[Clinical evaluation of positive- and negative-stranded HCV-RNAs in liver in relation to IFN therapy].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to K Hino.
Explore the source record for details and available documents.
Increased levels of soluble interleukin-2 receptor (sIL-2R) have been noted in the sera of patients with various diseases such as adult T cell leukemia, malignant lymphoma and autoimmune diseases. Using an enzyme-linked immunoabsorbent assay, we assessed sIL-2R levels in the sera of 16 patients with multiple myeloma (MM) and 27 normal subjects. There was a significant increase in the levels of sIL-2R in the patients with myeloma (963 +/- 523 U/ml) compared to normal subjects (213 +/- 80 U/ml). The levels of sIL-2R corresponded well with the clinical stage, M-protein, serum IL-6 and serum beta 2 microglobulin levels. Taking the evidence that the CD4/CD8 ratio decreased as the disease worsened into consideration, the increase in the serum sIL-2R levels of the patients with MM is considered to have some correlation with B and T cell activation through various cytokines including IL-6. Furthermore such evidence would support the role of sIL-2R as a disease monitor of MM.
Explore the source record for details and available documents.
Cloning of a cDNA from Cry j II, the second major allergen from Japanese cedar (Cryptomeria japonica) pollen, is described. An isolated Cry j II cDNA contained an open reading frame coding for 514 amino acid residues. The mature Cry j II protein consisted of 388 amino acid residues (R46-S433). According to a homology analysis, no amino acid sequence homology was observed between Cry j II and Cry j I, another major allergen. But Cry j II showed homology with polygalacturonase (PG) derived from tomato (40% identity) at the amino acid level. The sequence information can potentially be used to devise an effective course of immunotherapy for Japanese cedar pollinosis.
BACKGROUND: Although there are case reports of vertical transmission of hepatitis C virus (HCV), it remains uncertain to what extent infected mothers transmit this virus to their infants. METHODS: We investigated the transmission of HCV from infected mothers to their babies by analyzing HCV RNA in the blood. Three independent studies were performed. First, 7698 parturient women were tested for anti-HCV antibodies; 53 were positive. Their 54 infants (including one set of twins) were followed prospectively for at least six months and tested for HCV disease were prospectively studied. Third, the families of three HCV-infected infants were examined retrospectively. RESULTS: Of the 53 antibody-positive mothers, 31 were also positive for serum HCV RNA: Three of the 54 babies born to these mothers (5.6 percent) became positive for HCV RNA during the follow-up period. None of the babies of the 22 women who were antibody-positive but HCV RNA-negative became positive for HCV RNA: In the second study, HCV RNA was detected in one of the six infants of infected mothers. In the third study, HCV RNA was detected in the mothers of the three HCV-infected infants. In each of the seven infected infants we studied, the genomic sequence of HCV was almost identical to that from the mother. These seven mothers had significantly higher titers of HCV RNA than did the mothers of infants with no evidence of infection (mean [+/- SD], 10(6.4 +/- 0.5) vs. 10(4.4 +/- 1.5) per milliliter; P < 0.001). CONCLUSIONS: HCV is vertically transmitted from mother to infant, and the risk of transmission is correlated with the titer of HCV RNA in the mother.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Interferon induces remission in about 50% of patients with chronic hepatitis C, but it is difficult to predict which patients will respond. Host and viral factors were evaluated for correlation with response to interferon in patients with chronic hepatitis C. Recombinant interferon alpha-2b with a total dose of 480-560 million units was given to 136 patients, of whom 74 (54%) responded. Genotypes of hepatitis C virus (HCV) in sera, I, II, III, IV, and V, were determined by polymerase chain reaction (PCR) with type-specific primers. In 72 patients, pretreatment levels of HCV RNA were titrated by PCR in serial tenfold dilutions of RNA extracted from serum. Response to interferon occurred in 34 (40%) of 85 patients infected with HCV of genotype II, less frequently than in 22 (85%) of 26 with genotype III (P < 0.001) or in 7 (70%) of 10 with genotype IV. Of 51 patients with genotype II HCV, 6 of 8 (75%) with HCV RNA titers < 10(6) responded, more frequently than 4 of 43 (9%) with titers > or = 10(6) (P < 0.001). Responders were younger than non-responders (45.7 +/- 11.7 vs. 50.3 +/- 9.6 yr) and had received transfusions less frequently (26/74 or 35% vs. 37/62 or 60%, P < 0.01). Response to interferon correlated inversely with the severity of liver histopathology. These results indicate that response to interferon is influenced by HCV genotypes and pretreatment levels of HCV RNA in serum.
