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Biomedical subjects

K Kanda

Publications and source records attributed to K Kanda.

At least 55 records · Page 3Linked to original sources

Neuronal pathways from low-threshold hindlimb cutaneous afferents to motoneurons innervating trunk muscles in low-spinal cats.

Postsynaptic potentials (PSPs) evoked in motoneurons innervating the back and abdominal muscles in the lumbar part of the body by stimulating hindlimb cutaneous afferents were investigated in unanesthetized decerebate and spinal cats. Various types of PSP: pure excitatory postsynaptic potential (EPSP), pure inhibitory postsynaptic potential (IPSP), and mixed PSP (i.e., EPSP followed by IPSP, EPSP/IPSP; and IPSP followed by EPSP, IPSP/EPSP) were observed. The weak stimulation at 2 times threshold (2T) produced predominantly the EPSP, while at 5T the incidence of IPSP or EPSP followed by IPSP was increased. In about 20-50% of the various groups of motoneurons, PSPs evoked by ipsi- and contralateral nerves were qualitatively and quantitatively similar. For the other motoneurons, PSPs evoked by ipsi- and contralateral nerves were markedly different with respect to magnitude and/or polarity. These findings suggest that, within each motoneuron pool, some neurons act to increase stiffness of the trunk or to move vertically in response to an increased activity of cutaneous afferents, while the other motoneurons act to produce lateral bending of the trunk.

Afferent Pathways↗

Bathing before sleep in the young and in the elderly.

In this study we investigated the effects of bathing on the quality of sleep in 30 elderly people (ages 65-83 years) and in 30 young people (ages 17-22 years) in their homes. Room temperature did not vary significantly during the nights that data were acquired, ranging from 8 to 12 degrees C. After bathing and at the beginning of sleep, the mean (SE) rectal temperatures of the young and the elderly were 37.8 (0.08) and 37.5 (0.07) degrees C, respectively, and were higher by 0.7 (0.13) and 0.6 (0.07) degrees C, respectively, than when the subjects had not bathed. At the beginning of the sleep after bathing in the young subjects, skin temperature was 32.5 (0.24) and 1.5 (0.34) degrees C higher than when those subjects had not bathed. In the elderly, however, there were no significant differences in skin temperature with and without prior bathing because they used electric blankets during sleep. After bathing, the young people reported "warmth" in their hands and/or legs, while the elderly more often reported "good sleep" or "quickness of falling asleep". During the first 3 h of sleep, body movements were less frequent after bathing for both the young and the elderly subjects. The results suggest that a bath before sleep enhances the quality of sleep, particularly in the elderly.

Adolescent↗

Recurrent bladder adenocarcinoma in an ileal conduit stoma: a case report.

BACKGROUND: The first case of a patient with recurrent adenocarcinoma in an ileal conduit stoma 7 months after radical cystectomy is reported. RESULTS/DISCUSSION: The most likely explanation of this case is hematogenous metastasis based on the clinical diagnosis and the pathological immunostaining examination of cytokeratin.

Aged↗

MN/CA9 gene expression as a potential biomarker in renal cell carcinoma.

OBJECTIVE: To compare the levels of MN/CA9 expression with clinicopathological variables in renal cell carcinoma (RCC), and thus evaluate MN/CA9 expression as a possible biomarker for RCC. MATERIALS AND METHODS: The level of expression of MN/CA9 was evaluated in 76 surgically obtained tissue samples (49 from RCC, 22 from normal kidney and five from oncocytoma) using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. In RCC, MN/CA9 expression was compared with stage, grade and cell type. RESULTS: MN/CA9 was expressed in 42 of 49 (86%) RCC samples, but in only two of 22 (9%) normal kidney and none of five oncocytoma samples. Levels of MN/CA9 expression were significantly higher in tumours consisting only of clear cells than in those containing other cell types (P=0.0189), and MN/CA9 was expressed in 34 of 37 (92%) RCC samples consisting only of clear cells. Tumours of low clinical stage showed a striking increase in MN/CA9 expression, and high MN/CA9 expression was associated with a good patient outcome. CONCLUSION: These results suggest that MN/CA9 expression is a potential diagnostic biomarker of RCC, especially the clear-cell type, and can be targeted using molecular biological techniques.

Adult↗

A phase I/II study of continuous intra-arterial chemotherapy using an implantable reservoir for the treatment of liver metastases from breast cancer: a Japan Clinical Oncology Group (JCOG) study 9113. JCOG Breast Cancer Study Group.

