Biomedical subjects

Y Fukuda

Publications and source records attributed to Y Fukuda.

At least 595 records · Page 33Linked to original sources

PubMed1992

A comparison of histadine lactobionate solution with University of Wisconsin solution for rat liver and heart preservation.

We developed a new solution mainly composed of Na-lactobionate and histidine (HL) and compared the effectiveness of this solution with that of University of Wisconsin (UW) solution using orthotopic liver and heterotopic heart transplantation in rats. The new solution has a higher sodium content and a lower potassium content (Na, 90 mEq/l; K, 45 mEq/l) than UW. Hydroxyethyl starch, adenosine, dexamethasone and insulin are not included. Buffering capacity is increased by adding histidine (90 mM/l) together with KH2PO4 (20 mM/l). Rat liver was perserved in either UW or HL solution hypothermically for 24 h and then transplanted orthotopically into the recipient rat. The heart was preserved in either solution for 18 h and transplanted heterotopically into the recipient rat. The 1-week survival rate for rats receiving livers preserved in UW for 24 h at 4 degrees C was 29% (5/17). In contrast, the new solution (HL) gave a 78% (11/14) survival rate (P < 0.01). The 1-week heart graft survival rate, using UW solution was 50% (3/6), following 18-h cold preservation, whereas all hearts (7/7) continued to beat for over a week using new HL solution (P < 0.05). These results demonstrated that the new HL solution, with a substantial buffering capacity, was superior to UW solution in rat liver and heart preservation.

Adenosine↗

PubMed1992

Remarkable correlation between increased HLA-DQ antigen positive monocytes and prognosis of renal transplantation.

Since cyclosporin A (CsA), a widely used immunosuppressive drug, strongly suppresses interleukin-2 (IL-2) secretion, it is frequently difficult to estimate T lymphocyte activation in early acute rejection. We found that, when evaluated based on HLA-DQ antigen expression, monocyte activation in the peripheral blood of renal transplantation patients was a very sharp parameter in diagosing acute rejection. All of 16 episodes of early acute rejection, which were relatively easily suppressed by steroid pulse therapy, showed a sharp increase in the proportion of HLA-DQ antigen-positive monocytes (DQ+ mono) and a quick return of DQ+ mono to previous values, along with a fall in serum creatinine levels. Since, however, HLA-DR antigen-positive T lymphocytes (DR+ T) were markedly increased over a long period in episodes of therapy-resistant and chronic rejection, their prolonged high value was regarded as a parameter indicative of poor prognosis.

Cadaver↗

PubMed1992

Suppression of human lymphocyte proliferation and cytotoxic T lymphocyte generation by a soluble factor derived from K562 cells.

The human myeloid leukemia cell line, K562, secrets a lymphocyte growth-suppressive factor (LGSF). We report our investigation of the immunological and chemical features of this factor. LGSF showed no cytolytic effect on human peripheral blood mononuclear cells (PBMC). Nevertheless, LGSF adequately suppressed in vitro alloantigen- or mitogen (PHA, ConA, PWM)-stimulated human PBMC proliferation and alloantigen-induced cytotoxic T lymphocyte generation, in antigen-nonspecific and LGSF concentration-related manners. LGSF retained activity after filtration through a 0.22 microm filter membrane and storage at -80 degrees C for 6 months. Ultrafiltration experiments indicated that suppressive activity was retained in the higher molecular weight fraction (MW > 100,000) and that the activity was heat-labile at 56 degrees C for 30 min. These results strongly suggested that LGSF is a noncytotoxically immunosuppressive substance with a high molecular weight.

Humans↗

PubMed1992

Changes in ventilatory response to hypoxia in the rat during growth and aging.

The influence of aging on the ventilatory response to hypoxia was studied in the halothane-anesthetized male Wistar rats of various ages (1.5-20 months). The magnitude of increase in ventilation (normalized for body weight) during hypoxia in isocapnic conditions was attenuated in parallel with advancing age. However, ventilation in hyperoxia, normoxia or mild hypoxia did not differ among various age groups when the ventilatory volume was normalized for O2 consumption. Furthermore, threshold end-tidal PO2 for ventilatory depression in deeper hypoxia became progressively lower with advancing age. The results suggest that the age change in ventilatory response to hypoxia depends largely upon the progressive reduction in basal O2 requirement (consumption) with age.

