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Biomedical subjects

R Clark

Publications and source records attributed to R Clark.

At least 289 records · Page 16Linked to original sources
PubMed1989

Vimentin rather than keratin expression in some hormone-independent breast cancer cell lines and in oncogene-transformed mammary epithelial cells.

To characterize differences in gene expression between hormone-dependent and hormone-independent mammary carcinoma, we cloned complementary DNAs of genes expressed in a hormone-independent breast carcinoma cell line that were not expressed in a hormone-dependent line. One clone, which was isolated in many copies, coded for the intermediate filament protein vimentin. A complementary DNA clone 1.8 kilobases long included the entire protein-coding region for vimentin. Vimentin was expressed by more than one-half of the hormone-independent breast carcinoma cell lines tested but not by the hormone-dependent cell lines. The cell lines which expressed vimentin expressed only low levels of cytokeratins. The correlation between vimentin expression and more advanced stages of mammary cell transformation was tested in a model system in which immortal, nontumorigenic human mammary epithelial cells or derivative lines transformed with v-ras-H or SV40 T-antigen were found not to express vimentin, whereas a derivative highly tumorigenic cell line transformed by both v-ras-H and T-antigen did express vimentin. Analysis of several other kinds of epithelial carcinoma cell lines showed only rare examples of vimentin expression.

Base Sequence↗
PubMed1989

Vibrio cholerae non-O1 infection presenting as localized cellulitis.

Vibrio cholerae non-O1 characteristically causes gastrointestinal illness but can occasionally be responsible for extra-intestinal infections. The authors report an unusual case of a man presenting with extensive cellulitis that did not improve with conventional antimicrobial therapy. Vibrio cholerae non-O1 was later isolated from a cutaneous bulla. Although he had severe hepatic cirrhosis, the infection remained confined to the cutaneous tissues and he was never bacteremic. He improved dramatically with surgical debridement in conjunction with antibiotics. It is important to consider Vibrio cholerae non-O1 as a cause of cellulitis, especially in endemic areas.

Cellulitis↗
PubMed1989

Low rate of Rhesus immunization from Rh-incompatible blood transfusions during liver and heart transplant surgery.

Transfusion of one unit or more of Rh-positive red blood cells normally causes circulating anti-D antibody to appear 2-6 months later in 80-95% of Rh- persons. We asked whether transplant immunosuppression with cyclosporine and corticosteroids affects Rh immunization. Nineteen Rh- liver, heart, and heart-lung transplant recipients received 3-153 (median: 10) units of Rh+ RBCs at surgery and were tested for anti-D greater than 2 months later. Three patients developed anti-D at 11-15 days; one may have had an unusually rapid primary immune response and two were secondary to previous exposure by pregnancy. None of the other 16 patients had anti-D when tested 2.5-51 months later (13 patients, greater than 11.5 months). This low rate of Rhesus immunization in association with cyclosporine immunosuppression allows greater flexibility in meeting the transfusion needs of Rh- liver and heart transplant patients. Caution is still advised in young females and in patients who may have been previously exposed to Rh+ RBCs by transfusion or by pregnancy prior to the availability of perinatal Rh immune globulin twenty years ago. Other humoral immune responses to some vaccines or infectious agents may also be impaired in transplant patients.

Adult↗
PubMed1989

Multiple neurotrophic factors from skeletal muscle: demonstration of effects of basic fibroblast growth factor and comparisons with the 22-kilodalton choline acetyltransferase development factor.

Extracts of skeletal muscle contain chromatographically distinct molecules that enhance the cholinergic development of cultured embryonic rat spinal cord neurons. We have recently purified a 20-22 kilodalton anionic polypeptide choline acetyltransferase (ChAT) development factor (CDF) from rat skeletal muscle extracts that stimulates the development of ChAT activity in rat spinal cord cultures. The maximum increase in the level of ChAT activity achieved by this factor, however, is less than that achieved by the addition of the crude extract. We now show that muscle extract also contains mitogenic activity that is immunologically related to basic fibroblast growth factor (bFGF) and also that recombinant bFGF stimulates ChAT development in rat spinal cord cultures. bFGF, however, differs from CDF in its physiochemical, chromatographic, and immunological properties and by its action on nonneuronal cells. Individually, CDF and bFGF each enhance the level of ChAT activity in rat spinal cord cultures two- to threefold after 2 days of treatment. However, their combined actions result in a five- to sixfold enhancement of ChAT activity, suggesting that they are affecting cholinergic development through different means. The demonstration that extracts of rat skeletal muscle contain two biochemically and immunologically distinct polypeptides, with additive effects on cultured embryonic spinal cord neurons, provides additional evidence for the involvement of multiple target-derived neurotrophic factors in the regulation of cholinergic development.

