Biomedical subjects
Publications and source records attributed to D Saltman.
The author presents practical guidelines for writing a variety of medical articles. Newer forms of exposition, for example, poster presentations, are also explored. Guidelines and checklists for common grammatical problems are included.
A cDNA encoding a novel human subtilisin-like protease was identified by a polymerase chain reaction (PCR) methodology. PCR primers were designed to be specific for the subfamily of eukaryotic subtilisin-like proteases with specificity for paried basic amino acid residue processing motifs. The gene encoding this protease, designated PACE4, also encoded a smaller subtilisin-related polypeptide derived by alternate mRNA splicing. The deduced PACE4 protein sequence contained a number of interesting features not present in other family members, including an extended signal peptide region, and a relatively large carboxyl-terminal cysteine-rich region with no obvious membrane anchor sequence. As with the fur gene product, the tissue distribution of PACE4 was widespread, with comparatively higher levels in the liver. An additional relationship to the fur gene product was shown by chromosomal localization studies. The close proximity of the fur and PACE4 genes on chromosome 15 suggests that these genes probably evolved from a common ancestor by gene duplication.
Two new homeobox genes, PBX2 and PBX3, were isolated on the basis of their extensive homology to PBX1, a novel human homeobox gene involved in t(1;19) translocation in acute pre-B-cell leukemias. The predicted Pbx2 and Pbx3 proteins are 92 and 94% identical to Pbx1 over a large region of 266 amino acids within and flanking their homeodomains, but all three proteins diverge significantly near their amino and carboxy termini. Chromosome in situ hybridizations demonstrated that the PBX genes are not clustered but map to separate chromosomal loci: PBX1, 1q23; PBX2, 3q22-23; PBX3, 9q33-34. Expression of PBX2 or PBX3 was not restricted to particular states of differentiation or development, as mRNA transcripts of these genes were detected in most fetal and adult tissues and all cell lines, unlike PBX1, which is not expressed in lymphoid cell lines. Similar to PBX1 RNA, PBX3 RNA is alternatively spliced to yield two translation products with different carboxy termini, a feature not observed for PBX2. Their extensive sequence similarity and widespread expression suggest a generalized, overlapping role for Pbx proteins in most cell types. Differences in their amino and carboxy termini may modulate their activities, mediated in part by differential splicing and, for PBX1, protein fusion following t(1;19) chromosomal translocation.
The author presents practical guidelines for critical reading and appraisal of research articles. The IMRAD formula (Introduction, Methods, Results and Discussion) for the composition of such articles is explained, and the format of the structured abstract outlined. Guidelines for critical appraisal of the material from drug detailers are also presented.
We describe a case of severe tuberculous pancreatitis in a 26-year-old woman with miliary tuberculosis. Recognition of this complication is important as it may interfere with adequate absorption of anti-tuberculous drugs and it can lead to unnecessary laparotomy.
A new Epstein-Barr virus (EBV) transformed cell line was established from a patient with B-chronic lymphocytic leukemia (B-CLL). The karyotype of the cell line has remained normal for over 12 months in culture; however, identical heavy and light chain immunoglobulin (Ig) gene rearrangements in the patient's blood and the cell line provided evidence that the EBV transformed cells were derived from the neoplastic clone.
Explore the source record for details and available documents.
We have established a new Epstein-Barr virus transformed cell line from a patient with B-cell follicular lymphoma. Telomeric fusions were observed in several subclones, with the nonrandom involvement of chromosomes 1, 5, 12, and 17. Centromeric staining with immunofluorescent anti-kinetochore antibodies was positive in both centromeres of the fused chromosomes, suggesting they were both active. Unlike previously reported cases, we were unable to demonstrate telomeric fusions directly in cells from the patient's blood. However, the finding of identical immunoglobulin gene rearrangements in DNA from the patient's blood and cell line suggested that they originated from the same malignant B-cell clone.
Human somatic cell hybrids were generated from fusions between a tumorigenic B-cell line, and mononuclear cells from a patient with low-grade B-cell lymphoma in which the neoplastic cells largely corresponded to cells at an intermediate stage of differentiation. The resulting hybrids and the parent cells were immunophenotyped, karyotyped and genotyped in an effort to determine whether the stage of B-cell development of the fusion partners was important in the suppression of malignancy. The majority of hybrids demonstrated suppression of tumorigenicity as measured in immunodeprived mice. Chromosome markers and immunoglobulin gene rearrangements found in the patient's neoplastic cells were also present in several of the hybrids. One of the tumorigenic hybrids retained specific chromosomes also found in the non-tumorigenic hybrids, but demonstrated an immunophenotype and genotype possibly associated with a subset of early B-cells. In the non-tumorigenic hybrids that retained most of the chromosomes from both parents there was evidence of plasmacytoid differentiation. These results suggest that the ability of B-lymphocytes to suppress malignancy in human lymphoid hybrids may be dependent on the corresponding stage of normal B-cell ontogeny, and that suppression is associated with differentiation.
From 1984 to 1986 a prospective study was conducted of 104 general practice patients who started treatment with a benzodiazepine or an antidepressant drug. The duration of reported use of the drugs was two months for 45% of patients, four months for 17% of patients, and six months for 15%. Type of drug, age, and level of education were found to be predictive of continuing use. General practitioners have a significant effect on their patients' use of drugs and, with careful selection and review when prescribing, may help to prevent dependence on psychotropic drugs.