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Biomedical subjects

L Gross

Publications and source records attributed to L Gross.

At least 19 recordsLinked to original sources
PubMed1992

Characterization of bacteriophage T7 RNA polymerase by linker insertion mutagenesis.

Thirty-four mutants of phage T7 RNA polymerase (RNAP) were generated by linker-insertion mutagenesis and characterized with respect to their ability to carry out various steps in the transcription cycle. A number of mutants with interesting biochemical properties were identified. These include: (1) Mutant RNAPs that are catalytically active but that bind weakly to a T7 promoter; one of these mutants is affected in a region of the RNAP that exhibits homology with the sigma subunit of Escherichia coli RNAP. Another is affected in a region that has been previously implicated in the discrimination of T7 versus T3 promoters (Joho, et al., 1990). (2) Mutant RNAPs that can bind to the promoter but are transcriptionally inactive; some of these RNAPs lack catalytic activity, others are catalytically active but are unable to initiate productive transcription at a T7 promoter. Among the latter class of mutants are enzymes that appear to be weakened in their ability to melt open (or to remain associated with) double-stranded DNA; these RNAPs make only abortive initiation products and are unable to proceed to the formation of a productive elongation complex. The mutations causing this phenotype affect regions of the RNAP that exhibit homology with the catalytic site of DNA polymerase I (Delarue et al., 1990). (3) A C-terminal insertion mutant with properties similar to a previously characterized "foot" mutant (Mookhtiar et al., 1991). This RNAP appears to be defective in the very early steps of transcription and may be unable to translocate and/or empty the active site. (4) A mutant that is transcriptionally active, but is unable to complement the growth of T7 gene 1- phage. This phenotype may result from disruption of a function of the RNAP that is distinct from its role in RNA synthesis.

Amino Acid Sequence↗
PubMed1992

Spectroscopic evidence for an intermediate in the T6 to R6 allosteric transition of the Co(II)-substituted insulin hexamer.

The phenol-induced conformational transition in the insulin hexamer is known to involve a large change in structure wherein residues 1-8 of the insulin B-chain are transformed from an extended coil (T-state) to a helix (R-state). This change in protein conformation both exposes a cryptic protein pocket on each subunit to which phenol binds and forces the HisB10 zinc sites to undergo a change in coordination geometry from octahedral to tetrahedral [Derewenda, U., Derewenda, Z., Dodson, E. J., Dodson, G. G., Reynolds, C. D., Smith, G. D., Sparks, C., & Swensen, D. (1989) Nature 338, 593-596]. Substitution of Co(II) for Zn(II) at the HisB10 sites introduces a sensitive chromophoric probe of the structural and chemical events that occur during this allosteric transition [Roy, M., Brader, M. L., Lee, R. W.-K., Kaarsholm, N. C., Hansen, J. F., & Dunn, M. F. (1989) J. Biol. Chem. 264, 19081-19085]. In this study, using rapid-scannig stopped-flow (RSSF) UV-visible spectroscopic studies, we demonstrate that a transient chemical intermediate is formed during the phenol-induced conversion of Co(II)-substituted hexamer from the T-state to the R-state. Decomposition of the RSSF spectra gave a spectrum for the intermediate with d-d transitions consistent with the assignment of the intermediate as either a distorted tetrahedral or a 5-coordinate Co(II) species. Possible structures for the intermediate and the implications of these findings to the allosteric mechanism are considered.

Allosteric Site↗
PubMed1991

Unexpected, spontaneous conversion of a family of rats, from low-leukemic to high-leukemic inbred line.

From a nucleus of Sprague-Dawley rats received in 1960 from the National Institutes of Health, we have raised, by brother-to-sister mating, a colony of these animals. The incidence of leukemia in 313 females and 316 males was 1.6% and 1.2%, respectively. About 3 years ago, we observed a relatively high incidence of leukemia in offspring of a healthy female, no. 1. Among the offspring of this female, observed through 12 successive generations, there were 17 leukemias among 44 females (38.6%) and 21 leukemias among 40 males (52.5%), developing at ages varying from 6 to 11.6 months. The most frequent form of leukemia observed was acute myeloid, with a high count of myeloblasts, promyelocytes, and myelocytes; lymphatic form was relatively rare but was observed occasionally; pronounced anemia was common. In most instances, on autopsy, the pathological picture was that of an enlarged spleen and liver, with the exception of those few animals that developed lymphatic leukemia, with thymic and mesenteric lymphoid tumors. We have no satisfactory explanation for this sudden, unexpected conversion of a part of our Sprague-Dawley rat colony from low-leukemic to high-leukemic inbred line. As a working hypothesis, the possibility of a spontaneous activation of a hypothetical oncogenic virus should be considered. The high leukemic C58 inbred line of mice originated in a similar, unexplained manner [MacDowell, E.C. & Richter, M.N. (1935) Arch. Pathol. 20, 709-724]. However, leukemia developing in mice was subsequently found to be caused by a transmissible virus, whereas, thus far at least, no evidence of a transmissible virus has been found in leukemia developing spontaneously in rats.

