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Biomedical subjects

N Nagata

Publications and source records attributed to N Nagata.

At least 253 records · Page 14Linked to original sources

Detection of human cytomegalovirus DNA in breast milk by means of polymerase chain reaction.

Three hundred and twenty-five breast milk samples were examined for the occurrence of human cytomegalovirus (HCMV) by cell culture method. Virus was isolated from the milk in 1 of 177 samples collected within 6 days after delivery, 2 of 115 samples collected during the period of 7 days to 1 month after delivery, 10 of 33 samples collected over 1 month after delivery. Next, we tried to amplify HCMV DNA from the breast milk samples from HCMV seropositive mothers and seronegative mothers at 1 month after delivery by polymerase chain reaction. HCMV DNA was detected in 12 of 13 samples from seropositive mothers and in none of 7 samples from seronegative mothers. It was thought that all women seropositive for HCMV principally shed the virus into their breast milk at 1 month after delivery.

Antibodies, Viral↗

Attenuation of lpr-graft-versus-host disease (GVHD) in MRL/lpr spleen cell-injected SCID mice by in vivo treatment with anti-V beta 8.1,2 monoclonal antibody.

When MRL/lpr (H-2k) spleen cells were intraperitoneally injected into C.B-17-scid/scid (severe combined immunodeficient (SCID)) (H-2d) mice, the SCID (SCID-MRL/lpr) mice manifested a severe wasting syndrome with weight loss, splenic atrophy, and lymphoid cell infiltration in the liver and lung, as seen in lpr-GVHD. In contrast, MRL/+ spleen cell-injected SCID (SCID-MRL/+) mice did not show lpr-GVHD. The spleens of SCID-MRL/lpr mice showed progressive increases in donor CD4+ and CD8+ T cells from 4 to 12 weeks after injection and a decrease in B cells at 12 weeks. SCID-MRL/+ mice showed a stable engraftment of CD4+ and CD8+ T cells and a progressive increase in B cells. Analyses of T cell receptor (TCR) repertoires (V beta 6, V beta 8.1,2 and V beta 11) revealed that the V beta 8.1,2+ T cells were found more frequently in SCID-MRL/lpr mice than in SCID-MRL/+ mice. When SCID-MRL/lpr mice were treated with intraperitoneal injection of an anti-V beta 8.1,2 (KJ16) MoAb, V beta 8.1,2+ T cells were markedly depleted, and the severity of lpr-GVHD was attenuated at 4 and 8 weeks after treatment, in contrast to normal rat IgG-injected SCID-MRL/lpr mice. However, the KJ16 MoAb-treated SCID-MRL/lpr mice suffered from severe lpr-GVHD 12 weeks after treatment, although V beta 8.1,2+ T cells were still maintained at a low level. These findings suggest that V beta 8.1,2+ T cells are a major T cell population that mediates lpr-GVHD in the early stage of lpr-GVHD, but that in the later stage, the other T cell populations may proliferate naturally or in accordance with the depletion of V beta 8.1,2+ T cells, and contribute to the development of lpr-GVHD.

Animals↗

Minocycline-induced hemolytic anemia.

A case of drug-induced immune hemolytic anemia is described. A 2 year old boy exhibited sudden anemia and hemoglobinuria after administration of minocycline (MINO). The specific immunoglobulin G antibody against MINO was demonstrated in the patient's serum by western blotting. This is a rare example where anti-minocycline immune complex-mediated hemolysis was responsible for an intravascular hemolytic process.

Anemia↗

Parathyroid hormone-related protein during pregnancy and the perinatal period.

To evaluate whether parathyroid hormone-related protein (PTHrP) plays any role in calcium metabolism during pregnancy and the perinatal period, we measured parathyroid hormone (PTH), immunoreactive PTHrP and calcium in maternal serum of women during pregnancy and puerperium, and in maternal and cord serum at delivery. Serum PTH levels in pregnant women were lower than those in nonpregnant women (p < 0.01). However, serum PTHrP levels were similar in the two groups of women. Cord serum total and ionic calcium levels were higher, and cord serum PTH levels were lower compared to maternal values (p < 0.01). Cord serum PTHrP levels were higher than maternal values, and umbilical arterial levels were higher than umbilical venous levels (p < 0.01). Higher levels of PTHrP in umbilical arterial blood than in umbilical venous blood suggest that the main source of cord blood PTHrP may be the fetus. PTHrP is reported to stimulate placental calcium transfer from mother to fetus in animals. The elevated cord blood PTHrP level in association with the decreased PTH level suggests that stimulation of placental calcium transfer by PTHrP may also be operative in humans.

