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Biomedical subjects

C Gorman

Publications and source records attributed to C Gorman.

At least 163 records · Page 9Linked to original sources
PubMed1991

A generic intron increases gene expression in transgenic mice.

To investigate the role of splicing in the regulation of gene expression, we have generated transgenic mice carrying the human histone H4 promoter linked to the bacterial gene for chloramphenicol acetyltransferase (CAT), with or without a heterologous intron in the transcription unit. We found that CAT activity is 5- to 300-fold higher when the transgene incorporates a hybrid intron than with an analogous transgene precisely deleted for the intervening sequences. This hybrid intron, consisting of an adenovirus splice donor and an immunoglobulin G splice acceptor, stimulated expression in a broad range of tissues in the animal. Although the presence of the hybrid intron increased the frequency of transgenics with significant CAT activity, it did not affect the integration site-dependent variation commonly seen in transgene expression. To determine whether the enhancement is a general outcome of splicing or is dependent on the particular intron, we also produced equivalent transgenics carrying the widely used simian virus 40 small-t intron. We found that the hybrid intron is significantly more effective in elevating transgene expression. Our results suggest that inclusion of the generic intron in cDNA constructs may be valuable in achieving high levels of expression in transgenic mice.

Animals↗
PubMed1991

The factor structure and factor stability of the hospital anxiety and depression scale in patients with cancer.

An exploratory factor analysis of the HAD was carried out in 568 cancer patients. Two distinct, but correlated, factors emerged which corresponded to the questionnaire's anxiety and depression subscales. The factor structure proved stable when subsamples of the total sample were investigated. The internal consistency of the two subscales was also high. These results provide support for the use of the separate subscales of the HAD in studies of emotional disturbance in cancer patients.

Adolescent↗
PubMed1990

Identification of primary tumour site by immunolocalization of progastricsin in metastatic adenocarcinoma.

The aspartic proteinase zymogen, progastricsin, which occurs in normal gastroduodenal mucosa and prostate, has been localized by the immunogold-silver method in formalin-fixed, paraffin-embedded sections of metastatic adenocarcinoma in lymph nodes and liver, the primary site being known in each case. Progastricsin was demonstrated in 16 of 84 lymph node metastases, including 7 of 17 from stomach, 2 of 2 from prostate, and 7 of 65 from other sites. Progastricsin was also found in 19 of 98 hepatic metastases, including 8 of 22 from stomach, 6 of 24 from pancreas, and 5 of 52 from other sites. The presence of progastricsin in a metastasis correlated well with a primary tumour in the stomach or prostate or, less significantly, pancreas. Immunolocalization of progastricsin in a histological section of metastatic adenocarcinoma may help to locate the primary site.

Adenocarcinoma↗
PubMed1990

The treatment and long-term prognosis of children with intracranial tumors: a study of 610 cases, 1950-1981.

Six hundred and ten children aged under 16 years with intracranial tumors were referred for radiotherapy between 1950 and 1981: 579 were new cases and 31 had recurrent disease after primary treatment elsewhere. Radiotherapy was completed in 93% of all cases. The actuarial survival rate for all new cases was 53% at 5 years, 46% at 10 years, 40% at 20 years, and 39% at 30 years. The oldest children (10-15 years) had the best survival and the youngest (0-2 years) had the worst survival. Children treated with megavoltage x-ray equipment (1970 to 1981) had a significantly greater survival than those treated with orthovoltage X rays (1950-1969). Overall, a direct correlation was found between survival and maximum radiotherapy dose. Children having a total excision of the tumor prior to radiotherapy showed a greater survival than those treated by a subtotal or partial tumor removal. Children treated by radiotherapy alone had a survival comparable to those treated by sub-total excision and radiotherapy. There is a striking difference in survival expectation depending on initial functional category (I to III). The overall survival rates of 428 children completing treatment for glioma were 49% at 5 years, 43% at 10 years, and 40% at 15 years. The results according to certain specific tumor sites within the cerebral hemispheres are reported. Age is an important prognostic factor in low grade and also high grade astrocytomas, children having longer survivals than adults. Sub-total or partial excision of craniopharyngiomas combined with radical radiotherapy appears to give the best long-term results. Of 73 new cases, the 5-, 10-, and and 15-year survival rates were 92%, 84%, and 79%. Recurrent craniopharyngiomas treated by surgery alone can be salvaged by further conservative surgery and radical radiotherapy. Optic gliomas are slow growing low grade astrocytomas. Survival rates at 5, 10, and 15 years for 20 children with mostly chiasmal lesions were 89%, 89%, and 78%, respectively. In 73 children with brain stem tumors, 17% remained alive for up to 15 years. The risk of CNS seeding from intracranial ependymomas depends on site of origin and grade of malignancy, with 50% incidence occurring in cases with high grade lesions situated in the posterior fossa. Survivals at 5, 10, and 15 years in 51 children were 51%, 40%, and 31%. Adjuvant chemotherapy improves survival.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1989

Recombinant human enkephalinase (neutral endopeptidase) prevents cough induced by tachykinins in awake guinea pigs.