Animals↗
PubMed1991

Out of the mainstream: sexual minorities and the mass media.

In a society dominated by centralized sources of information and imagery, in which economic imperatives and pervasive sources of values promote the search for large, common-denominator audiences, it is useful to look at the fate of those who, for one reason or another, find themselves outside of the mainstream. This paper addresses the general questions of minority perspectives in the context of the study of mass media content and effects. More specific attention is paid to the situation of lesbian women and gay men as members of the mass media audience.

Communication↗
PubMed1990

Evidence for impaired T cell DNA methylation in systemic lupus erythematosus and rheumatoid arthritis.

Procainamide and hydralazine inhibit T cell DNA methylation and induce autoreactivity in cloned CD4+ T cells. These drugs also induce an autoimmune syndrome, suggesting a possible relationship between DNA hypomethylation, T cell autoreactivity, and certain autoimmune diseases. To test this relationship, DNA methylation was studied in T cells from patients with rheumatoid arthritis and patients with systemic lupus erythematosus, and was found to be impaired. These results support a relationship between DNA hypomethylation and some forms of autoimmune disease.

Adult↗
PubMed1990

Prevention of spontaneous and radiation-induced tumors in rats by reduction of food intake.

In our previous studies carried out on inbred Sprague-Dawley rats, we reported a striking increase in the incidence of tumors following total-body gamma-irradiation [150 rads (1.5 Gy) five times at weekly intervals]. Subsequently, we observed that two or three irradiations, and to a lesser extent even a single irradiation, were sufficient to induce an impressive increase in the incidence of tumors, particularly in females. A significant reduction of the incidence of radiation-induced tumors resulted when the rats were placed on calorically restricted diet. In experiments reported here, we increased slightly the amount of food given to animals on restricted diet. In the new study, among 102 irradiated females on full diet, 91 (89%) developed tumors, as compared with 29 out of 128 female rats (23%) also irradiated but maintained on restricted diet and 43 out of 89 (48%) untreated control females. None of 77 nonirradiated females on restricted diet developed tumors. Among 65 irradiated male rats, 29 (45%) developed tumors, as compared with 5 out of 74 (7%) rats also irradiated but maintained on restricted diet. Of the 49 males in the nonirradiated groups, 2 (4%) developed tumors. There was a significant weight reduction in both females and males maintained on restricted diet; animals on restricted diet lived longer than those on full diet.

Animals↗
PubMed1990

A hypnotherapeutic approach to the improvement of compliance in adolescent diabetics.

Adolescents with insulin-dependent diabetes mellitus (IDDM) have a rate of noncompliance in our clinic of approximately 20% despite all of the usual measures aimed at securing compliance. Seven IDDM patients ranging in age from 11 to 19 years were managed in our clinic with all of our usual modalities, but all remained in long-term poor control during the 6 months immediately prior to the study. To ensure that each patient would serve as his/her own control, no changes were made in his/her management other than the addition of hypnosis. Six of the seven patients were followed for more than 6 months. No changes were made in insulin, diet, or exercise as prescribed. Posttreatment, the average HgbA1C dropped from 13.2% to 9.7%, and the average fasting blood sugar from 426 mg/dl to 149 mg/dl, values which are consistent with good compliance.

Adolescent↗
PubMed1979

Spontaneous tumors in Sprague-Dawley and Long-Evans rats and in their F1 hybrids: carcinogenic effect of total-body x-irradiation.

