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Biomedical subjects

A Noguchi

Publications and source records attributed to A Noguchi.

At least 37 records · Page 2Linked to original sources

Elevation of serum hepatic aminotransferases during treatment of rheumatoid arthritis with low-dose methotrexate. Risk factors and response to folic acid.

Sixty-six rheumatoid arthritis (RA) patients were analyzed retrospectively to assess the incidence and risk factors for elevation of serum hepatic aminotransferases during methotrexate (MTX) therapy. The effect of folate supplementation on serum ALT and RA activity was evaluated prospectively in 14 patients who showed a sustained high serum level of ALT. The frequency of elevation of serum AST or ALT was 4-5 times greater than in patients taking other DMARDs. Multivariate linear regression analysis demonstrated that elevation of ALT was independently associated with sex (female), obesity, baseline ALT, MTX dose, and gastrointestinal side effects. Folate supplementation caused ALT levels to decrease in all patients within 3 months. Eleven patients showed no change of RA activity, but 3 patients dropped out of the study because of the exacerbation of RA. These results suggest that careful monitoring of serum hepatic aminotransferases is necessary in patients with predisposing factors, especially those receiving more than 0.15 mg/kg of MTX weekly. Folate supplementation can reverse the sustained elevation of ALT, but might cause exacerbation of RA in some patients.

Adrenal Cortex Hormones↗

Serum biochemical values in two inbred strains of mastomys (Praomys coucha).

Serum samples collected from 119 (72 male and 47 female) mastomys (Praomys coucha) of 2 specific-pathogen-free inbred strains (RI4 and RI7) were analyzed for 12 serum biochemical parameters. Sex-related differences (p < 0.01) were noted in alkaline phosphatase and glucose; the both higher in females than in males. Age-related changes (p < 0.01) were observed in total protein, albumin, total cholesterol, and alkaline phosphatase, with higher values for the first three parameters in the older group (200-250 days of age) than in the younger group (90-140 days of age). Four out of 12 parameters showed strain-related differences (p < 0.01), consistent with the large amount of genetic heterogeneity reported in this species. These serum biochemical reference values should provide information for the use of mastomys in laboratory research.

Animals↗

[A method for improving the accuracy in measurement of 99mTc-GSA liver uptake].

In order to improve the accuracy in the measurement of liver uptake rate of radioactivity at 15 minutes after injection of 99mTc-GSA, the corrected liver uptake rate (LU15VW) for tissue attenuation of gamma ray was measured. On the basis of the results of phantom studies, LU15VW was obtained as a ratio of the liver counts to the calculated counts of the injected dose supposed to homogeneously distribute in the liver of each patient and to decrease in count rate by the tissue attenuation of gamma ray, which was caused by the liver itself and body wall. The values of LU15VW were compared with those of the other 99mTc-GSA indices (LU15, LHL15, and HH15) and of the laboratory tests of liver function in 5 patients with chronic persistent hepatitis (CPH), 25 patients with chronic active hepatitis (CAH) 2A, 8 with CAH 2B, 8 with liver cirrhosis (LC), and 20 with hepatocellular carcinoma. LU15VW showed a good correlation with LU15, LHL15, and HH15 (r = 0.912, 0.864, and -0.869). The relationships between the results of LU15VW and the laboratory tests of liver function such as ICGR15, serum albumin, platelets counts, and hepaplastin test (r = -0.800, 0.684, 0.599, and 0.465) were more excellent as compared with those between the results of the other 99mTc-GSA indices and the laboratory tests. LU15VW was distinctly different in the mean values among the three groups of patients with CAH 2A, CAH 2B, and LC. These results indicated that LU15VW was an useful method for improvement of the accuracy in the measurement of liver uptake rate of 99mTc-GSA.

Humans↗

[A case of spontaneous pyeloduodenal fistula].

