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Biomedical subjects

J Yamada

Publications and source records attributed to J Yamada.

At least 127 records · Page 7Linked to original sources

Role of CD4+ T cells in immunobiology of orthotopic corneal transplants in mice.

PURPOSE: To determine, with the use of mice genetically deficient in expression of CD4 or CD8 molecules, which T cells are responsible for rejection of orthotopic corneal allografts in mice. METHODS: Corneas were prepared from major histocompatibility complex (MHC)-only incompatible, minor histocompatibility (H)- only incompatible, and MHC-plus-minor H incompatible donors and grafted orthotopically to eyes of CD4 knockout (KO), CD8KO, and wild-type control mice. Graft survival patterns were assessed clinically and compared. Mice that retained healthy corneal allografts beyond 8 weeks were evaluated for evidence of donor-specific tolerance and anterior-chamber-associated immune deviation (ACAID) using local adoptive transfer reactions and challenge with orthotopic skin allografts. RESULTS: Corneas grafted to CD8KO mice were rejected with an incidence and tempo indistinguishable from that in wild-type control animals. By contrast, MHC-only, and minor-H-only incompatible corneal grafts survived indefinitely in eyes of CD4KO mice. Approximately 50% of corneal grafts that confronted CD4KO recipients with both MHC and minor H alloantigens experienced delayed rejection, whereas similar grafts in wild-type recipients were rejected acutely. CD4KO mice with long-accepted grafts displayed neither donor-specific ACAID nor allograft tolerance. CONCLUSIONS: CD8+ T cells play little or no role in acute rejection of orthotopic corneal allografts. Instead, acute rejection is mediated almost exclusively by CD4+ T cells. Moreover, when corneal allografts survive for 8 weeks without acute rejection, CD4+ T cells promote donor-specific ACAID thereby insuring long-term graft acceptance.

Adoptive Transfer↗

Corneal transplantation in antibody-deficient hosts.

PURPOSE: To examine the role of donor-specific antibodies, with or without complement, in rejection of orthotopic corneal transplants by using mice as recipients in which the genes for the heavy chain of immunoglobulin or the third complement component have been eliminated by homologous recombination. METHODS: BALB/c corneas were transplanted into eyes of B-cell-deficient (n=17) or wild-type control C57BL/6 (n=30) mice and into eyes of complement (C3)-deficient (n=15) or wild-type control 129-C57BL/6 (n=13) mice. After surgery all grafts were evaluated over 8 weeks in a masked manner by biomicroscopy for signs of rejection. RESULTS: The rates of corneal transplant rejection were similar among B-cell-deficient and C3-deficient mice compared with rejection rates in their respective wild-type control subjects. This similarity applied to the time course of rejection and to cumulative survival rates. CONCLUSIONS: Neither donor-specific antibody nor the third component of complement play essential roles in acute rejection of orthotopic corneal allografts in mice.

Animals↗

p-Chloroamphetamine, a serotonin-releasing drug, elicited in rats a hyperglycemia mediated by the 5-HT1A and 5-HT2B/2C receptors.

The effects of a serotonin (5-HT) releasing drug, p-chloroamphetamine, on plasma glucose levels were investigated in rats. p-Chloroamphetamine elicited a significant hyperglycemia. The hyperglycemic effects of p-chloroamphetamine were completely prevented by the 5-HT synthesis inhibitor, p-chlorophenylalanine. Prior adrenodemedullation abolished the hyperglycemia elicited by p-chloroamphetamine. p-Chloroamphetamine-induced hyperglycemia was prevented by methysergide, which blocks the 5-HT1 and 5-HT2 receptor, the 5-HT1A/1B/2C receptor antagonist, (-)-propranolol, the selective 5-HT1A receptor antagonist, 4-(2'-methoxyphenyl-1-[2'-n-2"pyridinyl)-p-iodobenzamido]-ethyl-pi perazine (p-MPPI), the 5-HT2A/2B/2C receptor antagonists, ritanserin and 4-isopropyl-7-methyl-9-(2-hydroxy-1-methyl-propoxycarbonyl)-4,6A,7 ,8,9,10,10A-octahydro-indolo[4,3-FG]quinolone maleate(LY 53857). However, the 5-HT3 and 5-HT4 receptor antagonist, tropisetron, the 5-HT4 receptor antagonist, 2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino) ethyl ester (SDZ 205-557), and the 5-HT2A receptor antagonist, ketanserin, did not affect the p-chloroamphetamine-induced hyperglycemia. These results suggest that p-chloroamphetamine-induced hyperglycemia is elicited by an enhanced 5-HT release and facilitated adrenaline release. Moreover, our results indicate that p-chloroamphetamine-induced hyperglycemia is mediated by 5-HT1A and 5-HT2B/2C receptors.