Rats frequently develop various tumors, many of them malignant; the majority of tumors in the females develop in the mammary glands. In primary spontaneous tumors and lymphomas virus particles cannot be found on electron microscopic examination; transmission of the tumors by filtered extracts has not been successful. In our colonies of Sprague-Dawley rats the incidence of tumors was 22% in females and 5% in males; in Long-Evans rats the incidence of tumors and 28% in females and 10% in males. In (Sprague-Dawley x Long-Evans) F1 hybrids the incidence of tumors was 67% in females and 32% in males, about twice as high as in the parental strains. Fractionated total-body x-irradiation (150 rads five times at weekly intervals) (1 rad = 0.01 gray) increased the incidence of tumors in Sprague-Dawley rats from 22% to 93% in females and from 5% to 59% in males. In Long-Evans rats, irradiation increased the incidence of tumors from 28% to 63% in females and from 10% to 42% in males. The incidence of malignant tumors was almost twice as high in irradiated Sprague-Dawley and Long-Evans rats as compared with nonirradiated animals of the same strains. Partial shielding during irradiation had no significant effect on the incidence or on the forms of tumors developing in the irradiated animals. In striking contrast to results of experiments carried out on mice, the incidence of leukemia and lymphomas was not increased in the irradiated rats, as compared with control animals.

Animals↗
PubMed1979

Attempt to immunize guinea pigs against L2C leukemia with leukemia cells inactivated by gamma irradiation.

In previous studies, intradermal inoculation of small doses of L2C leukemic cell suspensions into strain 2 guinea pigs induced immunity against challenging reinoculation with leukemic cells; however, 50% of the guinea pigs developed leukemia in the course of immunization. We have now attempted to induce immunity by inoculation of L2C leukemic cells inactivated by in vitro gamma irradiation ranging from 750 to 8000 rads (1 rad = 0.01 gray). In preliminary experiments, irradiation with 750 to 2750 rads had no significant effect on leukemogenic potency of leukemic cells; however, doses exceeding 3000 rads inactivated the leukemogenic potency of L2C cells. Eighty-nine guinea pigs that survived intradermal, subcutaneous, or intraperitoneal inoculations with irradiated (1000-8000 rads) L2C cells were subsequently challenged by reinoculation with nonirradiated leukemic cells, and 83 of them (93%) developed leukemia. L2C leukemic cells contain spherical particles, about 103 nm in diameter; it is reasonable to assume that these particles represent the causative virus responsible for the development of L2C leukemia. Inactivation of leukemogenic potency of L2C leukemic cells by gamma irradiation in vitro does not necessarily imply that the virus particles consistently present in these cells were also inactivated. In previous experiments carried out on mouse leukemia, doses exceeding 1,000,000 rads were needed in order to inactivate the mouse leukemia virus in vitro.

Animals↗
PubMed1978

Relative loss of oncogenic potency of mouse leukemia virus (Gross) after prolonged propagation in tissue culture.

Since the initial development of the "passage A" mouse leukemia virus in 1957, this virus has been propagated in our laboratory by serial passage in newborn C3H(f) mice. At the present time, 10(-2)-10(-3) dilutions in physiological saline solution of this mouse-passaged virus induce lymphatic leukemia in practically all inoculated mice after a latency of 3-5 months. On the other hand, when the same virus was propagated on NIH 3T3 mouse embryo cells in tissue culture for more than 10 years, its leukemogenic potency became considerably reduced. Recent bioassay experiments carried out in our laboratory demonstrated that after such prolonged propagation in tissue culture this virus now induced leukemia in less than 15% of the inoculated suckling C3H(f) mice; only undiluted or 10% dilutions of the tissue culture fluid (very occasionally 10(-2) or 10(-3) dilutions) induced leukemia after a prolonged latency varying from 5.5 to 18 months. The passaged and the tissue-culture-grown virus strains are identical immunologically and indistinguishable in their morphology when examined by electron microscopy. The tissue-culture-grown virus, attenuated in its leukemogenic potency, does not, however, confer immunity against a challenge with the mouse-passaged virus.

AKR murine leukemia virus↗
PubMed1977

Multiclinic double-blind comparison of triazolam and flurazepam for seven nights in outpatients with insomnia.

In this two-clinic seven-day double-blind study, 0.5 mg triazolam (Halcion) was compared to flurazepam (Dalmane) in the treatment of insomnia. Two clinical investigators completed 118 outpatients, 61 on triazolam and 57 on flurazepam. Five patients, four on triazolam and one on flurazepam, discontinued because of side effects; and three patients, one on triazolam and two on flurazepam, discontinued because of ineffectiveness of the medication. Analysis of pooled data for the 110 evaluable patients showed that 0.5 mg triazolam was significantly better than 30 mg flurazepam on the following parameters: (1) how much the medication helped the patients sleep, (2) onset of sleep, (3) duration of sleep, (4) evaluation of duration of sleep, and (5) feeling of restfulness in the morning. The trend for all other parameters favored triazolam treatment, but the values did not reach statistical significance. Side effects were similar in both groups, with drowsiness being reported most frequently. No change in efficacy indicating tolerance development during the seven days of drug administration was observed in either group.

Adolescent↗