Biomedical subjects

K Kanda

Publications and source records attributed to K Kanda.

At least 37 records · Page 2Linked to original sources

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

[Results of clinical study with epirubicin hydrochloride injectable solution and cyclophosphamide in breast cancer].

A 10-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with breast cancer. One course of treatment consisted of one intravenous administration of Epirubicin-RTU at the dose of 60 mg/m2 followed by a 3-week drug-free interval and concomitant daily administration of oral cyclophosphamide at 100 mg/day during the period between Days 1 through 14. At least, two courses of treatment were given. Among 20 registered cases, all 20 cases were eligible and 16 cases completed the whole course of the study. In 16 completers, PR was observed in 5 cases, indicating the efficacy rate of 31.3% (5/16).. No local irritation was observed at the injection sites. Adverse reactions frequently observed were leukopenia, neutropenia, anorexia, alopecia, and nausea/vomiting, which were all reversible and tolerable. From the above results, Adverse reactions both locally and systemically were tolerable. Intravenous administration of Epirubicin-RTU was considered to be useful for the treatment of breast cancer.

Administration, Oral↗

PubMed1997

A phase II study of high-dose epirubicin (EPI) plus cyclophosphamide (CPA) with G-CSF for breast cancer patients with visceral metastases or hormone-independent tumors: a trial of the Japan Clinical Oncology Group.

To evaluate the efficacy and toxicity of high-dose epirubicin (EPI) plus cyclophosphamide (CPA) therapy, a phase II study of EPI, 130 mg/m2, plus CPA, 1000 mg/m2, with G-CSF every 3 weeks was carried out for 51 advanced or recurrent breast cancer patients by the Japan Clinical Oncology Group (JCOG). Fifty out of the 51 patients who were eligible for our criteria were treated with this regimen as first-line chemotherapy for visceral metastases or hormone-independent tumors. In this trial, 203 cycles were administered with an average of four cycles per patients. In 50 patients who were evaluable for response, there were 7 complete (CR) and 25 partial responses (PR) with an overall response rate of 64% (95% confidence interval, 50.1-75.9%). Symptomatic and hematological acute toxicity more than grade 3 occurred frequently; however, no treatment-related death occurred. The incidence of toxicities (> or = grade 3) was as follows: leukopenia 98%, thrombocytopenia 42%, nausea/vomiting 56% and hair loss 12%. In each cycle, daily administration of 2 micrograms/kg G-CSF (granulocyte-colony stimulating factor) was given on days 2-15 subcutaneously. The incidence of cardiotoxicity was low. Arrhythmia (< or = grade 2) was observed in 8% and a slight decrease of ejection fraction index (< or = grade 2) was observed in 2% in this trial. The median follow-up period for patients was 37.2 (24.6-51.5) months and the median survival period was 17.4 months. These data indicate that high-dose EPI + CPA combination chemotherapy was effective and well tolerated for breast cancer patients with visceral metastases or hormone-independent tumors. A randomized trial of high-dose EPI vs conventional chemotherapy is required to ascertain the usefulness of this regimen.

Adult↗

PubMed1997

[Effects of intermittent wakening on sleep pattern of nighttime caregiver: an EEG study with a single subject].

In order to investigate the effects of night wakening on sleep pattern of caregiver, a woman aged 45 years was studied using electroencephalogram (EEG). After two adaptation nights, her all-night EEG readings were recorded for six nights. During the first three consecutive nights, the subject slept by the side of a patient at a private ward of hospital and wakened by herself several times a night to provide care for the patient (care nights). Of the later three nights, her sleep EEGs were recorded at her home (free nights). The first free night was following three care nights and the other two free nights were after 2 weeks. The results were summarized as follows; 1) Sleep period time (SPT) of care nights differed in different nights. In contrast to the SPT range of 356-367 min during free nights, it was 271-391 min during the care nights. 2) The rhythm of sleep cycles of care nights was not stable, though the subject wakened by herself, not using an alarm clock. 3) Although there were few changes occurring in sleep efficiency (SE) and percent each stage for SPT (%SPT) between the first and second care night, SE of the third care night was more similar to SE of free nights than SE of the first two care nights, and so was %SPT of the third care night. 4) Sleep latency (SL) decreased during the four consecutive nights, i.e. the three care nights and the first free night, and SL of the third care night and the first free night were shorter than SL of the last two free nights. The accumulation of fatigue and stress of nighttime care was suggested.

