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Biomedical subjects

J A Robb

Publications and source records attributed to J A Robb.

At least 19 recordsLinked to original sources
PubMed1990

The distinction of small cell and non-small cell lung cancer by growth in native-state histoculture.

Histological analysis remains the primary method of distinguishing between small cell (SCLC) and non-small cell lung cancer (NSCLC). This distinction has significant impact therapeutically because of their relative difference in chemoresponsiveness (J.D. Minna et al., Principles and Practice of Oncology, pp. 396-474, 1981). Yet for at least 10% of lung tumors, pathologists will disagree upon the classification (A.R. Feinstein et al., Am. Rev. Respir. Dis., 101: 671-684, 1970). Furthermore, current neuroendocrine markers lack specificity for SCLC although the presence of these markers may help predict chemosensitivity (S.L. Graziano et al., J. Clin. Oncol., 7: 1375-1376, 1989; S.B. Baylin, J. Clin. Oncol., 7: 1375-1376, 1989; C.L. Berger et al., J. Clin. Endocrinol. Metab., 53: 422-429, 1981; A.F. Gazdar et al., Cancer Res., 45: 2924-2930, 1985). In vitro growth characteristics may more accurately reflect biological properties of aggressiveness and susceptibility to chemotherapy. In this study, 3-dimensional gel-histoculture was used to retrospectively distinguish between NSCLC and SCLC. Tumor explants from 78 patients with NSCLC and 13 patients with SCLC were grown in gel-supported histocultures with an overall success rate of 92%. These 2 tumor types were distinguishable by their 3-dimensional in vitro tissue architecture. In addition, proliferation rates were measured by histological autoradiography after 4-day incorporation of [3H]dThd. The percentage of cells labeled in the most proliferatively active regions of the autoradiograms was termed the growth fraction index (A.F. Gazdar et al., Cancer Res., 45: 2924-2930, 1985; R.A. Vescio et al., Proc. Natl. Acad. Sci. U.S.A., 84: 5029-5033, 1987; R.M. Hoffman et al., Proc. Natl. Acad. Sci. U.S.A., 86: 2013-2017, 1989). The mean growth fraction index for pure small cell lung cancer was 79 +/- 10%, differing markedly from that of 35 +/- 19% for mixed small cell/large cell tumors, adenocarcinoma (38 +/- 16%), large cell undifferentiated carcinoma (40 +/- 18%), and squamous cell carcinoma (33 +/- 15%) (P less than 0.001 in each case). We therefore conclude that 3-dimensional gel-histoculture is a useful means of distinguishing pure SCLC from NSCLC, which may improve treatment decision making.

Carcinoma, Non-Small-Cell Lung↗
PubMed1990

Phase I clinical comparative study of monoclonal antibody KS1/4 and KS1/4-methotrexate immunconjugate in patients with non-small cell lung carcinoma.

A Phase Ia clinical trial was undertaken to evaluate and compare murine monoclonal antibody KS1/4 and KS1/4-methotrexate immunoconjugate in patients with Stage IIIB or IV non-small cell carcinoma of the lung. Six patients received KS1/4 alone and five patients received KS1/4-methotrexate conjugate. The maximal total dose received per patient in both groups was 1661 mg. Mild to moderate side effects in both groups included fever, chills, anorexia, nausea, vomiting, diarrhea, anemia, and brief transaminasemia. One patient who received antibody alone had an apparent acute immune complex-mediated reaction. Ten of 11 patients had a human anti-mouse response. Posttreatment carcinoma biopsies revealed binding of monoclonal antibody KS1/4 and deposition of C3d and C4c complement fragments. Monoclonal antibody binding and complement deposition correlated with increasing doses of infused antibody. There was one possible clinical response.

Adult↗
PubMed1990

The future anatomic pathology laboratory for molecular diagnosis and prognosis: circa 1990-95.