Animals↗
PubMed1989

Transforming growth factor alpha production and epidermal growth factor receptor expression in normal and oncogene transformed human mammary epithelial cells.

We have characterized the expression of transforming growth factor alpha (TGF alpha) and its receptor, the epidermal growth factor receptor (EGF-R), in normal and malignantly transformed human mammary epithelial cells. Human mammary epithelial cells were derived from a reduction mammoplasty (184), immortalized by benzo-a-pyrene (184A 1N4), and further transformed by the oncogenes simian virus 40 T (SV40 T), v-Ha-ras, and v-mos alone or in combination using retroviral vectors. 184 and 184A 1N4 cells require EGF for anchorage-dependent clonal growth. In mass culture, they secrete TGF alpha at high concentrations and exhibit an attenuated requirement for exogenous EGF/TGF alpha. SV40 T transformed cells have 4-fold increased EGF-R, have acquired the ability to clone in soft agar with EGF/TGF alpha supplementation, but are not tumorigenic. Cells transformed by v-mos or v-Ha-ras are weakly tumorigenic and capable of both anchorage dependent and independent growth in the absence of EGF/TGF alpha. Cells transformed by both SV40 T and v-Ha-ras are highly tumorigenic, are refractory to EGF/TGF alpha, and clone with high efficiency in soft agar. The expression of v-Ha-ras is associated with a loss of the high (but not low) affinity binding component of the EGF-R. Malignant transformation and loss of TGF alpha/EGF responsiveness did not correlate with an increase in TGF alpha production. Thus, TGF alpha production does not appear to be a tumor specific marker for human mammary epithelial cells. Differential growth responses to EGF/TGF alpha, rather than enhanced production of TGF alpha, may determine the transition from normal to malignant human breast epithelium.

Animals↗
PubMed1989

Baculovirus expression of functional P210 BCR-ABL oncogene product.

The chronic myelogenous leukemia-associated P210 BCR-ABL oncogene protein product has been produced using the baculovirus expression system. High-level expression of the P210 BCR-ABL protein required the removal of GC rich 5' non-coding sequences. P210 BCR-ABL synthesized in insect cells is an active tyrosine protein kinase indistinguishable from P210 BCR-ABL isolated from human cells. Both proteins utilize angiotensin II as a phosphate acceptor in vitro with a Km for ATP of approximately 1.5 microM. P210 BCR-ABL produced in insect cells undergoes autophosphorylation in vitro and in vivo. Gel filtration of P210 BCR-ABL reveals that the protein elutes as a high molecular weight complex of about 800 kD. Approximately 4 to 5 mg of P210 BCR-ABL is produced in one liter of infected insect cells. Following cell disruption and a three-step ion exchange and gel filtration purification procedure, 0.4 mg of soluble P210 BCR-ABL is obtained per liter of suspension culture. An alternative procedure employing detergent extraction and immunoaffinity chromatography gave higher yields and purity from smaller amounts of infected cell extracts. The availability of intact, soluble and enzymatically active P210 BCR-ABL represents a significant advance for studying the biochemical and biophysical properties of the ABL oncogene family of proteins.

Animals↗
PubMed1989

Hyperalimentation with atherosclerosis reversal.

The authors discuss management of a patient treated for 7 months with total central parenteral nutrition, using hypertonic glucose and aminoacids. Previous disease accounted in part for failure of the pulmonary, cardiac, renal and gastrointestinal system.

Amino Acids↗
PubMed1989

The expanding role of lymphoscintigraphy in the management of cutaneous melanoma. First Place Winner: Conrad Jobst award.

