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Biomedical subjects

Y Kanno

Publications and source records attributed to Y Kanno.

At least 73 records · Page 4Linked to original sources
PubMed1996

Immunodeficiency and chronic myelogenous leukemia-like syndrome in mice with a targeted mutation of the ICSBP gene.

Interferon consensus sequence binding protein (ICSBP) is a transcription factor of the interferon (IFN) regulatory factor (IRF) family. Mice with a null mutation of ICSBP exhibit two prominent phenotypes related to previously described activities of the IRF family. The first is enhanced susceptibility to virus infections associated with impaired production of IFN(gamma). The second is deregulated hematopoiesis in both ICSBP-/- and ICSBP+/- mice that manifests as a syndrome similar to human chronic myelogenous leukemia. The chronic period of the disease progresses to a fatal blast crisis characterized by a clonal expansion of undifferentiated cells. Normal mice injected with cells from mice in blast crisis developed acute leukemia within 6 weeks of transfer. These results suggest a novel role for ICSBP in regulating the proliferation and differentiation of hematopoietic progenitor cells.

Animals↗
PubMed1996

Expression of IFN regulatory factor family proteins in lymphocytes. Induction of Stat-1 and IFN consensus sequence binding protein expression by T cell activation.

Interferon consensus sequence binding protein (ICSBP) is a transcription factor of the IFN regulatory factor (IRF) family. Evidence indicates that this family has a function in the immune system. Unlike other members of the family, ICSBP is expressed exclusively in the immune system. In this work, immunoblot analysis was performed to study expression of ICSBP and other members of the family in various murine lymphocytes. The results show that all IRF family members are expressed constitutively in B cells throughout development, and in resting and activated cells. In contrast, ICSBP expression was undetectable in thymocytes and resting T cells, while all other IRF proteins tested (IRF-1, IRF-2, and ISGF3-gamma) were detected in these cells. Induction of ICSBP (and weakly IRF-1, but not other members) was observed upon activation of T cells following anti-CD3 Ab binding or Con A stimulation. Once T cells were activated, ICSBP was expressed stably in both Th1 and Th2 cells. We show that Stat-1, which binds to the IFN-gamma-responsive element of the ICSBP promoter, was induced following anti-CD3 Ab and Con A stimulation. Stat-1 induction was found in T cells of IFN-gamma+/+, but not of IFN-gamma-/- mice, indicating that T cell activation stimulates the Stat pathway of transcription that is mediated through IFN-gamma. IFN-gamma-activated Stat-1 partly accounted for ICSBP induction in activated T cells, as levels of induction were lower in IFN-gamma-/- than in IFN+/+ T cells. Taken together, these results show that activation of ICSBP is coupled with T cell activation that is partly due to IFN-gamma-induced Stat-1.

Amino Acid Sequence↗
PubMed1996

Role of chloride channels in afferent arteriolar constriction.

The effects of IAA-94, a chloride channel blocker and/or low chloride perfusate on afferent arteriolar (AA) constriction by angiotensin II (Ang II), norepinephrine (NE) and increasing pressure (80 to 160 mm Hg) were assessed using isolated perfused hydronephrotic kidneys. In the first series of experiments, Ang II (0.3 nM) constricted AAs by 33 +/- 3% (N = 5, P < 0.01). Subsequent addition of diltiazem (10 microM) restored the decrements in the AA diameters. In the presence of diltiazem (10 microM), increasing pressure did not constrict AAs. In the second series of experiments. elevation of pressure constricted AAs by 20 +/- 2% (N = 7. P < 0.01). Subsequent addition of IAA-94 (30 microM) failed to alter the basal AA diameter and myogenic responsiveness. However, Ang II-induced AA constriction was abolished by IAA-94. In the third series of experiments, decreasing extracellular chloride exaggerated AA constriction by 0.1 nM of Ang II (from 13 +/- 2 to 20 +/- 3%, N = 6, P < 0.05). Similarly, low chloride perfusate enhanced NE (0.1 microM)-induced AA constriction (from 14 +/- 2 to 19 +/- 2%, N = 6, P < 0.05). In contrast, myogenic responsiveness was not influenced by reducing chloride concentrations. The present data provide evidence that both Ang II and NE induce AA constriction by opening chloride channels and subsequent activation of voltage-dependent calcium channels, and suggest that the myogenic response is mediated by activating voltage-dependent calcium channels independently of chloride channels.

