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Biomedical subjects

K Takasugi

Publications and source records attributed to K Takasugi.

At least 19 recordsLinked to original sources

Herpes simplex virus infection in adult patients after unrelated cord blood transplantation: a single-institute experience in Japan.

Herpes simplex virus (HSV) infection in adult patients who underwent cord blood transplantation (CBT) from unrelated donors was studied. None of nine HSV-seronegative patients developed HSV disease after CBT. Of 28 HSV-seropositive patients, seven (25%) developed HSV disease at a median of 92 days after CBT (range, 52-239 days). The cumulative incidence of HSV disease in HSV-seropositive patients was 27% at 12 months after CBT. The manifestations of HSV disease included gingivostomatitis (three patients), herpes labialis (two patients), localized herpes facialis of the nose (one patient), and disseminated eczema herpeticum (one patient). HSV disease recurred in two patients as gingivostomatitis and disseminated eczema herpeticum. All the patients responded to antiviral therapy. The presence of grade II-IV acute graft-versus-host disease (GVHD) was significantly associated with a higher rate of HSV disease after CBT (51 vs 8%, P=0.015). These results suggest that the recovery of HSV-specific immune responses is delayed in patients who develop grade II-IV acute GVHD after CBT.

Adult↗

Relative serum amyloid A (SAA) values: the influence of SAA1 genotypes and corticosteroid treatment in Japanese patients with rheumatoid arthritis.

OBJECTIVES: (1) To determine whether serum concentration of serum amyloid A (SAA) protein is influenced by the SAA1 allele in Japanese patients with rheumatoid arthritis (RA) as previously shown in a healthy control group; and (2) to analyse what factors, based on such an allelic bias, influence the relative SAA values of those patients. METHODS: SAA and C reactive protein (CRP) concentrations together with SAA1 genotypes were determined in 316 Japanese patients with RA. The relative SAA values were evaluated as an SAA/CRP ratio. RESULTS: Comparison of the three SAA1 homozygote groups showed that the SAA/CRP ratio was highest in the 1.5/1.5 group (mean 9.0, p<0.01 v the other two homozygote groups) followed by the 1.3/1.3 group (mean 7.2, NS v the 1.1/1.1 group) and the 1.1/1.1 group (mean 4.0). The SAA/CRP ratio was significantly higher in patients receiving corticosteroids regardless of the presence of allele 1.5. No clear differences in the ratio between patients with or without amyloidosis were found. CONCLUSION: The SAA1.5 allele and corticosteroid treatment had a positive influence on SAA concentrations in serum. These findings are important when evaluating SAA concentration in inflammatory diseases and when considering the cause or treatment of amyloidosis.

Adolescent↗

Neuroprotective action of a novel compound--M50463--in primary cultured neurons.

The neuroprotective effects of a novel synthetic compound, M50463, have been determined by using embryonic rat neocortical neurons in various culture conditions. M50463 was initially characterized as a potent specific ligand for a voltage-dependent sodium channel by radioligand binding studies. In fact, M50463 inhibited neuronal cell death induced by veratrine and inhibited an increase of the intracellular calcium level in neurons evoked by veratrine. In addition to such expected effects, M50463 had the ability to prevent glutamate neurotoxicity, to promote the neuronal survival in serum-deprived medium and to prevent nitric oxide-induced neurotoxicity. These results suggested that M50463 is not a simple sodium channel blocker, but a neuroprotective agent which has some crucial mechanism of action on neuronal death occurring in various situations, and it is a novel, innovative candidate for neuroprotective therapy for various neurodegenerative disorders.

Acetylcysteine↗

[Serum amyloid A (SAA) 1, SAA 2 and apolipoprotein E isotype frequencies in rheumatoid arthritis patients with AA amyloidosis].

