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Biomedical subjects

K Tamura

Publications and source records attributed to K Tamura.

At least 577 records · Page 32Linked to original sources
PubMed1996

Immunohistological features of basement membrane formation of uterine cervical epithelium.

The state of the basement membrane (BM) was investigated in the normal epithelium, dysplasia/carcinoma in situ (CIS) and invasive carcinoma of the uterine cervix as well as metastatic lymph nodes by performing immunohistological staining for the presence of laminin (LN) and type IV collagen (CIV) and periodic acid-methenamine silver (PAM) staining of the BM. Moreover, to clarify the relationship between the epithelial cells and the BM, simultaneous staining for proliferating cell nuclear antigen (PCNA) was performed on the repaired tissue after punch biopsy. In the normal tissues, positive linear staining was observed beneath the epithelium with both PAM staining and LN.C IV staining. Some of the cases of dysplasia/CIS were continuously positive with PAM staining. However, there were sites which showed weakening and disruption of the continuity of positive staining for LN and C IV. As a function of the histological type of invasive carcinoma, the intensity of staining for LN and C IV decreased in the order of keratinizing (K), large cell non-keratinizing (LNK) and small cell non-keratinizing (SNK) histological types. However, no correlation was found between the stage of the carcinoma and the intensity of staining. In addition, the staining of the metastatic lymph nodes was similar to that of the primary lesion, and cancer foci that were in direct contact with lymphocytes were also stained for LN and C IV. During the process of reformation of the BM, LN and C IV were already present at the time when the epithelial interstitium was still negative for PAM staining. Moreover, at the time when the epithelial basal cells were PCNA-positive, LN and C IV could not be detected, and, conversely, when PCNA was negative, LN and C IV were detected. The BM is a structure which is formed when the interstitium is in a static state, and it was surmised that the production of LN and C IV is carried out by epithelial cells, including cancerous cells. Furthermore, it was surmised that the BM is not a structure which can prevent cancer invasion and the discontinuity or intermittency of staining for LN and C IV in cancers is a result of changes in the capacity to produce the BM components due to canceration of the cells.

Basement Membrane↗
PubMed1996

A phase I study of idarubicin hydrochloride in patients with acute leukemia. The Idarubicin Study Group of Japan.

This phase I trial of idarubicin (IDA) was conducted in 32 patients with acute leukemia and chronic myelogenous leukemia (CML) in blastic crisis (CML/BC) who either had failed to achieve a complete remission (CR) after initial induction therapy or had relapsed after CR. IDA was administered at dosages ranging from an initial dose of 5 mg/m2/d for 3 days with an increment of 2.5 mg/m2/d to 15 mg/m2/d for 3 days. The dose-limiting toxicities (DLTs) were thought to be stomatitis and anorexia. The maximum tolerated dose (MTD) was determined to be 15 mg/m2/d for 3 days (45 mg/m2 per course). Bone marrow toxicity was significant when greater than 10 mg/m2/d of IDA was given. When IDA was administered at this dosage or higher, there were three CRs and four partial responses, with an overall response rate of 26.9% in 26 assessable patients. It is recommended that a phase II study be undertaken at an IDA dosage of 10 to 15 mg/m2/d for 3 consecutive days in the treatment of acute leukemia. Twenty-one of 32 patients were also studied for the pharmacokinetics of IDA. The terminal half-life (t1/2) values for IDA were 6.4 to 15.1 hours in plasma and 8.09 to 16.34 hours in blood cells. The t1/2 values for idarubicinol were much longer: 43.46 to 51.01 hours in plasma and 36.61 to 54.70 hours in blood cells. Concentrations of idarubicinol in plasma and blood cells exceeded those of IDA 2 to 4 hours after the start of treatment and remained elevated for a long time. The area under the curve (AUC) of idarubicinol in plasma was 5.16 to 8.36 times higher than that of IDA, and the AUC of idarubicinol in blood cells was 2.05 to 4.57 times higher than that of IDA. The AUCs of both IDA and idarubicinol increased dose-dependently over the dosage range of 5 to 15 mg/m2/d. When two-compartment multiple-dose models were used, plasma t1/2 alpha and t1/2 beta values of IDA were 0.25 +/- 0.13 and 9.4 +/- 3.4 hours, respectively. The steady-state volume of distribution (Vdss) was 934.9 +/- 370.7 L/m2, and the plasma clearance was 82.3 +/- 29.7 L/h/m2. The urinary excretion of IDA and its metabolite was low. The mean cumulative urinary recovery rates were 2.04% for IDA and 11.53% for idarubicinol up to 7 days.

