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K Dohi

Publications and source records attributed to K Dohi.

At least 325 records · Page 18Linked to original sources
PubMed1995

Localization of macrophage migration inhibitory factor (MIF) to secretory granules within the corticotrophic and thyrotrophic cells of the pituitary gland.

BACKGROUND: Macrophage migration inhibitory factor (MIF) was one of the first lymphokine activities to be discovered and was described almost 30 years ago to be a soluble factor(s) produced by activated T lymphocytes. In more recent studies, MIF has been "rediscovered" to be an abundant, pre-formed constituent of the anterior pituitary gland and the macrophage, and to be a critical component in the host response to septic shock. Pituitary-derived MIF enters the circulation after infectious or stressful stimuli and appears to act to counterregulate glucocorticoid suppression of cytokine production. MATERIALS AND METHODS: Immunoelectron microscopy utilizing a combination of anti-MIF and anti-pituitary hormone-specific antibodies was used to study the ultrastructural localization of MIF within the anterior pituitary gland. Pituitaries were obtained from resting, unstimulated mice and from mice 16 hr after endotoxin administration. The release of MIF also was investigated in vitro by examining the effect of corticotropin-releasing hormone (CRH_ on the AtT-20, corticotrophic cell line. RESULTS: MIF localizes to granules present exclusively in ACTH and TSH secreting cells. Within each cell type, a subset of granules was found to contain both MIF and ACTH, or MIF and TSH. The pituitary content of MIF-containing granules decreased significantly after experimentally induced endotoxemia. In seven pituitaries examined 16 hr after LPS injection, the number of MIF-positive granules diminished by 38% in corticotrophic cells and by 48% in thyrotrophic cells when compared with controls (p < 0.05). CRH was observed to be a potent MIF secretagogue in vitro, inducing the release of MIF from corticotrophic cells at concentrations lower than that required for ACTH release. CONCLUSION: These data provide ultrastructural information that identify MIF to be a novel anterior pituitary hormone, support earlier studies showing a time-dependent release of pituitary MIF during endotoxemia, and suggest an important, systemic role for MIF in the stress response to infection and other stimuli.

Adrenocorticotropic Hormone↗
PubMed1994

The significance of bile secretion after the transplantation of long-preserved livers in the rat.

Although one of the simplest indicators for predicting liver viability is bile secretion, it has never been proven whether it could be a good index for the viability of grafts in liver transplantation after cold ischemia. The present study, conducted on male Wistar rats, was undertaken to determine whether bile secretion reflects the viability of livers which have been preserved long-term. Livers were stored for up to 24 h in Euro-Collins (EC) or University of Wisconsin (UW) solution at 4 degrees C, and transplanted orthotopically. The correlation between 1-week survival, bile flow, and the tissue adenosine triphosphate (ATP) level 4 h after transplantation was then investigated for each subgroup. The survival rates of the animals in the UW subgroups were much higher than those in the EC subgroups. In the rats transplanted with livers preserved for 6 h in EC solution (EC-6), in which 100% survival was observed, both bile flow and ATP recovered sufficiently. Conversely, in the EC-12 group, in which only 10% survival was seen, restoration of bile flow, in ml/h per kg body weight, and ATP resynthesis, in mumol/g wet weight, were severely suppressed, with levels of 1.35 +/- 1.05 and 0.77 +/- 0.34, respectively. Moreover, in the EC-18 group, with 0% survival, neither bile flow nor ATP recovered. In the rats transplanted with livers preserved for 18 h in UW solution (UW-18), bile flow and ATP, being 1.03 +/- 0.56 and 1.12 +/- 0.59, respectively, were much higher than those in the EC-18 group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1994

Radiation induction of germline mutation at a hypervariable mouse minisatellite locus.

Paternal 60Co gamma-irradiation was tested for the induction of germline mutation at the mouse hypervariable minisatellite locus, Ms6hm. Male C3H/HeN mice were exposed to 3 Gy 60Co gamma-ray and mated with C57BL/6N females. Matings were made at 1-7, 15-21 and 71-77 days post-treatment to test spermatozoa, spermatids and spermatogonia stages. Reciprocal crosses were also made with irradiated C57BL/6N males. Southern analysis was carried out on DNA from parents and F1 mice. The paternal mutation frequencies per gamete of the Ms6hm locus were 8.3, 13, 28 and 15% for the C3H/HeN control, exposed spermatozoa, spermatids and spermatogonia stages, respectively. The paternal mutation frequencies per gamete were 7.7% for the C57BL/6N control and 13% for the C57BL/6N exposed spermatozoa stage. The increase in the paternal germline mutation frequency was statistically significant for C3H/HeN spermatids irradiation (p < 0.005). The induced mutation frequencies were of the order of 10(-1), and was too high to be accounted for by the direct action of radiation on the locus. These results suggest the presence of a previously unexpected mechanism of radiation induction of germline mutation. In addition, we demonstrate that the hypervariable minisatellite locus can serve as a sensitive monitor for genetic damages to germline cells.

Animals↗
PubMed1994

Improved purification of arylsulfate sulfotransferase from human intestinal bacterium by using polyclonal antibody.

Arylsulfate sulfotransferase (ASST) from a human intestinal bacterium stoichiometrically catalyzed the transfer of the sulfate group of phenylsulfate esters to phenolic compounds. Polyclonal antibodies against ASST were obtained from rabbit sera. These antisera did not inhibit ASST activity. ASST was recognized by the IgG fraction of the antisera, but rat liver phenol sulfotransferase did not show cross-reactivity to ASST on Western blot (immunoblot) analysis. The ASST was purified by an anti-ASST immobilized affinity column chromatography to homogeneity on SDS-PAGE. The NH2-terminal amino acid and partial sequence of the purified enzyme were serine and SVKYSFEDHIINRQYEAEQAMLAKF, respectively. We corrected the previous result that the NH2-terminal of ASST was arginine.

Amino Acid Sequence↗
PubMed1994

Intraglomerular expressions of IL-1 alpha and platelet-derived growth factor (PDGF-B) mRNA in experimental immune complex-mediated glomerulonephritis.

Both PDGF and IL-1 play important roles as autocrine growth factors for cultured mesangial cells, and may be closely associated with the progression of glomerulonephritis. In this study we investigated intraglomerular expressions of PDGF-B and IL-1 alpha mRNA in mice with bovine serum albumin (BSA) nephritis, a model of immune complex-mediated glomerulonephritis, using the reverse transcription-polymerase chain reaction (RT-PCR) method. We also quantified intraglomerular PDGF-B mRNA by the competitive PCR and studied the correlation between the level of intraglomerular PDGF-B mRNA expression and the degree of observed glomerular injury. While expression of neither PDGF-B nor IL-1 alpha mRNA was detected in glomeruli from control mice, both were strongly expressed in glomeruli from mice with BSA nephritis. IL-1 alpha mRNA in glomeruli showed low accumulation in mice with mild glomerular injury, and was increased in mice with moderate glomerular injury. In contrast, high intraglomerular expression of PDGF-B mRNA occurred in all mice with mild glomerular injury and continued throughout the course of the disease. We observed no correlation between the level of PDGF-B mRNA expression and the histologic grade of renal damage. These results suggest that PDGF and IL-1 have different growth properties, and PDGF might play a role as a competence factor rather than a progression factor in the pathogenesis of immune complex-mediated glomerulonephritis.

Animals↗
PubMed1994

Intraglomerular expression of transforming growth factor-beta 1 (TGF-beta 1) mRNA in patients with glomerulonephritis: quantitative analysis by competitive polymerase chain reaction.

TGF-beta 1 is involved in the pathogenesis of glomerular sclerosis. We studied the intraglomerular expression of TGF-beta 1 mRNA in patients with glomerulonephritis using competitive polymerase chain reaction (PCR). This method is sensitive enough to quantify cDNA copies of mRNA present in small amounts of samples. Renal biopsy specimens were obtained from 42 patients with various kinds of glomerulonephritis. Ten glomeruli were dissected from renal biopsy specimens. Normal glomeruli were also obtained from the resected kidneys of eight patients with renal cell cancer. Total RNA was extracted from the glomeruli and reverse transcribed into cDNA with reverse transcriptase. To prepare samples containing identical amounts of beta-actin cDNA (8 pg), we performed competitive PCR by co-amplifying mutant templates of beta-actin with a unique EcoRI site. Next, to measure TGF-beta 1 cDNA, we performed competitive PCR by co-amplifying mutant templates of TGF-beta 1. We observed a higher glomerular expression of TGF-beta 1 mRNA in cases of mesangial proliferative glomerulonephritis having a moderate increase in mesangial matrix, diabetic nephropathy and diffuse proliferative lupus nephritis, compared with normal glomeruli. Results suggest that the intraglomerular synthesis of TGF-beta 1 may be involved in the progression of glomerulonephritis in humans.