To determine whether recombinant enkephalinase (neutral endopeptidase, EC 3.4.24.11) prevents cough induced by exogenously applied and endogenously released neuropeptides, we measured cough responses to aerosolized solutions of substance P or of capsaicin for 2 min in random-source guinea pigs before or after exposing them to aerosolized recombinant human enkephalinase. Substance P (10(-16) M) increased coughing compared with its vehicle. Enkephalinase (120 micrograms) inhibited cough induced by subsequent exposure to substance P compared with the response to substance P alone, but after further exposure to the enkephalinase inhibitor leucine-thiorphan (10(-5) M), substance P increased cough significantly. Similar results were obtained for capsaicin-induced cough. In pathogen-free guinea pigs, after they inhaled inactive recombinant enkephalinase (33 micrograms), capsaicin (10(-13) M) increased cough significantly. In contrast, after they inhaled active recombinant enkephalinase (33 micrograms), capsaicin increased cough only slightly. These results suggest that aerosolized enkephalinase reaches the sites of release or actions of endogenous neuropeptides and, by degrading them, prevents cough induced by their release. Furthermore, these studies suggest that recombinant enkephalinase might be useful in the treatment of cough and other symptoms of diseases involving peptides cleaved by this enzyme.

Aerosols↗
PubMed1988

Recombinant expression and characterization of human activin A.

Activin, which stimulates the secretion of FSH from anterior pituitary cells, is a dimer of the beta-subunits of inhibin. Two species of activin (A and AB) have been purified from ovarian follicular fluid and characterized. We have been able to biosynthetically produce recombinant human activin A by constructing stable cell lines expressing the mRNA for the beta A subunit of human inhibin. These cell lines secreted a 24 kilodalton beta A dimer which stimulated FSH secretion in cultured pituitary cells. The ability of this protein to stimulate FSH secretion was sensitive to reduction of disulfide bonds, exhibited a slow onset of action, and was blocked by actinomycin D. In addition, recombinant activin A stimulated hemoglobin accumulation in K562 cells. These data show that recombinant activin A has the biochemical properties and biological activities that have been ascribed to native activin A. In addition, these results provide an independent confirmation, and thereby a final proof, of the structure and function of activin.

Activins↗
PubMed1986

Construction and characterization of an active factor VIII variant lacking the central one-third of the molecule.

The primary structure of factor VIII consists of 2332 amino acids that exhibit 3 distinct structural domains, including a triplicated region (A domains), a unique region of 909 amino acids (B domain), and a carboxy-terminal duplicated region (C domains), that are arranged in the order A1-A2-B-A3-C1-C2. The B domain (residues 741-1648) of factor VIII is lost when factor VIII is activated by thrombin, which proteolytically processes factor VIII to active subunits of Mr 50,000 (domain A1), 43,000 (domain A2), and 73,000 (domains A3-C1-C2). To determine if the B domain is required for factor VIII coagulant activity, a variant was constructed by using recombinant DNA techniques in which residues 797-1562 were eliminated. This shortened the B domain from 909 to 142 amino acids. This variant factor VIIIdes-797-1652 was expressed in mammalian cells and was found to be functional. The factor VIIIdes-797-1562 protein was purified and shown to be processed by thrombin in the same manner as full-length factor VIII. The factor VIIIdes-797-1562 variant also bound to von Willebrand factor (vWF) immobilized on Sepharose. These results indicate that most of the highly glycosylated B domain of factor VIII is not required for the expression of factor VIII coagulant activity and its interaction with vWF.

Amino Acid Sequence↗
PubMed1985

Evidence for active synapse formation or altered postsynaptic metabolism in visual cortex of rats reared in complex environments.

Animals placed in complex environments develop greater numbers of visual cortex synapses per neuron than animals housed in standard cages. Increased numbers of synapses could theoretically arise from (i) active formation of new synapses, or (ii) selective stabilization of constitutively produced synapses. The postsynaptic location of polyribosomal aggregates appears to be an indicator of newly forming synapses. In developmental synaptogenesis and adult reactive (to injury) synaptogenesis, polyribosomes are more frequently found at spine synapses and are more likely to appear in the spine head and stem. In the visual cortex of rats from complex environments, there was a greater frequency of spine synapses associated with polyribosomes, relative to rats from individual or group cages. Furthermore, a greater percentage of these spines had polyribosomes in the head and stem region. This suggests that synapses in this region may be actively induced by neural activity arising from the complex environment experience.