Accepted therapy for intermediate-thickness melanomas is wide local excision and regional lymphadenectomy for nodes known to be in the lymph drainage basin. Lymphoscintigraphy has been shown to be of great help in predicting the drainage pattern of truncal, shoulder, proximal extremity, and head and neck melanomas. Lymphoscintigraphy using Technetium-99 antimony sulfur colloid was performed on 17 patients with cutaneous melanomas at H. Lee Moffitt Cancer Center at the University of South Florida. Of 13 patients with primary truncal and shoulder lesions, drainage patterns were discordant 54 per cent of the time and resulted in dissection of nodal groups different than would otherwise have been planned. This resulted in several lymph nodes positive for metastatic disease removed from operative sites not expected to show metastatic spread by clinical experience alone. The discordant rate for head and neck drainage was also high with 2 of 3 forehead studies showing drainage to both anterior and posterior cervical chains when only anterior chain drainage was expected, while only one of these drained to the preauricular nodes. Again, this led to elective lymph-node dissections of nodal basins not anticipated on clinical grounds alone. After a mean follow-up of 2 years, in which 60 to 75 per cent of all recurrences from melanoma are expected to occur, there has been no lymph-node metastasis development in basins that were not predicted by the scan. It is clear from our data that well-known historical patterns of lymph drainage in addition to the clinical impression of experienced surgeons cannot reliably predict the lymphatic drainage of many truncal, shoulder, and head and neck melanomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Characteristics of successful and unsuccessful applicants to orthopedic residency training programs.

In 1985 there were 288 applicants for the ten postgraduate Year 1 orthopedic residency positions in Galveston and San Antonio, of which 119 (41%) applicants successfully obtained a residency position in one of 76 orthopedic programs approved by the Accreditation Council for Graduate Medical Education. Successful applicants were younger and had higher Medical College Admissions Test scores, National Board of Medical Examiners, Part I (NBME-I) scores, and medical school grade point averages than unsuccessful applicants. Variables that increased acceptance rates were medical student status, an NBME-I score above 500, class rank in the top 40%, and membership in Alpha Omega Alpha honor society. Foreign citizenship and prior residency experience in a different specialty strongly decreased acceptance rates. Variables that did not affect acceptance rates were: gender, military experience, marital status, graduate degree, research, publications, or NBME-II scores.

Adult↗
PubMed1988

Transformation of human mammary epithelial cells by oncogenic retroviruses.

We have introduced viral oncogenes into human mammary epithelial cells through the use of murine retroviruses. A continuous cell line (184A1N4) derived from benzo(a)pyrene treatment of normal breast epithelial cells was used as a recipient for the ras, mos, and T-antigen oncogenes. Each of these oncogenes enabled the 184A1N4 cells to grow in a selective medium, thus demonstrating the potential utility of these cells for oncogene detection and isolation. 184A1N4 cells transformed by T-antigen were nontumorigenic in athymic mice, but v-ras transformants were weakly tumorigenic. Transformants bearing both the T-antigen and ras oncogenes were strongly tumorigenic, however. The karyotype of these double transformants shows a high degree of stability. These results demonstrate the stepwise acquisition of the fully malignant phenotype by normal human epithelial cells in vitro.

Animals↗
PubMed1988

Heparin protects heparin-binding growth factor-I from proteolytic inactivation in vitro.

Heparin inhibits proteolytic digestion of heparin-binding growth factor-I (HBGF-I) by trypsin, plasmin and other proteases. This property is lost after thermal denaturation of HBGF-I, suggesting that a heparin:HBGF-I structural interaction rather than a heparin:trypsin interaction is responsible for the resistance of HBGF-I to digestion with trypsin. Heparin is also able to partially protect HBGF-I from thermal denaturation as demonstrated by the ability of heparin to protect HBGF-I from trypsin digestion. The protective effect of heparin is dependent upon the concentration of heparin as well as temperature and duration of denaturation. Autoradiography of 125I-HBGF-I incubated with human umbilical vein endothelial cells demonstrates near complete protection of HBGF-I from proteolytic modification when the incubation is performed in the presence of heparin. These data suggest that (i) the mechanism of the heparin-induced increase in human endothelial cell number at confluence involves the protection of HBGF-I by heparin against proteolytic inactivation and (ii) heparin provides conformational stability to the proteolytic growth factor which reduces the susceptibility of HBGF-I to denaturation.

Animals↗
PubMed1988

The differing requirements of collateral clients and primary alcohol users in outpatient treatment.

Treatment data were collected on 134 clients of the Alcohol Counseling and Education Program, Taunton, Massachusetts: 31 of these clients were collateral clients; 103, primary users. Short-term improvements in the emotional status (i.e., improvements that occurred within the period of treatment) of collateral clients seem dependent upon different treatment modalities than do those of primary users. Collateral clients seem, on the one hand, responsive to individual counseling; primary users, on the other, to group (including self-help, Alcoholics Anonymous) therapy.

Adaptation, Psychological↗