OBJECTIVES: To examine the relationship between polymorphism of serum amyloid A (SAA) 1, SAA 2 and Apolipoprotein E (Apo E) and susceptibility to AA amyloidosis (AA) in rheumatoid arthritis (RA). METHODS: We compared the frequencies of SAA 1 alleles (alpha, beta, gamma), SAA 2 alleles (alpha, beta) and apo E alleles (epsilon 2, epsilon 3, epsilon 4) in AA-positive RA with those in AA-negative RA. Each isotype was analyzed by the following method: SAA 1 and SAA 2 by PCR-RFLP and Apo E by Western blotting method. Blood samples were obtained from 50 AA-positive RA patients with SAA 1 isotype, 50 AA-negative RA patients with SAA 1 isotype, 27 AA-positive RA patients with SAA 2 isotype, and 26 AA-negative RA patients with SAA 2 isotype, respectively. Likewise, Apo E isotype was determined by withdrawing blood samples from 61 AA-positive RA cases and 51 AA-negative RA cases. RESULTS: In AA-positive RA, each frequency of three different alleles of SAA 1, i.e., alpha, beta and gamma was 15%, 32% and 53%, while it was 32%, 28% and 40% in AA-negative RA. The allelic distribution between AA-positive RA group and AA-negative RA group was significantly different (P = 0.00163) with a lower frequency of alpha allele and a higher gamma allele frequency observed in AA-positive RA group. The frequency of each SAA 2 alleles (alpha & beta) was almost identical: 88.9% and 11.1% in AA-positive RA versus 90.4% and 9.6% in AA-negative RA with p value of 0.8007. Each frequency of three different Apo E alleles (epsilon 2, epsilon 3 & epsilon 4) was 4.9%, 85.2% and 9.8% in AA-positive RA, while in AA-negative RA it was 7.8%, 86.3% and 5.9%, respectively. The AA-positive RA group showed a slightly higher prevalence of epsilon 4 allele than the AA-negative RA group, yet the difference did not reach statistical significance (P = 0.3969). CONCLUSIONS: These results suggest the possibilities that SAA 1 alpha may be working protectively against and SAA 1 gamma provocatively for the development of AA amyloidosis in RA. However, there was no significant association between SAA 2 isotype patterns and the development of AA amyloidosis in RA. Furthermore, there was no discernible association between AA amyloidosis in RA and Apo E 4 isotype.

Amyloidosis↗

Correction of CAPD catheter displacement using gastric biopsy forceps: the push-pull method.

We corrected malpositioned continuous ambulatory peritoneal dialysis catheters in six patients using a new technique named the "push-pull method". A gastric biopsy forceps was advanced through the catheter to near its tip. After manipulating the tip of the forceps through the abdominal wall, the forceps was opened and pulled out slowly. Repeated insertion and removal of the forceps induced the catheter to return to the pelvic cavity. This push-pull method was successful for Swan neck straight (n=2) and coiled (n=4) catheters in all patients. The time required for the procedure was only 5-10 minutes and there were no complications.

Adult↗

Mixed Micellar Properties of Nonionic Saccharide and Anionic Fluorocarbon Surfactants in Aqueous Solution

Mixed micellar properties of nonionic saccharides (n-decyllactobionamide, C10Glu2; n-dodecyllactobionamide, C12Glu2) and anionic fluorocarbon surfactants (lithium perfluorooctanesulfonate, LiFOS) in aqueous solutions have been studied by means of surface tensiometry, NMR, and light scattering. The interaction parameters estimated from the modified regular solution theory are -5.0 for the C10Glu2/LiFOS system and -0.2 for the C12Glu2/LiFOS system. This difference could be due to the interaction of the surfactant tails. The average aggregation number is almost identical over a wide mole fraction of C12Glu2 for the C12Glu2/LiFOS system, while it shows a minimum at a C10Glu2 mole fraction of 0.4 for the C10Glu2/LiFOS system. It is also found from NMR measurements that the segmental motions of surfactants in the mixed micelles of C12Glu2 and LiFOS are not restricted, whereas they are restricted at a C10Glu2 mole fraction of 0.4 for the C10Glu2/LiFOS system. These motional changes as well as micellar composition reflect the solubilization of decafluorobiphenyl in the mixed micelles. Copyright 1998 Academic Press. Copyright 1998Academic Press

Journal Article↗

Identification of the gene loci that predispose to rheumatoid arthritis.

