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Biomedical subjects

A Shimizu

Publications and source records attributed to A Shimizu.

At least 91 records · Page 5Linked to original sources
PubMed2000

Responses of immunocompetent cells in the dental pulp to replantation during the regeneration process in rat molars.

Responses of immunocompetent cells to tooth replantation during the regeneration process of the dental pulp in rat molars were investigated by immunocytochemistry using antibodies to class II major histocompatibility complex (MHC) molecules (OX6 antibody), monocyte/macrophage lineage cells (ED1 antibody) and protein gene product 9.5 (PGP 9.5), as well as by histochemical reaction for periodic acid-Schiff (PAS). Tooth replantation caused an increase in both the number of OX6- and ED1-positive cells and their immunointensity in the replanted pulp, but almost all PGP 9.5-immunoreactive nerves diminished in the initial stages. By postoperative day 3, many OX6- and ED -immunopositive cells had accumulated along the pulp-dentin border to extend their cytoplasmic processes into the dentinal tubules in successful cases. Once reparative dentin formation had begun after postoperative day 7, OX6- and ED1-immmunopositive cells became scattered in the odontoblast layer, while reinnervation was found in the coronal pulp. The temporal appearance of these immunocompetent cells at the pulp-dentin border suggests their participation in odontoblast differentiation as well as in initial defense reactions during the pulpal regeneration process. On postoperative day 14, the replanted pulp showed three regeneration patterns: (1) reparative dentin, (2) bone-like tissue formation, and (3) an intermediate form between these. In all cases, PAS-reactive cells such as polymorphonuclear leukocytes (PML) and mesenchymal cells occurred in the pulp space. However, the prolonged stagnation of inflammatory cells was also discernible in the latter two cases. Thus, the findings on PAS reaction suggest that the migration of the dental follicle-derived cells into the pulp space and the subsequent total death of the proper pulpal cells are decisive factors for eliciting bone-like tissue formation in the replanted pulp.

Animals↗
PubMed2000

Atherosclerosis and omega-3 fatty acids in the populations of a fishing village and a farming village in Japan.

The effect of different dietary habits on atherosclerosis was investigated by examining the content of ordinary diets and relevant risk factors through a mass health survey on two village populations in Japan. In total, 261 inhabitants in the fishing village and 209 in the farming village were examined for body build, blood pressure, and blood chemistry. Information on smoking habits and food consumption was obtained using a semi-quantitative item-frequency questionnaire. Pulse wave velocity of the aorta, intima-media thickness of the carotid artery, and atherosclerotic plaques as obtained by ultrasonography were used as measures of atherosclerosis. All measures of atherosclerosis are lower in the fishing village than in the farming village in both men and women. There is a striking 5-8-fold difference in the number of atherosclerotic plaques (P < 0.0001) between the populations. The observed differences in atherosclerosis parallels differences in dietary habits and differences in the serum essential fatty acids. Evaluation of the omega-3 fatty acids over the combined populations reveals a negative association with the number of plaques in the common carotid while the omega-6 fatty acids shows a weak positive association with plaques.

Adult↗
PubMed2000

Mechanisms of tolerance induction and prevention of cardiac allograft vasculopathy in miniature swine: the effect of augmentation of donor antigen load.