Calcium↗

A case of 17 alpha-hydroxylase deficiency with retained menstruation.

A patient with 17 alpha-hydroxylase deficiency (17OHD) who continued to menstruate is reported. A 24-year-old woman who presented with hypertension, hypokalemia and irregular menses had increased plasma ACTH and mineralocorticoids without any increase in glucocorticoids or sex steroids, and a bilateral adrenal enlargement on abdominal X-ray CT. ACTH stimulation test revealed hyperresponse of the metabolites of the mineralocorticoid pathway and blunted or absent response of those of the glucocorticoid and androgen pathway. Almost all of the abnormalities disappeared after dexamethasone administration. While 17OHD is usually known to accompany hypergonadotropic hypogonadism, the patient continued to menstruate, though irregularly. Although human chorionic gonadotropin administration failed to induce response, basal plasma levels of ovarian steroid (estradiol) and gonadotropins as well as response to LHRH stimulation test were all normal. Thus, the clinical and biochemical features of this case is compatible with the partial deficiency of both adrenals and ovaries, being less severe in the latter. A further analysis especially at molecular level is needed to elucidate the basis for the heterogeneity of this disorder.

Adrenal Hyperplasia, Congenital↗

Differentiation between physiologic and pathologic sinusoidal FHR pattern by fetal actocardiogram.

Two cases of physiologic sinusoidal FHR pattern and one case of pathologic sinusoidal FHR pattern recorded on fetal actocardiograms are reported. The physiologic sinusoidal FHR patterns were recorded during periodic fetal respiratory movements and sucking movements. The physiologic sinusoidal FHR patterns were accompanied and synchronized with periodic fetal movement bursts. The pathologic sinusoidal FHR pattern observed in a case of severe fetal anemia due to massive fetal-to-maternal hemorrhage was not accompanied by any fetal movement bursts. It is suggested that with the use of fetal actocardiogram physiologic sinusoidal FHR pattern can be distinguished from pathologic sinusoidal FHR pattern.

Adult↗

The biological significance of glycyrrhizin- and glycyrrhetinic acid derivative-induced selective phosphorylation of histones H2A and H2B by A-kinase in vitro.

Histones H2A and H2B were found to be glycyrrhizin (GL)-binding proteins, because (i) the two histones H2A-H2B pairs were isolated selectively from the crude histone preparations of calf thymus by means of GL-affinity column chromatography (HPLC); (ii) phosphorylation of these two histones by A-kinase was remarkably stimulated by native GL or oGA (a derivative of glycyrrhetinic acid) at 20 microM; and (iii) in the crude histone preparations of calf thymus, these two histones were selectively phosphorylated by A-kinase in the presence of both dsDNA and 20 microM oGA or 20 microM GL. The provided data suggest that the GL-induced selective phosphorylation of histones H2A and H2B by A-kinase may be implicated in the transcriptional activation involved in the biological activities of the drug.

Animals↗

Autoimmune diseases as stem cell disorders.

Using an animal model for insulin-dependent diabetes mellitus (IDDM), the NOD mouse, we have demonstrated that allogeneic bone marrow transplantation (BMT) has a preventative effect on IDDM, and that a combined transplantation of pancreas and bone marrow can be used to treat IDDM. We have also shown that BMT has a curative effect on systemic autoimmune disease in (NZB x NZW) F1, BXSB, and (NZW x BXSB) F1 mice but not in MRL/lpr mice. Since MRL/lpr mice possess abnormal radioresistant hemopoietic stem cells (HSCs), they suffer a relapse 5 months after BMT. Recently, we have found that major histocompatibility complex (MHC)-matched stromal cells in the bone marrow are essential to the support of HSCs in the Go phase. We therefore attempted to treat autoimmune diseases in MRL/lpr mice by the transplantation of stromal cells with HSCs. Transplantation of HSCs with bone to recruit stromal cells was indeed found to have a curative effect on autoimmune diseases in the mice. These results indicate that BMT with bone graft will become a valuable strategy for the treatment of patients with both systemic and organ-specific autoimmune diseases. To prove that autoimmune diseases originate from defects in HSCs, we transferred the HSCs of autoimmune-prone mice to normal mice. BMT or transplantation of stem-cell concentrates induced organ-specific and/or systemic autoimmune diseases in [NOD-->C3H/HeN] and [(NZW x BXSB)F1-->C3H/HeN or C57BL/6J] chimeric mice. These results provide direct evidence that the etiopathogenesis of autoimmune diseases, including both organ-specific and systemic autoimmune diseases, is attributable to defects in the HSCs themselves. We further provide that various intractable diseases such as non-insulin-dependent diabetes mellitus and chronic nephritis (focal glomerulosclerosis) are also organ-specific autoimmune diseases, and that BMT can be used to treat them.

