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Biomedical subjects

R G Martin

Publications and source records attributed to R G Martin.

At least 127 records · Page 7Linked to original sources

Herpesvirus in sensory and autonomic ganglia after eye infection.

In herpesvirus hominis (HVH) infections, virus harbored in the sensory ganglia is now thought to be the main source of recurrent infection at peripheral sites. Experimental HVH infection of the external eye in rabbits produces an acute infection and then latent infection of the trigeminal ganglion. In this study, acute infection of the automatic ganglia serving the eye (superior cervical and ciliary) as well as trigeminal ganglia occurred after HVH inoculation of rabbits' corneas with a herpes type 1 strain (RE). Latent virus infection was detected in the trigeminal ganglion of one of five animals tested six months after initial infection. Since the superior cervical and other autonomic ganglia serving the eye become infected during acute herpes simplex virus infection of the external eye in rabbits, it is possible that these ganglia are also sources of reinfection in recurrent herpetic disease of the eye. Following the initial eye disease with this virus strain, HVH shedding could not be demonstrated even after induction attempts by topically applied epinephrine or systemic use of cyclophosphamide. Thus, establishment of latent HVH infection in the ganglia and chronic shedding of virus into the external eye is not a constant feature of this animal model, but may depend on the specific strain of herpesvirus used.

Animals↗

A clinical and pathological staging system for soft tissue sarcomas.

A system for staging the clinical status of patients with soft tissue sarcomas is presented, based on the clinical characteristics of the primary tumor (size, extension), the involvement of lymph nodes, the presence of metastases, and the grade of the tumor. This represents the TNM system with grade of tumor (G) added. The system evolved was based on examination of 1215 cases of 13 types of soft tissues sarcomas, primarily in the extremities (fibrosarcoma, liposarcoma, etc.). Nine stages are described, and they are correlated with survival in the cases reviewed. The staging system now can be used for case evaluation for therapy determination and for intercomparison of series of patients as to incidence of different kinds of tumors, effects of treatment, and survival.

Adult↗

Initiation points for DNA replication in nontransformed and simian virus 40-transformed Chinese hamster lung cells.

Randomly growing Chinese hamster lung cells were pulse-labeled with 3H-thymidine, and the replicating forks of individual DNA fibers were visualized by autoradiography. When grown in complete medium, wild-type SV40-transformed cells had more forks per unit length of DNA than nontransformed cells. In isoleucine-depleted medium, wild-type SV40-transformed cells had fewer forks per unit length than those few nontransformed cells (1-3% of the population) which continued DNA replication. Cells transformed by a tsA mutant of SV40 when grown at the permissive temperature had more forks per unit length in complete medium and fewer forks per unit length in depleted medium than nontransformed cells, but when grown at the restrictive temperature, the tsA-transformed cells behaved like nontransformed cells.

Animals↗

Primary osteosarcoma of bone. Clinicopathologic investigation of 243 cases, with necropsy studies in 54.

Two hundred forty-three patients who had pathologically verified primary osteosarcomas of bone, treated at The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute over a 24-year period, form the basis of this study. These cases provide a basis for comparison of those patients currently receiving adjuvant chemotherapy with those who did not receive such treatment. Anatomic findings in 54 cases subjected to complete postmortem examinations were analyzed. Three significant findings emerged: pulmonary metastases were observed in all but one case, lymph-node metastases were found in only four cases, and in all metastases the histologic pattern reproduced that of the primary lesion. In addition, patients less than 26 years old had a significantly earlier appearance of pulmonary metastases than patients past this age. Patients with osteoblastic tumors had the poorest survival rate, followed by those with chondroblastic lesions. Those with fibroblastic tumors survived longest. In the overall study of 243 cases, tumors in the distal end of the femur and the proximal end of the tibia accounted for 147 cases, representing 60.5% of the cases. The highest incidence of the tumor was in the second decade of life, with 76.5% of the cases occurring in patients less than 25 years old. Three-year survival for the series was 21.7%, with only 12.6% surviving five years. Persons with primary lesions in the facial bones had the highest survival rate. Those with lesions in the humerus, tibia, and distal end of the femur had decreasingly lower survival rates. The lowest survival rates were for patients with lesions of the torso. In the femoral cases, size was a factor in survival; no patient with a tumor larger than 10 cm survived longer than five years. The surgery, irradiation, and chemotherapy employed--individually or in combination--did not alter appreciably the mortality rate for this tumor; only 12.6% of the patients survived five years or longer. Survivals were directly attributable to surgical procedures, including resection of pulmonary metastases. The data analyzed in this study provide a firm baseline of experience in analyzing results of treatment for osteosarcoma prior to the use of adjuvant chemotherapy, which is currently producing a vastly improved therapeuttic response.