We have searched the human genome for genes that predispose to rheumatoid arthritis (RA) using fluorescence-based microsatellite marker analysis and affected sib-pair linkage study. A panel of 41 Japanese families, each with at least two affected siblings, was typed for genome-wide 358 polymorphic microsatellite marker loci. Markers were amplified by the PCR using fluorescence-tagged primers and sized based on the difference of CA repeats on DNA. Linkage analysis was made using maximum lod score (MLS). The MLS for D1S214 and D8S556 was 3.27 and 3.33, while the MLS for the HLA-DRB1 region was <3.0. According to detailed analysis by single-point analysis using MAPMAKER/SIBS, the MLS for D1S253 and D1S214 was 3.77 and 3.58. The MLS by multipoint analysis was 6.13 for D1S253. The MLS for D8S556 by single-point analysis was 4.20. The MLS for DXS1232 was 2.35 by single-point analysis, whereas the MLS for the region 2 cM right to DXS1232 and the region between DXS1227 and DXS1200 was 3.03 and 2.93 by multi-point analysis. Three principal chromosome regions of linkage, D1S253/214, D8S556 and DXS1232, have been identified which we call RA1, RA2 and RA3 for RA disease loci.

Arthritis, Rheumatoid↗

Decreased serum apolipoprotein AII/AI ratio in systemic amyloidosis.

OBJECTIVE: To investigate if serum apolipoprotein A-I and A-II (apoAI and apAII) concentrations change in subjects with systemic amyloidosis secondary to underlying disorders. METHODS: Serum concentrations of apoAI and apoAII were measured in 21 multiple myeloma patients, including eight with amyloidosis; 95 rheumatoid arthritis patients, including 45 with amyloidosis; and 73 haemodialysis patients, including 32 with amyloidosis. RESULTS: ApoAII values tended to be reduced in subjects with amyloidosis in each group, but could not effectively distinguish amyloidosis. However, apoAII/AI ratios were significantly lower in subjects with amyloidosis in all groups. The ratio of 0.2 had diagnostic sensitivity and specificity for amyloidosis; 50% and 100%, respectively, in multiple myeloma; 80% and 78%, respectively, in rheumatoid arthritis; and 46% and 90%, respectively, in patients requiring long term haemodialysis. CONCLUSION: The apoAII/AI ratio can be a useful biochemical marker of suspect amyloidosis in patients with underlying diseases, especially those with rheumatoid arthritis.

Amyloidosis↗

Detection of interstitial pneumonitis in patients with rheumatoid arthritis by measuring circulating levels of KL-6, a human MUC1 mucin.

In rheumatoid arthritis (RA), interstitial-pneumonitis is one of the major extraarticular complications that worsens a patient's prognosis. KL-6, a human MUC1 mucin, has been reported to be a sensitive serum marker for activity of interstitial pneumonitis. We investigated the clinical significance of serum KL-6 level in patients with RA. Serum levels of KL-6 and RA-associated inflammatory markers were evaluated in 177 RA patients. The diagnosis of active interstitial pneumonitis was made by clinical symptoms, pulmonary function tests, chest X-ray film, and high resolution CT. Serum KL-6 was increased in 8 of 9 (88.9%) RA patients with active interstitial pneumonitis but in only 1 of 168 (0.6%) RA patients without active interstitial pneumonitis. No significant correlation was found between KL-6 level and conventional clinical parameters. In RA, abnormal elevation of serum KL-6 strongly indicates the complication of active interstitial pneumonitis.

Adult↗

Intractable diarrhoea associated with secondary amyloidosis in rheumatoid arthritis.