Adrenergic beta-Antagonists↗
PubMed1996

Calcium channel blockers versus ACE inhibitors as antihypertensives in polycystic kidney disease.

The effects of calcium channel blockers (CCBs) and angiotensin converting enzyme (ACE) inhibitors on blood pressure and the progression of renal dysfunction were compared in hypertensive patients with polycystic kidney disease (PKD). Twenty-six patients with PKD and hypertension who had been treated with other antihypertensive agents, such as diuretics, beta-blockers, or alpha-methyldopa, were followed up for two years, during which their blood pressure and renal function were monitored. Patients were divided into two groups classified according to the type of antihypertensive agents given. Group 1 (n = 14) received CCBs, while group 2 (n = 12) received ACE inhibitors. No significant differences were found in their blood pressure control and serum creatinine levels throughout the study. The creatinine clearances were decreased in both groups. However, the decreases in creatinine clearance were smaller (p < 0.05) in the group treated with CCBs. In addition, two patients in group 2 showed rapid increases in serum creatinine. Our data suggest that CCBs reduced blood pressure effectively and preserved renal function in PKD patients at least as well as ACE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Interleukin-4 modulates collagen synthesis by human mesangial cells in a type-specific manner.

Several studies have suggested an involvement of interleukin (IL)-4 in the pathophysiology of glomerulonephritis (GN). To elucidate its possible role in GN, we have investigated the effect of IL-4 on collagen accumulation by human mesangial cells (MC). After incubation with IL-1 alpha and/or IL-4 for 48 h, type I, III, and IV collagens in both soluble and cell-associated forms were identified by Western blotting. IL-1 alpha stimulated type I and IV collagen synthesis, lacking significant effect on type III collagen synthesis. In contrast, IL-4 stimulated type III collagen synthesis without affecting type I and type IV synthesis. Enzyme-linked immunosorbent assay confirmed the dose-dependent effect of IL-4 on collagen type III secretion (2.0-fold at 10 ng/ml). Importantly, IL-1 alpha-stimulated type I and IV collagen synthesis was suppressed by concomitant IL-4 treatment. Northern analysis of type I and III procollagen mRNAs displayed consistent results. These data indicate that IL-4 selectively stimulates type III collagen synthesis but also suppresses IL-1 alpha-stimulated type I and IV collagen synthesis. Therefore IL-4 could potentially contribute to the pathological changes in glomerular diseases in cooperate with other cytokines.

Blotting, Western↗
PubMed1996

Evidence for the involvement of vasopressin in the pathophysiology of adriamycin-induced nephropathy in rats.

The effect of orally available, nonpeptide vasopressin V1 and V2 receptor antagonists on chronic progressive glomerular disease was investigated in Wistar rats with Adriamycin-induced nephropathy. At weeks 0 and 3, Adriamycin was injected twice, and at week 3 drugs started to be given as follows: groups 2 and 3 were treated with V1 and V2 antagonists, respectively, while the untreated group 1 served as control. To block the effects of vasopressin totally, both V1 and V2 antagonists were simultaneously administered (group 4). At weeks 8 and 10, V1 and V2 antagonists given either alone or combined significantly reduced the urinary protein excretion to the same levels. Urinary volume increased in groups 3 and 4 from week 4. Systolic blood pressure did not significantly increase in all groups during the study. Histological alterations in the kidney of groups 2, 3 and 4 were significantly attenuated compared to the control. These results suggest that both vasopressin V1 and V2 agonism plays a role in the pathophysiology of Adriamycin-induced nephropathy despite plasma levels of vasopressin within the normal range. These findings also lead to the notion that in some types of nephrotic patients these orally available V1 and/or V2 receptor antagonists may be effective for reduction of proteinuria and for retardation of progression of renal failure.