Chronological measurements of various HCV markers were conducted to clarify the course and prognosis of acute hepatitis C. Among 49 patients with acute non-A, non-B hepatitis, 32 (65.3%) were diagnosed as having acute hepatitis C by these markers. Twenty-four (82.8%) of 29 patients with posttransfusion hepatitis were type C, while only eight (40.0%) of 20 patients with sporadic hepatitis were type C. Patients were also divided into those who returned to normal within one year based on changes in s-ALT levels and unresolved cases. Anti-HCV was present in 11 (44.4%) of 25 resolved cases and in 21 (87.1%) of 24 unresolved cases. Only one case was continuously positive for HCV-RNA although s-ALT levels returned to normal. In addition, quantitative determinations were conducted on those positive for anti-HCVs. Anti-second generation tested positive in all HCV-RNA-positive cases and positive rates were highest from the onset of hepatitis. In unresolved patients with continuous HCV infection, anti-core increased and titers at 12 months were 10 units or more in all cases. On the other hand, in eight of 10 resolved cases, titers declined gradually after initial seroconversion and titers were 10 units or less at 12 months. From these results, second generation anti-HCV was considered most useful in early diagnosis of acute hepatitis C and anti-core titer was considered most useful in predicting prognosis of acute hepatitis C.
Explore the source record for details and available documents.
We developed hydroxyapatite composite resin (CAP) as a new type of bioactive bone cement. CAP is composed of 80% w/w hydroxyapatite granules (mean particle size: 2 microns) and bis-phenol-A glycidyl methacrylate-based resin. The setting time is 5 min and the peak curing temperature during polymerization is 46 degrees C. In this study, the mechanical strength of CAP and the biological behaviour of the CAP-bone interface were examined. The compressive strength of CAP was 260 MPa and this was about three times greater than that of commercial polymethylmethacrylate (PMMA) bone cement. The tensile strength and fracture toughness of CAP also exceeded those of PMMA cement. CAP was implanted into the femoral condyles of rabbits. Two weeks later, new bone formation was already seen on the surface of the CAP implants. At 8 wk, bone was growing directly onto the surface of the CAP implants and no intervening fibrous tissue could be observed at the CAP-bone interface. These results show that CAP is a promising material which possesses superior mechanical strength and the biological property of achieving direct contact with bone.
The molecular basis of the Philadelphia chromosome (Ph1) is a structurally altered c-abl (bcr/abl) gene which encodes an abnormally large protein with protein tyrosine kinase activity. Herbimycin A, an inhibitor of tyrosine kinase, preferentially inhibited the growth of Ph1-positive acute lymphoid leukemia (ALL) cell lines, as well as Ph1-positive chronic myeloid leukemia (CML) cell lines. Although noncytotoxic concentrations of herbimycin A induced erythroid differentiation of two CML-derived cell lines, K562 and KU812, in a previous study, the differentiation-inducing effect of herbimycin A on Ph1-positive ALL cell lines was less strong. Herbimycin A enhanced some differentiation-associated properties of one Ph1-positive ALL cell line, L2, but the effect of herbimycin A on the other Ph1-positive ALL cell lines was cytotoxic rather than cytostatic (differentiation-inducing). Several derivatives of herbimycin A were synthesized and their effects on the cell proliferation of Ph1-positive CML and ALL cell lines were examined. The sensitivities of the Ph1-positive cell lines to herbimycin A derivatives were different from the data on the rat kidney cell line infected with Rous sarcoma virus (v-src) derived from a previous study, suggesting bcr/abl kinase may differ in sensitivity from other tyrosine kinases. Moreover, the sensitivities of the ALL cell lines were not the same as those of the CML cell lines. These results suggest that a specific inhibitor of bcr/abl kinase could be an effective antileukemic agent against Ph1-positive CML or ALL.
