Problems entailed in the definition and pathology of anaplastic astrocytoma

Three-tiered system dividing supratentorial astrocytic neoplasms into the astrocytoma, anaplastic (malignant) astrocytoma and the glioblastoma multiforme has been widely used. However, the pathology of anaplastic astrocytoma is defined in different ways according to different classifications. A total of 42 biopsy specimens from 35 cases diagnosed as anaplastic astrocytoma were reviewed pathologically and their features were correlated with a follow-up clinical study to discuss the prognostic usefulness of the subdivision of anaplastic astrocytoma. In WHO classification, anaplastic astrocytoma is defined as "astrocytoma containing areas of anaplasia". Follow-up study of 7 cases with the histology as such revealed that 5 cases had survived more than one year and seven months. The other 28 cases showed a varied histology and were subclassified into an astrocytoma in which moderately anaplastic cells are found throughout the tumor, an astrocytoma formed by anaplastic fusiform cells, an astrocytoma composed of predominantly rounded anaplastic cells, and a pleomorphic astrocytoma with or without intracytoplasmic hyaline inclusions. A follow-up study of cases with these types of astrocytoma disclosed death in 15 cases within one year and 7 months following the first surgery and that three cases displayed typical histological features of glioblastoma at autopsy. It is considered that there would be a considerable overlap between the group of anaplastic astrocytoma and that of glioblastoma, if we use the term "anaplastic astrocytoma" in a broader category.     

Three TNFalpha single nucleotide polymorphisms in the Japanese population

BACKGROUND: Tumour necrosis factor-alpha (TNFalpha) is an essential regulator of immune responses and is implicated to relate to several types of disease susceptibilities. Population information on polymorphisms is essential for the study of genetic diseases. AIM: To obtain accurate information about single nucleotide polymorphisms (SNPs) in the TNFalpha gene in the Japanese population. SUBJECTS AND METHODS: The entire TNFalpha gene was screened for SNPs by directly sequencing 48 chromosomes derived from 24 unrelated Japanese individuals. Allele frequencies of each polymorphism were determined and compared with those previously reported in other populations. RESULTS: Three SNPs, -308G/A at nt -308, IVS1 + 125G/A at nt 492 and IVS3 + 104G/A at nt 1359 were observed, of which one (IVS3 + 104G/A at nt 1359) was novel. In addition, allele frequencies of -308G/A were remarkably different from those presented in the NCBI dbSNP, indicating a significant ethnic difference. CONCLUSIONS: The polymorphisms and allele frequencies obtained in this study will be useful for genetic studies of common diseases such as osteoporosis and rheumatoid arthritis in the Japanese population.     

The structure of the avian fast skeletal muscle troponin T gene: seven novel tandem-arranged exons in the exon x region

To elucidate the mechanism that produces enormous molecular diversity in troponin T (TnT) of fast skeletal muscle, we determined the 5-half genomic sequence of the chicken fast muscle TnT gene. The sequence of ca. 16 kb included seven exons (exons 1, 2, 3, 4, w, 5, and 6), which have been reported previously and presumed by sequencing TnT cDNAs. Additionally we found six 15 nt and one 18 nt sequences in the region between exons 5 and 6 (i.e. the exon x region). They were encompassed by consensus splice donor and acceptor sites and preceded by putative branch sites, and designated herein as exons xa to xg. Our result shows that the sequence derived from exons x1, x2, and x3, the exons presumed previously by cDNA sequencing, is actually encoded by the seven exons xa to xg, establishing the precise gene structure in the exon x region. Based on our data, together with that on the 3-half genomic sequence of the quail fast muscle TnT gene, we conclude that the avian fast skeletal muscle TnT gene includes 27 exons, 16 of which are alternatively spliced.     

Detection of antibodies to hepatitis C virus (HCV) structural proteins in anti-HCV-positive sera by an enzyme-linked immunosorbent assay using synthetic peptides as antigens.