OBJECTIVE: To examine the clinical characteristics of intractable diarrhoea associated with secondary amyloidosis in rheumatoid arthritis (RA). METHODS: Of 179 RA patients with biopsy confirmed secondary amyloidosis, 24 cases (23 women and one man) with intractable diarrhoea lasting for more than one month were retrospectively evaluated. RESULTS: The mean (SD) duration of diarrhoea was 87 (64) days. Prodromal symptoms of gastrointestinal dysfunction (n = 21) and impaired peristalsis (n = 16) were observed. Laboratory data showed hypoproteinaemia (4.7 (0.85) g/dl) caused by malabsorption or protein loss and high values of C reactive protein (17.0 (9.3) mg/dl). Recurrence of intractable diarrhoea (n = 4) and transition from intractable diarrhoea to other gastrointestinal problems of amyloidosis (ischaemic colitis (n = 2) and intestinal pseudo-obstruction (n = 4)) were observed. In 19 patients (25 episodes) the duration of intravenous hyperalimentation at remission (18 episodes) was 68 (52) days. Corticosteroid pulse therapy was administered to 10 patients (11 times) and the time elapsed from the end of corticosteroid pulse therapy to the end of diarrhoea was 18 (14) days. One and five year survival rates after the onset of intractable diarrhoea were 73.4% and 38.9%. Seven of 13 patients (54%) had died as a result of infectious diseases. CONCLUSION: Intractable diarrhoea associated with secondary amyloidosis in RA is a serious clinical entity and the prognosis is poor. Although it is assumed that intravenous hyperalimentation treatment and corticosteroid pulse therapy are favourable regimens for intractable diarrhoea, the patients should be monitored for possible infectious complications.

Adult↗

Secondary amyloidosis in patients with rheumatoid arthritis: diagnostic and prognostic value of gastroduodenal biopsy.

Upper gastrointestinal endoscopy was performed in patients with rheumatoid arthritis (RA) during the period 1989-1991, and biopsy specimens were obtained from the stomach and from the duodenum for examining amyloid deposits. Among 407 patients, gastrointestinal amyloidosis was confirmed in 54 (13.3%). Twenty-two patients were regarded as having slight amyloid deposits, while 32 patients were categorized as having marked amyloid deposits. The incidence of clinical manifestations suggestive of systemic amyloidosis was more frequent in the marked deposits group than in the slight deposits group (47% vs 14%, P<0.05). Among the patients who died of manifestations associated with amyloidosis, the survival period following endoscopy was shorter in the marked deposits group than in the slight deposits group. These findings suggest that gastroduodenal biopsies may be useful for diagnosing secondary amyloidosis and that the degree of amyloid deposits seems to be correlated with the clinical manifestations of RA.

Amyloid↗

[Clinical characteristics and genetic background of secondary amyloidosis associated with rheumatoid arthritis in Japanese].

In order to examine the clinical characteristics and genetic background of secondary amyloidosis associated with rheumatoid arthritis, we analyzed clinical features and HLA typing of 85 patients in a multicenter study. Eighty-five patients with secondary amyloidosis associated RA were studied. The diagnosis of secondary amyloidosis were made on histological findings by biopsy or autopsy. The most common biopsy site was gastrointestinal tract (79.5%). Clinical symptom and the frequency at the time of diagnosis were; diarrhea (35 cases), abdominal pain (22 cases) and vomiting and nausea (16 cases). Abnormalities and the frequency in a laboratory test included proteinuria (49 cases), increased serum creatinine (32 cases), anemia (30 cases) and hematuria (15 cases). Twenty-eight patients were dead and 57 patients were alive at the time of the study. The average duration between diagnosis of amyloidosis and death was 19.4 +/- 18.5 (SD) months among the dead patients. The average duration after diagnosis of amyloidosis was 24.2 +/- 19.5 (SD) months in surviving patients. The causes of death were renal failure complicated with heart failure (6 patients), heart failure alone (3 patients) and renal failure alone (2 patients). Fifty-nine patients in the control group who were negative to amyloid deposition on biopsies at more than one site in the gastrointestinal tract, were clinically compared with patients in the amyloidosis group. No difference were noted in the age of RA occurrence and the stage between the two groups. As to the class, however, the number of patients with severe functional disorder (class 3 or severe) was larger in the amyloidosis group. There were no significant difference between the two groups in Lansbury's activity index. On hematology, biochemistry and urinalysis, the incidences of increased white blood cell count, anemia, increased platelet count, increased serum creatinine, hypoproteinemia, hypoalbuminemia, increased IgA, and increased urine and blood BMG were statistically significantly higher in the amyloidosis group than in the control group. HLA-A, -B, -C, and DR-locus antigens were compared in the 53 patients in the amyloidosis group and in the 59 subjects in the control group. There were no significant differences in frequency of HLA-A, and -B antigens between two groups. Frequency of CW7 antigen was significantly decreased in the amyloidosis group (13.2%) than in the control group (39.0%). Frequency of DR1 antigen was decreased in the amyloidosis group (3.8%) than in the control group (22.0%), although the difference was not significant. These findings suggest the possible involvement of genetic factors in the occurrence of amyloidosis. It is suggested that the occurrence of amyloidosis is suppressed by some genes which are linked with CW7 antigen.