Animals↗
PubMed1996

Does combined therapy of Ca-channel blocker and angiotensin converting enzyme inhibitor exceed monotherapy in renal protection against hypertensive injury in rats?

Either calcium channel blocker (CCB) or angiotensin converting enzyme inhibitor (ACEi) is used as an antihypertensive agent, and we are recommended to use them in combination to refractory hypertension with evidence dependent on clinical observations. We examined the renal protective effect of the combined therapy with calcium channel blocker (amlodipine) and angiotensin converting enzyme inhibitor (enalapril) against hypertensive renal injury in 5/6 nephrectomized spontaneously hypertensive rats (SHRs) with salt loading, comparing with monotherapy of each drug. Forty males SHRs with 5/6 nephrectomy and salt loading were divided to five groups: group 1 as control (n = 8), group 2 received 0.2 mg/kg/day of amlodipine (n = 8), group 3 received 0.2 mg/kg/day of enalapril (n = 8), group 4 (n = 8) and group 5 (n = 8) that were treated with 0.1 mg/kg/day and 0.2 mg/kg/day of each drug in combination respectively. Either amlodipine or enalapril had remarkable effects on reducing the increases in blood pressure and urinary protein excretion. In histopathological examination, it also suppressed renal injury significantly. Additional significant effect of combined therapy was not observed in blood pressure and urinary protein. There were not remarkable, additional effects of the combination of CCB and ACEi on protecting the remnant kidney in 5/6 nephrectomized SHRs fed a high-salt diet, possibly because sodium retention was not alleviated by the combination.

Amlodipine↗
PubMed1996

Antihypertensive agents and renal protection: calcium channel blockers.

This study defines the nature of the renal protective effects of calcium channel blockers (Ca blockers) and the effects of the Ca blocker, amlodipine, compared to those of the angiotensin-converting enzyme inhibitor (ACEI), enalapril, on the progression of renal injury in 5/6 nephrectomized spontaneously hypertensive rats (SHR) fed a high-salt diet. Furthermore, we studied the effects of various Ca blockers on the glomerular afferent and efferent arterioles using the isolated perfused hydronephrotic kidneys of six-week-old male Sprague-Dawley rats. In the first study, forty 6-week-old male SHRs which underwent 5/6 nephrectomy were equally divided into five groups. One group received no therapy. In two groups, therapy was started at four weeks post-nephrectomy, one with amlodipine and the other with enalapril. In the remaining two groups, amlodipine or enalapril therapy was started at eight weeks postnephrectomy. Amlodipine was more effective than enalapril in reducing proteinuria and glomerulosclerosis in the group that was started on drug therapy eight weeks after surgery. In the second study, at concentrations of 10(-6) to 10(-9) M, nifedipine, nicardipine and amlodipine dilated the afferent, but not the efferent, arteriole preconstricted with angiotensin II. On the other hand, efonidipine and manidipine clearly dilated angiotensin II-induced constriction of both the afferent and efferent arterioles. These results indicated that Ca blockers are effective at reducing renal injury in 5/6 nephrectomized SHR, and that they are more effective than ACEI in advanced stages of renal injury. The observation that only certain Ca blockers can dilate the efferent arteriole suggests that the renal protective effect of Ca blockers is not necessarily dependent on the dilation of the efferent arterioles.

Amlodipine↗
PubMed1996

Sodium balance and hypertension in obese and fatty rats.