We have defined 10 linear immunogenic regions encoded by the putative hepatitis C virus (HCV) structural proteins (core and envelope) by employing an enzyme-linked immunosorbent assay (ELISA) and by using 17 sequential synthetic peptides covering the N-terminal 330 amino acids of the structural polyproteins as antigens. These peptides correspond to amino acids 1 to 24, 21 to 44, 42 to 68, 64 to 91, and 100 to 120 of the putative core protein and amino acids 192 to 212, 223 to 238, 236 to 258, 250 to 266, and 307 to 330 of the putative envelope protein. In particular, the peptide covering amino acids 21 to 44 of the core protein was reactive with all but one (40 of 41) of the serum samples giving a positive signal in the passive hemagglutination assay (PHA) using the core and nonstructural proteins (NS 3/4) of the virus as antigens. We detected the HCV genome in 25 (61%) of 41 PHA-positive serum samples by the polymerase chain reaction (PCR) test. Of 25 PCR-positive serum samples, 17 serum samples had reactivity to the peptides derived from the envelope protein. On the other hand, only 1 of the 16 PCR-negative serum samples had reactivity to the peptides derived from the envelope protein. Interestingly, we often observed high serum alanine aminotransferase levels in PCR-positive individuals bearing antibodies to the envelope protein.     

INTRAUTERINE CANDIDA INFECTION IN PREMATURE BABY

An autopsy case of pulmonary candidiasis occurring in a neonatal girl was reported. The mycological examination of the lung taken at autopsy revealed only Candida albicans and followed by the elucidation under the microscopic sections prepared with special stains; periodic acid-Schiff and methenamine silver, in the lung, stomach, umbilical cord, and amnion. The presence of Candida vaginitis in her mother supported the concept that Candida albicans was the etiological agent of the pulmonary candidiasis.     

Genetic polymorphisms of orosomucoid and alpha-2-HS-glycoprotein in Thai,Sri Lankan and Paraguayan populations

The genetic polymorphism of orosomucoid (ORM) and alpha-2-HS-glycoprotein (AHSG) were studied in Thai, Sri Lankan and Paraguayan populations using isoelectric focusing. Gene frequencies in these populations were compared with those in other populations. Four new ORM variants were detected:ORM1 ^* 15 in Thai,ORM1 ^* 16 in Paraguayan,ORM2 ^* 21 andORM2 ^* 22 in Sri Lankan.     

Long-Term Follow-Up of the Changes in Circulating Cytokines, Soluble Cytokine Receptors, and White Blood Cell Subset Counts in Patients with Rheumatoid Arthritis (RA) After Monoclonal Anti-TNFα Antibody Therapy

To investigate the mechanism of the long-lasting efficacy of chimeric monoclonal anti-TNF antibody (cA2) therapy for rheumatoid arthritis (RA), eight patients with refractory RA were treated with a single infusion of cA2 and the changes in circulating cytokines (IL-1, IL-6, TNF, and IL-10), soluble cytokine receptors (TNF-RI, RII, and sIL-6R) and peripheral white blood cell (WBC) subset counts were followed up long-term (12 weeks) after cA2 therapy in them. Significant clinical responses (>20% improvement according to Paulus' criteria) were observed just after cA2 infusion and lasted more than 4 weeks in all patients, as reported elsewhere. Moreover, five of the eight patients showed prolonged clinical responses (>12 weeks). The elevated serum IL-6 and sTNF-RI (or RII) levels before treatment rapidly decreased after treatment. The serum IL-10 levels also significantly elevated before treatment. The elevations of serum IL-10 levels were augmented after treatment and stayed higher than the baseline in four patients with prolonged clinical responses. No significant TNF, IL-1 and -, or sIL-6R were detected in the sera of the patients before treatment and during the whole study period. On the other hand, peripheral lymphocytes as well as total WBC and neutrophils increased for 4 weeks after treatment. However, thereafter, only the lymphocyte count decreased gradually and stayed below the baseline long-term (12 weeks). FACS analysis revealed the predominance of T lymphocytes in the decrease in lymphocyte counts. These results suggest that the augmentation of IL-10 production and the decrease in T cells might partly contribute to the long-lasting efficacy of cA2 treatment in RA.     

Calcium pump expression in human bone and soft tissue tumours

Ninety-one cases of human bone and soft tissue tumours were studied for calcium pump expression by strepto-avidin-biotin immunohistochemical staining with a monoclonal antibody against sarcoplasmic reticulum calcium-ATPase (mAb6F5). Two out of 5 cases of embryonal rhabdomyosarcoma, 1 out of 5 cases of biphasic synovial sarcoma, 4 of 4 cases of chordoma and all of 3 chondrosarcoma cases were positive for mAb6F5. Although this novel monoclonal antibody can be used as a marker of myogenic tumours, the present positive result for endoplasmic reticulum calcium-ATPase (calcium pump) in other tumours including chordoma, chondrosarcoma and synovial sarcoma indicates a wider immunoreactivity. The findings further suggest that intracellular calcium may play an important role in cell proliferation and/or differentiation.