A new technique of endoscopic treatment for gastric varices is presented here, which was applied in 10 patients, either electively (n = 9) or as emergency therapy for bleeding (n = 9) or as emergency therapy for bleeding (n = 1). A detachable snare is placed endoscopically, tightened around the varix, and then detached using a similar principle to that of band ligation. Following one or two treatment sessions (one snare applied in seven cases, two snares applied in three cases), eradication of gastric varices was observed in all patients. No significant complications were encountered, and nine of 13 snares passed spontaneously, the remaining ones being removed when found during follow-up endoscopy. Short-term follow-up (4-12 months, mean: 7.2 months) did not show either reappearance of varices or rebleeding in any of the patients. Angiography and endoscopic ultrasonography performed in four patients before and after treatment showed regression or disappearance of intramural vessels. Further studies will show the relative value of this new technique compared to other treatment modalities such as banding or cyanoacrylate injection.
Explore the source record for details and available documents.
As indicators to determine the diagnosis, condition, and prognosis of hepatitis C, methods have been developed such as the detection of HCV-RNA by the nested RT-PCR method, quantitative assay of HCV-RNA by the competitive RT-PCR method, qualitative and quantitative assay of various anti-HCV IgG and IgM antibodies, and identification of viral type (genotype and serological group). The clinical utility of these HCV markers in early diagnosis and prognosis of acute hepatitis C, for differentiating it from acute flare in HCV carriers, and in distinguishing between past and current infection in second-generation-anti-HCV-positive patients with normal serum alanine aminotransferase has been evaluated.
The current status of interferon (IFN) therapy in chronic hepatitis C is presented, focusing on the results of studies in Japan. Depending on the IFN treatment regimen used in chronic hepatitis C, it is possible to eradicate HCV in a relatively high percentage of patients (about 40%) and to achieve a cure for chronic hepatitis C. The objective of treatment should therefore be the eradication of HCV. The efficacy of IFN in chronic hepatitis C is dependent on the dosage of IFN, duration of treatment, liver histology findings, serum HCV-RNA levels, and HCV genotype. Besides a flu-like syndrome, many adverse reactions are associated with high-dose, long-term IFN treatment. However, as a rule, full recovery or improvement follows prompt withdrawal of IFN. By modification of the IFN, it will be possible to reduce adverse reactions and to create a more effective IFN to further enhance the effect of IFN in chronic hepatitis C.
We prospectively studied side effects about 54 patients with chronic hepatitis C treated with 3 to 10 MIU a day of interferon (IFN) alpha, which was administrated for 16 to 24 weeks. Every day, all of them wrote down every symptoms, by themselves, during its treatment. Any symptoms occurred in all patients and each incidence of symptoms such as fever, fatigue, headache, anorexia, arthalgia, myalgia, chill, itching, insomnia, nausea, numbness of hand and foot, irritability, diarrhea, eye ball pain, vomiting, were all higher than those which have been reported by some papers in Japan. So, it was considered that the symptom self-wrighting method by patient was useful to evaluate the entity of side effects. Furthermore, we studied 26 patients, who discontinued IFN treatment because of side effects and analyzed the background factors. Each incidence of symptoms of these patients were not always compatible to those incidences. But by observation of those symptoms, we could know severe side effects earlier.