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Biomedical subjects

R Kasukawa

Publications and source records attributed to R Kasukawa.

At least 37 records · Page 2Linked to original sources

Analysis of biochemical and virological efficacy of human lymphoblastoid interferon (IFN) in patients with compensated type C liver cirrhosis: comparative study between increase in individual IFN dose and prolonging of treatment period, using a multicenter randomized controlled trial.

A controlled trial was conducted to compare the efficacy of interferon (IFN) between two groups of patients with type C liver. Thirty-five patients were randomly assigned to group A (17 patients) or group B (18 patients). The former received 3 megaunits (MU) of human lymphoblastoid IFN six days per week for two weeks, followed by three days per week for 50 weeks; the latter group received 6 MU six days per week for two weeks followed by three days per week for 24 weeks. The percentages of biological sustained responders (B-SR) and virological sustained responders (V-SR) were 29.4 and 23.5%, respectively, in group B, and 17.6% for both in group A. The therapeutic effects were not different between two groups. HCV genotype 2 accounted for significantly higher percentage of B-SR and V-SR (both 57.1%, respectively). These findings indicate that IFN is effective in type C cirrhosis with genotype 2.

Adult↗

Adherence of cyanoacrylate which leaked from gastric varices to the left renal vein during endoscopic injection sclerotherapy: a histopathologic study.

We report a case involving leakage of cyanoacrylate (CA) to the inferior vena cava (IVC) through a gastrorenal shunt and left renal vein. A 72-year-old man with liver cirrhosis was admitted to our hospital to undergo emergency treatment for massive hemorrhage of gastric varices. Endoscopic injection sclerotherapy (EIS) using CA was performed on the varices. Radiographic fluoroscopy revealed that most of the injected CA had adhered firmly to the gastric varices, but a certain portion of the CA had flowed to the IVC through the gastrorenal shunt and left renal vein. At that point, the patient did not complain of any symptoms. However, 6 months later, he died of hepatic failure and an autopsy was performed. Histopathologic examination of the wall of the IVC and renal vein, to which CA had adhered, revealed that the CA was covered with endothelial cells of the vessel and no nearby thrombus was present. Long-term anticoagulant therapy may not be indicated in cases of leakage of CA from the gastric varices to other veins, since the leaked CA may be readily covered with endothelium without thrombus formation as in our patient. It is possible for CA to flow to the IVC and have a fatal impact. Our patient was fortunate, and for safe EIS it is important that these complications are prevented.

Aged↗

Simultaneous measurements of serum alpha-fetoprotein and protein induced by vitamin K absence for detecting hepatocellular carcinoma. South Tohoku District Study Group.

OBJECTIVE: We evaluated the measurements of serum alpha-fetoprotein (AFP) and the protein induced by vitamin K absence (PIVKA-II) in 734 patients with chronic hepatitis (CH) and liver cirrhosis (LC) who had been followed-up for the development of hepatocellular carcinoma (HCC). METHODS: Serum AFP and PIVKA-II were measured every month and abdominal ultrasonography was performed every 3 months. Youden's index (sensitivity + specificity -1) was calculated. RESULTS: On an average follow-up period of 374.5 days, HCC was detected in three HBsAg-positive LC patients (10.0%/yr), four anti-HCV-positive CH patients (1.35%/yr), 21 anti-HCV-positive LC patients (7.8%/yr), and one patient with both HBsAg- and anti-HCV-positive LC (22.7%/yr). At the time of HCC detection, the size of HCC was 4.7+/-0.6 (mean +/- SD) cm in HBsAg-positive patients and 2.4+/-1.3 cm in anti-HCV-positive patents. Cut-off values of 20 ng/ml for AFP (Youden's index = 0.422) and 60 mAU/ml for PIVKA-II (Youden's index = 0.316) gave the highest index for each marker. When these two markers were combined, cut-off values of 40 ng/ml for AFP and 80 mAU/ml for PIVKA-II gave the highest index (Youden's index = 0.500, sensitivity = 65.5%, specificity = 85.5%, positive predictable value = 14.8%, negative predictable value = 98.3%). The levels of AFP or PIVKA-II increased within three months before the detection of HCC. CONCLUSIONS: Simultaneous measurements of serum AFP and PIVKA-II levels that are performed every 3 months are useful for detecting a developing HCC. The optimal cut-off values for AFP and PIVKA-II may be 40 ng/ml and 80 mAU/ml, respectively.

Adult↗

Athymic nude rats develop severe pulmonary hypertension following monocrotaline administration.