Aging↗

PubMed1992

Correlation between detection of anti-viral antibody and histopathological disease activity in an epidemic of hepatitis C.

There was an epidemic of non-A non-B hepatitis in a small area of a town in the central part of Japan, which began with an outbreak of several patients in 1981 and then spread extensively with the result that about one third of the inhabitants showed abnormality in serum liver function tests at the health check performed in 1985. We determined histological diagnoses on that occasion for 167 individuals of the abnormal population and recently assayed antibodies against hepatitis C virus (HCV) for most of their sera left available. Histologically, chronic active hepatitis (CAH) was the major pattern, accounting for 59.3% (99 cases) of the total. Others were chronic persistent hepatitis (CPH) (13.2%), chronic lobular hepatitis (CLH) (16.2%), liver cirrhosis (LC) (6.6%) and fatty liver (4.8%). In the serological studies, the newly developed system to detect antibodies against the viral core protein p 22 was found to be much more sensitive than the conventional system to detect anti C 100-3 antibodies. By using these two methods in combination, we found that 82% were antibody-positive, indicating strong implication of HCV in this epidemic. This was further supported by direct detection of the viral genome in patients' sera by polymerase chain reaction following reverse transcription. We further found a strong correlation between the histological inflammatory activity and the antibody prevalence, since nearly all (97.6%) of the CAH cases were antibody-positive by at least either of the antibody assays, while only about 50% were positive in the less active cases such as CPH and CLH.

Base Sequence↗

PubMed1992

Morphological comparisons between outer and inner ramifying alpha cells of the albino rat retina.

The somato-dendritic morphologies of large ganglion cells were studied by intracellular injections of Lucifer yellow in perfused in vitro preparations of the albino rat retina. The ganglion cells were prelabeled with retrogradely transported granular blue or labeled with acridine orange dropped into the perfusate of in vitro preparations. After the dye injection, somato-dendritic morphologies were successfully studied for 210 cells, the majority of which had a large soma more than 20 microns in diameter and were identified as alpha cells. According to the level of dendritic extensions within the inner plexiform layer (IPL) these alpha cells were further classified into inner ramifying (inner) and outer ramifying (outer) cells. Both qualitative and quantitative observations led us to conclude the following: 1) The outer cells have a spherical soma with relatively few primary dendrites, while inner cells have a large polygonal soma with more primary dendrites. 2) The dendritic field of inner cells was always larger than that of outer cells at every retinal location. The dendritic field diameter tended to increase as a function of retinal eccentricity from the optic disk, the tendency being more clear among inner cells. 3) The dendrites of outer cells branch more frequently in the proximal part of the dendritic field while those of inner cells branch more distally. 4) Total dendritic length of outer cells increases linearly with eccentricity whereas that of the inner cells does not change much irrespective of retinal location.

Animals↗

PubMed1992

The liver in systemic lupus erythematosus: pathologic analysis of 52 cases and review of Japanese Autopsy Registry Data.

We present pathologic findings for 52 livers (51 autopsy specimens and one wedge biopsy specimen) from patients with systemic lupus erythematosus (SLE). Hepatic congestion was the most common disease (40 livers), followed by fatty liver (38), arteritis (11), cholestasis (nine), peliosis hepatis (six), chronic persistent hepatitis (six), nonspecific reactive hepatitis (five), cholangiolitis (four), nodular regenerative hyperplasia of the liver (three), and hemangioma (three). The data obtained here suggest that arteritis of the SLE liver is more common than has been recognized previously. One patient had hepatic infarction complications induced by arteritis. On the basis of the findings in the present study and a review of the literature, we suggest that hepatic infarction resulting from arteritis is rare in SLE. On the other hand, while occurrence of nodular regenerative hyperplasia of the liver in SLE patients has been considered to be rare, our findings suggest that it may be more common than has been recognized previously. Although congestion and cholestasis may be acute terminal illnesses, fatty change is considered to be specific to the SLE liver. Statistical analysis indicates that exposure to a large dosage of glucocorticoids is a significant factor in the etiology of severe fatty liver. In addition, our review of Japanese autopsy registry data for 1,468 patients with SLE indicates that the incidence of chronic liver diseases in SLE autopsy cases is as follows: chronic hepatitis, 2.4%; cirrhosis, 1.1%; and liver fibrosis, 0.8%.

Adolescent↗

PubMed1992

Polymerase chain reaction--single-strand conformation polymorphism analysis of polymorphism in DPA1 and DPB1 genes: a simple, economical, and rapid method for histocompatibility testing.

A new technical trial was carried out to detect polymorphism in HLA-DP genes, based on the diversity in electrophoretic mobility of single-stranded DNA (single-strand conformation polymorphism, SSCP). Genomic DNAs from 31 cell lines homozygous for 2 and 14 different DPA1 and DPB1 alleles, respectively, and from peripheral blood cells of a normal individual homozygous for another DPB1 allele were subjected to polymerase chain reaction (PCR) to amplify the polymorphic exon 2 of DPA1 or DPB1 genes. The PCR samples were denatured by heating in the presence of formamide to obtain single-stranded DNA, electrophoresed in a neutral polyacrylamide gel, and visualized by silver staining. Allelic differences were detected by the distinctive electrophoretic pattern of each single strand, depending on the sequence-specific conformation. Fifteen DPB1 alleles showed 11 distinct electrophoretic patterns, leaving four allelic combinations not distinguished. These four allelic combinations could be further distinguished by using another couple of primers in PCR, with which a part of the exon was amplified, and by subsequent SSCP analysis. The use of four pairs of primers in PCR allowed for discrimination of all the 15 DPB1 alleles tested. Two allelic differences in exon 2 of DPA1 gene could be clearly demonstrated. In addition, putative new alleles of DPA1 and DPB1 genes were detected by SSCP analyses. The PCR-SSCP analysis is simple and rapid, requires neither radioactive materials nor restriction enzymes, and is expected to be a useful tool for investigating the fine HLA-matching required for clinical transplantation of organs.

Alleles↗

PubMed1992

Effect of ICRF-187 on the pulmonary damage induced by hyperoxia in the rat.

Histological and ultrastructural studies were made of the lungs of rats that were exposed to 100% oxygen for 60 h and were treated with either normal saline or with ICRF-187, a bis-diketopiperazine derivative of EDTA that has the capacity to chelate iron. This metal is thought to be needed to catalyze the formation of toxic oxygen free radicals. ICRF-187 (20 mg/kg) was given intraperitoneally at approximately 12 h intervals (5 doses) during the 60 h exposure. Seven of the ten saline-treated rats exposed to oxygen died prior to the end of the study whereas only one of the 10 rats in the ICRF-187-treated group died. This difference in mortality is found to be statistically significant (P less than 0.05). All saline-treated rats showed light and electron microscopic evidence of pulmonary damage. ICRF-187 attenuated the morphologic alterations observed by light microscopy (intra-alveolar edema, inflammatory exudates and bronchiolar epithelial cell swelling and hyperplasia; P less than 0.05). In addition, electron microscopic evaluation revealed that capillary thrombi, endothelial cell alterations and alveolar epithelial cell damage also were less severe in ICRF-187-treated rats. It is concluded that ICRF-187 may provide a new and useful approach for the prevention of hyperoxia-induced pulmonary damage.

Animals↗

PubMed1992

Glomerular alterations in children with biliary atresia.

To investigate the association of glomerular involvement with biliary atresia, we carried out the following studies: (1) review of the clinical records of 120 patients, (2) histologic study of the kidneys obtained at autopsy from 28 patients, and (3) measurements of circulating immune complexes. Of 90 patients with adequate follow-up information, 40 (44.4%) had hematuria, proteinuria, or both. All the kidney specimens showed a wide variety of mesangial proliferation, and immunoglobulins were present in 23 of 26 cases. There was a good correlation between the glomerular alterations and the period of reduced hepatic function. When IgA was present in the mesangium, IgA2 and secretory components were detected. Elevated serum IgA and circulating IgA-containing immune complex levels were found in patients with prolonged obstructive jaundice. These findings indicate that glomerular alterations may occur subsequently in patients with biliary atresia, and that IgA of intestinal mucosal origin plays some role in the development of these lesions.

Antigen-Antibody Complex↗

PubMed1992

Effect of He-Ne laser irradiation on synaptic transmission of the superior cervical sympathetic ganglion in the rat.

The effect of low-power He-Ne laser on synaptic transmission was studied in the superior cervical sympathetic ganglion of Wistar rats. Extracellular and intracellular recordings were made from isolated ganglia before and after laser irradiation. In addition, effects of ganglion irradiation on skin blood flow were observed in in vivo preparations. Irradiation on the isolated ganglion decreased the amplitude of evoked compound action potentials in the extracellular recordings. Intracellular recordings from ganglion cells revealed that the neuronal membrane was hyperpolarized, while threshold potential and latency of response were unchanged. The reduction of skin blood flow during preganglionic nerve stimulation lessened by irradiation on the ganglion. Our results indicate that low-power He-Ne laser depresses sympathetic ganglionic transmission, and hyperpolarization of ganglionic cells takes part in the mechanism of action.

Animals↗

PubMed1992

Dendritic regrowth of retinal ganglion cells in adult rats.

IN adult rat retinal ganglion cells, we investigated how their dendrites are maintained during axonal regeneration induced by a peripheral nerve (PN) graft. Intracellular Lucifer Yellow injection revealed that rapid dendritic retraction occurred immediately after axotomy and grafting. However, dendrites that probably sprouted after axotomy were often found in the regenerating ganglion cells, and their dendritic field tended to recover in area by 3 months after grafting. Although such dendrites were also found in an axotomized cell receiving no PN graft, they are much more frequently observed in the regenerating cells. Therefore, a PN graft can facilitate the rat ganglion cells to regrow their dendrites.

Animals↗

PubMed1992

Lack of evidence that a transplanted liver causes acute graft-versus-host disease in rats. A comparison of liver and spleen grafts.

In this study, we used rat transplant models to investigate whether--and, if so, to what extent--transplanted liver had the potential to incite graft-versus-host disease, compared with the disease induced by a spleen graft. Livers from PVG(RT1c) rats were transplanted orthotopically into (DAxPVG)F1 (RT1a/c) rats and vascularized spleen grafts from PVG rats were transplanted heterotopically into (DAxPVG)F1 recipients. The intensity of the GVH disease was assessed by the recipients' morbidity and mortality, recipient-type serum class I (RT1Aa) antigen titer, and histological examination. The recipients of spleen grafts died within 14 and 23 days of transplantation; all animals had lost body weight and showed typical GVH signs, such as ear erythema, diarrhea, and alopecia. However, all the recipients bearing liver grafts survived indefinitely and did not demonstrate weight loss or the typical symptoms associated with GVH disease. The skins, tongues, and intestines of the liver-grafted rats were virtually normal at histological examination, whereas the livers, salivary glands, and skins of spleen-grafted rats were infiltrated by immunoblasts. The recipient-type serum RT1Aa antigen titer increased progressively until death in the spleen graft but not the liver graft recipients. These results provide evidence that suggest that transplanted liver is less likely than transplanted spleen to initiate the GVH disease in rats.

Acute Disease↗

PubMed1992

A comparison of some simplified lactobionate preservation solutions with standard UW solution and Eurocollins solution for pancreas preservation.

Fifty-two rat pancreas transplants were performed to investigate which components of the UW solution were essential for successful pancreas preservation. LEW rats were used and the pancreata stored at 4 degrees C for 48 hr after flushing with commercial UW solution (ViaSpan, DuPont Pharmaceuticals) or a number of simplified solutions. Following storage the pancreata were transplanted into syngeneic recipient animals with streptozotocin-induced diabetes mellitus. Graft function was assessed by regular postoperative blood sugar measurements and a glucose tolerance test on the 14th postoperative day. With commercial UW solution, 4 of 9 recipients (44%) showed satisfactory graft function, while only one of 5 pancreata preserved using Eurocollins solution demonstrated satisfactory function. With solution A, in which hydroxyethyl starch and insulin were omitted from the standard UW solution, 3 of 7 recipients (43%) showed satisfactory function. Omission of glutathione, allopurinol, and adenosine from this solution (solution B) gave satisfactory function in 4 of 8 cases (50%). Substitution of raffinose in solution B with an equimolar concentration of glucose (solution C) resulted in acceptable function in 5 of 8 cases (62%). Increasing the raffinose concentration in solution B to 100 mM/L resulted in only 2 of 8 grafts (25%) with adequate function. By contrast, reversing the Na/K concentrations in solution A resulted in 100% (7/7) satisfactory graft function. We conclude that the rat pancreas can be successfully transplanted following 48-hr cold preservation using UW solution and some simplified versions, and that a substantially simplified lactobionate-based solution with a reversed sodium/potassium ratio improved survival.

Adenosine↗

PubMed1992

An examination of the effects of solutions containing histidine and lactobionate for heart, pancreas, and liver preservation in the rat.

Fifty-five rat pancreas transplants, 18 rat heart transplants, and 41 rat liver transplants were performed using standard UW solution, the new HL solution (HL-I), or a modified HL solution (HL-II). Storage times of 18 hr were used in the heart preservation experiments, 24 hr in the liver preservation experiments, and 48 or 72 hr in the pancreas preservation experiments. HL-I solution was superior to both HL-II and UW solution for heart preservation (1-week graft survival rates of 100% [7/7], 0% [0/5], and 50% [3/6], respectively). HL-I and HL-II were superior to UW for 24 hr liver preservation (1-week graft survival rates of 78% [11/14], 80% [8/10], and 29% [5/17], respectively). In contrast, HL-II was superior to both HL-I and UW solutions for pancreas preservation following both 48-hr preservation and 72-hr preservation. Satisfactory graft function was achieved in 100% (7/7), 40% (6/15), and 44.4% (4/9) of pancreases transplanted after 48 hr using HL-II, HL-I, and UW solutions, respectively, and in 50% (4/8), 0% (0/8), and 0% (0/8) following 72-hr preservation. Histidine- and lactobionate-containing solutions thus represent a further improvement in organ preservation by simple cold storage.

Adenosine↗

PubMed1992

Calcium supplementation and thyroid hormone protect against gentamicin-induced inhibition of proximal tubular Na+,K(+)-ATPase activity and other renal functional changes.

Gentamicin can cause proximal tubule necrosis. We have shown that inhibition of PT Na+,K(+)-ATPase activity is rapidly induced by gentamicin. We have now investigated whether manipulations known to attenuate the negative effects of gentamicin on renal excretory capacity, i.e. high calcium intake and L-thyroxine treatment, will also attenuate gentamicin-induced inhibition of Na+,K(+)-ATPase activity and ameliorated signs of proximal tubule damage. Rats were gentamicin- or vehicle-treated for 7 days. Sub-groups were given 4% calcium (Ca) supplements or L-thyroxine 20 micrograms 100 g-1 body weight daily. Gentamicin significantly reduced the glomerular filtration rate and increased the urinary excretion of the proximal tubule lysosomal enzyme, N-acetyl-beta-D-glucosaminidase. Gentamicin significantly reduced proximal tubule Na+,K(+)-ATPase activity, measured in single permeabilized proximal tubule segments. Sodium excretion was inversely correlated to proximal tubule Na+,K(+)-ATPase activity. Both calcium and L-thyroxine alleviated all gentamicin-induced side-effects on renal function as well as on proximal tubule Na+,K(+)-ATPase activity. Calcium and L-thyroxine had no significant effect on renal function. L-thyroxine, but not calcium, increased proximal tubule Na+,K(+)-ATPase activity in control rats. Renal cortical tissue gentamicin concentration was not influenced by calcium but was significantly lowered by L-thyroxine. Two procedures which, via different mechanisms, afford protection from gentamicin-induced changes in renal function also give protection from gentamicin-induced inhibition of Na+,K(+)-ATPase activity. This suggests that loss of integrity of the Na+,K(+)-ATPase enzyme contributes to gentamicin-induced nephrotoxicity.