4-Aminobenzoic Acid↗

Effects of the non-selective 5-HT receptor agonist, 5-carboxamidotryptamine, on plasma glucose levels in rats.

The effects of the 5-HT1A/1B/1D/5/7 receptor agonist, 5-carboxamidotryptamine (5-CT), on blood glucose, insulin and glucagon levels in rats were investigated. 5-CT above the dosage of 0.05 mg/kg elicited significant hyperglycemic effects and 0.1 mg/kg, induced a 35% increase in plasma glucose levels. 5-CT did not affect plasma glucagon, and serum insulin levels increased following the high dose of 5-CT. Adrenodemedullation abolished the 5-CT-induced hyperglycemia. Hyperglycemia induced by 5-CT was prevented by pretreatment with the 5-HT1/2/7 receptor antagonist, metergoline, and the 5-HT1/2/5/7 receptor antagonist, methysergide, although the 5-HT2A receptor antagonist, ketanserin, the 5-HT2A/2B/2C receptor antagonist, ritanserin, and the 5-HT3/4 receptor antagonist, tropisetron, had no effect. Although 5-CT has a high affinity with 5-HT1A receptors, the 5-HT1A and 5-HT1B and beta receptor antagonist, (-)-popranolol, did not affect 5-CT-induced hyperglycemia. These results indicate that 5-CT-induced hyperglycemia is elicited by facilitation of adrenaline release from the adrenal gland and that 5-CT-induced hyperglycemia is mediated by the 5-HT7 receptor unrelated to 5-HT1A, 5-HT1B, 5-HT2, 5-HT3, 5-HT4 or 5-HT5 receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

cDNA cloning and genomic organization of peroxisome proliferator-inducible long-chain acyl-CoA hydrolase from rat liver cytosol.

The cDNA for a peroxisome proliferator-inducible long-chain acyl-CoA hydrolase from rat liver cytosol, referred to as rLACH2, was isolated and its genomic structure was determined. The cDNA encoded a 419-amino-acid polypeptide with a calculated molecular weight of 46,011. Sequence analysis identified an active-site serine motif (Gly-x-Ser-x-Gly) common to carboxylesterases and lipases. When expressed in Escherichia coli, the cDNA directed expression of a protein immunoreactive to an anti-rLACH2 antibody with a molecular mass of 47 kDa, identical to that of purified rLACH2. Northern blot analysis showed marked induction of rLACH2 mRNA in the liver after feeding rats with di(2-ethylhexyl)phthalate, a peroxisome proliferator. The rLACH2 gene spanned about 19 kb and comprised 3 exons, the intron/exon boundaries of which were consistent with the donor/acceptor splice rule. A putative peroxisome proliferator response element (AGGTCATGGTTCA) was identified in the 5'-flanking region, suggesting the involvement of peroxisome proliferator-activated receptors in the regulation of rLACH2 gene expression.

Amino Acid Sequence↗

Effects of adrenalectomy on hyperphagia induced by the 5-HT1A receptor agonist 8-OH-DPAT and 2-deoxy-D-glucose in rats.

Effects of adrenalectomy on the 5-HT1A receptor agonist 8-hydroxy-2-di-n-(propylamino)tetralin (8-OH-DPAT)- and 2-deoxy-D-glucose (2-DG)-induced hyperphagia were investigated in rats. Prior adrenalectomy completely inhibited 2-DG-induced hyperphagia, although it did not affect increases in food intake elicited by 8-OH-DPAT. These results suggest that 8-OH-DPAT-induced hyperphagia is independent of the adrenal hormone, corticosterone while 2-DG-induced hyperphagia is closely related to corticosterone.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Interleukin 1 receptor antagonist suppresses allosensitization in corneal transplantation.