BACKGROUND: Liver metastasis from breast cancer has a poor prognosis. While there are some reports of good response rates of hepatic metastasis from breast cancer by hepatic intra-arterial infusion chemotherapy, no phase I study including pharmacokinetic analysis has been reported. We performed a phase I/II study of intra-arterial infusion chemotherapy using adriamycin and 5-fluorouracil to find the maximum tolerated dose and response rate in patients with advanced or recurrent breast cancer. METHODS: A hepatic arterial catheter with an access port was inserted into the proper hepatic artery. Patients received 30 mg/m2 adriamycin on days 1 and 8 and 100 mg/m2 5-fluorouracil at level 1, 200 mg/m2 at level 2,300 mg/m2 at level 3 and 400 mg/m2 at level 4 continuously from day 1 through day 14 every 28 days. At least two cycles were required before evaluation. Twenty-eight patients were entered into this study and 26 patients were evaluable. Seventeen patients had hepatic metastasis only, although nine patients had additional metastasis to other sites. RESULTS: Dose-limiting toxicity of thrombocytopenia and neurotoxicity occurred at level 4. Leukocytopenia (ECOG grade 3-4) was observed in five (19%), thrombocytopenia in three (12%) and anemia in two (8%) patients. There were 11 catheter-related complications which were not dose dependent. Seven out of 13 evaluable patients (54%) responded at level 3. The median duration of response was 5.8 months (range, 1-23+) and median survival was 25.3 months (range, 6.2-54.7+). CONCLUSION: Hepatic arterial infusion therapy appears to be safe and effective but catheter-related complications must be overcome before starting a phase III trial.

Adolescent↗

Isolation and characterization of the glyceraldehyde-3-phosphate dehydrogenase gene of Lentinus edodes.

The glyceraldehyde-3-phosphate dehydrogenase (GPD) gene of Lentinus edodes was isolated from a genomic DNA library and cDNA corresponding to this gene was isolated from a mycelium cDNA library. The L. edodes GPD gene was found to encode a 337-aa protein. By comparison of the cDNA and genomic DNA sequences, the presence of eight introns in the GPD gene was confirmed. The putative amino acid sequence of the L. edodes GPD gene product showed high similarity to those of other basidiomycetes. The results of Southern blot analyses suggested that only one copy of the GPD gene is present in the genome of L. edodes. The promoter region was found to contain a CT-rich stretch, two CAAT boxes and a consensus TATA box. In addition, the transcript of the GPD gene was found to be expressed constitutively and strongly. These results suggest that the promoter of the L. edodes GPD gene may be very useful as a component of transformation vectors.

3' Untranslated Regions↗

The Epstein-Barr virus nuclear antigen 2 (EBNA2), a protein required for B lymphocyte immortalization, induces the synthesis of type I interferon in Burkitt's lymphoma cell lines.

Epstein-Barr virus nuclear antigen 2 (EBNA2), a protein involved in cell transformation, interferes with the cellular response to type I interferons (IFN-alpha/beta). We investigated the function of conditionally expressed EBNA2 in the context of the IFN response in Burkitt's lymphoma cell lines. Expression of EBNA2 led to the transcriptional activation of both endogenous or transfected IFN-stimulated genes (ISGs), genes which contain within their promoters either the interferon-stimulated response element (ISRE) or the gamma interferon activation site (GAS). In search of a molecular mechanism for the transcriptional induction of ISGs, we observed an EBNA2-dependent synthesis of IFN-beta mRNA at low levels and the secretion of low amounts of IFN. A transfected IFN-beta promoter responded to EBNA2 activation, and a sequence closely resembling a RBP-Jkappa binding site was pinpointed as a potential target of EBNA2 activity. EBNA2-dependent transcriptional induction of the IFN-beta promoter occurred in EBV-negative Burkitt's lymphoma cells, indicating that other EBV genes were not required for the induction of IFN-beta synthesis.

B-Lymphocytes↗

Biologic markers in prostatic intraepithelial neoplasia: immunohistochemical and cytogenetic analyses.