Animals↗
PubMed1984

The use of iodine as a thyroidal blocking agent in the event of a reactor accident. Report of the Environmental Hazards Committee of the American Thyroid Association.

In the event of a nuclear reactor accident, radioactive materials could be released into the environment: radioisotopes of iodine could constitute a major component of such a release. Upon such exposure, radioiodines could enter the body and accumulate in an unprotected thyroid gland where they would remain for varying periods of time. A number of methods have been proposed to protect those at risk of exposure. Administration of thyroid-blocking agents (such as potassium iodide) to exposed populations could be effective, but their use has raised a number of questions since there are considerable gaps in the scientific information available about the possible effects of low-level radiation from radioiodine. In addition, there are only limited data available about potential toxic side effects of potassium iodide distributed widely to large, unsupervised populations. Concern about these issues led the American Thyroid Association to appoint a committee of its members with special interest and competence in these areas to review the problems in detail and develop an advisory statement on the questions at issue for those to whom this matter might be of concern.

Accidents↗
PubMed1983

High efficiency DNA-mediated transformation of primate cells.

Tissue culture cells from several mammalian species, including three primate lines, were transfected with recombinant vectors carrying Escherichia coli xanthine-guanine phosphoribosyltransferase or Tn5 aminoglycoside phosphotransferase dominant selectable markers. Human HeLa and SV40-transformed xeroderma pigmentosum cells exhibited stable transformation frequencies of at least 10(-3) (0.1 percent). CV-1, an African green monkey kidney cell line, could be stably transformed with the exceptionally high frequency of 6 X 10(-2) (6 percent).

Animals↗
PubMed1983

Thyroid remnant ablation: questionable pursuit of an ill-defined goal.

Ablative therapy with I-131 in 30-mCi doses, directed to postsurgical remnants in patients with differentiated thyroid cancer, reduced visible I-131 uptake to zero or nearly zero in 81% of patients but did not protect against tumor recurrence in six of 69 patients who were followed for 2-5 yr. Recurrences developed within 5-37 mo. Effectiveness of 30-mCi doses of I-131 in producing ablation did not correlate with I-131 uptake by the thyroid remnant, surgeon's estimate of remnant size, or delivered dose to the remnant in rads, calculated using reasonable assumptions. These findings emphasize the difficulty of dosimetric measurements and calculations. The value of postsurgical ablative therapy in diminishing morbidity and mortality in patients with differentiated thyroid cancer has not yet been firmly established, and until this is done we advocate a conservative, economical approach to thyroid ablation with 30-mCi treatment doses of I-131 and 1-mCi neck-scanning doses to check on effectiveness of therapy.

Adenocarcinoma↗
PubMed1982

Host-specific activation of transcription by tandem repeats from simian virus 40 and Moloney murine sarcoma virus.

The simian virus (SV40) 72-base pair (bp) tandem repeated sequences have recently been shown to function as activators or enhancers of early viral transcription. A recombinant viral genome was recently constructed by inserting 72-bp tandem repeats from the Moloney murine sarcoma virus (MSV) in place of the 72-bp repeats of SV40. Although this genome replicates in monkey kidney cells, its rate of large tumor antigen expression and replication is considerably slower than that of wild-type SV40. In mouse cells, however, equivalent levels of large tumor antigen appear to be expressed from both wild-type and recombinant genomes, suggesting a relationship between the level of enhancer activity and the host cell. To confirm this observation, we have applied a sensitive quantitative assay for gene expression based on the conversion of chloramphenicol to its acetylated forms. The gene encoding the enzymatic function chloramphenicol acetyltransferase was inserted into two vectors in which the enhancer sequences from SV40 or MSV were placed adjacent to the early SV40 promoter. The SV40 tandem repeats appear to activate gene expression to significantly higher levels in monkey kidney cells, but the MSV repeats are more active in two lines of mouse cells. These findings suggest that the tandem repeat elements may interact with host-specific molecules and, furthermore, may constitute one of the elements determining the host range of these eukaryotic viruses.

Acetyltransferases↗
PubMed1977

Hamster embryo cells transformed by herpes simplex virus: reactions with adeno-associated satellite virus (AAV) and its adenovirus helpers.

We have studied the reactions of hamster embryo cells transformed by ultraviolet-inactivated herpes simplex type 2 (333-8-9 T cells) to infections with adeno-associated satellite virus (AAV) and its adenovirus helpers. Resident HSV structural antigens were not detectable in early or late passage of 333-8-9 T cells. AAV structural antigens were not detected in these cells unless the cells were coinfected with a helper adenovirus. In early passage 333-8-9 T cells were permissive to infections with simian adenovirus SV15 whereas normal hamster cell line LSH was nonpermissive. In some late passages of 333-8-9 T cells infections with SV15 adenovirus led to the production of viruslike particles whose morphology was identical with reoviruses.

Adenoviridae↗