OBJECTIVE: To investigate the significance of the presence or absence of the thymus in the development of pulmonary hypertension (PH) following monocrotaline (MCT) administration, the degree of MCT-induced PH (MCT-PH) in athymic nude (F344/N Jcl-rnu) rats was compared with that in their euthymic (rnu/+) littermates. METHODS: Histopathological studies of the lung in terms of interstitial edema, congestion, thickening of the alveolar wall, inflammatory cell infiltration and degeneration of arteries were performed by staining with hematoxylin-eosin (HE), elastin van Gieson and Masson's trichrome. The medial wall thickness of the small pulmonary arteries and the weight ratio of the right ventricular free wall (RV) to that of the left ventricle plus septum [RV/(LV + S) weight ratio] were used as indices of the degree of PH. Toluidine blue staining was performed to estimate the number of the mast cells in the lung interstitium. RESULTS: Interstitial edema was significantly severer in MCT- injected euthymic rats than in MCT-injected athymic nude rats (p < 0.01); in contrast, the thickening of the alveolar wall was severer in MCT-injected athymic nude rats than in MCT-injected euthymic rats (p < 0.05). The degree of MCT-PH, as determined by the medial wall thickness of the small pulmonary arteries and RV/(LV + S) weight ratio in MCT-injected athymic nude rats, was significantly severer than in MCT-injected euthymic rats (p < 0.05 and p < 0.01, respectively). The number of mast cells was significantly greater in MCT-injected athymic nude rats than in MCT-injected euthymic rats (p < 0.01). The degree of the medial wall thickness of the small pulmonary arteries was significantly correlated with RV/(LV + S) weight ratio (p < 0.05) as well as with the number of mast cells in MCT-injected rats. CONCLUSIONS: Athymic nude rats developed severer PH than euthymic rats along with a greater number of mast cells and severer histopathological changes, such as thickening of the alveolar wall. Mast cell proliferation was considered to play a pivotal role in the development of PH in MCT-PH.

Animals↗

Sjögren's syndrome with primary biliary cirrhosis, complicated by transverse myelitis and malignant lymphoma.

A 53-year-old woman with Sjögren's syndrome (SS) and primary biliary cirrhosis (PBC) complicated by transverse myelitis (TM) and malignant lymphoma (ML) is reported. TM has been described only in seven cases of primary SS, including three with PBC and four without PBC. The features of SS associated with PBC and complicated by TM were less typical compared with those seen in SS without PBC complicated by TM. This case is the first report of a case with SS, PBC, TM and ML. SS in association with PBC is, in general, overlooked, but such cases must be investigated with great caution for extraglandular complications.

Abdomen↗

Magnetic resonance imaging findings in primary amyloidosis-associated arthropathy.

The MRI findings of amyloid arthropathy associated with primary amyloidosis are presented here possibly for the first time in the literature. Two types of lesions are noted: (1) capsular and tendon lesions; these regions are thickened, hypointense and enhanced by gadolinium (Gd) on T1 weighted imaging (T1WI), and hyperintense on T2 weighted imaging (T2WI), and (2) periarticular and osseous lesions; these regions appear to be tumor-forming and hypointense on both T1WI and T2WI and are not enhanced by Gd. It is necessary to differentiate these findings from other diseases such as chondrosarcoma, rhabdomyosarcoma and chronic inflammatory lesions such as tuberculosis.

Amyloidosis↗

Takayasu's arteritis in a 69 year-old woman.

Takayasu's arteritis and temporal arteritis share many clinical and pathological features. The most discriminatory feature between the two diseases is the age at onset; the mean age at onset of the disease was reported as being 26 years for Takayasu's arteritis and 69 years for temporal arteritis. Here we report a 69-year-old woman who presented with a weak right radial artery pulse. The ethnic background and the presence of vascular insufficiency of the right upper extremity and the absence of clinical signs such as shoulder stiffness and tender scalp indicate that her diagnosis is Takayasu's arteritis. It must be emphasized that the two conditions could be differentiated based on the clinical findings even in a patient as old as 69 years old.

Age of Onset↗

Primary antiphospholipid syndrome presenting with cerebral ischemia, thrombocytopenia, anemia and proteinuria successfully treated with warfarin potassium.

A 30-year-old woman with primary antiphospholipid syndrome (PAPS) presented with cerebral ischemia, thrombocytopenia, anemia and proteinuria. Administration of warfarin potassium, without concomitant corticosteroid administration, significantly improved all of these symptoms along with a decrease in the titers of antiCL-beta2-GP-I antibodies and a shortening of prolonged APTT. Therefore, the antiphospholipid antibodies in this patient could have been evoked by vitamin-K-dependent coagulation factors or plasma proteins which are assumed to undergo conformational changes exposing cryptic epitopes. This case report provides clues to the mechanisms underlying the production of antiphospholipid antibodies in patients with PAPS.

Adult↗

Atypical Cogan's syndrome successfully treated with corticosteroids and pulse cyclophosphamide therapy.