Acute Disease↗
PubMed1996

Myocardial sympathetic dysinnervation in doxorubicin cardiomyopathy.

Single photon emission computed tomography (SPECT) using I-123 metaiodobenzylguanidine (MIBG) was evaluated for the detection of doxorubicin (DXR) cardiomyopathy in seven patients with malignant lymphoma receiving DXR doses ranging from 70 to 530 mg (DXR group), and 20 normal subjects without hypertension, diabetes mellitus or electrocardiographic abnormalities (control group). The ratio of the heart to mediastinal counts (H/M) and the washout rate (WR) in MIBG SPECT images were compared between the two groups. Correlation of total doses of DXR with H/M and the relationship of H/M to WR were investigated. The H/M of the DXR group was lower than that of the control group (3.00 +/- 0.97 vs 4.90 +/- 1.08, p < 0.001). The WR of the DXR group was higher than that of the control group (30.9 +/- 10.5% vs 16.5 +/- 9.1%, p < 0.001). Total DXR doses were inversely correlated with H/M (r = -0.86), H/M correlated inversely with the WR (r = -0.83) only in the DXR group. Pathological findings of one patient, who died of DXR cardiomyopathy, showed atrophic and fibrotic nerve fibers in the apical inferior segment of the left ventricle where MIBG uptake was reduced markedly. DXR cardiomyopathy can be detected with MIBG SPECT as cardiac sympathetic nervous dysinnervation. The pathological findings correspond to the MIBG SPECT findings.

3-Iodobenzylguanidine↗
PubMed1996

Clinical significance of abnormal postexercise systolic blood pressure response in patients with hypertrophic cardiomyopathy.

The clinical significance of abnormal postexercise systolic blood pressure (SBP) response in patients with hypertrophic cardiomyopathy (HCM) was assessed by treadmill exercise testing in 30 normal subjects and 96 patients with HCM. SBP recovery ratios were derived by dividing the SBP at 1 and 3 min after exercise by the peak exercise SBP. The upper normal limit of the SBP ratio was defined by two standard deviations (SD) from the mean in 30 normal subjects. A postexercise SBP ratio that exceeded the upper normal limits of the SBP ratio was considered to be an abnormal SBP response in patients with HCM. Twenty-seven (28%) of 96 patients with HCM showed an abnormal SBP response. Compared with the normal SBP response group (69 cases) among patients with HCM, the abnormal SBP response group had lower SBP response during exercise (22 +/- 25 vs 62 +/- 26 mmHg : mean +/- 1 SD, p < 0.05), more prolonged QRS width (110 +/- 21 vs 92 +/- 20 msec, p < 0.05), higher incidences of ventricular tachycardia (12 vs 7 cases, p < 0.001), and sudden death (7 vs 0 cases, p < 0.0001). The defect area of Tl-201 myocardial scintigraphy was more extensive in the abnormal SBP response group (2.9 +/- 1.7 segments) than in the normal SBP response group (1.1 +/- 1.3 segments, p < 0.05). During atrial pacing (120/min), pulmonary artery wedge pressure was slightly elevated from 10 +/- 2 (at rest) to 14 +/- 3 mmHg (during pacing) (p<0.001), cardiac index showed no significant changes, and time constant T was shortened from 58 +/- 13 to 48 +/- 10 msec (p < 0.001) in the normal SBP response group, but in the abnormal SBP response group pulmonary artery wedge pressure was highly elevated from 12 +/- 5 to 20 +/- 3 mmHg (p < 0.0001), cardiac index was decreased from 2.5 +/- 0.7 to 2.1 +/- 0.6 l/min/m2 (p < 0.05), and the time constant T had no significant changes. These observations suggest that patients with HCM and abnormal postexercise SBP response have an abnormal cardiac response during exercise and extensive myocardial damage.

Blood Pressure↗
PubMed1996

[A case of medial medullary infarction with prominent deep sensory impairment].