Adolescent↗

[Incidence of cancer among Japanese patients with rheumatoid arthritis].

Most follow-up studies of patients with rheumatoid arthritis demonstrate no increase in the incidence of cancer apart from approximate doubling of the incidence of lymphoproliferative malignancies. A consecutive series of 1832 Japanese patients with rheumatoid arthritis seen at the center was studied to determine their cancer morbidity. Overall, 35 cancers were diagnosed in the series from 1982 through 1995 and were not significantly in excess of the expected number. No association was found between rheumatoid arthritis and subsequent development of cancer at any site, either.

Aged↗

[Effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate on low density lipoprotein in rabbits].

The hypolipidemic effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E) on cholesterol diet-fed rabbits were studied. EPA-E (300 mg/kg, p.o. x 4 weeks) decreased total cholesterols in the lipoprotein fractions of very low-density lipoprotein and intermediate lipoprotein+low-density lipoprotein (LDL), but not in high-density lipoprotein. Furthermore, the properties of LDL were investigated in rabbits given EPA-E (300 mg/kg, p.o. x 2 weeks). EPA-E had no influence on the lipid composition in LDL, and the cholesterol accumulation into macrophages was not increased by the incubation with EPA-E-treated LDL. However, the omega 3 polyunsaturated fatty acids contents of LDL were increased by the administration of EPA-E. EPA-E-treated LDL was also studied on the binding to the hepatic membranes. The binding of EPA-E-treated LDL to the hepatic membranes was higher than that of ordinary LDL. These results suggest that EPA-E causes a modification of LDL, such that EPA-E has an enhancing effect on the hepatic uptake of LDL. These effects may contribute to the hypolipidemic action of EPA-E.

Animals↗

[Pneumocystis carinii pneumonia associated with low dose methotrexate treatment for malignant rheumatoid arthritis].

Low dose pulse methotrexate (MTX) has become a widely used therapy for rheumatoid arthritis (RA) because of its good response rate profile. With the increased use of MTX, reports of opportunistic infections associated with MTX therapy have appeared. Fourteen cases of pneumocystis carinii (PC) pneumonia in patients receiving low dose MTX have been previously reported. Yet, no case of PC pneumonia associated with low dose MTX has so far been reported in Japan. We report the first case in Japan of PC pneumonia occurring in a patient with rheumatoid vasculitis who was receiving low dose MTX. A 70-year old woman with 13 year history of RA presented with 3-day history of rapidly aggravating dyspnea, dry cough and fever. She had been receiving MTX 7.5 mg/week for 2.5 months because of her vasculitis symptoms. She had also been receiving prednisolone 7.5 mg/day which had been successfully tapered from an initial dose of 15 mg/day. At the time of her presentation with respiratory symptoms, all of her vasculitis symptoms had been alleviated. A chest radiograph revealed diffuse interstitial shadowing bilaterally and bilateral hilar and right lower lung field infiltrates. Her arterial blood gas showed severe hypoxemia (PaO2 27.7 torr). Polymerase chain reaction assay of bronchoalveolar lavage fluid showed PC. Although the patient required ventilatory support for 9 days, she was successfully treated with trimethoprime-sulphamethoxazole and methylprednisolone pulse therapy. Eight months later, the patient was well with no evidence of vasculitis or respiratory symptoms.

Aged↗