To investigate the role of sodium in obesity induced hypertension, Wistar fatty rats (WFR) were employed. This rat has the following characteristics: (1) hyperglycemia, (2) hyperinsulinemia, and (3) hypertriglycemia. Four percent sodium chloride with constant amount of food intake was administered to these rats from 8 to 16 weeks. During this period, body wt, food intake, water consumption, urine volume, systolic blood pressure, urinary excretion of sodium and potassium, urinary albumin excretion, plasma sodium and potassium, and plasma glucose and immunoreactive insulin (IRI) were measured before, and twice more during eight weeks. No remarkable changes were observed in plasma glucose level during these periods between the two groups. On the other hand, in group 1 IRI significantly increased compared with group 2. Mean blood pressure was increased from 110 +/- 5 to 130 +/- 8 mm Hg (P < 0.01). To ascertain whether this salt sensitivity relates to the abnormalities in pressure-natriuresis responses, the pressure-natriuresis (P-N) was characterized. The P-N curve in WFR was shifted to the right and its slope was flattened compared to its control Wistar lean rats. In conclusion, an excess of dietary sodium intake may contribute to an elevation of blood pressure in Wistar fatty rat with hyperglycemia and hyperinsulinemia. This salt sensitivity may change the abnormal pressure-natriuresis responses.

Animals↗
PubMed1995

Involvement of intracellular calcium ions in the release of the fluorescent dye calcein by cholinergic and alpha-adrenergic agonists from rat parotid acinar cells.

Effects of cholinergic and adrenergic agonists on the secretion of the fluorescent dye calcein were examined to clarify the involvement of calcium ions in the secretion of calcein from acinar cells dispersed from the rat parotid gland. Addition of carbachol (CCh) and noradrenalin (NA), but not isoproterenol (IPR), enhanced the net release of calcein from acinar cells during the subsequent 10 min in a dose range from 10(-8) M to 10(-6) M. The net release of calcein reached a maximum 7 min after the addition of CCh. The release of calcein was suppressed by the simultaneous additions of atropine with CCh, or phenoxybenzamine with NA. Addition of CCh induced a sustained dose-dependent increase in the intracellular levels of calcium ions, ([Ca2+]i). Addition of NA at 10(-6) M increased [Ca2+]i. Phenoxybenzamine completely inhibited the NA-induced increase, but propranolol did not. The removal of extracellular calcium ions did not influence the release of calcein induced by 10(-6) M CCh, but it abolished the sustained increase in [Ca2+]i. The transient increase in [Ca2+]i induced by CCh was observed in the absence of extracellular calcium ions. A calcium ion chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) inhibited the CCh-induced release of calcein. The calcium ionophore, A23187 (2.5 x 10(-6) M), but not 10(-3) M dibutyryl cAMP, evoked the release of calcein. It also increased [Ca2+]i. Removal of extracellular calcium ions suppressed the A23187-induced release of calcein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Different localizations of 21 and 27 kDa gap-junction proteins in rat salivary glands.

Antibodies against 21 and 27 kDa gap-junction proteins from rat liver were used to examine the identification and localization of gap-junction proteins in rat salivary glands. Acinar cells of the submandibular glands and parotid glands stained well for the 27 kDa gap junction protein and less intensely for the 21 kDa protein. Acinar cells of the sublingual glands were stained heavily for the 27 kDa gap junction protein and stained well for 21 kDa gap junction protein. No 27 kDa protein was observed in the ducts of the salivary glands. The 21 kDa gap-junction protein was distributed in some of the intercalated ducts in the parotid and submandibular glands. Immunoblotting of an extract of parotid glands with antibodies against 21 and 27 kDa gap-junction proteins revealed the presence of 21 and 27 kDa proteins in the parotid glands. It is concluded that the 27 kDa gap-junction protein is distributed as a major component of the gap junctions in the acinar cells of all the salivary glands; the 21 kDa protein is localized as a minor component in the acinar cells and some portions of the intercalated ducts in the salivary glands. It is possible that these gap-junction proteins might contribute to the regulation of function of the salivary glands.

Animals↗
PubMed1995

Delayed inhibition of gap-junctional intercellular communication in the acinar cells of rat submandibular glands induced by parasympathectomy and cholinergic agonists.