OBJECTIVE: Cotransplantation of a donor kidney along with a heart allograft can induce tolerance to both organs and prevent cardiac allograft vasculopathy in miniature swine. To determine whether the tolerogenic effect of donor kidney cotransplantation was due to an effect specific to the kidney graft or to an increase in donor antigen load, we compared heart-kidney recipients with recipients receiving two class I disparate hearts or with recipients receiving donor peripheral mononuclear cells at the time of isolated heart transplantation. METHODS: Recipients of major histocompatibility complex class I disparate allografts received 12 days of cyclosporine (INN: cyclosporin; 10-13 mg/kg administered intravenously on days 0-11). Group 1 animals received a heart alone (n = 5). Group 2 animals received heart and kidney allografts (n = 4). Group 3 animals received two major histocompatibility complex-matched heart allografts (n = 4). Two double-heart recipients were thymectomized 21 days before transplantation. Group 4 animals received a heart allograft and an infusion of high-dose donor peripheral blood leukocytes (2.5 x 10(9) cells/kg, n = 2). RESULTS: Vasculopathy developed in group 1 recipients and the allografts were rejected within 55 days. Group 2 recipients accepted their heart and kidney allografts indefinitely without vasculopathy. Euthymic recipients from group 3 accepted their hearts long-term (>190 and >197 days), but vascular lesions developed. In thymectomized recipients from group 3, the hearts were rejected in 63 and 96 days with severe vasculopathy. Group 4 recipients demonstrated transient macrochimerism but their hearts were rejected within 47 and 63 days. CONCLUSIONS: The beneficial effects of donor kidney cotransplantation on cardiac allograft survival and prevention of cardiac allograft vasculopathy are likely to involve both an increase in donor antigen load and an effect specific to the kidney allograft.

Animals↗
PubMed2000

Laparoscopic adrenalectomy for functioning adrenal tumors: clinical experiences with 38 cases and comparison with open adrenalectomy.

We reviewed 38 cases of transperitoneal or retroperitoneal laparoscopic adrenalectomy for unilateral benign functioning adrenal tumors and compared the results with those of a recent series of 36 patients undergoing an open adrenalectomy. The tumors were removed successfully in all but two cases with laparoscopy that required open laparotomy. In the other 36 cases of the laparoscopy group, mean operative time and blood loss were 225 minutes and 138 mL, respectively. Mean operative time was significantly longer for the laparoscopy group (122 minutes for open surgery: P < 0.0001), whereas mean blood loss of the laparoscopy group was almost equal to that of the open surgery group. Mean intervals to first ambulation and oral intake, and postoperative hospital stay of the laparoscopy group were significantly less than those of the open surgery group (1.4 vs 2.0 days: P = 0.014; 1.8 vs 2.9 days: P < 0.0001; and 8.5 vs 12.9 days: P < 0.0001, respectively). We conclude that laparoscopic adrenalectomy is equally effective and less invasive than open adrenalectomy. and that it should be considered as the first-choice therapy for benign adrenal tumors.

Adrenal Gland Neoplasms↗
PubMed2000

Discovery of novel trans-3,5-disubstituted pyrrolidinylthio-1beta-methylcarbapenems.

Novel trans-3,5-disubstituted pyrrolidinylthio-1beta-methylcarbapenems were designed and synthesized to provide J-111,347 (1a) as the first example of an exceptionally broad-spectrum antibiotic, showing activity against methicillin-resistant Staphyloccocus aureus (MRSA) as well as Pseudomonas aeruginosa. Further derivation of 1a afforded J-111,225 (2a), J-114,870 (3a), and J-114,871 (3b). which showed improved safety profiles and retained broad-spectrum antibacterial activities.

Animals↗
PubMed2000

Rejection of peritubular capillaries in renal allo- and xeno-graft.

The microvasculature plays an important role in the pathogenesis of humoral- and cell-mediated renal allo- and xeno-graft rejection. Peritubular capillary (PTC) endothelium expresses the major histocompatibility complex (MHC) class I and II antigens in the resting phase, as does the glomerular capillary endothelium, suggesting that these cells may be major immune targets. However, the role of PTCs in renal allo- and xeno-graft rejection is unclear. In this review, we discuss injury and subsequent remodeling of PTCs in both humoral- and cell-mediated rejection in allo- and xeno-grafts. Recent evidence suggests that PTC injury and endothelial cell death occur during both cell- and humoral-mediated rejection. Severe PTC rejection contributes to deterioration of graft function and acute graft loss. The mild but recurrent form of PTC rejection is associated with progressive interstitial fibrosis and chronic rejection. Following endothelial injury, the remaining PTC endothelium activates with up-regulation of allo-antigens and adhesion molecules, and down-regulation of anti-coagulant proteins. Subsequent to this, more severe rejection and graft dysfunction occur. Therefore, a careful analysis of cellular- and antibody-mediated rejection in PTCs is important in the diagnosis of rejection, prediction of graft prognosis, and in further development of new anti-rejection therapies.