OBJECTIVE: We evaluated the biological properties of High-grade prostatic intraepithelial neoplasia (PIN) by immunohistochemistry and fluorescence in situ hybridization (FISH) analysis in relation to normal tissue and carcinoma lesions. MATERIALS AND METHODS: Immunohistochemical staining and FISH were performed on 23 formalin-fixed radical prostatectomy specimens taken from patients with PIN. Assays were performed using MIB-1, chromogranin A (CGA) and an anti-androgen receptor antibody (AR). A centromere probe for chromosome 8 was used to test for aneuploidy. RESULTS: The MIB-1 index of cancerous specimens (16.2 +/- 10.5%) was significantly higher than that of benign (1.9 +/- 1.6%, p < 0.0001) or PIN (4.0 +/- 4.5%, p < 0.0001) specimens. The percentage of CGA positive cells was significantly lower in normal tissue (1.2 +/- 1.8%) than in PIN (3.5 +/- 2.9%, p = 0.012) or carcinoma (5.4 +/- 4.9%, p = 0.005) lesions. Positive staining for AR was consistently observed in the nuclei of both benign and malignant epithelial cells, but positive cytoplasmic staining was also seen in PIN epithelial cells. No significant difference in FISH detected anomalies were found between PIN and carcinoma specimens. CONCLUSIONS: Our studies concerning proliferative activity, NE differentiation and chromosomal anomalies of prostatic specimens support the hypothesis that PIN is a biologically intermediate stage in the pathogenesis of prostatic carcinoma. The cellular distribution of AR was altered in PIN cells, but the role of AR in PIN is not yet clear.

Aged↗

Detection of single-stranded cohesive ends in the genome of Bacillus thuringiensis temperate phage KK-88.

Cohesive ends (cos sites) were detected in the genome of temperate KK-88 phage in Bacillus thuringiensis after analysis of the phage DNA generated by the 3'-5' exonuclease activity of Klenow fragment of DNA polymerase I. In addition, unlike the 5'-protruding ends of coliphage lambda genome, the ends of KK-88 phage genome were found to be 3'-protruding. The restriction map of the phage genome was also constructed on the basis of position of the cos fragments.

Bacillus thuringiensis↗

Polysynaptic neuronal pathways from group I and group II afferents innervating tail muscles to hindlimb motoneurons in the cat.

Postsynaptic potentials evoked in motoneurons innervating m. posterior biceps and semitendinosus (PBSt) and m. triceps surae (GS) by low threshold afferents from various tail muscles located at the level of the second-third caudal vertebrae were investigated in the non-anesthetized and spinalized cat. Afferent inputs from tail muscles on both sides predominantly evoked depolarizing potential in PBSt motoneurons and hyperpolarizing potential in GS motoneurons. The findings suggest that in general, tail muscle afferents facilitate flexor and inhibit extensor hindlimb motoneurons through polysynaptic pathways, so that the pelvic girdle is kept in a low position to maintain the stability of the body irrespective of different movements or posture of the tail.

Afferent Pathways↗

Role of the matrix metalloproteinase and tissue inhibitors of metalloproteinase families in noninvasive and invasive tumors transplanted in mice with severe combined immunodeficiency.

OBJECTIVES: To elucidate the role of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human urothelial cancers, we studied gene expressions of MMPs, TIMPs, and membrane-type 1 matrix metalloproteinase (MT1-MMP) in noninvasive or invasive tumor lines transplanted in mice with severe combined immunodeficiency (SCID). METHODS: The UCT-1 tumor line, derived from bladder cancer, is a noninvasive transplantable tumor with no evidence of metastasis. The UCT-2 tumor line, derived from a renal pelvic tumor, extensively invades without metastasis. We examined gene expressions of MMPs-1, 2, 3, 7, 8, 9, 10, and 11, TIMPs-1, 2, and 3, and MT1-MMP in UCT-1 and 2 by semiquantitative polymerase chain reaction analysis. RESULTS: Significantly higher gene expression of MMP-2 was detected in the invasive UCT-2 tumor line than in the noninvasive UCT-1 tumor line. Although both tumor lines expressed TIMP-1 and MT1-MMP, stronger gene expression of MT1-MMP was observed in the UCT-2 tumor line than in the UCT-1 tumor line. The other MMPs or TIMPs were not detected in either of the lines. CONCLUSIONS: MMP-2 and MT1-MMP may have an important role in the invasion mechanism of urothelial cancers.

Aged↗

Effects of long-term physical exercise on age-related changes of spinal motoneurons and peripheral nerves in rats.