In this study, the effects of parasympathectomy and cholinergic agonists on gap-junctional intercellular communication and salivary secretion were investigated to clarify the involvement of salivary secretion in delayed uncoupling between acinar cells of rat submandibular glands. Gap-junctional intercellular communication was monitored as dye-coupling in the acinar cells of isolated acini by the transfer of Lucifer Yellow CH. Parasympathectomy induced dye-uncoupling in the acinar cells isolated from denervated salivary glands 12 hr after parasympathectomy-induced salivary secretion. Intraperitoneal application of carbachol (CCh), acetylcholine, pilocarpine, but not isoproterenol, stimulated salivary secretion, and then induced dye-uncoupling in the acinar cells 12 hr later. Atropine suppressed both the salivary secretion and delayed dye-uncoupling induced by parasympathectomy and CCh, when atropine was applied intraperitoneally before the induction of salivary secretion. However, atropine did not suppress the delayed dye-uncoupling by intraperitoneal application of CCh, when atropine was injected after the cessation of CCh-induced secretion. These results suggest that delayed inhibition of gap-junctional intercellular communication by parasympathectomy and cholinergic agonists in rat submandibular glands might be related to the change of secretory function after salivary secretion.

Animals↗
PubMed1995

Effects of novel, nonpeptide vasopressin antagonists on progressive nephrosclerosis in rats.

Effects of novel, nonpeptide vasopressin V1 and V2 receptor antagonists on partially nephrectomized and salt-loaded spontaneously hypertensive rats (SHR), which develop severe hypertension and progressive nephrosclerosis, were investigated. SHR were 5/6-nephrectomized and fed a high salt diet. The rats were divided into four groups: group 1 was an untreated control, group 2 received the V1 antagonist OPC-21268, group 3 received the V2 antagonist OPC-31260, and group 4 received both the V1 and V2 antagonists. The V1 antagonist alone or combined with the V2 antagonist significantly decreased the increase in blood pressure (BP) of groups 2 and 4 rats, but the V2 antagonist alone did not reduce the increase in BP of the group 3 rats. The V2 antagonist alone or combined with the V1 antagonist induced a significant diuresis of rats in groups 3 and 4. The increase in urinary protein excretion and the progression of renal hyaline arteriolosclerosis were attenuated by the V1 antagonist with or without the V2 antagonist in rats in groups 2 and 4, but not by the V2 antagonist alone in rats in group 3. This implies that the progressive nephrosclerosis in SHR with partial renoablation and salt-loading was associated with V1 agonism.

Animals↗
PubMed1995

Renal responses to angiotensin receptor antagonist and angiotensin-converting enzyme inhibitor in partially nephrectomized spontaneously hypertensive rats.

To investigate the role of the renin-angiotensin system (RAS) on nephrosclerosis in salt-loaded, partially nephrectomized spontaneously hypertensive rats (SHR), we evaluated the effects of angiotensin II (ANGII) blockade on the progression of nephrosclerosis with an angiotensin type 1 receptor (AT1rec) antagonist [TCV-116 (TCV)] and an angiotensin-converting enzyme (ACE) inhibitor (enalapril) at the doses equivalent in reducing systemic blood pressure (BP). SHR were five/sixths nephrectomized and were fed a high-salt diet. In addition to being significantly preventive against an increase in systolic BP, both TCV and enalapril significantly attenuated the increases in proteinuria and the renal histopathological alterations. Transcription of AT1rec mRNA in the remnant kidney was enhanced with the progression of nephrosclerosis, but was inhibited by TCV as well as enalapril. In these aspects, there were no apparent differences between effects of TCV and enalapril. The RAS system plays an important role in nephrosclerosis in partially nephrectomized SHR despite a high-salt diet, and direct ANGII blockade certainly protected the kidney against hypertensive injury in this model.

Angiotensin Receptor Antagonists↗
PubMed1995

Vesicular stomatitis virus infection induces a nuclear DNA-binding factor specific for the interferon-stimulated response element.