Adolescent↗

Expression and thermal stability of simian virus 40 tumor-specific transplantation antigen and tumor antigen in wild type- and tsA mutant-transformed cells.

We have explored aspects of a suggested relationship between the expression of simian virus 40 tumor-specific transplantation antigen (TSTA) and tumor antigen (TA). A unique rat embryo cell line transformed by a temperature-sensitive A mutant that loses TA during exposure to the nonpermissive temperature (A28-RE) was found to lose TSTA. On the other hand, a typical control tsA-transformed cell line (A239-MB) expressed both TA and TSTA at the non-permissive temperature. TA in lysates obtained from A239-MB cells was found to be three to four times more thermolabile by covwt-mb) when incubated at either 33 or 40 degrees C. These data complement previous reports using TA from lytic infection and are consistent with the suggestion that TA is virus encoded. In contrast to TA, which even in wild-type-transformed cells was completely destroyed in less than 10 min at 50 degrees C, TSTA, assayed in vivo by tumor rejection, and tumor-specific surface antigen(s) TSSA) defined by an in vitro cytolytic assay, were thermostabile. Even after 24 h of incubation of extracts of 50 degrees C, high levels of TSTA and TSSA activity were present. Since these surface antigens when obtained from cells transformed by tsA mutants were also thermostabile, they could not be distinguished from the wild-type antigens. These results (i) indicate a coordinate expression of TA and TSTA in transformed cells; (ii) confirm that TA is virus encoded; and (iii) confirm that tha antigenic and immunogenic determinants that characterize TA and TSTA activities are distinct. However, the possibility that TSTA, like TA, is of viral rather than cellular origin is not excluded.

Animals↗

Biological and biochemical studies of cells transformed by simian virus 40 temperature-sensitive gene A mutants and A mutant revertants.

The growth properties of hamster cells transformed by wild-type Simian virus 40 (SV40), by early SV40 temperature-sensitive mutants of the A complementation group, and by spontaneous revertants of these mutants were studied. All of the tsA mutant-transformed cells were temperature sensitive in their ability to form clones in soft agar and on monolayers of normal cells except for CHLA-30L1, which was not temperature sensitive in the latter property. All cells transformed by stable revertants of well-characterized tsA mutants possessed certain growth properties in common with wild-type-transformed cells at both temperatures. Virus rescued from tsA transformants including CHLA30L1 was temperature sensitive for viral DNA replication, whereas that rescued from revertant and wild-type transformants was not thermolabile in this regard. T antigen present in crude extracts of tsA-transformed cells including CHLA30L1, grown at 33 degreeC, was temperature sensitive by in vitro immunoassay, whereas that from wild-type-transformed cells was relatively stable. T antigen from revertant transformants was more stable than the tsA protein. Partially purified T antigen from revertant-transformed cells was nearly as stable as wild-type antigen in its ability to bind DNA after heating at 44 degrees C, whereas T antigen from tsA30 mutant-transformed cells was relatively thermolabile. These results further indicate that T antigen is a product of the SV40 A gene. Significantly more T antigen was found in extracts of CHLA30L1 grown to high density at the nonpermissive temperature than in any other tsA-transformed cell similarly grown. This is consistent with the suggestion that the amount of T antigen synthesized in CHLA30L1 is large enoughto allow partial expression of the transformed phenotype at the restrictive temperature. Alternatively, the increase in T antigen concentration may be secondary to one or more genetic alterations that independently affect the transformed phenotype of these cells.

Animals↗

Expression of tumor-specific transplantation antigen in cell lines transformed by wild-type of tsA mutant simian virus 40.

The simian virus 40-induced tumor-specific surface antigen(s) (TSSA) and tumor-specific transplantation antigen(s) (TSTA)were detected in cells transformed by wild-type or temperature-sensitive mutant simian virus 40 by an antibody-mediated cytolytic assay for TSSA and an immunization test for TSTA. Cells transformed by tsA mutants, which lose their transformed phenotype when grown at nonpermissive temperatures, nonetheless do express TSSA and TSTA as well as T-antigen at both temperatures.

Animals↗

Interaction of Simian Virus 40 chromatin with Simian Virus 40 T-antigen.

We have studied the binding of the tumor antigen (T-antigen) of simian virus 40 to simian virus 40 chromatin (minichromosomes). The minichromosomes isolated from infected cells by a modification of standard techniques were relatively free of contaminating RNA and cellular DNA and had a ratio (by weight) of protein to DNA of approximately 1; their DNA was 50 to 60% digestible to an acid-soluble form by staphylococcal nuclease. Cleavage of this chromatin with restriction endonucleases indicated that the nuclease-resistant regions were randomly distributed in the population of minichromosomes, but were not randomly distributed within minichromosomes. Only 20 to 35% of these minichromosomes adsorbed nonspecifically to nitrocellulose filters, permitting binding studies between simian virus 40 T-antigen and chromatin to be performed. Approximately two to three times as much T-antigen was required to bind chromatin as to bind an equivalent amount of free DNA. When T-antigen was present in excess, both chromatin and free DNA were quantitatively retained on the filters. On the other hand, when DNA or chromatin was present in excess, only one-third as much chromatin as DNA was retained. We suggest that T-antigen-chromatin complexes may be formed by the cooperative binding of T-antigen to chromatin, whereas T-antigen-DNA complexes may be formed by simple bimolecular interactions.

