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Biomedical subjects

N Green

Publications and source records attributed to N Green.

At least 73 records · Page 4Linked to original sources
PubMed1983

Effect of ethanol on vascular prostacyclin (prostaglandin I2) synthesis, platelet aggregation, and platelet thromboxane release.

A series of experiments with platelets from healthy volunteers showed a concentration related inhibitory effect of ethanol on platelet aggregation and release of thromboxane A2. This effect was observed at blood alcohol concentrations ranging between 66 and 132 mg/dl (14.3 and 28.6 mmol/l), which are commonly found in alcoholics. Investigations carried out by incubating ethanol with platelet rich plasma in vitro also showed an inverse linear correlation between ethanol concentration and platelet thromboxane synthesis. In contrast, the incubation of a wide range of concentrations of ethanol with human endothelial cells and rat aortic rings did not alter the ability of these systems to synthesise prostacyclin (prostaglandin I2). This finding of a selective inhibition of thromboxane A2 synthesis and platelet aggregation without an alteration of prostaglandin I2 synthesis may provide an explanation for the reported ethanol mediated protection against vascular disease. This effect of ethanol may also be relevant to the induction of acute gastrointestinal haemorrhage that occurs after bouts of excessive alcohol consumption.

Adenosine Diphosphate↗
PubMed1983

Induction of tolerance in influenza virus-immune T lymphocyte clones with synthetic peptides of influenza hemagglutinin.

Antigen-specific human T cell clones specific for defined peptides of influenza A hemagglutinin were found to be rendered unresponsive by incubation with moderately high concentrations of antigen. This was the case whether the synthetic peptide antigen was present for the duration of the culture or the cloned T cells were preincubated with antigen for 3-18 h at 37 degrees C, before stimulation with T-depleted irradiated sheep erythrocyte non-rosette-forming lymphocytes (E-) pulsed with the optimal dose of peptide. Tolerance could not be overcome by culture with various numbers of E- cells and antigen. The induction of unresponsiveness was antigen specific, since it depended upon incubation with the appropriate peptide recognized by that clone. In addition, the tolerant T cells remained unresponsive to stimulation with the specific peptide for at least 7 d after induction even though maintained in culture in the presence of T cell growth factor. This state of antigen-specific unresponsiveness is akin to immunological tolerance. Furthermore, the experiments reported here demonstrate that the helper T cell clone can be inhibited by the relevant peptide in the absence of any suppressor cells or their precursors. This suggests that antigen-induced unresponsiveness need not always depend on the presence of suppressor T cells. The induction of tolerance in T cell clones does not result in early T cell death, since cells that no longer proliferate in response to the specific antigen and accessory cells still proliferate in response to T cell growth factor.

Antibodies, Viral↗
PubMed1983

Antibodies that react with predetermined sites on proteins.

Contrary to previous predictions, relatively short synthetic peptides that mimic part of a protein sequence are routinely capable of eliciting an antiserum that reacts with the partially mimicked protein. Peptides capable of eliciting protein-reactive serums are frequently represented in the primary sequence of a protein, can be characterized by a set of simple chemical rules, and are confined neither to immunodominant regions of intact proteins nor to the amino or carboxyl terminals. As such, synthetic peptide immunogens are valuable for eliciting reagents with predetermined specificity that can be used for basic research. In addition, some synthetic peptides are capable of mimicking regions of virus proteins and eliciting immune responses in animals that are protective against the viral agents. Such peptides may thus serve as the basis for safe, chemically defined synthetic vaccines.

Antibody Specificity↗
PubMed1983

Radiation therapy in bulky seminoma.

Between 1969 and 1980, 17 patients with bulky retroperitoneal seminoma and 1 patient with bulky mediastinal seminoma were treated with radiation therapy. One patient had resection of gross retroperitoneal disease, and 1 patient had resection of gross mediastinal disease. Fifteen patients received adjuvant irradiation to the mediastinum and paraclavicular lymph nodes, and 1 patient received adjuvant chemotherapy. At last follow-up, 17 of 18 patients (94%) remain free of disease. No patient has sustained treatment-related morbidity or mortality.

Dysgerminoma↗
PubMed1983

The avoidance of small intestine injury in gynecologic cancer.

The evolution of systematized operative staging and radical surgical procedures in the management of gynecologic cancer has increased the complexities of integrating radiation therapy. High dose irradiation to large treatment volumes has been associated with an increased incidence of small intestine injury. This complication is morbid and often fatal. Although predisposing factors have been extensively studied, there has been a paucity of reports evaluating preventative measures. Between 1975 and 1980, 140 patients with gynecologic cancer were treated at the Valley Presbyterian Hospital in the Division of Radiation Therapy. Twenty-six patients with cervix cancer received definitive irradiation and seven received adjunct irradiation. Seventy-two with corpus cancer received adjunct irradiation, seven received definitive irradiation and three palliative irradiation. Eleven patients with ovarian cancer received adjunct irradiation and 15 palliative irradiation. Eight-five patients were at potential risk for small intestine injury and had treatment planning small intestine X rays. Fixation was observed in 7/39 (18%) without prior pelvic surgery and 30/46 (65%) with prior pelvic surgery. Information from the small intestine X rays were used in 41 patients to make 60 treatment modifications. