Immunoenhancing activity of synthetic muramyl dipeptide (MDP) was investigated in relation to the activation of rainbow trout (Oncorhynchus mykiss) phagocytes and to nonspecific protection against challenge with the fish pathogen Aeromonas salmonicida. Head kidney phagocytes collected from MDP-injected fish showed significant chemotactic activity against zymosan-activated normal rainbow trout serum, and phagocytic activities against both A. salmonicida and plastic beads. The MDP-activated phagocytes also showed enhanced superoxide generation. When normal phagocytes were exposed to supernatants of phagocyte or peripheral blood lymphocyte cultures of MDP-injected fish, the cells showed significant chemotactic activity, indicating that the MDP-activated cells produced phagocyte-activating factor. Injection of MDP to fish provided protection against challenge with virulent A. salmonicida.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMedDate not supplied

A synthetic translation-terminator gene. A tool for dissecting the translation direction of a gene.

A 41-nucleotide-long duplex DNA, which contains the translation termination codon TAA in six reading frames and lactose operator sequence of Escherichia coli, has been synthesized. This fragment may be useful not only for producing a truncated protein encoded in a plasmid, but also for the identification of the precise coding region and translation direction of a bacterial gene in the cloned chromosomal segment. The synthetic fragment was inserted into beta-lactamase structural gene in pBR322 in order to test the in vivo activity. The plasmid produced mutant beta-lactamase reduced in size, as expected from the insertion site, and rendered the host bacterium constitutive for beta-galactosidase. Thus, termination codons and lactose operator in synthetic nucleotide appear to be functional in vivo.

Base Sequence↗

PubMedDate not supplied

Myocardial inflammatory cell infiltrates in cases of dilated cardiomyopathy: light microscopic, immunohistochemical, and virological analyses of myocardium specimens obtained by partial left ventriculectomy.

OBJECTIVE: Partial left ventriculectomy was introduced for the treatment of refractory dilated cardiomyopathy (DCM). To determine the presence and degree of inflammatory cell infiltrates in DCM and the correlation between the underlying myocardial injury and early clinical outcomes after the operation, we performed histopathological, immunohistochemical, and virological studies of the resected myocardium. METHODS: Posterolateral walls of the left ventricle from 13 idiopathic DCM patients (9 males and 4 females; mean age = 53+/-14 years) were examined. Qualitative and quantitative analyses of the interstitial fibrosis and of the infiltrating inflammatory cells were conducted. For the immunohistochemistry, leukocyte surface markers and antibodies to adhesion molecules and cytokines were used. The histopathological findings were compared with the clinical results, including outcome within 1 year, and pre- and postoperative hemodynamic data. Genomic analysis of the myocardium with polymerase chain reaction was performed for enterovirus, mumps, influenza A, cytomegalovirus, and hepatitis C virus. RESULTS: (1) The three patients who died of cardiac insufficiency after surgery had a higher count of infiltrating inflammatory cells than the eight survivors (32.1+/-10.4 vs 16.3+/-11.9 cells/mm2, p = 0.07). The severity of interstitial fibrosis (percent fibrosis) did not differ significantly between these two groups (28.3+/-15.0 vs 24.0+/-11.7%). (2) In patients who died of myocardial dysfunction, focal accumulations of lymphocytes were common, in which cytotoxic/suppressor T cells and helper/inducer T cells were observed. (3) Enterovirus genome was detected in the myocardium of two patients, both of them died after surgery. CONCLUSIONS: Inflammatory cell infiltrates or active myocarditis appear in some cases to play an important role in the etiology and pathophysiology of clinically diagnosed DCM. There is a possibility that those patients with a more severe or ongoing inflammatory process might have poor outcomes after partial left ventriculectomy.

Adult↗

PubMedDate not supplied

Decreasing trend in incidence and mortality from stroke in Hisayama residents, Japan.

The incidence and mortality from stroke during the period 1961 to 1976, among 1,621 subjects aged 40 and over at entry, in Hisayama community, Kyushu Island, Japan, were analyzed. A major age-related decline in the incidence of cerebral infarction occurred in both sexes. The average annual incidence of cerebral infarction also fell continuously in both sexes throughout the whole observation period. The 5-year annual mortality rate from cerebral hemorrhage also showed a decrease in men, but fluctuated in women. The 5-year mortality from cerebral infarction slightly increased in both sexes.

Adult↗

PubMedDate not supplied

Acute lymphoblastic leukemia of Burkitt's type (L3-ALL) without chromosome abnormality and lacking surface and cytoplasmic immunoglobulins.

A case of heterogeneous acute lymphoblastic leukemia of the Burkitt type (L3-ALL) is reported. A 58-year-old woman was admitted to our hospital with complaints of palpitation and shortness of breath in December 1988. On admission, the peripheral blood showed severe pancytopenia. The bone marrow was hypercellular with abnormal lymphoblasts; the cytoplasm was moderately abundant and intensely basophilic with prominent vacuoles. A diagnosis of L3-ALL was made. Cytogenetic analysis of bone marrow cells revealed a karyotype of 46,XX. The leukemic blasts were HLA-DR+, CD10+, CD19+ and CD20+, but no surface or cytoplasmic immunoglobulins were detected. This is the first report in Japan of a case of L3-ALL without chromosome abnormality and lacking surface and cytoplasmic immunoglobulins.

Antigens, CD↗

PubMedDate not supplied

Hepatocellular carcinoma and bladder cancer as complications following five years of chemotherapy for acute myeloblastic leukemia.

Acute myeloblastic leukemia (AML) was diagnosed in a 54-year-old male, a chronic hepatitis B surface antigen (HBsAg) carrier, in June, 1983. Prompt remission was achieved, and maintenance and intensification chemotherapy were given for five years. He was readmitted in March, 1988 because of a mass in the liver and was diagnosed as having hepatocellular carcinoma (HCC). Curative right segmentectomy was performed in May, 1988. In December, 1988, transitional cell carcinoma of the bladder was discovered, and resected transurethrally. These secondary neoplasms, HCC and bladder cancer, were thought to be associated with the long-term chemotherapy given for the AML.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Conditions of curability after endoscopic resection for colorectal carcinoma with submucosally massive invasion.

The deepest invasive portion of colorectal carcinoma (CRC) is considered to be the part, which ultimately will invade, spread locally and give metastasis. We have previously reported that histologic differentiation at the deepest invasive portion of CRC closely correlate with metastatic potential and is useful in understanding the curability of endoscopic mucosal resection (EMR). The aim of this study is to clarify the conditions of curative EMR for CRC with submucosally (sm) massive invasion. A total of 521 cases with sm invasive CRC (Group A, 470 surgically resected cases; Group B, 51 followed-up cases after EMR) were studied. The depth of sm invasion was defined as the practically measured distance from muscularis mucosae. Histologic subclassification was performed at the deepest invasive tumor margin as: well-differentiated (W), moderately differentiated (M) and poorly differentiated (Por). By assessing glandular configuration and cellular arrangement, M type was further subdivided into two different groups; moderately-well differentiated (Mw) and moderately-poorly differentiated (Mp). In group A, lymph node (LN) metastasis was detected in 45 (9.6%) of 470 cases. W or Mw lesions showed LN metastasis in 4.9% (19/388). Mp or Por lesions showed LN metastasis in 37.3% (25/67) (W/Mw vs Mp/Por; p<0.01). Of 45 cases with LN metastasis that could be measured the practical distance of sm invasion, W or Mw lesions showed no LN metastasis in cases within 1,500 micrometer invasion. However, Mp or Por lesions showed LN metastasis in cases within 1,500 micrometer invasion (5/15, 33.3%, minimum 400 micrometer invasion; so-called scanty invasion). In group B, none of 51 cases died of LN metastasis and showed no other metastasis, although 17 cases (33.3%) showed an sm invasion more than 1,500 micrometer. These results indicated that CRC even with sm massive invasion can be cured by complete EMR on conditions that the depth of sm invasion is within 1,500 micrometer and histologic grade at the deepest invasive portion is W or Mw, if there are no vessel involvement. However, cases with Mp or Por grade were not curative by EMR, even if they showed an sm scanty invasion.

Colorectal Neoplasms↗

PubMedDate not supplied

pS2 expression as a possible diagnostic marker of colorectal carcinoma in ulcerative colitis.

This study was performed to evaluate the significance of pS2 and MUC1 expressions in ulcerative colitis (UC)-associated colorectal neoplasias. Tissues were collected from 6 patients with UC-associated colorectal neoplasias treated surgically. Specimens were 13 adenocarcinomas, 40 dysplasias (20 high-grade dysplasias, 20 low-grade dysplasias), and 60 normal mucosae. Tissues were also collected from patients without UC treated surgically or endoscopically. pS2, p53, and MUC1 expressions were examined immunohistochemically and compared. The K-ras codon 12 mutation was investigated by single-strand conformation polymorphism analysis. In patients with UC, the incidence of pS2 expression was significantly higher (p<0.01) in adenocarcinomas than it was in dysplasias, and no pS2 expression was seen in normal mucosae. p53 overexpression was detected in 50% (10/20) even in low-grade dysplasias. MUC1 expression was seen only in invasive carcinomas, but it was seen in 100% of cases (3/3). K-ras gene mutations were detected in 2 (20%) of 10 carcinomas. In low and high-grade dysplasias, the incidences of pS2 expression were significantly (p<0.01) lower than the incidences of p53 overexpression, however, in UC-associated carcinomas there was no significant difference; pS2 expression and p53 overexpression were detected in 13 of 13 (100%) cases and in 12 of 13 (92%) cases, respectively. These results suggest that p53 overexpression may be a diagnostic marker of neoplasia, and that pS2 expression may be a diagnostic marker of colorectal carcinoma in case of UC.

Adult↗

PubMedDate not supplied

ABCB1 C3435T polymorphism influences methotrexate sensitivity in rheumatoid arthritis patients.

OBJECTIVE: Methotrexate (MTX) is most widely used for the treatment of rheumatoid arthritis (RA). However, it has certain drawbacks with regard to individual differences in its therapeutic effects as well as the differences in the patients' response to MTX therapy. We investigated whether multi-drug resistance-1 (ABCB1) C3435T, reduced folate carrier-1 (RFC1) G80A, 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC) C347G and a 6bp-deletion polymorphism in the 3'-untranslated region of the thymidylase synthase (TYMS) gene are predictive of MTX sensitivity and its adverse effects. METHODS: Patients whose last maintenance dosage of MTX was 6 mg/week or those in whom MTX therapy was changed due to poor response to MTX were regarded as non-responders. The data of 124 RA patients who had received MTX treatment were retrospectively analyzed for polymorphisms in the ABCB1, RFC1, ATIC and TYMS genes, MTX sensitivity and MTX toxicity. RESULTS: There were no significant differences in MTX sensitivity among the genotypes of RFC1, ATIC and TYMS genes. ABCB1 3435TT cases included statistically significantly more non-responders than 3435CC cases according to univariate analysis (crude odds ratio (OR) = 8.91, p = 0.001) and multivariate analysis (adjusted OR = 8.78, p = 0.038). There were no significant differences in MTX toxicity among the genotypes of all the genes. CONCLUSION: These results suggested that the genetic diagnosis of ABCB1 C3435T can be applied to determine MTX sensitivity for the treatment of RA patients. However, further pharmacokinetics studies are required in this regard.

ATP Binding Cassette Transporter, Subfamily B↗