Animals↗
PubMed2000

Detection of measles virus genome in bronchoalveolar lavage cells in a patient with measles pneumonia.

Measles is frequently complicated with pneumonia that could be fatal in numerous occasions. However, a prompt and precise diagnosis of measles is not easily made particularly in the early stage of the disease, or in immunocompromised individuals because of the lack of typical clinical features or the defect in antigen-specific antibody production. In the present paper, we describe a 27-yr-old male who developed fever, skin rash typical of measles, and diffuse pulmonary infiltrates associated with respiratory failure. Infection of lung cells with measles virus was proved by detection of viral genome ribonucleic acid within alveolar macrophages and lymphocytes recovered by bronchoalveolar lavage using reverse transcription-polymerase chain reaction amplification. These techniques may offer a useful tool to make the swift and precise diagnosis of measles pneumonia, thus allowing appropriate therapeutic approaches to the disease.

Adult↗
PubMed2000

Acute humoral xenograft rejection: destruction of the microvascular capillary endothelium in pig-to-nonhuman primate renal grafts.

The major cause of xenograft loss beyond hyperacute rejection is a form of injury, traditionally termed delayed xenograft rejection (DXR), whose pathogenesis is unknown. Here we analyze the immunologic and morphologic features of DXR that develops in pig kidney xenografts transplanted into nonhuman primates. Kidneys from miniature swine were transplanted into cynomolgus monkeys (n = 14) or baboons (n = 11) that received regimens aimed to induce mixed chimerism and tolerance. No kidney was rejected hyperacutely. Morphologic and immunohistochemical studies were performed on serial biopsies, and an effort was made to quantify the pathologic features seen. The early phase of DXR (Days 0-12) was characterized by focal deposition of IgM, IgG, C3, and scanty neutrophil and macrophage infiltrates. The first abnormality recognized was glomerular and peritubular capillary endothelial cell death as defined by in situ DNA nick-end labeling (TUNEL). Damaged endothelial cells underwent apoptosis and, later, frank necrosis. The progressive phase developed around Day 6 and was characterized by progressive deposition of IgM, IgG, C3, and prominent infiltration of cytotoxic T cells and macrophages, with a small number of NK cells. Thrombotic microangiopathy developed in the glomeruli and peritubular capillaries with TUNEL+ endothelial cells, platelet aggregation, and destruction of the capillary network. Only rare damaged arterial endothelial cells and tubular epithelial cells were observed, with rare endothelialitis and tubulitis. In the advanced phase of DXR, interstitial hemorrhage and infarction occurred. During the development of DXR, the number of TUNEL+ cells increased, and this correlated with progressive deposition of antibody. The degree of platelet aggregation correlated with the number of TUNEL+ damaged endothelial cells. We conclude that peritubular and glomerular capillary endothelia are the primary targets of renal DXR rather than tubular epithelial cells or arterial endothelium and that the earliest detectable change is endothelial cell death. DXR was characterized by progressive destruction of the microvasculature (glomeruli and peritubular capillaries) and formation of fibrin-platelet thrombi. Both cytotoxic cells and antibodies potentially mediate the endothelial damage in DXR; however, in this model, DXR is largely humorally mediated and is better termed "acute humoral xenograft rejection."

Acute Disease↗
PubMed2000

Mapping of the chicken immunoglobulin heavy-chain constant region gene locus reveals an inverted alpha gene upstream of a condensed upsilon gene.