We examined the number and size of motoneurons and myelinated nerve fibers innervating the medial gastrocnemius (MG) muscle in the hindlimb of rats that were subjected to swimming for 10 months (30 min, 3 days/week) from 17 to 27 months of age. The number of MG motoneurons in exercised aged rats was slightly, but not significantly, greater than that in sedentary aged rats, and the number for both aged groups was significantly less compared to that in middle-aged (17-month-old) rats. The size of motoneuronal somata in the exercised aged rats was significantly larger than that in sedentary aged rats. Morphological parameters (fascicular area, fiber density, and axonal diameter) for the MG nerve in the exercised rats showed intermediate values between those for middle-aged and sedentary aged rats, although all of the differences in the means between groups were not significant. Thus, the overall changes seen in the exercised rats seem less compared to the changes in the sedentary rats, suggesting that long-term moderate exercise retards the progressive changes in motoneurons and peripheral nerves that develop in old age.

Aging↗

Semi-quantitative analysis of telomerase activity in exfoliated human urothelial cells and bladder transitional cell carcinoma.

OBJECTIVE: To determine the utility of detecting telomerase activity in transitional cell bladder cancer, using the telomeric repeat amplification protocol (TRAP) assay, and thus provide a test for the detection and monitoring of bladder cancer, especially low-grade tumours. PATIENTS, SUBJECTS AND METHODS: Telomerase activity was assayed in bladder cancer tissues and the exfoliated urothelial cells from 29 patients with bladder cancer, 10 with benign disease, and in 10 healthy subjects using the TRAP assay. The levels were assessed semiquantitatively by calculating the ratio to an internal telomerase assay standard. RESULTS: Telomerase activity was very low in the exfoliated urothelial cells from all healthy subjects and patients with benign disease, with a mean (SD) ratio of 0.25 (0.03) and 0.33 (0.04), respectively. A threshold ratio of 0.4 was calculated as the mean +/- 2 SD of the telomerase activity level of the exfoliated urothelial cells from patients with benign disease. Using this threshold, telomerase activity was negative in exfoliated urothelial cells from all benign cases (100% specificity) and positive in all 26 bladder cancer tissue samples assayed. In tumour tissue, telomerase activity was not associated with tumour grade, size or stage. Telomerase activity in exfoliated urothelial cells from patients with bladder cancer was positive in 25 of 29 samples (86% sensitivity). The sensitivity of telomerase activity in exfoliated cells was seven of nine in G1, 10 of 12 in G2 and all eight G3 tumours; the corresponding sensitivity for voided urine cytology in G1, G2 and G3 tumours was two of nine, six of 12 and six of eight, respectively. CONCLUSION: These results indicate that telomerase activation occurs as an early step in carcinogenesis and the semi-quantitative analysis of telomerase activity in exfoliated urothelial cells could be a minimally invasive and useful method for detecting bladder cancer, even in low-grade tumours.

Aged↗

Effects of N-[2-(1-azabicyclo[3,3,0]octan-5-yl)ethyl]2-nitroaniline fumarate (SK-946), a novel cognition activator, on learning and memory in rodent models.

We examined the effects of N-[2-(1-azabicyclo[3,3,0]octan-5-yl)ethyl]2-nitroaniline fumarate (SK-946) on cognition in various rodent models. SK-946 slightly suppressed spontaneous motor activity, but had no effect on scopolamine-induced motor facilitation. SK-946 ameliorated scopolamine-, pirenzepine-, cycloheximide- and electric shock-induced passive avoidance deficits in rodents when administered before acquiring the training. In an active avoidance test, SK-946 accelerated avoidance acquisition in the later half of training without a marked increase in lever-pressing. In more reliable models of cognitive disorders, i.e. an AF64A intracerebroventricular infusion model using the step-through passive avoidance test, an aged rat model using the step-down passive avoidance test and methylazoxymethanol (MAM)-induced microencephalic rat model using the Morris water maze test, SK-946 ameliorated impaired learning and memory. These results suggest an ability of SK-946 to enhance cognitive functions.

Aging↗

Characterization of the neurochemical effects of N-[2-(1-azabicyclo[3,3,0]octan-5-yl)ethyl]2-nitroaniline fumarate (SK-946) as a cognition activator.

