Search PubMed⌕ Search

Biomedical subjects

Y Kondo

Publications and source records attributed to Y Kondo.

At least 433 records · Page 24Linked to original sources

Concomitant use of prostaglandin E1 and prednisolone; inhibition of superoxide anion production by polymorphonuclear leucocytes.

We investigated the effect of prostaglandin E1 (PGE1) or prednisolone on superoxide anion production by polymorphonuclear leucocytes (PMN) stimulated by opsonized zymosan (OZ). The production of superoxide anion by PMN was significantly suppressed by treatment with either PGE1 or prednisolone. Concomitant use of PGE1 and prednisolone suppressed it significantly more than PGE1 or prednisolone alone. Both PGE1 and prednisolone suppressed the Ca2+ influx into PMN, which was a crucial event for production of superoxide anion in stimulation by OZ. The effect of concomitant use of PGE1 and prednisolone in vivo was confirmed in rat peritonitis. The additional use of PGE1 with prednisolone may provide a strategy to reduce the amount of prednisolone required in treatments.

Alprostadil↗

[A study on health and caregiving status of the elderly over age 75 living in urban Tokyo--comparing 1987 with 1993].

The purpose of this study is to propose the improvement of the community care service and caregivers' support system. A questionnaire was sent to the elderly over age 75 living in Chuo Ward of Tokyo, on their living place, previous illness, health status, degree of assistance needed, and their caregivers. The same kind of surveys were made in 1987 and 1993, and the health status and home care were compared and changes in caregiver services were examined. Valid responses of 3,294 (response rate of 81.3%) in 1987 and 3,409 (response rate of 76.3%) in 1993 were analyzed and compared with each other. The results are following; (1) The total number of bedridden elderly persons decreased from 214 (6.5% of the total) in 1986 to 61 (1.8% of the total) in 1993. The number of elderly over age 75 with high health status increased. (2) The rate of the elderly who stay only indoors, although physically non-handicapped and in good health, was 20%. (3) The statistic of caregivers' concern about care services in the answer to open ended questions showed the increase of the desire for the supply of information, and the fact of more suitable pieces of advice having been given about the resources for care, care-give service, and family adjustment. It is necessary to establish the system to support and develop home care in the community in the future. Social support will also be necessary not only for infirm or handicapped elderly people, but also for demented, living in solitude, or non-social withdrawn healthy aged people to make use of community care service, counseling of care service and short stay at nursing homes. Especially the importance of community care service to prevent the elderly from being bedridden was suggested. Moreover, general broad support is necessary, such as social education, income guarantee and housing measure as well as that from the point of view of health and welfare.

Activities of Daily Living↗

[A study on health and caregiving status of the elderly over age 75 living in urban Tokyo--social services and caregiving for the bedridden and senile elderly].

Interviews during home visits were used to assess social services and caregiving status for the bedridden and senile elderly living at home in urban Tokyo. In Chuo ward 197 bedridden and senile elderly were identified from 3,409 mailed surveys (response rate 5.8%). This study analyses data from 110 subjects who were followed up with interviews during home visits. As indicated by the Karasawa senile scale, 70% of the respondents have communication problems with the elderly person in their care. Incontinence problems are reported in 56.7% of the frail elderly. There is no significant association between incontinence problems and decisions by caregivers to institutionalize the elderly. The mean age of the main caregiver is 61.9 +/- 12.7 years. There are 55.5% of the families with secondary caregivers. The mean period of care is 6.3 +/- 8.2 years. Even the families who take care of their elderly relative for longer periods of time have no one to consult about caregiving. Caregiver strain was measured by the Family Maslach Burnout Inventory. The subscale, emotional exhaustion, occurs most frequently. Only 25.0% of caregivers indicate willingness to accept social services, on the other hand 63.5% of the caregivers desire family care. The questionnaire listed twenty five resources currently available for families in this ward for social services. Only 52.2% know about resources for social services. Only 8.5% of the respondents use social services. Respondents know about and use social services for direct care of their elderly relative more than they use support for adapting the home environment for the care of the elderly. These findings suggest the following: (1) In order to promote effective use of social services a systematic case finding and assessment plan is needed. (2) Development of services from the viewpoint of prevention and emotional support are needed. (3) Case management is needed to achieve a mix of both the family care and social services.

Aged↗

Promotional effect of two-generation exposure to a high-fat diet on prostate carcinogenesis in ACI/Seg rats.