OBJECTIVE: To delineate the mechanisms by which topical interleukin 1 receptor antagonist (IL-1RA) treatment promotes orthotopic corneal allograft survival. METHODS: Corneal buttons were prepared from eyes of C57BL/6 mice and placed orthotopically in normal or neovascularized (high-risk) eyes of BALB/c mouse recipients. Topical IL-1RA (or vehicle alone) was applied to grafts 3 times daily until the grafted eyes were enucleated. Corneal specimens were evaluated for content of Langerhans cells. A week after enucleation, 1 group of recipients was tested for allospecific delayed-type hypersensitivity elicited by intrapinnae injections of donor splenocytes. In companion experiments, a second group of mice that underwent transplantation, IL-1RA treatment, and enucleation was challenged with orthotopic skin grafts from B10.D2 donor mice (sharing minor H antigens with C57BL/6 mice) to determine whether the second group of mice could reject grafts bearing corneal donor minor H alloantigens in an accelerated fashion. RESULTS: Mice whose orthotopic corneal allografts were treated topically with IL-1RA acquired neither donor-specific delayed-type hypersensitivity (P<.001) nor the capacity to reject orthotopic donor-type skin allografts in an accelerated manner (P<.05), whereas controls treated with vehicle alone developed delayed-type hypersensitivity and rejected B10.D2 grafts in an accelerated manner. Moreover, IL-1RA-treated grafts placed in both high-risk (P = .01) and normal-risk (P = .004) eyes displayed significantly reduced levels of infiltrating Langerhans cells compared with vehicle-treated controls. CONCLUSIONS: Topical IL-1RA promotes corneal allograft survival in large part by preventing activity of recipient Langerhans cells, and thereby preventing these cells from inducing systemic allosensitization. These data suggest that IL-1 plays a key role in promoting allosensitization when corneal allografts are placed orthotopically. CLINICAL RELEVANCE: Suppression of allosensitization by topical IL-1RA may prove a clinically useful method for enhancing corneal transplant survival.

Animals↗

Effects of anxiolytics, diazepam and tandospirone, on immobilization stress-induced hyperglycemia in mice.

The benzodiazepine anxiolytic diazepam did not affect immobilization-elicited hyperglycemia, although a high dose increased blood glucose levels in normal mice. The serotonergic anxiolytic tandospirone reduced immobilization-induced hyperglycemia dose-dependently. Hyperglycemia elicited by immobilization stress was completely prevented by adrenalectomy but not by pretreatment with the corticosterone synthesis inhibitor dexamethasone. These results suggest that the effects of two anxiolytics, diazepam and tandospirone, on immobilization stress-induced hyperglycemia are quite different, although both drugs reduce anxiety. Furthermore, our results indicate that immobilization stress-elevated hyperglycemia is closely related to adrenaline release from the adrenal gland and that tandospirone may inhibit stress-induced hyperglycemia by modifying this mechanism.

Animals↗

Fate of orthotopic corneal allografts in C57BL/6 mice.

Our aim was to determine whether corneal allografts placed in normal eyes of C57BL/6 mice enjoy immune privilege, and whether recipients of long-standing grafts acquire donor-specific ACAID. C57BL/6 mice received corneal grafts from BALB/c, C57BL/6, C3H, B10.D2 or BALB.B mice; for comparison, BALB/c mice received C3H or C57BL/6 corneal allografts. Delayed hypersensitivity and anterior chamber associated immune deviation (ACAID) induction were assessed in recipient mice at four and eight weeks after grafting. It was found that C57BL/6 mice resemble BALB/c mice in mounting more vigorous rejection reactions against minor H, rather than MHC, alloantigenic corneas, and in the acquisition of donor-specific DH within four weeks of engraftment. In addition, C57BL/6 mice with long-standing, healthy allografts display donor-specific ACAID. However, C57BL/6 mice differ from BALB/c mice in that (1) fewer allodisparate corneal grafts were accepted indefinitely; and (2) rejection in these eyes correlated with sustained donor-specific DH. It was concluded that immune privilege is less secure in the eyes of C57BL/6 mice, compared to BALB/c mice. This conclusion is discussed in terms of known polymorphic differences between these mouse strains at genetic loci governing (a) immune responsiveness, (b) alloform of Fas ligand, and (c) bias of immune response toward Th1 or Th2 phenotypes.

Animals↗

Three-dimensional development of bovine reticular cell (Cellula reticuli).

This paper describes the three-dimensional construction of the reticular cell, cellula reticuli, in bovine reticulum and its ontogenetic development. Reticular cells of fetal suckling calf and adult tissues were investigated both at the surface of intact mucosa and macerated samples using scanning electron microscopy. At the third month of gestation, the formation of the reticular cells on the mucosal surface started from the center of the cell and just above the reticular crest. The reticular crests were observed on the surface of the macerated sample at an earlier period of gestation (third month). In the eighth month of gestation, primary, secondary and tertiary reticular crests and papillae could be observed from the mucosal surface. Macerated samples showed that those structures were already formed completely under the epithelium by the first half of the seventh month of gestation. It is suggested that the development of the reticular papillae starts from the lower to the upper parts of the reticular cell.

Age Factors↗

Topical modulation of interleukin-1 activity in corneal neovascularization.