The neurochemical effects of SK-946, N-[2-(1-azabicyclo[3,3,0]octan-5-yl)ethyl]2-nitroaniline fumarate, were investigated in an attempt to elucidate cognition activating properties. In rat brain cortical membranes and in cloned human receptors expressed in Sf9 cells, SK-946 had submicromolar affinities for muscarinic receptors with a moderate selectivity for M1 (m1) sites. Although no increase in the antagonist (N-methylscopolamine)/agonist (oxotremorine-M) binding ratio was observed, SK-946 exhibited a partial agonistic effect on receptor-stimulated phosphoinositide hydrolysis in primary cultured rat fetal hippocampal cells. Heterogeneous, reversible and concentration-dependent excitations of the hippocampal neuronal cells treated with SK-946 (10(-5)-10(-3) M) were confirmed as increases in cytosolic Ca2+ concentrations measured in Fura-PE3 preloaded cells. Furthermore, SK-946 (>10(-5) M) increased [3H]myo-inositol uptake into the hippocampal cells. On the other hand, SK-946 had no effect on adenylate cyclase activities in primary cultured rat heart cells, and showed a weak antagonistic effect on carbachol-induced adenylate cyclase inhibition, suggesting that it is an M2 antagonist. Using in vivo microdialysis, it was found that relatively low concentrations (<10(-7) M) of SK-946 increased acetylcholine release and decreased choline content in that hippocampal area in rats. These results suggest that SK-946 accelerates muscarinic neuronal transmission in the central nervous system.

Acetylcholine↗

Comparison of ICAM-1 and VCAM-1 expression in various human endothelial cell types and smooth muscle cells.

The diversity in the local manifestation of inflammatory vascular lesions might be partially attributable to heterogenous cell adhesion molecule (CAM) expression among endothelial cells (EC) derived from different anatomical locations. We compared basal and tumor necrosis factor-alpha (TNFalpha, 0-100 ng/ml, 0-48 h)-induced intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression in cultured human aortic EC (HAEC), vena cava EC (HVCEC), dermal microvascular EC (HMVEC), and vena cava smooth muscle cells (HVCSM), using a fluorescent ELISA and the competitive quantitative RT-PCR. We found marked differences in basal ICAM-1 expression, both at the protein and mRNA levels, such that HAEC>HVCEC approximately equal to HMVEC>>HVCSM. Basal VCAM-1 mRNA levels were significantly lower in HVCEC than in HAEC and HVCSM, while protein levels were indistinguishable. TNFalpha-induced ICAM-1 and VCAM-1 levels in all EC were similar and significantly higher than in HVCSM (2.5- and 5-fold, respectively). Dissimilar levels of basal and TNFalpha-induced CAM expression in vascular cells may explain the varied predisposition of different blood vessels to developing certain vasculopathies.

Cells, Cultured↗

Association of plasmid integrative J7W-1 prophage with Bacillus thuringiensis strains.

A region homologous to the genome of plasmid integrative phage J7W-1 was detected in the largest plasmid in 3 out of 22 type strains of Bacillus thuringiensis, dendrolimus (DEN), aizawai (AIZ) and indiana (IND). Phage induction by ethidium bromide observed particularly in the J7W-1 lysogen was identified in DEN and IND but not AIZ strains. The morphology of the phage induced in DEN and IND strains was identical to J7W-1, but the phage production in IND strain was lower as compared to the J7W-1 lysogen. Although the restriction analysis indicated that the prophage in DEN strain possessed a complete J7W-1 genome, modification and/or deletion had presumably occurred in AIZ and IND strains.

Bacillus Phages↗

Changes in urinary excretion of deoxypyridinoline in tail-suspended rats: effects of a bisphosphonate, YH529.

Urinary excretion of deoxypyridinoline (D-Pyr) has been shown to be a useful marker for bone resorption. In this study, we investigated whether D-Pyr could be used to monitor the changes in bone resorption of the hind limb induced by tail-suspension. Male Wistar rats 5-weeks old were tail-suspended in a metabolic cage to unload the hind limbs. The control rats were not suspended. YH529 (YH), an inhibitor of bone resorption, or a vehicle (phosphate buffered saline=PBS) was administered daily starting 3 days before the commencement of tail-suspension. In the non-suspended rats receiving PBS, urinary excretion of D-Pyr did not show any significant change during the one-week experimental period. In the non-suspended rats receiving YH, D-Pyr excretion significantly decreased on day 5 and 7 when compared with that observed on day 0, in accordance with the systemic inhibition of bone resorption by YH. In the tail-suspended rats receiving PBS, D-Pyr excretion showed a tendency to increase on day 1, which is in agreement with our previous report that tail-suspension causes an early (on day 1 of suspension) and transient increase in bone-resorption of the hind limbs. In the tail-suspended rats treated with YH, the increase in D-Pyr excretion on day 1 was not observed, and a significantly lower excretion was noted from day 3 to 7 during the tail-suspension. It was suggested that D-Pyr excretion might reflect the transient increase in hind limb bone resorption induced by tail-suspension. As observed in-YH treated rats, D-Pyr excretion could serve as a good marker for the inhibition of systemic bone resorption.

Amino Acids↗