Epidemiological studies have shown an association between a high-fat diet and a high mortality rate from breast, colon, and prostate cancer. However, the promotional effect of a high-fat diet on experimental carcinogenesis has not been fully established for the prostate. In this study, the effect on prostatic carcinogenesis of two-generation exposure to a high-fat diet was investigated using ACI/Seg rats, a strain with high incidence of spontaneous prostate cancer. A high-fat diet (20% corn oil) or a low-fat diet (5% corn oil) was given to mother rats during pregnancy and the newborn male rats were fed the same diets for 60 or 100 weeks after weaning. At 100 weeks, atypical hyperplasia and adenocarcinoma of the prostate were respectively found in 73.3% (11/15) and 20.0% (3/15) of the high-fat diet group and in 20.0% (3/15) and 0% (0/15) of the low-fat diet group. There was a significant increase of atypical hyperplasia in the high-fat diet group (P < 0.05). The serum concentrations of sex hormones and the prostatic proliferative activity as measured by flow cytometry or bromodeoxyuridine labeling were not significantly affected by diet. These results showed that feeding a high-fat diet before conception and from the beginning of organogenesis had a marked promotional effect on the early stage of prostate carcinogenesis in rats.

Animals↗

Genistein, an inhibitor of protein tyrosine kinase, is also a competitive antagonist for P1-purinergic (adenosine) receptor in FRTL-5 thyroid cells.

Genistein, a potent inhibitor for protein tyrosine kinase, remarkably inhibited the stimulatory action of N6-(L-2-phenylisopropyl)adenosine (PIA), an A1-adenosine receptor agonist, on thyrotropin (TSH)-induced phospholipase C activation in FRTL-5 thyroid cells. This drug also suppressed both the A1-receptor-mediated inhibition of cAMP accumulation in the cells and binding of [3H]8-cyclopentyl-1,3-dipropylxanthine, a specific antagonist for A1-receptor, to the cell membranes in a competitive manner. Adenosine-induced cAMP accumulation through A2-receptor in pertussis toxin-treated cells was also competitively antagonized by genistein. We conclude that genistein is also a competitive antagonist for P1-purinergic receptors.

Adenosine Deaminase↗

Reduced choline acetyltransferase activity and muscarinic M1 receptor levels in aged Fisher 344 rat brains did not parallel their respective mRNA levels.

Differences in the acetylcholine (ACh)-mediated neuronal system of the brain between aged and young rats were studied by measuring choline acetyltransferase (ChAT) activity, muscarinic M1 receptor (M1-R) and their respective mRNA levels. In aged rats, ChAT activity and the M1-R level were significantly reduced in the cerebral cortex, hippocampus and striatum compared with that in young rats. On the other hand, there was no difference in the ChAT mRNA level in the striatum and the basal forebrain, or the M1-R mRNA level in the cerebral cortex, hippocampus and striatum between aged and young rats. The effects of chronic administration of bifemelane (4-(2-benzylphenoxy)-N-methylbutylamine hydrochloride), which is used for the treatment of sequelae of cerebrovascular diseases, were also evaluated. In aged rats chronically administered bifemelane, the ChAT activity recovered to the level in the young rats in the cerebral cortex and hippocampus, and the M1-R level recovered completely in the cerebral cortex, hippocampus and striatum. However, the ChAT mRNA level and the M1-R mRNA level were not affected by bifemelane administration. Thus, the decreases and recoveries in ChAT activity and M1-R level did not parallel the changes in their respective mRNAs. These results suggest that the age-related impairments in ACh-mediated neuronal system are considered to be caused primarily by disorders of post-transcriptional events.

Aging↗

Protection by sinomenine against endotoxin-induced fulminant hepatitis in galactosamine-sensitized mice.

Sinomenine, an epimorphinan alkaloid, was tested for protecting hepatitis induced by lipopolysaccharide (LPS) in galactosamine (GalN)-sensitized mice. Sinomenine protected against the hepatic injuries in the dose range of 10-100 mg/kg in a dose-dependent manner and suppressed the production of tumor necrosis factor (TNF), which appeared in serum earlier than aminotransferases in GalN/LPS-treated mice. Sinomenine significantly suppressed the in vitro production of superoxide anion and hydrogen peroxide in the macrophage cultures stimulated with phorbol 12-myristate acetate. It is discussed that sinomenine prevents GalN/LPS-treated hepatic failure by suppressing TNF production and/or reactive oxygen generation.

Analgesics↗

Effects of SK&F 96365, an inhibitor of receptor-mediated Ca2+ entry, on Ca2+ influx and catecholamine secretion in bovine adrenal chromaffin cells.

