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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↗
PubMed1988

Inhibition of the development of tumors or leukemia in mice and rats after reduction of food intake. Possible implications for humans.

Recent data referring to the influence of a restricted diet on the incidence of radiation-induced tumors and leukemia in rats and mice are reviewed. The incidence of tumors developing in rats exposed to total-body gamma irradiation was reduced from 93% to 35% in female rats and from 59% to 7% in male rats after restriction of food intake. In a similar study carried out on mice, the incidence of leukemia in irradiated mice of both sexes was reduced from 50% to 4% after restriction of food intake. Radiation-induced leukemia in mice is caused by a transmissible virus activated by total-body gamma irradiation. In most of the animal species investigated thus far, tumors, leukemia, and lymphomas were found to be caused by transmissible viruses. It appears that activation of some of these latent viruses could be prevented by restriction of food intake. If the results of experiments carried out on mice and rats are extrapolated for humans, it would follow that all of us (particularly those who have had multiple cases of cancer or leukemia among family members) should aim at holding our weight below the limits considered normal for our age, sex, and height. This appears particularly important for persons that have been exposed to large doses of ionizing radiation.

Animals↗
PubMed1988

Incidence and nature of tumors induced in Sprague-Dawley rats by gamma-irradiation.

In our previous studies carried out on inbred rats of the Sprague-Dawley strain (L. Gross and Y. Dreyfuss, Proc. Natl. Acad. Sci. USA, 76: 5910-5913, 1979), the tumor incidence was increased following irradiation (150 rads, 5 times, at weekly intervals), from 22 to 93% in females and from 5 to 59% in males. Experiments here reported suggest that 2 consecutive total-body gamma-irradiations of 150 rads each are sufficient to induce in rats the development of tumors, some malignant; 18 of 19 females (94.7%) developed tumors at an average age of 11.4 mo, and seven of the 14 males in this group (50%) developed tumors at an average age of 10.4 mo. In the second group, which received 3 consecutive gamma-irradiations, 20 of 23 females (86.9%) and 5 of 13 males (38.4%) developed tumors at average ages of 9.1 and 7.5 mo, respectively. In the third group, among rats which received 4 consecutive gamma-irradiations, 17 of 19 females (89.4%) and 4 of 12 males (33.3%) developed tumors at average ages of 9.4 and 10.5 mo, respectively. The etiology of tumors either developing spontaneously or induced by irradiation in rats remains to be clarified. Our attempts to detect virus particles by electron microscopy in such tumors or lymphomas have not been successful. As a working hypothesis, we are tempted to theorize that tumors or lymphomas developing spontaneously or induced by gamma irradiation in rats are caused by latent viral agents which are integrated into the cell genome and are cell associated, i.e., not separable from the rat tumor cells by conventional methods thus far used.

Animals↗
PubMed1988

Plasma levels and therapeutic response with trimipramine treatment of endogenous depression.

In a 6-week, double-blind study involving 34 endogenously depressed patients, plasma trimipramine levels of two dosage groups, 75-mg/day and 150-mg/day, were compared with regard to clinical efficacy as determined by scores on the Hamilton Rating Scale for Depression, the Clinical Global Impressions scale, and the Zung Self-Rating Depression Scale. Both dosage levels of trimipramine produced prompt, consistent, and progressive antidepressant effects. No correlation between plasma levels and clinical efficacy was found.

Adult↗
PubMed1987

Isolated gonadotropin-releasing hormone neurons harvested from adult male rats secrete biologically active neuropeptide in a regular repetitive manner.

Immunochemical treatments for the recovery of viable GnRH neurons from adult male rats have previously been described by this laboratory. In the present report, efforts were made to limit cellular adhesion, as well as the proteolytic and mechanical damage which occurred during isolation of the neurons, in order to determine if such damage may account for failure of the isolated cells to exhibit spontaneous neuropeptide release. These modifications prevented the loss of assayable GnRH during the isolation process, and neurons recovered from individual rats in this study contained 10.7 +/- 2.5 ng GnRH. Further, all isolated neuronal preparations exhibited spontaneous peptide release which continued in a regular repetitive manner. When maintained in closed chambers, these preparations released 105 +/- 42 pg/ml biologically active GnRH at 18.9 +/- 0.4-min intervals. In contrast, GnRH release from heterologous preparations was characterized by erratic low level pulses. The results from this work suggest that independent neuroendocrine properties of GnRH neurons may be responsible for tonic gonadotropin secretion in castrated adult male rats and that the erratic patterns of gonadotropin release in gonadally intact males may be related, in part, to coupling between GnRH neurons and unidentified neuronal factors.

Animals↗
PubMed1987

Steroid effects on the secretory modalities of gonadotropin-releasing hormone release.