An 18-year-old woman was admitted to the medical center near her home with complaints of high fever and severe headache in June 1995. A diagnosis of adult-onset Still's disease was suspected and 50 mg/day of prednisolone was orally administered. In early April 1997, the patient suffered from sudden bilateral hearing loss and high fever. Pure tone audiogram taken at the same time showed an asymmetric bilateral neurosensorial hearing loss. A diagnosis of Cogan's syndrome was made. Administration of 60 mg prednisolone daily improved fever. Audiogram taken one month after administration of prednisolone showed improvement in the right ear. Monthly cyclophosphamide pulse therapy 700 mg combined with oral prednisolone was instituted. This combination therapy enabled the successful tapering of prednisolone without recurrence of hearing loss. Combined corticosteroid and pulse cyclophosphamide therapy would appear to be one effective regimen for Cogan's syndrome.

Adolescent↗

[DNA vaccines against allergy].

DNA vaccines induce a T-helper-1(Th1)-biased immune response through a Th1-promoting adjuvant effect of immunostimulatory DNA sequences(ISS) with unmethylated CpG motifs present in plasmid DNA. Th1 responses induced by DNA vaccines were shown to modify an ongoing Th2 immune response. This potency was explored as therapy for allergy and asthma. In murine models vaccination with plasmid DNA encoding an allergen reduced an ongoing IgE response to the allergen and lowered the levels of eosinophils in the lung after allergen challenge. Therefore DNA vaccines would be a widely appreciated application for allergic diseases.

Adjuvants, Immunologic↗

Suppression of collagen induced arthritis in mice utilizing plasmid DNA encoding interleukin 10.

OBJECTIVE: To investigate the therapeutic efficacy as well as the immunological effects of inoculation of an expression vector encoding interleukin 10 (IL-10) in murine type II collagen induced arthritis (CIA). METHODS: CIA was induced in DBA/1 Lac/J mice by immunization with bovine type II collagen (CII) in Freund's complete adjuvant (FCA), followed by immunization of CII in Freund's incomplete adjuvant (FIA) 3 weeks later (CIA mice). The plasmid cytomegalovirus (pCMV) vector encoding IL-10 (pCMV-IL-10) was inoculated intradermally into DBA/1 Lac/J mice (pCMV-IL-10 CIA mice) one week prior to first immunization with CII. CIA mice inoculated with the backbone pCMV vector instead of pCMV-IL-10(pCMV CIA mice), mice inoculated with the pCMV vector alone, without subsequent immunization with CII (pCMV-C mice), and mice not subjected to any treatment (C mice) were examined as controls. At the 3rd and 5th week after 2nd immunization with CII, booster injections of CII in FIA were administered. Foot pad thicknesses were measured weekly and the histopathological changes in the ankle joints and the titers of IgG1 (Th2 type) and IgG2a (Th1 type) isotype antibodies to CII were examined at the 10th week. RESULTS: pCMV-IL-10 CIA mice showed lesser foot pad thicknesses (p < 0.01 except at Weeks 1-3), less severe histopathological changes (p < 0.01 or 0.05) and lower IgG2a/IgG1 ratios of antibodies to CII (p <0.01) than CIA mice. CONCLUSION: Inoculation of pCMV-IL-10 suppressed CIA through suppression of the Th 1 type immune response in CIA, and offers promise as a potential therapeutic strategy for rheumatoid arthritis.

Animals↗

[Overlap syndrome].

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Amino Acyl-tRNA Synthetases↗

Adjuvant effect of a 14-member macrolide antibiotic on DNA vaccine.

Macrolide antibiotics have unique immunomodulatory actions apart from their antimicrobial properties. We examined the effect of erythromycin (EM), a 14-member macrolide, on the immune response to a DNA vaccine that induces a T-helper-1 (Th1)-biased immune response through a Th1-promoting adjuvant effect of unmethylated CpG motifs within plasmid DNA. EM enhanced Th1 responses in plasmid DNA-immunized mice as measured by antigen-specific IgG2a antibody production, interferon-gamma production by antigen-specific CD4(+) T cells, and cytotoxic T lymphocyte responses. EM augmented the accessory cell activity of unmethylated CpG DNA-stimulated antigen-presenting cells (APCs), suggesting that EM enhances Th1 responses to a DNA vaccine, possibly through augmentation of accessory cell activity of APCs stimulated with CpG motifs within plasmid DNA.

Adjuvants, Immunologic↗

Frequency of clonally expanded T cells evaluated by PCR from a single cell.

In analyses of antigen-specific immune responses, it is essential to estimate the frequency of individual T cell clonotypes. This frequency has been estimated, however, only indirectly by the frequency of T cell receptor (TCR) mRNA. We have developed a method to determine T cell frequency directly by cell count using reverse transcription polymerase chain reaction (RT-PCR) amplification of TCR beta genes from single cell-derived cDNA (single cell PCR). In a study of clinical samples, the frequency of clonally expanded T cells estimated by TCR frequency analysis was found to be higher than that by single cell PCR. Single cell PCR can estimate T cell frequency accurately, as it is not affected by skewed PCR amplification or different TCR mRNA expressions in individual T cells.

Arthritis, Rheumatoid↗