SK&F 96365 (1-[3-(4-methoxyphenyl)propoxyl]-1-(4-methoxyphenyl)ethyl-1H- imidazole HCl) (1-50 microM), an inhibitor of receptor-mediated Ca2+ entry, reduced both acetylcholine (ACh)- and 56 mM K+ (high K+)-induced 45Ca2+ influxes and catecholamine secretion in bovine adrenal chromaffin cells. However, SK&F 96365 at lower concentrations (1-3 microM) inhibited only ACh-induced 45Ca2+ influx and secretion but not their high K(+)-induction. In Na(+)-free medium, ACh-induced 45Ca2+ influx and secretion were also considerably decreased by SK&F 96365 at low concentrations (1-3 microM). These results suggest that in the chromaffin cells, not only voltage-sensitive calcium channels but also ACh receptor-operated calcium channels at least in part contribute to the influx of Ca2+ which triggers the catecholamine secretion from the cells when the cells are exposed by ACh.

Acetylcholine↗

Single retinal ganglion cells projecting bilaterally to the lateral geniculate nuclei or superior colliculi by way of axon collaterals in the cat.

In most mammals with frontalized eyes, retinal ganglion cells in the nasal or temporal retina send their axons to the contralateral or ipsilateral half, respectively, of the brain. Previous studies in the cat, however, have indicated a retinal region of "nasotemporal overlap" from which arise the retinal projections to both the contralateral and ipsilateral halves of the brain. The present study thus examined in the cat whether any retinal ganglion cells give rise to bifurcating axons that innervate both halves of the brain. By employing fluorescent retrograde double labeling, we investigated whether or not single retinal ganglion cells project bilaterally to the lateral geniculate nuclei or superior colliculi by way of axon collaterals. After Fast Blue was injected into the lateral geniculate nucleus on one side and Diamidino Yellow was injected contralaterally into the lateral geniculate nucleus, 100-200 ganglion cells in each retina were double labeled with both tracers. These double-labeled cells were distributed primarily in the temporal retina, including the region around the vertical meridian and, additionally, in the nasal retina. About 60-80% of the double-labeled cells had large cell bodies (more than 25 microns in diameter), and the others had medium-sized ones (15-25 microns in diameter). The pattern of distribution of double-labeled cells, which was observed after the combined injection into both superior colliculi, was similar to that seen after the combined injection into both lateral geniculate nuclei; more than 90% of double-labeled cells, however, were large.(ABSTRACT TRUNCATED AT 250 WORDS)

Amidines↗

A new cancer-associated antigen defined by a monoclonal antibody against a synthetic carbohydrate chain.

Carbohydrate antigens can be designed by referring to previously defined carbohydrate structures. We have generated a novel monoclonal antibody (MAb) (F1 alpha-75) against an artificially designed antigen (F1 alpha), using organic-synthetic chemistry methods and hybridoma technology. F1 alpha (Gal beta 1-->4GlcNAc beta 1-->6GalNAc alpha 1-->Ser/Thr) belongs to core type 6 of O-linked glycans, which has not been previously reported in human cancers. To produce antibodies against F1 alpha, a glycolipid was synthesized which carries the carbohydrate portion of F1 alpha on a ceramide foundation (Gal beta 1-->4GlcNAc beta 1-->6GalNAc alpha 1-->Cer). The MAbs we obtained (F1 alpha-75, F1 alpha-87) specifically recognized F1 alpha and had only a very weak or no cross-reactivity with other glycolipids similar to F1 alpha. We investigated the expression of F1 alpha in human tissues, including 110 gastric cancers, 73 colon cancers and 42 pancreatic cancers. F1 alpha was found in human cancerous tissues but not in normal adult tissues. The rate of positive staining with F1 alpha-75 was 80.0% for gastric cancer, 52.4% for pancreatic cancer and 38.4% for colon cancer. F1 alpha-75 also reacted with the tissues neighboring gastric and pancreatic tumors but not intensely. Among fetal tissues, F1 alpha-75 reacted with the pyloric glands of the stomach, the centro-acinar cells of the pancreas, the convoluted tubules of the kidney and the terminal bronchioles of the lung.

Antibodies, Monoclonal↗

Phospholipase C activation and Ca2+ mobilization by cloned human somatostatin receptor subtypes 1-5, in transfected COS-7 cells.