A 61-year-old woman visited our hospital complaining of right flank pain and fever. The radiograph demonstrated multiple renal calculi. Radio renography showed no uptake in the right kidney. Therefore, we diagnosed her with pyonephrosis, and recommended open nephrectomy. However, she selected the conservative treatment with extra corporeal shockwave lithotripsy (ESWL). In spite of disappearance of multiple calculi, pyuria continued for 3 months after ESWL. Retrograde pyelography showed a fistula from the right pelvis into the duodenum. The patient was successfully treated by nephrectomy and duodeno-fistelectomy.

Duodenal Diseases↗

[Pheochromocytoma of the urinary bladder: a case report].

A 49-year-old man was hospitalized with the chief complaint of coagulation in urine. The patient was not hypertensive. Cystoscopic examination showed a submucosal tumor in the left lateral wall of the bladder. A transurethral sonogram revealed a low echoic nodule. Transurethral resection of the tumor in the urinary bladder was performed. The histopathological diagnosis indicated pheochromocytoma. Blood pressure was stable. After operation, the patient's course was uneventful, and there has been no recurrence for one year after surgery. This patient is the 52nd patient with pheochromocytoma of the urinary bladder reported in the Japanese literature.

Follow-Up Studies↗

Membrane fusion plays an important role in gene transfection mediated by cationic liposomes.

By confocal laser scanning microscopy (CLSM) we have studied the membrane fusion between cationic liposomes and the endosome membranes involved in gene transfection mediated by cationic liposomes. Antisense oligonucleotides were transferred by cationic liposomes with a cationic cholesterol derivative, cholesteryl-3beta-carboxyamidoethylenedimethylamine (I). Cationic liposomes were made by a mixture of the derivative I and DOPE. The intracellular distribution of fluorescein-conjugated antisense oligonucleotides (phosphorothioate) was studied by CLSM. The images showed that the antisense oligonucleotides were preferentially transferred into the nucleus of target cells (NIH3T3, COS-7 and HeLa cells) by the liposomes with derivative I. However, their transfection was completely blocked by nigericin which was able to dissipate the pH gradient across the endosome membranes, although the liposome/DNA complex was found in the cytoplasm of the target cells. This was quite in contrast with the fluorescence images of the target cells treated with wortmannin, an inhibitor of endocytosis. The results suggest that at least two steps are effective for gene transfection mediated by the cationic liposomes with cationic cholesterol derivatives. One is the endocytosis of the liposome/DNA complex into the target cells and the other is the removal of antisense oligonucleotides (plasmid DNAs) from the complex in the endosomes. The latter step was preferentially preceded by the membrane fusion between the cationic liposomes and the endosome membranes at around pH 5.0.

3T3 Cells↗

Enhanced engraftment of human peripheral blood lymphocytes into anti-murine interferon-gamma monoclonal antibody-treated C.B.-17-scid mice.

To improve the engraftment of human peripheral blood lymphocytes (PBL) to severe combined immunodeficient (SCID) mice, and to elucidate the factors which prevent the PBL's survival, we treated SCID mice with mAb, which neutralizes murine IFN-gamma's ability to activate cell-mediated immunity. Compared with untreated mice, mAb-treated mice retained significantly higher numbers and ratios of human PBL in the peritoneal cavity and spleen, as well as significantly higher serum titers of human IgG and IgM. Histologically, host versus graft reaction (HVGR) was less severe in the mAb-treated mice. Moreover, these phenomena were completely abrogated when mice were also treated with murine recombinant IFN-gamma. These results suggest that murine IFN-gamma plays an important role in the rejection of human cells in SCID mice and that its depletion by means of mAb treatment can significantly reduce HVGR and improve the engraftment of human PBL.

Animals↗

Atomic force microscopy for studying gene transfection mediated by cationic liposomes with a cationic cholesterol derivative.