Chicken antibodies are increasingly being used as diagnostic and therapeutic tools. As only the genomic organization of the micro encoding gene was previously known, we analysed the chicken immunoglobulin Y (IgY) and IgA (upsilon and alpha chain) immunoglobulin heavy-chain constant region (IGHC) genes and the organization of the chicken IGHC locus. The alpha gene is encoded by four separate exons, whereas, surprisingly, there is no intervening DNA sequence between the CH1 and CH2 domains of the IgY heavy chain, which is thus encoded by three exons separated by two introns. DNA sequence analysis shows that the exon boundaries of the chicken IGHC genes are not consistent with published domain borders. Furthermore, differences in DNA sequence confirm the existence of IgY, IgA and IgM allotypes in chickens. Finally, our results show that the IGHC genes of chicken (IgY, IgA and IgM) are all colocated on chromosome E18C15W15, where the alpha gene is located upstream of the upsilon gene in an inverted transcriptional orientation. The distances between the mu and alpha genes and the alpha and upsilon genes are about 18 and 15 kilobases, respectively, and thus, the size of the whole chicken IGHC locus is approximately 67 kilobases.

Animals↗
PubMed2000

Double ventricular response by a single ventricular extrastimulus to the inner loop of reentry in a patient without apparent heart disease.

In a patient without apparent heart disease, a ventricular extrastimulus delivered from the left ventricular apex where the electrogram was recorded 30 ms after the onset of the QRS complex during VT advanced the second QRS complex, but not the first QRS complex. The morphology of the second QRS complex was the same as that of VT. The postpacing interval was the same as the cycle length of the VT. These findings indicated that the site of stimulation was at the inner loop of the reentry circuit of the VT. A ventricular extrastimulus with a shorter coupling interval advanced the first and second QRS complexes, indicating that the ventricle was activated by antidromic and orthodromic activation from the extrastimulus. Radiofrequency ablation at that site of stimulation terminated the VT and no further VT could be induced.

Aged↗
PubMed2000

Intragraft events preceding chronic renal allograft rejection in a modified tolerance protocol.

BACKGROUND: Inbred miniature swine treated for 12 days with high-dose cyclosporine A develop tolerance to histocompatibility complex (MHC) class I-mismatched renal allografts. When this protocol was modified by adding thymectomy before transplant, all animals developed acute rejection. Thereafter, by day 100, one half developed chronic rejection (progression group) and the other half recovered (recovery group). This provides an excellent experimental model to identify the mechanisms of chronic rejection as well as the early changes that may predict chronic rejection. METHODS: We assessed the cellular infiltration, immune activation, humoral immunity, and cell- and antibody-mediated graft injury in the progression and the recovery groups. In addition, we also examined circulating donor reactive cytotoxic T lymphocyte (CTL) and antidonor antibody in both groups. RESULTS: From days 8 to 18 after transplantation, the two groups were indistinguishable. Both showed acute rejection with endarteritis (type II); had IgG and IgM deposition in glomeruli and small vessels; had an infiltrate with similar numbers of T cells, proliferating (PCNA+) and activated (interleukin-2 receptor+) cells; and had a similar degree of parenchymal cell apoptosis [in situ DNA nick-end labeling (TUNEL)+]. However, by days 30 to 60, the two groups could be distinguished by several intragraft features. The recovery group became tolerant and had diminished T-cell infiltration, activation and proliferation, and no detectable antibody deposition. The number of TUNEL+-injured parenchymal cells decreased. In contrast, the progression group showed persistent cell infiltration with activation and proliferation. Significantly prominent TUNEL+ apoptotic parenchymal cells in tubules, glomeruli, peritubular capillaries and arteries were seen from day 30 to day 100. Circulating donor reactive CTL and antidonor class I IgG were detected in the progression group at higher levels than in the recovery group from days 30 to 60. CONCLUSION: In tolerance-induction protocols, unstable tolerance induction is associated with the persistent immunologic activation that mediates immunologic destruction of graft parenchymal cells and chronic rejection. Certain of the described immunopathologic findings (activation, proliferation, apoptosis, and antibody deposition) may be useful in distinguishing the type of rejection, that is, whether the allograft will progress to chronic rejection or recovery.