We transfected the COS-7 cells with cDNAs encoding different human somatostatin receptor (hSSTR) subtypes, and found that hSSTR subtypes mediate not only the inhibition of forskolin-induced cAMP accumulation but also the stimulation of phospholipase C (PLC) and Ca2+ mobilization. Activation of PLC by 1 microM somatostatin (SRIF) was in the order of: hSSTR5 > hSSTR2 > hSSTR3 > hSSTR4 >> hSSTR1. Pertussis toxin (PTX) treatment completely or partially reversed the PLC activation. 1 nM SRIF was equally effective for adenylate cyclase (AC) inhibition in a PTX-sensitive manner, in all the cells expressing different hSSTRs, except for hSSTR1. Nevertheless, SRIF stimulated AC even in the presence of forskolin at higher doses of SRIF in PTX-treated hSSTR5-expressing cells. We conclude that the cloned hSSTRs differentially couple to PTX-sensitive and -insensitive G-proteins to modulate PLC, Ca2+ mobilization and AC.

Calcium↗

Invasive growth patterns of hepatic hilar ductal carcinoma. A histologic analysis of 18 surgical cases.

BACKGROUND: Postoperative recurrence of hepatic hilar ductal carcinoma usually occurs in a localized region around the surgical margin, such as the bile duct. This study was aimed at assessing the invasive patterns of the hepatic hilar ductal carcinoma by histologically examining surgical specimens obtained by extended liver resection, especially the involvement of intrahepatic duct. METHODS: Eighteen resected specimens of hepatic hilar ductal carcinoma were histologically investigated. Multiple sections vertical to the extrahepatic and intrahepatic bile duct were made at a 5-mm interval. The extension of carcinoma was evaluated on each of three layers (mucosal, extramucosal-intramural, and extramural), and routes of the invasion were examined. RESULTS: Extramucosal extent toward the hepatic side was observed in 14 patients (77.8%) and that toward the duodenal side in 8 patients (44.4%) (P < 0.05). The distance of extramucosal tumor extent was also significantly longer (P < 0.05) in the hepatic side than in the duodenal side. Histologic tumor margin was usually identified in the extramural layer. Two patients had discontinuous extramucosal invasion. The lymphatic invasions were observed most frequently, followed by perineural invasion, and venous invasion was rare. In the extramucosal invasion of the liver, the left dominant carcinomas had extended toward the left, whereas those right dominant had extended toward the right (P < 0.05). Well differentiated differentiated tubular adenocarcinomas extended to the liver more extensively than moderately and poorly differentiated ones, but not significantly. CONCLUSIONS: The authors examined the extramucosal invasion of hepatic hilar ductal carcinoma. This invasion extended more frequently and further to the hepatic side than to the duodenal side, usually by the route of the extramural layer.

Adenocarcinoma↗

Changes in lipid peroxidation, Cu/Zn-superoxide dismutase and its mRNA following an intracerebroventricular injection of 6-hydroxydopamine in mice.

A single i.c.v. injection of 6-hydroxydopamine (6-OHDA) in mice resulted in a biphasic increase in lipid peroxidation as assayed by the level of thiobarbituric acid-reacting substances (TBARS). An increase in Cu/Zn-superoxide dismutase (SOD) activity was temporally related with the first peak of TBARS but remained unchanged during the second TBARS peak. This suggests that a free radical species other than O2- may be involved in the late onset increase in TBARS. The level of Cu/Zn-SOD mRNA did not immediately reflect the change in Cu/Zn-SOD activity but rather increased gradually reaching significantly higher levels only 8 weeks after i.c.v. an injection of 6-OHDA. This increase in Cu/Zn-SOD mRNA likely occurs in response to a consumption of intrinsic SOD. Thus, short- and long-term increases in lipid peroxidation likely occur by different mechanisms and studies of both are needed to elucidate the neurodegenerative process.

Animals↗

Quick-freeze, deep-etch studies of renal basement membranes.

The fine structure of the renal (i.e., glomerular, tubular, and capillary) basement membranes was re-evaluated with the aid of a deep-etch replica method. The structure of the laminae rarae interna and externa of the rat glomerular basement membrane (GBM) and laminae lucida of other basement membranes were basically identical in that 6 to 8 nm fibrils were interconnected to form a three-dimensional, polygonal network. By contrast, all of the laminae densa examined were composed of closely packed granules, and a filamentous substructure was identified only in a limited area. These granular components were demonstrated to be an integral component of the lamina densa. From additional observations on the trypsinized bovine GBM, it appeared that the basic structure of renal basement membranes was almost identical, namely, that a three-dimensional fibrillar meshwork existed throughout the individual layers to form a structural framework upon which fine particles were variably attached. In addition, we observed some of the fine structure of the pars fibroreticularis; the laminae densa of the tubular and capillary basement membranes continued to the fibrillar meshwork resembling the structural backbone of the glomerular basement membrane. The network was sometimes directly connected to the extracellular matrix, but more often changed into a rough fibrillar framework and connected to the extracellular matrix.