Atomic force microscopy (AFM) was used for studying gene transfection mediated by cationic liposomes which contain a cationic cholesterol derivative with a different spacer arm. Cationic liposomes were made by a mixture of one of eight cationic cholesterol derivatives and 1,2-dioleoyl-sn-glycero-3-phosphatidyl ethanolamine (DOPE). AFM images showed that vesicles made of the liposome/DNA complex had various diameters depending on each cationic cholesterol derivative with a different spacer arm. The results showed that the diameter of the liposome/DNA complex was well related to the transfection activity of plasmid pSV2CAT DNA to a cultured cell line (NIH3T3). From the results it was found that the vesicles with moderate diameters (from 0.4 to 1.4 microm) were moste effective for gene transfection of plasmid pSV2CAT DNA into the target cell. Neither smaller vesicles (< 400 nm) nor larger vesicles (> 1.4 microm) were adequate for gene transfection. As the gene transfection by the cationic liposomes was mostly inhibited by wortmannin, an inhibitor of endocytosis, it is suggested that the vesicles with moderate diameters were useful for gene transfection by endocytosis.

3T3 Cells↗

Heating rate of egg albumin solution and its change during Ohmic heating.

Ohmic heating of egg albumin solution (10 w/v%) was examined at 50-10 kHz under a constant 10 V/cm. The heating rate of the solution was almost constant and increased slightly as the frequency increased. The gel formation was observed at about 75 degrees C and the heating rate increased above this temperature irrespective of the frequency used. The solution and gel showed almost the same impedance at the examined temperature (20-90 degrees C) and frequency (10 Hz-100 kHz). When the concentration of egg albumin was reduced to 2 w/v%, no gel was formed and a constant heating rate at over 75 degrees C was observed. The breaking strength of the gels showed little difference among the gels prepared by boiling water or Ohmic heating. These results suggest that the liquid components are not compartmentalized in the gel and that the sudden increase of heating rate above 75 degrees C was caused by the reduction of heat transfer of the gel at its phase change to the gel. Ohmic heating was also applied to the fresh egg white at the same conditions as that of the egg albumin solution. The fresh egg white did not show any sudden increase of heating rate until it reached 90 degrees C. However, the homogenized fresh egg white and its soluble part separated beforehand showed a slightly reduced heating rate and a sudden increase at about 60 degrees C. These results suggest that the gelatinous component of fresh egg white such as ovomucin represses the transfer of generated heat during Ohmic heating.

Animals↗

Peritoneal macrophages play an important role in eliminating human cells from severe combined immunodeficient mice transplanted with human peripheral blood lymphocytes.

To elucidate the mechanism of human cell elimination from severe combined immunodeficient (SCID) mice transplanted with human peripheral blood lymphocytes (hu-PBL-SCID mice), we explored the immunocytes in the peritoneal cavity in SCID mice where human PBL were transferred. When the phenotype of peritoneal exudate cells (PEC) was compared by flow cytometry among three congenic strains of SCID mice that differ in their acceptability for human PBL, the PEC in NOD-scid mice, which exhibit the highest acceptability, contained the smallest number of F4/80lo/-Mac-1(+)-activated macrophages. Moreover, the proportions of natural killer cells in PEC of the three strains of SCID mice were not always correlated with the acceptability. These findings suggest the possibility that peritoneal macrophages eliminate human cells in hu-PBL-SCID mice. To verify this hypothesis, we evaluated the engraftment of human PBL into SCID mice that were treated with liposome-encapsulated dichloromethylene diphosphonate, which selectively depletes macrophages by inducing apoptosis, or 8-aminoguanidine hemisulphate salt, an inhibitor of inducible nitric oxide synthase of macrophages. As a result, both of these regimens improved engraftment of human PBL, indicating that peritoneal macrophages take part in human cell elimination in the peritoneal cavity of hu-PBL-SCID mice and that it is mediated, at least in part, by direct macrophage cytotoxicity utilizing nitric oxide.

Animals↗

[Clinical relapse of rheumatoid arthritis (escape phenomenon) during low-dose methotrexate therapy].

OBJECTIVE: To clarify the incidence and background of clinical relapse (escape phenomenon) during low-dose methotrexate therapy for rheumatoid arthritis. METHODS: Seventy one patients with rheumatoid arthritis (RA) were analyzed. They were started on therapy with methotrexate (MTX) between April 1, 1991 and May 30, 1995. Among them, 60 patients showed clinical improvement within 6 months after the start of the therapy and were subjected to the analysis for clinical relapse (escape phenomenon). RESULTS: Twelve patients showed an initial improvement followed by a relapse with increased serum CRP and number of painful joints despite the MTX therapy was continued. Two types of the relapses were seen; (1) early, escape (relapse after an initial brief improvement) in 7 patients, and (2) late escape (relapse after a long-term improvement with MTX therapy) in 5 patients. The early escape was seen at 9.0 +/- 0.7 months after the start of therapy while the late escape was seen at 23.3 +/- 4.8 months. Patients with both types of escape phenomenon had the longer duration of the disease and more advanced stage. There was no relationship between clinical relapse and age, baseline RA activity, MTX dose, or concurrent use of corticosteroids and other disease modifying anti-rheumatic drugs. The efficacy of MTX for RA was restored by increasing dose of MTX in 11 patients. CONCLUSION: These results suggest that clinical relapse is not rare in RA patients during low-dose methotrexate therapy, but could be improved by increasing dose.

Antirheumatic Agents↗

[A surgical case of cervical canal stenosis caused by atlas hypoplasia in an elderly patient].

We report an 81-year-old man with hypoplastic atlas resulting in a severe stiff feeling in the bilateral shoulders, spastic tetraparesis, and hypesthesia below the C2 segment level of the spinal cord. These symptoms are compatible with compression of the high cervical cord. Neuroimaging studies revealed a narrowing of the spinal cord by compression of the hypoplastic atlas. Laminoplasty of the atlas was performed under general anesthesia, and the patient's symptoms were resolved. Operated cases of older patient's with atlas hypoplasia have been rarely reported. Laminoplasty of the atlas is a safe and useful procedure for high cervical compression due to hypoplastic atlas.

Aged↗

Chylothorax in a polysplenia infant with cor triatriatum, pulmonary stenosis and sick sinus syndrome.

An infant with chylothorax and polysplenia is described. Her chylothorax was refractory and related to right-sided heart failure derived from pulmonary stenosis, cor triatriatum, and sick sinus syndrome. In addition to Brock operation and cardiac pacing, thoracic duct ligation was performed, but it resulted in an only transient amelioration of the chylothorax. Eventually, the chylothorax resolved when total cardiac repair was performed for cor triatriatum. We propose that, in a patient with chylothorax and right-sided heart failure caused by compound cardiac malformations, as in this patient early surgical treatment for the underlying disease of right-sided heart failure should be considered.

Chylothorax↗

Characterization of CD4+CD8+ thymocytes observed in SCID-bg mice.

Previously, we reported that a strain of severe combined immunodeficient (SCID) mice, namely SCID-bg, spontaneously develop CD4+CD8+ double positive (DP) thymocytes despite their scid mutation. In the present study, we intend to further characterize the DP thymocyte population in SCID-bg mice with Southern hybridization and flow cytometry. Southern hybridization analyses of sorted DP thymocytes in SCID-bg mice showed rearrangement of T cell receptor (TCR) beta and TCR gamma gene segments, although the expression of TCR beta and gamma delta TCR molecules was absent. The phenotype of the DP thymocytes in SCID-bg mice was CD44- heat-stable antigen (HSA)+CD25-, and they did not express CD69. Interestingly, the expression of thymus leukaemia (TL) antigen was observed in the DP thymocytes of SCID-bg mice but not in their CD4-CD8- double negative (DN) fraction. Fas expression was higher and bcl-2 expression was down-regulated in the DP thymocytes as compared to the DN thymocytes in SCID-bg mice, suggesting that they are not immortalized cells having escaped from apoptosis. Taken together, these results show that the phenotype of the DP thymocytes in SCID-bg mice is similar to that of the earliest phase of the DP thymocytes in normal mice, although the expression of the molecules in the pre-TCR complex is absent.