We report a patient with medial medullary infarction who showed deep sensory impairment as his prominent neurological manifestation. A 54-year-old man with a history of hypertension was admitted to our hospital with numbness of the bilateral upper and lower extremities, followed by dysarthria and right hemiparesis. Physical examination revealed no abnormalities except for high blood pressure. He hiccuped continuously. On neurological examination, he exhibited dysarthria, mild dysphagia and right hemiparesis without facial or lingual paresis. Sensitivity to light touch and pinprick was normal, but sensitivity to vibration and joint position was severely decreased in the bilateral upper and lower extremities, predominantly in the lower extremities and on the right side in the upper extremities. He had been treated with antiedema agents and thromboxane synthetase inhibitor. His hiccups stopped within two weeks, and his right hemiparesis gradually improved within one month. However, his deep sensory impairments remained prominent. Blood examinations disclosed positive lupus anticoagulant. MRI showed bilateral infarction at the medial portion of the upper medulla oblongata, extending to both pyramids, especially on the left. Somatosensory evoked potentials (SEP) after median nerve stimulation showed P14 and the later components with prolonged latency. No SEP were recorded after posterior tibial nerve stimulation. The latency of P14 was well correlated with the severity of deep sensory impairments in the upper extremities. Neurological manifestations of our patient are not typical of medial medullary infarction, and are informative about the functional anatomy of the deep sensory tract in the medulla oblongata. We discuss the relation of the intractable hiccups to the bilateral medial medullary lesions, and emphasize the importance of lupus anticoagulant as one of the risk factors in brainstem infarction.

Cerebral Infarction↗
PubMed1996

[Measurement of bone density by ultrasound bone densitometer in normal pregnant women].

The bone mineral density in reproductive aged and pregnant women was measured with an ultrasound bone densitometer (Achilles, Luner Co, USA). Both parameters of bone density on Os calsis, sound of speed (SOS) and broad ultrasound attenuation (BUA) were significantly correlated with bone mineral density in lumbar2-4 measured by dual energy X-ray absorptiometry (DXA) (p < 0.01) in reproductive aged women (mean age; 24.5 +/- 2.3, n = 30). The changes in bone density during pregnancy and at delivery were studied. In a cross-sectional study, no significant changes in SOS, BUA and stiffness were observed, but in a longitudinal study (n = 21), all of these parameters decreased as pregnancy advanced. The markers of bone turnover (serum Ca, alkaline phosphatase, procollagen type 1-C peptide, urinary Ca/Cr and deoxypyridinoline/Cr) did not change during pregnancy. Ten pregnant women with low bone density (less than-1.5 SD mean value) were found. There was no significant difference between the markers of bone turnover in pregnant women with low and normal bone density. The clinical usefulness of the screening of bone density of reproductive aged and pregnant women to detect osteopenia is suggested.

Adult↗
PubMed1996

Eradication of Helicobacter pylori followed by reinfection.

Eradication therapy for Helicobacter pylori is now common, since eradication of this organism reduces the recurrence rate of peptic ulcer. We evaluated the eradication of H. pylori 4 weeks after the cessation of eradication treatment, and encountered recolonization in patients in whom eradication had been confirmed. Using a urease probe, we analyzed the Ure B restriction fragment length polymorphism (RFLP) of the DNA of the recolonized H. pylori by Southern blotting and compared it with that of the H. pylori strain cultured before eradication therapy. RFLP patterns before and after the treatment were identical, indicating that the recolonization of H. pylori was an exacerbation of the primary infection, rather than a reinfection.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

[Home care that meets the wishes of patients with terminal stage cancer and their families].

As our ward is a general surgical ward, we formerly had difficulties providing appropriate care for patients with terminal cancer. To solve the problem, we have formed a nursing study group in order to provide home care that would meet the wishes of such patients and their families. Our specific approach was as follows: 1) preparation of a form on which patient information is collected; 2) a support system for home care (such as pain control and home parenteral nutrition; and 3) a solid collaboration system between ward nurses and visiting nurses. Such a program enables us to understand the wishes of patients and families and to provide various support where needed. The project helps to lessen the anxiety and the burden that patients and families feel in home care, and improve the quality of life (QOL).

Aged↗
PubMed1996

Effects of physical therapy on immunological parameters in patients with cerebrovascular diseases.