PURPOSE: To determine whether inflammatory corneal neovascularization (CNV) is associated with interleukin-1 (IL-1) activity and if so, to assess the efficacy of topical interleukin-1 receptor antagonist (IL-1ra) to suppress CNV. METHODS: Inflammatory CNV was induced on day 0 by placement of paracentral intrastromal sutures in BALB/c murine eyes. Quantification of IL-1alpha and -beta cytokine levels was done by a sandwich enzyme-linked immunosorbent assay (ELISA) on the supernatants of incubated corneas excised at specified time points after induction of CNV (n = 6 per time point studied). To study suppression of CNV by IL-1ra, animals were divided into treatment subgroups that received topical 20 mg/ml of IL-1ra mixed in 0.2% sodium hyaluronate (n = 28) or placebo (vehicle) alone (n = 22) 3 times daily during days 0-35. Other groups of animals received placebo for 1 (n = 10) or 2 (n = 14) weeks before being switched and retained on IL-1ra. Neovascularization was assessed biomicroscopically and graded by using a standardized scheme. RESULTS: Induction of CNV stimulus was associated with a significant surge in the expression of both IL-1alpha (p < 0.001) and IL-1beta (p < 0.001) as early as 2 h after the stimulus, which peaked at 24 h, before decreasing substantially in the case of IL-1beta and returning to basal levels by day 7. Topical application of IL-1ra led to a significant suppression of CNV for the duration of therapy only if initiated early after induction of the neovascular stimulus. Initiation of therapy 1 week after CNV induction was associated only with a transient suppression in the angiogenic response. CONCLUSION: Our data strongly implicate IL-1 as a critical mediator in the early phase of CNV and suggest that IL-1ra can be an effective modality in suppressing CNV if initiated sufficiently early after the inflammatory neovascular stimulus.

Administration, Topical↗

Production and immunohistochemical characterization of monoclonal antibodies against ovarian antigen of the common tree shrew (Tupaia glis).

To study the ovarian function of the common tree shrew (Tupaia glis), monoclonal antibodies (MAb) against its ovarian antigen were produced. Several positive hybridomas were cloned and MAb-T2C9 (IgG) was examined for reactivity. Strong immunoreactivity of MAb-T2C9 was localized within the cytoplasm of luteal cells and in the theca interna cells of Graafian follicles. MAb-T2C9 reacted also with testicular interstitial cells and adrenocortical cells, except those of the zona glomerulosa. Similar reactions were seen in the goat and sheep. Western blotting analysis of the ovine corpus luteum after reaction with MAb-T2C9 revealed a single positive band of approximately 60 kDa. These findings suggest that MAb-T2C9 recognized protein molecules related to steroid synthesis.

Adrenal Cortex↗

Immunohistochemical colocalization of serotonin, substance P and Met-enkephalin-Arg6-Gly7-Leu8 in the endocrine cells of the ruminant duodenum.

The duodenum of various ruminants was examined by immunohistochemical staining for serotonin, substance P and Metenkephalin-Arg6-Gly7-Leu8 (MENK8). Serotonin- and substance P-immunoreactive endocrine cells were detected in samples from cow, calf, sheep, goat, and barbary sheep, MENK8-immunoreactive endocrine cells were detected exclusively in samples from cow and calf. Substance P and MENK8 immunoreactivity was found in serotonin-immunoreactive endocrine cells of cattle. Substance P- and MENK8-immunoreactive nervous elements were detected in all ruminants examined. The present results suggest that the expression and/or the mechanism that controls the expression of each peptide might differ between endocrine cells and nerve cells and might also depend on animal species.

Aging↗

Histochemistry of complex carbohydrate in the major salivary glands of hoary bamboo rats (Rhizomys purinosus).

The major salivary glands (parotid glands, monostomatic sublingual glands and submandibular glands) were obtained from hoary bamboo rats (Rhizomys purinosus) and fixed in Bouin's solution. Paraffin sections were subjected to a battery of staining methods including lectin staining for demonstration of complex carbohydrates. Among the three major salivary glands, unique histochemical features were observed in the submandibular gland. Different from most myomorpha species, submandibular glands of the hoary bamboo rats have two types of secretory cells in the secretory endpieces. One type of cells showed positive reactions with Alcian blue (AB)(pH2.5), periodic acid-Schiff (PAS) and some lectins (peanuts agglutinin, Griffonia simplicifolia I, Maclura pomifera agglutinin). The granular ducts, which exist in animals belonging to suborder myomorpha, were not observed in the submandibular glands of this animal.