Animals↗

CD4 and CD8 expressions in African green monkey helper T lymphocytes: implication for resistance to SIV infection.

We found that most peripheral CD4 cells co-express a low density of CD8 alpha antigen in African green monkeys (AGM). Further, the cell surface expression of CD4 and the expression of CD4 mRNA underwent a decrease when purified CD4CD8low cells were cultured with mitogen and IL-2. These observations suggest that AGM CD4 cells are subject to loss of CD4 expression after lymphocyte activation. Part of the peripheral CD8 fraction exhibited a significant helper activity which suggested the phenotypic conversion in helper T cells from CD4+ to CD4- in vivo. Simian immunodeficiency virus (SIV) grew well in CD4 panning cells following SIV infection. In contrast, CD4CD8low cells were resistant to SIV infection after their conversion to CD4- cells.

Animals↗

The influence of the wider use of surfactant therapy on neonatal mortality among blacks and whites.

BACKGROUND: Surfactant therapy reduces morbidity and mortality among premature infants with the respiratory distress syndrome (RDS). Fetal pulmonary surfactant matures more slowly in white than in black fetuses, and therefore RDS is more prevalent among whites than among blacks. We reasoned that the increased use of surfactant after its approval by the Food and Drug Administration (FDA) in 1990 might have reduced neonatal mortality more among whites than among blacks. METHODS: We merged vital-statistics information for all 1563 infants with very low birth weights (500 to 1500 g) born from 1987 through 1989 or in 1991 and 1992 to residents of St. Louis with clinical data from the four neonatal intensive care units in the St. Louis area; we then compared neonatal mortality during two periods, one before and one after the FDA's approval of surfactant for clinical use (1987 through 1989 and 1991 through 1992). RESULTS: The use of surfactant increased by a factor of 10 between 1987 through 1989 and 1991 through 1992. The neonatal mortality rate among all very-low-birth-weight infants decreased 17 percent, from 220.3 deaths per 1000 very-low-birth-weight babies born alive (in 1987 through 1989) to 183.9 per 1000 (in 1991 through 1992; P = 0.07). This decrease was due to a 41 percent reduction in the mortality rate among white newborns with very low birth weights (from 261.5 per 1000 to 155.5 per 1000; P = 0.003). In contrast, among black infants, the mortality rate for very-low-birth-weight infants did not change significantly (195.6 per 1000 and 196.8 per 1000). The relative risk of death among black newborns with very low birth weights as compared with white newborns with similar weights was 0.7 from 1987 through 1989 and 1.3 from 1991 through 1992 (P = 0.02). The differences in mortality were not explained by differences in access to surfactant therapy, by differences in mortality between black and white infants who received surfactant, or by differences in the use of antenatal corticosteroid therapy. CONCLUSIONS: After surfactant therapy for RDS became generally available, neonatal mortality improved more for white than for black infants with very low birth weights.

Adrenal Cortex Hormones↗

Transient expression of CD20 antigen (pan B cell marker) in activated lymph node T cells.

In contrast to the case of peripheral T cells, the surface expression of CD20 antigen and the expression of CD20 mRNA in monkey lymph node (LN) T cells underwent a noticeable increase when they were cultured with mitogen and interleukin-2 (IL-2). To confirm in vivo regulation of CD20 expression during the activation of LN T cells, we examined LNs derived from monkeys experimentally inoculated with simian immunodeficiency virus (SIV). Significant expression of CD20 antigen was detected in the T cells of the LNs at the stage of lymphadenopathy. These findings suggest that lymphocyte activation in the LNs induced expression of the CD20 molecule in some T cells.

Animals↗