Actins↗
PubMed1994

Effects of intrahepatic arterial and intraportal administration of FK 506 on liver allograft survival in rats.

Rejection is still the limiting factor for successful organ transplantation, and overdosage of immunosuppressive drugs often results in severe viral infection, side-effects and toxicity. Thus, more specific immunosuppression to lessen these side-effects is highly desirable. In this study, we compared the effects of FK 506 administered by different routes (hepatic artery, portal vein and systemic circulation) on the inhibition of rejection. FK 506 was given to recipient LEW rats with PVG liver grafts via the penile vein (systemic administration), portal vein or hepatic artery (local administration) for 3 or 7 successive days after liver transplantation. In control LEW rats without immunosuppression, the PVG liver allografts were rejected between 9 and 21 days after transplantation. Intravenous administration of FK 506 for 3 days (0.32 and 1.28 mg/kg daily) only had a marginal effect on prolonging liver allograft survival (21.1 +/- 12.5 and 32.0 +/- 24.0 days, respectively; control 14.1 +/- 4.1 days). However, systemic administration of FK 506 (0.08-1.28 mg/kg daily) for 7 days suppressed liver allograft rejection markedly (42.3 +/- 5.9 to 80.5 +/- 53.4 days; control 14.1 +/- 4.1 days), and 50% of the recipient rats survived for at least 60 days after liver transplantation. Moreover, when a low dose of FK 506 (0.32 mg/kg) was infused into the hepatic artery or portal vein of the transplanted liver for 3 days only, liver allograft survival times were prolonged markedly, and 54% of rats with grafts survived for at least 60 days. This effect was almost equal to that after 7 days systemic treatment with FK 506. In conclusion, 7 days' treatment with FK 506 administered systemically was an effective regimen for the suppression of liver allograft rejection in rats. Furthermore, local immunosuppression with low-dose, short-term (3 days) FK 506 treatment administered via the hepatic artery or portal vein of the transplanted liver dramatically improved allograft salvage.

Animals↗
PubMed1994

Successful 48-h liver preservation by controlling nutritional status of donor and recipient.

The nutritional status of the donor has been shown to affect the outcome of liver transplantation in the rat. It has been proposed that this may be due to inhibition of Kupffer cell induced injury to the reperfused organ, which leads to an inflammatory type response. In this study we investigated how altering the nutritional status of the recipient affects the outcome of liver transplantation after preservation of the liver for 44 or 48 h in the University of Wisconsin (UW) solution. The nutritional status of the rats was altered by either fasting or by feeding an essential fatty acid free diet (EFAD) for 2 months. This type of diet has been shown to reduce significantly the inflammatory response in rats. Survival after 44-h preservation of livers from fed donors (fed a standard laboratory diet) transplanted to fed recipients was 29% (2/7) but increased to 80% (4/5) when the recipient was fed the EFAD diet. After 48-h preservation, there were no survivors under either of these two dietary combinations. However, survival was 100% after 48-h preservation if the donor had been fasted for 4 days and the recipient was fed the EFAD. These results showed that the nutritional status of the donor and recipient are important factors in the outcome of liver transplantation. How nutritional factors affect liver preservation and transplantation are not clear but may be related to the inflammatory response regulated by Kupffer cells and circulating neutrophils in the liver, both of which are influenced by the diet of the animal.

Adenosine↗
PubMed1994

In vivo near-infrared monitoring of nitric oxide production and tissue oxygen sufficiency in rat liver allografts during the acute rejection reaction.

We established a new technique of in vivo near-infrared (NIR) spectroscopy that can estimate both nitric oxide (NO) production and tissue oxygen sufficiency in living organs during the alloimmune response. The present study was aimed at evaluating the potential of this technique for monitoring the rejection response utilizing the rat model of orthotopic liver transplantation without arterialization. The relative changes of nitrosyl-hemoglobin, oxyhemoglobin and oxidized-cytochrome oxidase in the graft livers were quantified by use of this method. Nitrosyl-hemoglobin in the allogenic grafts was elevated at the onset of the rejection response and was suppressed when the rejection reaction was treated by the administration of 15-deoxyspergualin. Oxy-hemoglobin and oxidized-cytochrome oxidase were decreased in accordance with parenchymal disorder determined histologically. These results demonstrated that the new technique of in vivo NIR spectroscopy can assess simultaneously both the immune response and graft function after liver transplantation.

Animals↗