Animals↗

The healing process of chronic colitis in rats, induced by 2,4,6-trinitrobenzene sulfonic acid, with special reference to the role of fibronectin.

BACKGROUND: The healing process of rat chronic colitis was investigated to evaluate the role of fibronectin produced by fibroblasts in the healing tissue. METHODS: Chronic colitis was produced by intrarectal instillation of 2,4,6-trinitrobenzene sulfonic acid. The healing process was observed by light and electron microscopy and immunocytochemistry. Time course of fibronectin mRNA expression was measured by Northern blot hybridization. RESULTS: By light and electron microscopy, an abundance of young fibroblasts had gathered at the healing tissue and were involved in incorporation into the endothelium of the preexisting vessels, as vasoformative cells, and in transformation to new muscle cells in muscular regeneration. Such processes became pronounced from day 3 and persisted for 6 weeks. Immunocytochemical data showed that fibronectin, produced in the rough endoplasmic reticulum of the fibroblasts and released to the extracellular surface, played inductive roles in the movement and aggregation of such cells and in their contacts with neighboring endothelial cells of the preexisting capillaries. Northern hybridization showed that mRNA coding for fibronectin rapidly reached maximum on day 3 and gradually decreased almost to the control level at 6 weeks. CONCLUSIONS: These observations elucidate the role of young fibroblasts, as multipotent cells, and of fibronectin in acceleration of the healing process in this model of chronic colitis.

Animals↗

Analyses of lpr-GVHD by adoptive transfer experiments using MRL/lpr-Thy-1.1 congenic mice.

When MRL/Mp- +/+ (MRL/+) mice are lethally irradiated and then reconstituted with MRL/Mp-lpr/lpr (MRL/lpr) spleen and/or bone marrow cells (BMCs), the mice develop a graft-versus-host disease (GVHD)-like syndrome which is known as lpr-GVHD. We analyzed lpr-GVHD by adoptive transfer experiments using congenic MRL/lpr-Thy-1.1 mice to distinguish the donor and recipient cells. MRL/+ mice were lethally (9.5 Gy) irradiated and then reconstituted with BMCs of MRL/lpr-Thy-1.1 mice treated with anti-Thy-1.1 monoclonal antibody (mAb) plus complement (C). The mice were sacrificed 5 to 6 weeks after bone marrow transplantation (BMT), and the spleen cells were transferred to second recipients. The second recipients (MRL/+ or MRL/lpr mice) were non-irradiated, sublethally (6 Gy) irradiated or lethally (9.5 Gy) irradiated. The lethally irradiated mice were also injected with syngeneic BMCs treated with anti-Thy-1.2 mAb plus C. When whole spleen cells (1 x 10(8) were injected into lethally irradiated MRL/+ mice, the mice showed short survival (1.2-1.5 months) and severe histological changes in the spleen (atrophy and fibrosis), liver (lymphoid infiltration in the Glisson's sheath) and lung (lymphoid infiltration around the bronchus and vessel). The sublethally irradiated MRL/+ mice at 2 months after transfer showed histological changes similar to the lethally irradiated MRL/+ recipients, although the former survived more than 3 months, suggesting that histological changes do not reflect on mortality. These GVH-like diseases were not transferable to MRL/lpr mice; they developed autoimmune diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[A case of bronchiolitis obliterans organizing pneumonia: diagnostic utility of bronchoalveolar lavage and CT scan].

A 54-year-old female was admitted to our hospital because of abnormal shadows on chest X-ray at annual checkup. She complained of dyspnea on exertion. Chest X-ray findings showed an increase in density at the bilateral lower lung fields and unclearness of the silhouette of the heart and the diaphragm. CT scan findings revealed irregular opacities of various density with many small cystic changes and air bronchograms and air bronchiolograms. The pulmonary function test showed restrictive ventilatory disturbance and reduced diffusing capacity. BALF findings revealed an increase in the total cell count, an increase in the percentage of lymphocytes and a decrease in the OKT4+/OKT8+ ratio. TBLB specimen showed infiltration of mononuclear cells in alveolar septa and organizing exudate in alveolar ducts. These findings suggested a diagnosis of BOOP rather than IPF, and an open lung biopsy was performed. Open lung biopsy specimen showed obstructive bronchiolitis with polypoid granulation tissue and thickening of alveolar septa with infiltration of mononuclear cells, and she was diagnosed as having BOOP. She responded well to corticosteroid and is free from any abnormalities on chest X-ray, CT scan and pulmonary function test at present. Analysis of BALF and CT scan findings are useful for the differential diagnosis of BOOP and IPF.