Molecular biology provides analytical tools for the study of human disease. These clinical assays can help make a diagnosis, predict a prognosis, or elucidate the pathogenesis of poorly understood diseases. The detection and/or quantitation of specific genes, messenger RNA's, and their protein products provide diagnostic and prognostic information for physicians. Illustrative applications of some of these techniques in human virus infection and breast cancer will suggest the future direction that an anatomic pathology laboratory should consider if it is to provide optimal and competitive service to physicians.

Antibodies, Monoclonal↗
PubMed1990

Cancer biology for individualized therapy: correlation of growth fraction index in native-state histoculture with tumor grade and stage.

There is a need for individualization of all aspects of cancer therapy. Because of significant heterogeneity within a tumor class, there is a need to develop an in vitro test to accurately gauge tumor aggressiveness. Such a measurement would greatly aid treatment decision making. Current methodologies such as flow cytometry, which lacks unambiguous interpretation of cell-proliferative data, and determination of the thymidine-labeling index, which measures nucleotide uptake in a nonphysiological state, have not reproducibly attained this goal. We have developed an in vitro native-state three-dimensional gel-supported histoculture system that allows the growth of all human solid tumor types for relatively long time periods. The native-state system was used to identify the percent of cells capable of incorporating [3H]thymidine over a 4-day period, which we term the growth fraction index (GFI). We have compared the ability of cancer tissue to proliferate in native-state culture to the stage and histological grade of four major types of human carcinomas: breast, ovarian, colon, and lung. Eighty percent of tumor explants could be evaluated, even when sent from across the country. We have determined that the GFI correlates with tumor stage and grade for breast and ovarian carcinoma. In colon carcinoma, there is a trend toward higher GFIs in tumors of more advanced stage and grade. In non-small cell lung carcinomas, GFI, stage, and grade do not correlate. These results suggest the applicability of gel-supported three-dimensional native-state histoculture for prognostic purposes in patients with breast and ovarian cancers and demonstrate the clinical relevance of the native-state histoculture system.

Carcinoma, Non-Small-Cell Lung↗
PubMed1979

Differentiation between SV40 large-T and U antigenic sites.

Radioimmune precipitation, SDS-polyacrylamide slab gel electrophoresis and fluorography were used to investigate the SV40 large-T and U antigenic sites on species of proteins synthesized during wild type and tsA58 mutant infections in TC7 monkey cells. Wild type infection at 33 and 41.5 degrees C and the A58 infection at 33 degrees C produced similar profiles of three species ranging in mol. wt. from 84000 to 94000, all of which had both the large-T and U antigenic sites. The A58 infection at 41.5 degrees C, however, produced an additional four discrete species ranging in mol. wt. from 60000 to 74000 that contained the large-T site(s), but not the U site(s). A subpopulation of the 74000 mol. wt. species contained both sites. Therefore, the region of the A58 mutant 94000 mol. wt. species containing the U antigenic site(s), the COOH-terminal region, appears to be more sensitive to processing, probably proteolytic cleavage, than does the region containing the large-T antigenic site(s).

Animals↗
PubMed1977

Transformation of human cystinotic fibroblasts by SV40: characteristics of transformed cells with limited and unlimited growth potential.

Human skin fibroblasts derived from patients with nephropathic cystinosis were transformed with SV40 virions, cloned and permitted to enter the degenerative stage of growth termed "crisis," characteristic of SV40 transformed human cells. Nephropathic cystinosis is an autosomal recessively inherited metabolic disorder resulting in the intracellular accumulation of the amino acid cystine. A transformed cystinotic cell line which was recovered from the crisis stage was indistinguishable from its transformed precrisis parental cell strain in growth rate in media containing either 1% or 10% serum, cloning efficiency on plastic, in semisolid media, or upon confluent monolayers of normal skin fibroblasts, expression of SV40 T antigen, or production of virus. However, the modal DNA content of the recovered postcrisis transformed cystinotic cell line was different from that of the cloned parental precrisis transformed cell strain, suggesting that the postcrisis line was derived from a small subpopulation of the precrisis strain. The DNA content of the established cystinotic cell line continued to be unstable during subsequent subculturing and gave rise to subclones with both more and less DNA per cell. This line now has an apparently infinite growth potential and still has the hallmark of the cystinotic parental line, the storage of abnormally large amounts of intracellular nonprotein cystine.

