch-Fab-A7.

Adenocarcinoma↗