Bronchoalveolar Lavage Fluid↗

[Effect of deliberate hypotension on renal functions during epidural block plus inhalation anesthesia: a comparison of prostaglandin E1 and trimethaphan].

To clarify the effect of prostaglandin E1 (PGE1) or trimethaphan (TMP) on the kidney during deliberate hypotension induced with epidural block plus inhalation anesthesia, we compared renal functions and renal tubular injury between the patient with PGE1-induced hypotension (n = 22) and those with TMP-induced hypotension (n = 18) undergoing spherical acetabular osteotomy. Hypotension was maintained at 75-80 mmHg of the systolic radial artery pressure for two hours. The urine volume, creatinine clearance, fractional sodium excretion and free water clearance were maintained within normal limits and they were not different between the two groups. The mean NAG index increased significantly to normal upper limits during hypotension in the PGE1 group but did not increase in the TMP group. However, there was no difference in the NAG index between the two groups. The changes in serum ADH level were not different between the two groups perioperatively. These results suggest that renal functions are not influenced by controlled hypotension induced with PGE1 or TMP during epidural plus general anesthesia.

Adult↗

[A case of limited Wegener's granulomatosis with hemophilia A, complicated by empyema, bronchopleural fistula and herpes zoster during therapy].

A 36-year-old man with hemophilia A was admitted to hospital because of otalgia, hearing loss, nasal obstruction, nonproductive cough, and high fever. His laboratory data showed high-grade acute inflammatory reactions. His chest X-ray and CT films showed multiple cavitary masses in the right lower lung field. Bronchoscopy performed at our institution revealed bronchial nodules in the intermediate truncus, and BAL revealed increases in the neutrophils and an IgG index (BAL IgG/albumin divided by serum IgG/albumin). Biopsy specimens obtained from nasal mucosa showed epithelioid granulomas with Langerhans' giant cells and necrotizing vasculitis. Antineutrophil cytoplasmic antibodies were also positive, but no evidence of glomerulonephritis was observed. The diagnosis of limited Wegener's granulomatosis was thus made. He was treated with standard therapy (daily cyclophosphamide and glucocorticoids), but within 1 month he had complications of empyema with herpes zoster, and bronchopleural fistula. The complications resolved with appropriate treatment.

Adult↗

[Warm heart surgery facilitates atrioventricular valve repair].

The valve structure varies with cases in children's atrioventricular valvular regurgitation. Filling the left ventricle simply with cold saline solution and testing the valve competency in the cold cardioplegic arrest do not clarify true valve function, although it was the widely used method. Three dimensional evaluation of the lesion in the dynamic and more nearly normal state and the very fine operative procedure in the static state are required for the successful repair. For this purpose we employed the warm heart surgery on 12 children for valve repair (age 1.3-10.1 years, body weight 6.6-28.2 kg). Because no topical cooling was used, preparation of the heart from the adhesion caused by previous operation was not necessary. The aorta was cross clamped at the temperature of 34 degrees of centigrade with continuous coronary perfusion and the lesion in the valve structure and the regurgitation stream were inspected in the beating state, then the repair was performed in the arrest state obtained by infusing the potassium into the coronary perfusion line. Beating and arrest was repeated 2-5 times by on-off potassium infusion until the repair seems satisfactory. In two cases, the repair was not feasible and mitral valve replacement was performed, but in other 10 cases, the postoperative regurgitation decreased down to the grade 2. Despite prolonged aortic cross clamping (65-216 min), post-operative course was quite satisfactory without low-output syndrome in any cases. Postoperatively administered maximum dose of Dopamine was 4.0 +/- 2.2 micrograms/kg/min. CK-MB at 1 POD was also within normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Temperature↗

[A patient with Guillain-Barré syndrome in association with Campylobacter jejuni enteritis (PEN19:LIO7) in a patient with HLA-B52 antigen].