The effects of physical therapy on immunological parameters were evaluated in 22 patients (14 males, aged 68.1 +/- 9.9 years) with cerebrovascular diseases in a stable situation 3 to 6 months after the onset of stroke who were entered into a rehabilitation program in our hospital between 1990 and 1993. The proportion of CD4+ cells was significantly increased but that of CD8+ cells was decreased throughout the rehabilitation program, resulting in an increase in the ratio of CD4+/CD8+ cells. The lymphocyte response to phytohemagglutinin and concanavalin A was increased, while no significant differences were observed in CD3+ cells, natural killer cell activity, and serum levels of immunoglobulins, interleukin-1 beta, interleukin-2 and interleukin-6. These findings suggest that repeated physical exercise may activate the immune system, especially T-cell function, for possible prevention of infectious diseases that are often complicated in patients with cerebrovascular diseases.

CD4-CD8 Ratio↗
PubMed1996

Asymptomatic multiple myeloma with concomitant neoplasms of two different origins.

A 63-year-old Japanese male with a four-year history of asymptomatic hypogamma-globulinemia is presented. On admission, he had a mild bone marrow plasmacytosis at about 10% of the total nucleated cells, but had no anemia, no paraproteins nor bone lesions. Flow cytometric analysis showed a predominant proliferation of kappa chain-positive cells in the bone marrow and peripheral blood, and an increase in the proportion of natural killer cells in the peripheral blood. Furthermore, coexistent meningioma and transitional cell carcinoma of the bladder were subsequently found 9- and 15-months after the admission, respectively. We considered that a myeloma-induced, possible latent immunodeficiency may have allowed the additional tumor growth, and that this process may have been controlled by the cytotoxic subset of immune effector cells.

Carcinoma, Transitional Cell↗
PubMed1995

Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J kappa/Su(H).

BACKGROUND: The mammalian transcription factor RBP-J kappa binds to the DNA sequence motif CGTGGGAA and is involved in the regulation of gene expression; for example, it plays a part in the transactivation of viral and cellular genes by Epstein-Barr virus nuclear antigen-2. The Drosophila homologue of RBP-J kappa is the product of the Suppressor of Hairless (Su(H)) gene. Su(H) is a neurogenic gene that acts downstream of Notch, which encodes a cell-surface receptor. Furthermore, in the mouse, the phenotypes of homozygous mutant Notch1 embryos are very similar to those of homozygous mutant RBP-J kappa embryos. Recent studies, using the yeast two-hybrid system, have led to the suggestion that the CDC10/ankyrin-like repeats of the Drosophila Notch protein interact with the Su(H) protein. RESULTS: We searched for proteins that interact with mouse RBP-J kappa using the yeast two-hybrid system, and in this way identified a short intracellular region (mRAM23) of the mouse Notch1 protein that lacks any known sequence motif. In vitro interaction studies, using proteins fused to glutathione-S-transferase, showed that RBP-J kappa and Su(H) bind directly to the RAM23 regions of mouse Notch1 and Drosophila Notch, respectively. Immunoprecipitation analysis showed that RBP-J kappa and the mRAM23 region of mouse Notch1 also interact in vivo. Further studies, including site-directed mutagenesis experiments, narrowed down the region of mouse Notch1 that interacts with RBP-J kappa. The results indicate that this region is less than 50 amino-acid residues in length, and lies immediately downstream of the transmembrane region. CONCLUSIONS: We show that the transcription factor RBP-J kappa/Su(H) interacts directly with a novel intracellular domain of the cell-surface receptor Notch. RBP-J kappa/Su(H) does not appear to interact with Notch via the CDC10/ankyrin repeats implicated in previous studies.

Amino Acid Sequence↗
PubMed1995

Ischemic preconditioning improves cardiac functional recovery following preservation with University of Wisconsin solution.