Acute Disease↗
PubMed2000

Class switch recombination of the chicken IgH chain genes: implications for the primordial switch region repeats.

In mammals and the amphibian, Xenopus, isotypes of antibodies have been shown to be changed through class switch recombination within the IgH chain gene locus. Here, we identified switch (S) repetitive sequences in the 5' introns of the Ig C(mu) and C(gamma) genes of the chicken. The S(mu) region is composed of two homologous regions, S(mu)1 and S(mu)2. The S(mu)1 region is an upstream 3.7 kb sequence composed of 37 repeats of a consensus sequence containing tandem repeats of the decamer ACCAGTATGG. The S(mu)2 region is a downstream 1.4 kb sequence consisting of simple tandem repeats of a decamer CCCAGTACAG. The S(gamma) region contains repeats of the decamer TATGGGGCAG. Analysis of chicken IgG-producing hybridomas revealed that the C(mu) gene was deleted from the chromosome by the recombination occurring between the S(mu) and S(gamma) regions. Recombination breakpoints at the C(mu) gene of splenocytes from an immunized chicken were scattered around the S(mu) region and two such breakpoints, the precise position of which were determined, were located within possible hairpin loop structures at the palindromic sequence of S(mu)1. A primordial palindromic sequence from which the prevalent switch repeat motifs of mammals, chickens and amphibians may have diverged is presented.

Animals↗
PubMed2000

Prolonged survival of musculoskeletal xenografts with combined cyclosporine and 15-deoxyspergualin.

This study was undertaken to evaluate the feasibility of performing vascularized musculoskeletal xenografts between mice and rats using immunosuppression. Vascularized musculoskeletal grafts were harvested from the hind limb of C57BL/6J (B6) mice, transplanted heterotopically into Lewis rats, and revascularized by microanastomoses of the graft artery and the recipient femoral artery and the graft vein to the recipient femoral vein. Recipient rats were divided into four groups. Group 1 received no immunosuppression (n = 10), group 2 was treated with cyclosporine (10 mg/kg/day; n = 10), group 3 was treated with 15-deoxyspergualin (5 mg/kg/day; n = 10), and group 4 received both cyclosporine and 15-deoxyspergualin (n = 10). Graft survival was directly examined on postoperative days 4, 7, and 14. In vitro assays were performed using mixed lymphocyte reactions and anti-donor cytotoxic antibody assays to assess the recipient's immune response. Grafts were examined by histology and immunohistochemistry. All grafts in group 1 were rejected by day 4. In groups 2 and 3, all grafts were rejected by day 7. In group 4, however, 8 of 10 recipients had viable grafts on day 14. Data from mixed lymphocyte reactions showed that cell-mediated immune responses were uniformly suppressed in groups 2, 3, and 4 compared with group 1. However, anti-donor antibody production was only partly suppressed in groups 2 and 3, suggesting that graft rejection was primarily caused by circulating cytotoxic anti-donor antibodies in groups 1, 2, and 3. Histologic observations in groups 1, 2, and 3 confirmed the important role of the humoral mechanism in xenograft rejection. Furthermore, immunohistochemical results demonstrated that the small vessels in the rejected grafts showed anti-rat immunoglobulin and complement depositions. Only a combination therapy of cyclosporine and 15-deoxyspergualin attenuated the rejection of xenografts.

Animals↗
PubMed2000

Isolation of tannin-degrading lactobacilli from humans and fermented foods.

Lactobacilli with tannase activity were isolated from human feces and fermented foods. A PCR-based taxonomic assay revealed that the isolates belong to Lactobacillus plantarum, L. paraplantarum, and L. pentosus. Additional studies on a range of Lactobacillus species from established culture collections confirmed that this enzymatic activity is a phenotypic property common to these three species.

Animals↗