Vesicular stomatitis virus (VSV) has a broad host range. It replicates in the cytoplasm and causes rapid cytopathic effects. We show that following VSV infection, a nuclear factor that binds to a select set of interferon-stimulated responsive elements (ISRE) is induced in many cell types. This factor, tentatively called VSV-induced binding protein (VIBP), was estimated to have an approximate molecular mass of 50 kDa and was distinct from known members of the interferon regulatory factor family, that are known to bind to the ISRE. Induction of VIBP required tyrosine kinase activity but did not require cellular transcription. Treatment of cells with cycloheximide, which inhibits translation, only partially inhibited induction of VIBP. However, type I interferons and staurosporine, both of which inhibit VSV transcription, inhibited VIBP induction. Moreover, a double-stranded RNA analog, poly(I)-poly(C) also induced a DNA-binding activity very similar to that of VIBP. These results indicate that a preexisting cellular protein is activated upon VSV infection and that this activation requires primary viral transcripts. The functional activity of VIBP was analyzed in cells stably transfected with a herpesvirus thymidine kinase-luciferase reporter gene that is under control of the ISRE. While activity of the control promoter without ISRE was strongly inhibited following VSV infection (as a result of virus-mediated transcriptional shutdown of the host cell), the inhibition was reversed by the ISRE-containing promoter, albeit partially, which suggests that VSV infection differentially affects transcription of host genes. Although VIBP was induced in all other cells tested, it was not induced in embryonal carcinoma cells after VSV infection, suggesting developmental regulation of VIBP inducibility.

Amino Acid Sequence↗
PubMed1995

Relationship among seminal characteristics, fertility and suitability for semen preservation in draft stallions.

Seminal characteristics, fertility and the response to semen preservation (liquid storage and cryopreservation) were evaluated in 4 Draft stallions (Percheron 2, Breton 2). Seminal characteristics (gel-free volume, sperm concentration, sperm morphology, percentage of motile spermatozoa) were assessed in 5 ejaculates from each of the 4 stallions. The fertility of the stallions was calculated retrospectively as the accumulated pregnancy rate over 3 breeding seasons. Five ejaculates from each of the stallions were subjected to liquid storage at 5 degrees C. The percentage of motile spermatozoa (PMS) was assessed at 0, 24, 48 and 72 hr. Cryopreservation was done with a glucose-EDTA-lactose egg yolk extender and a skim milk-based extender containing clarified egg yolk (4 replicates per stallion). PMS and the percentage of spermatozoa with an intact plasma membrane (IPM) were evaluated before and after freezing. Although semen characteristics and fertility were within a physiological range, significant differences among stallions were found for gel-free volume, percentage of morphologically normal spermatozoa, PMS, and fertility but there was no clear relationship between these parameters. The response to liquid storage of diluted semen samples differed among stallions and best results were obtained in a stallion with the highest initial motility. The freezability of semen from the 4 stallions was poor with both of the freezing protocols (PMS range 13.8%-26.3%; IPM range 19.5%-38.0%). Results of liquid storage and cryopreservation were not correlated in individual stallions and were not related to their fertility. Since predictability for the response to semen preservation is low, the suitability of individual stallions for semen preservation has to be examined carefully.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effect of nonpeptide vasopressin receptor antagonists on developing, and established DOCA-salt hypertension in rats.

Efficacy of orally available, selective vasopressin V1 and V2 receptor antagonists on the developing and established stage of DOCA-salt hypertension was investigated. Twenty-nine Wistar rats were heminephrectomized, and administered DOCA (50 mg/kg; intraperitoneally twice a week) and salt (5% NaCl diet) from week 0 to the end of study. Group 1 rats were served as control. Group 2 and 5 rats were given a V1 antagonist, and groups 3 and 6 rats were given a V2 antagonist, while groups 4 and 7 rats received both V1 and V2 antagonists. Each drug was started to groups 2, 3 and 4 at week 0, and to groups 5, 6 and 7 at week 4. Significant amelioration of the increase in blood pressure was observed in groups 3 and 4 at week 10, and a reduction in blood pressure occurred in groups 6 and 7 at week 10. Otherwise, a V1 antagonist alone slightly attenuated blood pressure rise in the group 2 without significance, and failed to lower blood pressure of the group 5 during the study. These results suggest that both V1 and V2 agonisms are involved in an increase in blood pressure at the developing stage of DOCA-salt hypertension, and that V2 agonism, but not V1 plays a major role in the maintenance of high blood pressure at the established stage.

Administration, Oral↗