GnRH neurons isolated immunochemically from the brain of adult male rats were used to determine whether testosterone (T), dihydrotestosterone (DHT), estradiol-17 beta (E(2)17 beta), 20H-estrone (OHE1), or progesterone (P4) have a direct effect on the spontaneous neurosecretion and/or cellular content of GnRH. Neurons harvested from individual rats were treated with a single steroid pulse; samples were collected before treatment, during the steroid pulse, and at 24 h post treatment. Androgen treatments of 100 pg/ml or 1 ng/ml media elicited an increase in GnRH pulse frequency 1-6 min after steroid exposure without affecting the amplitude of release; these modalities persisted at 2 h. The frequency of GnRH pulses was increased 24 h after the neurons received the brief 100 pg/ml or 1 ng/ml T or 1 ng/ml DHT treatments. Neurons exposed to androgen treatments also appeared to express large amplitude GnRH pulses infrequently at this time whereas there was no androgen affect on the cellular GnRH concentration. In contrast, E(2)17 beta, OHE1, and P4 treatments had no affect on the mean media GnRH concentration, baseline GnRH concentration, or on the frequency and amplitude of GnRH pulses at any time point. However, the 1 ng/ml P4 and the 1 ng/ml OHE1 treatments both reduced cellular GnRH content at 48 h post treatment. These results suggest that T and DHT may specifically interact with GnRH neurons to elicit immediate and/or long-term changes in the modalities of neuropeptide release and that under physiological conditions GnRH neurons of adult male rats are not directly influenced by E(2)17 beta, the catecholestrogen OHE1, or P4.

Animals↗
PubMed1986

Adult-type osteopetrosis presenting as carpal tunnel syndrome.

We describe a patient with adult-type osteopetrosis presenting as carpal tunnel syndrome. Radiographs demonstrated sclerosis of the carpal bones, bone biopsy revealed wide bone spicules containing areas of cartilage, and electrophysiologic studies confirmed the diagnosis of median nerve entrapment in the carpal tunnel. Any condition which alters the size or shape of the carpal canal or its contents may result in median nerve compression.

Bone and Bones↗
PubMed1986

Inhibition of the development of radiation-induced leukemia in mice by reduction of food intake.

We have reported previously that the incidence of tumors induced in Sprague-Dawley rats by total-body gamma-ray irradiation can be considerably reduced by restriction of food intake [Gross, L. & Dreyfuss, Y. (1984) Proc. Natl. Acad. Sci. USA 81, 7596-7598]. In experiments reported here we investigated the influence of reduced food intake on the development of radiation-induced leukemia in C3H(f) mice. The incidence of spontaneous leukemia in mice of this strain does not exceed 0.5%, but it can be considerably increased by total-body x-irradiation. In our study, two groups of C3H(f) mice were submitted to fractionated total-body gamma-irradiation (150 rads, five times at weekly intervals; 1 rad = 0.01 gray). The first group received a full ad lib diet (4.5-5.4 g of Purina Rodent Lab Chow pellets per day, each). In this group 31 out of 58 females (53.4%) and 24 out of 50 males (48%) developed leukemia at an average age of 8 months. In the second group, consisting of sisters and brothers of the first group, and submitted to the same gamma-irradiation but receiving a restricted diet (2 g of Purina Lab Chow pellets each, followed by 3 g on alternate days), only 2 out of 55 females (3.6%), and 1 out of 36 males (2.8%), developed leukemia at an average age of 9 and 12 months, respectively. Leukemia in both groups was predominantly of the lymphatic or lymphoblastic form, the leukemic cells infiltrating most organs, particularly the thymus, mesenteric and peripheral lymph nodes, spleen, liver, kidneys, and bone marrow; in most instances the peripheral blood was also leukemic.

Animals↗
PubMed1986

C-type virus particles in spontaneous and virus-induced leukemia and malignant lymphomas in mice and rats.

The presence and numbers of C-type virus particles in an animal model consisting of mice and rats with either spontaneous or virus-induced leukemia and lymphomas were studied, in order to determine the relation of the appearance of virus particles to viral etiology of such neoplasms. The numbers and distribution of C-type virus particles in organs from 13 mice with spontaneous leukemia and lymphomas were compared with the presence of virus particles in organs of 13 mice with leukemia and lymphomas induced by passage A (Gross) virus inoculation. C-type virus particles were present in organs of all mice with either spontaneous leukemia or leukemia and lymphomas induced by virus inoculation. However, the number of particles observed was significantly higher in those mice in which leukemia was induced by virus inoculation. Virus particles were also observed, but in substantially smaller numbers, in organs of 13 of 25 untreated, healthy mice of the nonleukemic C3H(f) inbred line. In contrast to mice, C-type, or any other virus particles, were not found in organs of 10 Sprague-Dawley, Long-Evans or Sprague-Dawley X Long-Evans F1 hybrid rats with spontaneous leukemia. However, C-type virus particles were consistently present in organs of 11 Sprague-Dawley rats with leukemia induced by rat-adapted passage A (Gross) mouse leukemia inoculation. The virus particles appeared in the organs of the inoculated rats 5 days after i.p., and 11 days after s.c. inoculation. Virus particles were not found in organs of 10 healthy untreated Sprague-Dawley rats. The implications of these observations are discussed.

Animals↗