Antigens, Viral↗
PubMed1977

Identification of simian virus 40 tumor and U antigens.

The synthesis and identity of the tumor and U antigens of simian virus 40 (SV 40) have been examined during productive infection in monkey cells, abortive infection in mouse cells, and in SV40-transformed mouse cells by using sodium dodecyl sulfate/polyacrylamide slab gel electrophoresis to analyze [35S]methionine-labeled radioimmune precipitates. The following observations were made: (i) the tumor and U antigenic sites are on the same 94,000, 89,000, and 84,000 molecular weight species detected during productive infection; a 94,000 species made during abortive infection; and a 94,000 species found in transformed cells. (ii) The 94,000 species is relatively unstable compared to the relatively stable 89,000 and 84,000 species produced during productive infection. (iii) The stable 89,000 and 84,000 molecular weight species are differentially extracted from productively infected cells, which suggests an intracellular compartmentation and/or different affinities of these species for cellular substrates. (iv) The 94,000 species synthesized during abortive infection is more stable than the comparable 94,000 species synthesized in transformed cells. (v) Three tsA group mutants overproduce several unstable species of tumor antigen at restrictive temperature.

Antigens, Neoplasm↗
PubMed1977

Skeletal scintimaging and radiography in the diagnosis and management of Paget's disease.

Experiences in sue of skeletal scintimaging, primarily with 99mTc EHDP, is reported in 108 patients with Paget's disease. The results are compared with other reports and suggest that the mean age of this sample at the time of initial diagnosis and study is somewhat younger than patients in series reported in the literature. In correlation of scintimaging with skeletal radiography only approximately 67% of lesions are seen with the latter. Lesions seen only on scintimaging primarily are associated with early symptomatic lesions and lesions seen only on radiography with older sclerotic "burned out" type lesions. Scintimaging reveals a relatively low incidence of monostotic distribution of lesions, and is superior to skeletal radiography for diagnosis of metastatic bone disease. Qualitative skeletal scintimaging is valuable for objective assessments of therapeutic management by new modes of therapy while clinical radiography is not.

Alkaline Phosphatase↗
PubMed1976

Regulation of SV40-induced cell division and tumor antigen by dibutyryl adenosine 3'-5'-monophosphate.

Simian virus 40 (SV40) induces cell division in microcultures of sparsely plated nongrowing mouse BALB/3T3 cells during acute infection at moderate multiplicities of infection (MOI = 10-100). The infected cells are killed when a MOI of 1,000 is used. SV40 tumor (T) antigen is synthesized in the infected cells, but viral DNA, virion antigen, and progeny virions are not synthesized (abortive infection). The addition of exogenous dibutyryl adenosine 3'-5'-monophosphate (dbcAMP) at the time of infection stimulates the SV40-induced cell division at all MOI and inhibits SV40-induced cell death at high MOI. The percentage of T antigen-positive cells, as monitored by immunofluorescence, is also increased by the addition of dbcAMP at the time of infection. This regulation of SV40-induced cell division and T antigen formation by exogenous dbcAMP occurs within the first 6 hr after infection at 37 degrees C and is dependent upon both the MOI and the concentration of added dbcAMP. The addition of dbcAMP to productively infected TC7 monkey cells has litte effect on the SV40-induced cell death or T antigen formation.

Antigens, Viral↗
PubMed1976

Femoral trabecular-pattern index and bone mineral content measurement by photon absorption in senile osteoporosis.

A comparative study of the usefulness of the femoral trabecular-pattern index (Singh index) and bone mineral content measurement by photon absorption in senile osteoporosis was performed in 106 white women, seventy to ninety-five years old. In 17% of the subjects adequate hip roentgenograms could not be obtained. Interpretation of the Singh index was not found to be simple and easily reproducible. A positive correlation was noted between the bone mineral content and the Singh index. The incidence of previous vertebral and non-vertebral fracture was noted to be inversely related to both bone mineral content and the Singh index, but neither method clearly separated subjects with fracture from those without fracture.

Aged↗