Animals↗

Immunohistochemical study of endocrine cells in the gastrointestinal tract of the Philippine carabao (Bubalus bubalis).

The distribution and frequency of occurrence of endocrine cells in the gastrointestinal tract of the Philippine carabao (Bubalus bubalis) were studied by immunohistochemistry. Fourteen types of immunoreactive (IR) endocrine cells were revealed. Among the cell types, only chromogranin, serotonin, and bovine pancreatic polypeptide (BPP) were present in the entire gut, while the others showed restricted distribution: somatostatin, gastrin, and cholecystokinin in the abomasum and small intestine; methionine-enkephalin-Arg6-Gly7-Leu8, motilin, neurotensin, secretin, gastric inhibitory peptide, and substance P in the small intestine; peptide tyrosine tyrosine (PYY) in the large intestine; and glucagon in the whole intestinal tract. Most of the cell types showed peak density in the pyloric, duodenal, or rectal region. The highest cell type heterogeneity was observed in the duodenum. The distribution profile of the gut endocrine cells in the carabao is closely related to that in the Holstein cattle. Important findings include the occurrence of BPP-IR cells in the entire gut and the high frequency of PYY-IR cells in the large intestine.

Abomasum↗

Familial occurrence of congenital bile duct cysts.

Congenital bile duct cysts are now a well-documented anomaly of the biliary tree, and have become more common in Japan. Familial occurrence of congenital bile duct cysts, however, is extremely rare, with only six reported cases in the literature. We report a familial pattern of congenital bile duct cysts in a mother and her daughter. A 33-year-old female was admitted for evaluation of right upper quadrant abdominal pain and fever 6 days after an uneventful delivery of her second child. A computed tomography (CT) and ultrasound scan (US) revealed an obstructed biliary tract. Percutaneous transhepatic biliary drainage was then performed, and a cholangiogram revealed a Scholtz type B choledochocele without an anomalous connection of the pancreaticobiliary ducts. Endoscopic US demonstrated that the choledochocele was associated with a stone in the cyst. A pylorus-preserving pancreatoduodenal resection was performed, and a histological study revealed that the choledochocele was lined by biliary mucosa without evidence of malignancy. The newborn infant had an abdominal tumour. An US and CT revealed a congenital bile duct cyst. An operation was performed and the intraoperative cholangiogram showed an Alonso-Lej type I congenital bile duct cyst with an anomalous connection of the pancreaticobiliary ducts. Whether congenital bile duct cysts are hereditary remains to be elucidated.

Adult↗

Inhibin secretion in the stallion.

To examine the physiological role of inhibin in the stallion, a heterologous radioimmunoassay (RIA) based on a bovine RIA was validated and used to measure immunoreactive (ir)-inhibin concentrations in plasma and testicular homogenates. The bioactivity of equine testicular inhibin was also examined using an assay for suppression of FSH secretion from rat anterior pituitary cells. In addition, to identify the cell responsible for secreting testicular inhibin, the localisation of inhibin in the testis was investigated by an immunohistochemical method using a polyclonal antibody against (Tyr30)-porcine inhibin alpha(1-30) NH2. In the RIA, parallel dose response curves were obtained for the bovine inhibin standard and serial dilutions of stallion plasma and equine testicular homogenates. Parallel FSH inhibition curves were also observed for the bovine inhibin standard and serial dilutions of equine testicular homogenates in the bioassay. The inhibition of FSH secretion from rat pituitary cells by equine testicular homogenates was neutralised by an antiserum against bovine inhibin in vitro. Plasma concentrations of ir-inhibin, testosterone and oestradiol-17beta in stallions decreased abruptly after bilateral gonadectomy and FSH and LH concentrations in the plasma subsequently increased. Therefore, circulating inhibin in the stallion appeared to be largely of testicular origin. The histochemical results showed for the first time that strong immunopositive staining for inhibin occurred in the Leydig cells of the testes. Sertoli cells were also stained by the inhibin antibody but the reaction was weaker than that in Leydig cells. These results indicate clearly that both Leydig and Sertoli cells are potential sources of testicular inhibin in the stallion. A clear increase in plasma ir-inhibin concentrations was observed during the natural breeding season. Similar seasonal changes in the plasma concentrations of testicular steroid hormones and pituitary gonadotrophins occurred throughout the year. In conclusion, the testes appear to be the main source of inhibin, and testicular inhibin is secreted by Leydig and Sertoli cells in stallions. The positive correlations between plasma ir-inhibin and testicular activity during both the breeding and nonbreeding seasons indicate that plasma ir-inhibin is a useful indicator of reproductive activity in the stallion.

Animals↗