Animals↗

Permissive stimulation of Ca(2+)-induced phospholipase A2 by an adenosine receptor agonist in a pertussis toxin-sensitive manner in FRTL-5 thyroid cells: a new 'cross-talk' mechanism in Ca2+ signalling.

We have described the pertussis toxin (PTX)-sensitive potentiation of P2-purinergic agonist-induced phospholipase C activation, Ca2+ mobilization and arachidonic acid release by an adenosine receptor agonist, N6-(L-2-phenylisopropyl)adenosine (PIA), which alone cannot influence any of these cellular activities [Okajima, Sato, Nazarea, Sho and Kondo (1989) J. Biol. Chem. 264, 13029-13037]. In the present study we have found that arachidonic acid release was associated with lysophosphatidylcholine production, and conclude that arachidonic acid is produced by phospholipase A2 in FRTL-5 thyroid cells. This led us to assume that PIA augments P2-purinergic arachidonic acid release by increasing [Ca2+]i which, in turn, activates Ca(2+)-sensitive phospholipase A2. The arachidonic acid-releasing response to PIA was, however, always considerably higher (3.1-fold increase) than the Ca2+ response (1.3-fold increase) to the adenosine derivative. In addition, arachidonic acid release induced by the [Ca2+]i increase caused by thapsigargin, an endoplasmic-reticulum Ca(2+)-ATPase inhibitor, or calcium ionophores was also potentiated by PIA without any effect on [Ca2+]i and phospholipase C activity. This action of PIA was also PTX-sensitive, but not affected by the forskolin- or cholera toxin-induced increase in the cellular cyclic AMP (cAMP), suggesting that a PTX-sensitive G-protein(s) and not cAMP mediates the PIA-induced potentiation of Ca(2+)-generated phospholipase A2 activation. Although acute phorbol ester activation of protein kinase C induced arachidonic acid release, P2-purinergic and alpha 1-adrenergic stimulation of arachidonic acid release was markedly increased by the protein kinase C down-regulation caused by the phorbol ester. This suggests a suppressive role for protein kinase C in the agonist-induced activation of arachidonic acid release. We conclude that PIA (and perhaps any of the G1-activating agonists) augments an agonist (maybe any of the Ca(2+)-mobilizing agents)-induced arachidonic acid release by activation of Ca(2+)-dependent phospholipase A2 in addition to enhancement of agonist-induced phospholipase C followed by an increase in [Ca2+]i.

Animals↗

Transfected human somatostatin receptor type 2, SSTR2, not only inhibits adenylate cyclase but also stimulates phospholipase C and Ca2+ mobilization.

COS-7 cells were transfected with human somatostatin (SRIF) receptor type 1 and 2 (human SSTR1 and SSTR2, respectively) cDNAs. In human SSTR2-expressing cells, SRIF not only inhibited forskolin-induced cAMP accumulation but also stimulated phospholipase C and Ca2+ mobilization. While the inhibition of cAMP accumulation was completely reversed by pertussis toxin (PTX) treatment of the cells, SRIF-induced activation of phospholipase C and Ca2+ mobilization was partially but not completely inhibited by the toxin treatment. In human SSTR1-expressing cells, however, SRIF induced only slight inhibition of cAMP accumulation and stimulation of phospholipase C-Ca2+ system. We conclude that the transfected SSTR2 can couple to phospholipase C as well as adenylate cyclase in a stimulatory and inhibitory manner, respectively. Both PTX-sensitive and -insensitive GTP-binding proteins may be involved in the SSTR2 signal transduction mechanisms.

Adenosine Triphosphate↗

Differential effects of chronic L-dopa treatment on lipid peroxidation in the mouse brain with or without pretreatment with 6-hydroxydopamine.

Whether or not chronic L-dopa treatment (100 mg/kg, intraperitoneally (i.p.), twice daily for 4 weeks) alters lipid peroxidation in the brain as an indicator of neuronal damage was examined in normal mice and mice in which catecholamine (CA) neurons had been injured previously by the administration of 6-hydroxydopamine (6-OHDA), followed by recovery. In normal mice, chronic L-dopa treatment reduced the thiobarbituric acid reacting substances (TBARS) level, an indicator of lipid peroxidation, in the cerebral cortex. In contrast, in mice with CA neuronal injury induced by pretreatment with 6-OHDA, the chronic L-dopa treatment markedly increased the TBARS in the striatum and frontal cortex, despite recovery of the striatal dopamine levels similar to those in the control mice. These findings suggest that the long-term high-dose administration of L-dopa enhances the progression of neuronal damage in patients with injured CA neurons such as those with Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