We report a 15-year-old boy with Guillain-Barré syndrome (GBS) in association with Campylobacter jejuni enteritis. A neurologic examination revealed distal-dominant weakness and areflexia. Compound muscle action potentials were markedly reduced in amplitude, but the decrease in motor conduction velocities was slight. C. jejuni was isolated from his stool culture and the serotype belonged to PEN19:LIO7. Thin-layer chromatography-immunostaining showed that his serum IgG reacted strongly with GM1 and weakly with GD1b. The patient had HLA-B52 antigen, whose epitope is very similar to that of B35 antigen.

Adolescent↗

A murine nephritogenic monoclonal antibody binds to both single-stranded deoxyribonucleic acid and glomerulus.

BACKGROUND: Autoantibodies such as anti-DNA and antimyeloperoxidase (MPO) antibodies have been shown to cause glomerulonephritis in experimental animal models. To analyze pathogenic autoantibodies, we developed hybridomas from spleen cells of nontreated FGS mice, in which focal segmental glomerular sclerosis develops spontaneously. EXPERIMENTAL DESIGN: Reactivity and specificity of a monoclonal antibody (FG1H5) were examined using enzyme-linked immunosorbent assay and cryosections of mouse organs as substrates. Immunoprecipitation was performed to analyze reactive antigens. Hybridoma cells were injected ip into severe combined immunodeficiency (SCID) mice to examine their nephritogenicity in vivo. RESULTS: The binding of FG1H5 to single-stranded DNA (ssDNA) was inhibited by ssDNA and also MPO. The binding of FG1H5 to MPO was weak, not inhibited by MPO, and markedly enhanced by the presence of ssDNA. This marked enhancement of the binding to MPO was abolished by DNase I-treatment of the mixture of FG1H5 and ssDNA. When MPO was introduced into ssDNA-coated wells, the binding of FG1H5 to ssDNA was inhibited. On the other hand, when ssDNA was introduced into MPO-coated wells, the binding of FG1H5 to MPO was markedly enhanced. Inhibition tests using double-stranded DNA revealed that FG1H5 is specific for ssDNA. Histologic examination of FG1H5-reactive antigen using SCID mouse kidney showed positive stainings in the nucleus and glomerulus (mainly the mesangium). These positive stainings were abolished after the incubation of FG1H5 with ssDNA. The DNase I treatment of kidney sections markedly reduced the nuclear staining, but the staining of the glomerulus was preserved. Immunoprecipitation of a soluble fraction of SCID mouse kidney with FG1H5 revealed that FG1H5-reactive antigen in the glomerulus is an approximately 28-kilodalton molecule. When FG1H5 hybridoma cells were injected ip into SCID mice, the mice showed glomerulonephritis with the increases in mesangial cells and matrix as well as immunoglobulin M deposition mainly in the mesangium. CONCLUSIONS: Data demonstrate that FG1H5 binds strongly and specifically to ssDNA (but weakly and nonspecifically to MPO), and that ssDNA and MPO bind to each other. One monoclonal antibody reacts with both the nucleus and glomerulus (mainly the mesangium), and glomerular staining is not caused by nonspecific DNA binding. FG1H5, which binds to ssDNA, can induce glomerulonephritis, probably because of a direct crossreactivity to glomerular components.

Animals↗

[New technique of non-conduit repair for type III transposition of the great arteries: differences from Lecompte procedure and how to do it].

Lecompte reported in 1982 an innovative technique to reconstruct the pulmonary outflow tract without using prosthetic conduit in the transposition of the great arteries (TGA) with ventricular septal defect (VSD) and pulmonary stenosis (PS). In this group, however, the Lecompte procedure appears to have some difficulties translocating the pulmonary bifurcation anterior to the ascending aorta and unable to make a physiological right ventricular outflow tract preventing pulmonary valve regurgitation. A new technique now we present consists of following:(1) The main pulmonary trunk is transected subvalvularly and connected directly to the right ventriculotomy via the left side of the ascending aorta from behind and (2) intraventricular tunnel is made with prosthetic patch directing the left ventricular blood to the aorta via VSD and (3) right ventricular outflow tract is reconstructed with PTFE patch which bears a sinus-formed monocusp possessing corpora Arantii. Three consecutive patients, aged 5.8, 3.7 and 2.2 years, were treated by this technique, with excellent result. Transannular systolic pressure gradients ranged 4 to 20 mmHg (mean 10 mmHg) and each monocusp was highly competent preventing pulmonary regurgitation. All the patients were able to return home within a month after the operation. We conclude that the main pulmonary trunk can be directly connected to the right ventricle by the natural route if its full extent is efficiently utilized. This technique also facilitates the insertion of competent pulmonary valve which brings good result in the postoperative cardiac performance.

Cardiac Surgical Procedures↗