Antigens, Viral↗

Team approach to management of non-Hodgkin's lymphomas: past and present.

A detailed review of our results of radiotherapy for stage I and II non-Hodgkin's lymphomas has been presented as background for our current multidisciplinary approach which uses multiple-agent chemotherapy, radiotherapy, and immunotherapy for nodular and diffuse stage I, II, and III lymphomas of the poorly differnetiated lymphocytic, mixed, and histiocytic varieties. Optimum management is based on coordinated efforts of medicine, radiotherapy, pathology, diagnostic radiology, and surgery. In stage I, II, and III disease, routine staging procedures include lymphangiography, bilateral iliac crest needle biopsies of the bone marrow, and percutaneous needle biopsies of the liver. Staging laparotomy is considered essential to our present program for stage I, IE, II and IIE disease. In our opinion, staging laparotomy is not indicated in stage II or IIIE disease. Although very preliminary, results for these programs are encouraging. This paper presents the concept of team management and a specific plan for its implementation.

BCG Vaccine↗

Clindamycin in the treatment of human ocular toxoplasmosis.

Clindamycin was used systemically and periocularly to treat six patients with ocular toxoplasmosis who had a total of eight attacks. Although it appeared to quiet the attack promptly, several side effects were noted. Transient diplopia occured after large periocular doses and papillitis resulted from retrobulbar administration. Despite its efficacy, the results do not seem to warrant high systemic doses for prolonged periods in view of its systemic toxicity. Clindamycin may be most useful as a periocular injection in moderate dosage. A controlled double-blind study is needed.

Adult↗

SV40 transformation of mouse brain cells: critical role of gene A in maintenance of the transformed phenotype.

Brain cells derived from the NIH Swiss mouse strain have been established in tissue culture. Astrocytic neuroglial cells, identified by morphology and staining properties, predominate. The brain cell culture was successfully transformed with SV40 wild type virus and with a representative early (A239) and late (C219) mutant. When subjected to growth analysis the A239 transformant displayed selective loss of six characteristics of the transformed phenotype at the restrictive temperature (40.5 degrees C): doubling time, saturation density, ability to grow in low serum, efficiency of growth on plastic and on normal brain cell layers, and cloning in soft agar. Temperature shift experiment demonstrated the reversibility of the differences in saturation density. T-antigen was expressed at both temperatures. Alteration in uptake of 2-deoxyglucose was not a characteristic of the transformed phenotype. The cell lines may be utility in brain culture work and in studies on the mechanism of SV40 transformation.

Antigens↗

Resting state in normal and simian virus 40 transformed Chinese hamster lung cells.

Normal cell deprived of amino acids or serum factors enter a resting state, whereas cells transformed by wild-type simian virus 40 do not. The ability to enter a resting state is temperature-sensitive (ts) in cells transformed by a tsA mutant of simian virus 40. We shown further: (i) that when complete medium is added to resting cells, the length of time until the onset of DNA synthesis often exceeds the length of G1 in growing cells; (ii) that the length of this interval depends upon the conditions used to arrest cell growth; but (iii) that transferring cultures from medium depleted for one factor to medium depleted in a second factor never leads to a round of DNA synthesis; and (iv) that DNA synthesis does not resume rapidly when a resting culture of cells transformed by the tsA mutant is transferred to the permissive temperature in suboptimal medium. A model proposing that in suboptimal conditions cells leave the cell cycle and traverse a branch pathway to enter the resting state is consistent with these findings.

Cell Division↗

A comparative study to evaluate three separate computer programs for electrocardiographic interpretation.

To compare the efficiency and accuracy of three separate computer programs for interpreting electrocardiograms, 50 EKGs run on patients hospitalized in our institution were transmitted to each of the three participating computer programs. The EKGs were then inspected individually by three cardiologists who later correlated and compared their results with the interpretations provided by the computer. The computer program used by Telemed Corporation provided the greatest frequency of totally correct and clinically acceptable interpretations as well as the least number of unacceptable or incorrect interpretations. The Bonner program was an acceptable second. The Mayo-Smith program had a much larger number of disagreements with the clinical cardiologists, and was far less acceptable for clinical use in their opinion.

Diagnosis, Computer-Assisted↗