Single or multiple brief periods of regional or global ischemia and reperfusion prior to a prolonged ischemic insult showed cardioprotective effects. Although this phenomenon (ischemic preconditioning [IPC]) has been described in ischemic reperfusion models, the effect of IPC on heart preservation has not been previously reported. We, thus, investigated the effect of IPC on heart preservation. Hearts isolated from male Wistar rats (250-350 g) were mounted on a Langendorff apparatus to estimate baseline function (aortic flow, coronary flow, cardiac output, heart rate, systolic pressure, and rate pressure product). All hearts were divided into 5 groups. In groups 1 and 4, the hearts were subjected to 8 and 12 hr of preservation, respectively. The hearts in group 2 were subjected to a single 2.5-minute cycle of normothermic global ischemic episode (IPC) before 8 hr of preservation. In groups 3 and 5, the hearts were subjected to two 2.5-min IPC cycles and stored for 8 or 12 hr. The hearts were arrested with University of Wisconsin solution and stored at 4 degrees C. Following storage, the hearts were reperfused and measured postpreservative function to assess cardiac functional recovery. Lactate and troponin-T leakage in the coronary perfusate was also measured. In group 3, the treatment of two 2.5-min IPC cycles significantly increased cardiac output, but the treatment of single 2.5-min IPC cycle did not affect the result. In the extended preservation group (group 5), the recovery (%) of both coronary flow and cardiac output were significantly increased compared with group 4. Furthermore, lactate leakage was significantly reduced in groups 2 and 3. These results suggest that IPC improves cardiac functional recovery following simple cold storage and has cardioprotective effects in rat heart preservation.

Adenosine↗
PubMed1995

Specific inhibition of vascular cell adhesion molecule-1 expression by type IV collagen in endothelial cells.

The effects of matrices on the expression of adhesion molecules were studied in cultured human umbilical cord vein endothelial cells(HUVEC). The expression of vascular cell adhesion molecule-1 (VCAM-1) but not of intercellular adhesion molecule-1 stimulated with various substances was remarkably low in HUVEC cultured on type IV collagen, the major component of the basement membrane, compared with that on type I collagen. This inhibition was observed not only at the protein level but also at the mRNA level. These data suggested that VCAM-1 expression in endothelial cells is strictly regulated by the underlying basement membrane.

Basement Membrane↗
PubMed1995

Inhibitory effect of YM060 on 5-HT3 receptor-mediated depolarization in colonic myenteric neurons of the guinea pig.

We used conventional intracellular recording methods to examine the effects of YM060 [(-)-(R)-5-[(1-methyl-1H-indol-3-yl)carbonyl]-4,5,6,7- tetrahydro-1H-benzimidazole monohydrochloride), a novel 5-HT3 receptor antagonist, on 5-hydroxytryptamine (5-HT, serotonin)-evoked fast membrane depolarization in myenteric neurons of the guinea pig distal colon, and compared its potency to that of other 5-HT3 receptor antagonists. Microapplication of 5-HT from fine-tipped pipettes evoked both fast and slowly activating depolarizing responses in 78% and 40% of colonic myenteric neurons, respectively. The selective 5-HT3 receptor agonist 2-methyl-5-HT applied with short pressure pulses (100-300 ms) mimicked the fast but not the slow response. The 5-HT3 receptor antagonists YM060, granisetron and ondansetron suppressed the 5-HT-evoked fast response in 98% of colonic myenteric neurons in a concentration-dependent manner with pIC50 values of 8.62, 7.77 and 6.90, respectively. Methysergide and GR113808 did not affect the fast responses at concentrations sufficient to block 5-HT1, 5-HT2 and 5-HT4 receptors, respectively. YM060 did not affect the slowly activating response to 5-HT or any other electrophysiological parameter of the neurons including resting membrane potential, input resistance and the amplitude of action potentials evoked by injection of depolarizing current. Stimulus-evoked fast excitatory postsynaptic potentials were unchanged by YM060 at concentrations up to 10(-8) M, excluding any possible local anesthetic or anticholinergic effects of YM060. The results confirm that the fast component of the two depolarizing responses to 5-HT in colonic myenteric neurons is mediated by 5-HT3 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

High-performance liquid chromatographic determination of irinotecan (CPT-11) and its active metabolite (SN-38) in human plasma.

A simplified method for the simultaneous determination of irinotecan (CPT-11, I) and its active metabolite (SN-38, II) in human plasma by high-performance liquid chromatography (HPLC) with fluorescence detection has been developed. Following the addition of the internal standard (I.S.) camptothecin, the drugs were extracted from plasma using methanol. The average extraction efficiencies were 87% for I, 90% for II and 90% for the I.S. Chromatography was performed using a TSK gel ODS-80Ts column, monitored at 556 nm (excitation wavelength, 380 nm) and the mobile phase was acetonitrile-50 mM disodium hydrogen phosphate (28:72) containing 5 mM heptanesulphonate (pH 3.0). The linear quantitation ranges for I and II were 30-2000 and 1-30 ng/ml, respectively.

Antineoplastic Agents, Phytogenic↗