Caregivers↗

PubMed1997

[A study of nursing systems in transition in developed countries].

The present study was designed to investigate nursing systems in other countries in comparison with the current system in Japan, and thereby assess how nursing personnel should be in order to improve the quality of nursing. The study focused on the actual situation of the nursing system and licensed practical nurses (LPNs) or second-level nurses similar to LPNs in other countries. The survey was conducted in regard to six countries considered to be advanced in the development of nursing activities and likely to provide useful suggestions for the future direction of nursing in Japan: Australia, Canada, France, Sweden, the United Kingdom and the United States. Questionnaires were sent to the heads or staff of a total of 29 organizations, including WHO Collaborating Centers and professional organizations for nursing, in these countries. Nineteen organizations responded (response rate: 65.5%), and an effective response with completed questionnaire forms was obtained from 15 organizations. In addition, an interview survey was conducted on three nursing administration and education experts in the United States in order to acquire clear understanding of the actual state of nursing in health care practice. The results were as follows: 1. Six countries (Japan included) excluding France had LPNs. Educational preparation for LPNs has been discontinued in the United Kingdom. 2. The number of nurses per 1,000 population was lowest in Japan: the total number of registered nurses (RNs) and LPNs in Japan was less than the number of RNs in the United Kingdom. Only in Japan the proportions of LPNs and RNs were similar, while in other countries of number of LPNs was one-third to one-fourth of the number of RNs. 3. In the five other countries having LPNs, the nurse's competency or scope of practice was clearly defined for both LPNs and RNs. In contrast, no clear line was drawn between the two in Japan. 4. The length of education required for LPNs ranged from 11 to 14 years (including the period of compulsory education) and was shortest in Japan (11 years). The educational requirement for admission to LPN school in Japan was 9 years of compulsory education (graduation from junior high school), whereas in other countries it was at the level of senior high school graduation. 5. Four countries had conversion programs for LPNs to become RNs, and the conversion courses were positioned within the framework of higher education comparable to the university level. 6. In the United Kingdom, where the educational preparation for LPNs has been discontinued, nurses are included in a single higher level profession. At the same time there was found to be a need to train and educate auxiliary personnel in order to maintain multi-level care services. Because of the increasing tendency toward advanced medical technology and highly specialized medical care associated with the rapidly increasing care needs in the community, the current educational preparation for LPNs in Japan in unsatisfactory as a training and educational system for nursing manpower to cope with the current situation. The above findings suggest that the education system for LPNs be reviewed with a view to discontinuing it and consolidating nursing education in Japan.

Australia↗

PubMed1996

Expression of neuronal nitric oxide synthase in spinal motoneurons in aged rats.

We investigated the expression of nitric oxide synthase (NOS) in motoneurons of aged rats by the nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (NADPH-d) reaction. The number of NADPH-d positive neurons (i.e. presumed motoneurons) in the motor nucleus at L4-L6 level of the spinal cord was 0.0 +/- 0.0 for 13- to 15-month-old rats, 2.2 +/- 0.8 for 24-month-old rats, and 7.9 +/- 5.4 for 29- to 32-month-old rats. These NADPH-d positive neurons were multipolar in shape and the soma cross-sectional area was 820 +/- 245 mu2 (n = 56; range, 359-1460 mu2) which was similar to the value for alpha-motoneurons. The results indicate that nitric oxide (NO) may be produced by a few motoneurons in the aged rat spinal cord and may lead these neurons to eventual death.

Aging↗