Acetylglucosaminidase↗

PubMed1992

Monoclonal antibodies against the native urease of Helicobacter pylori: synergistic inhibition of urease activity by monoclonal antibody combinations.

Monoclonal antibodies (MAbs) against the native urease of Helicobacter pylori NCTC 11637 were found to clearly inhibit the urease activity. Interestingly, synergistic inhibition by two MAbs recognizing different subunits was also observed. Ten MAbs were produced and classified as two isotypes of the immunoglobulin G (IgG) subclass, IgG1, and IgG2a. Western blot (immunoblot) analysis using sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that five MAbs recognized the large subunit and the other five recognized the small subunit of the urease. Among the MAbs, L2 and S2, which recognized the large and the small subunits, respectively, were also able to inhibit the urease activity of clinical isolates from H. pylori-infected patients. The combination of L2 and S2 led to augmented synergistic inhibition. L2, but not S2, could also inhibit the urease activity from Helicobacter mustelae; enzyme-linked immunosorbent assay and Western blot analysis showed that L2 cross-reacted with this urease. These results suggested that the epitope recognized by L2 had a structure common to both Helicobacter species and may be involved in the active site of the urease. In contrast to the MAbs, a polyclonal antibody in sera from mice immunized with H. pylori urease did not have the ability to inhibit H. pylori urease activity. However, the polyclonal antibody retained the ability to abolish the inhibitory action of these MAbs. Moreover, other MAbs which could not inhibit H. pylori urease activity also abolished the inhibitory action.

Antibodies, Bacterial↗

PubMed1992

Detection of cytomegalovirus in urine samples by an enzyme-linked immunosorbent assay using a monoclonal antibody against the viral 150-kilodalton protein.

McKeating et al. (J.A. McKeating, P.D. Griffiths, and J.E. Grundy, J. Gen. Virol. 68:785-792, 1987; J. A. McKeating, J. E. Grundy, Z. Varghese, and P. D. Griffiths, J. Med. Virol. 18:341-348, 1986; J. A. McKeating, S. Stagno, P. R. Stirk, and P. D. Griffiths, J. Med. Virol. 16:367-373, 1985) reported previously that beta 2 microglobulin inhibits the detection of human cytomegalovirus (CMV) in urine specimens by an enzyme-linked immunosorbent assay (ELISA) with a monoclonal antibody against the glycoprotein of CMV. They postulated that beta 2 microglobulin binds to the viral glycoproteins and masks the antigenic determinants. We developed here an ELISA method for the detection of CMV in urine by using a monoclonal antibody against the viral 150-kDa protein to capture the viral antigen. This assay detected CMV both in culture medium and in urine specifically at concentrations higher than 10(3) PFU/ml and quantitatively at concentrations higher than 10(4) PFU/ml. The sensitivity of the ELISA increased about 10-fold when peroxidase-labeled F(ab')2 from goat anti-human immunoglobulin G was used as a secondary detecting antibody in combination with concentration of the virus in urine samples by ultracentrifugation. The inhibition of ELISA by beta 2 microglobulin was not observed in this ELISA system. When 56 urine specimens from renal transplant recipients were examined for CMV antigens, the ELISA system had a sensitivity of 78% and a specificity of 97%. The positive and negative predictive values of the assay were 95 and 86%, respectively. Furthermore, CMV antigens in urine were quantitated by the assay during the course of typical CMV disease of renal transplant recipient. These results suggest strongly that the measurement of CMV antigens in urine by our rapid and quantitative ELISA system provides very useful data for the monitoring of CMV infections in renal transplant recipients and making decisions about therapy.

Antibodies, Monoclonal↗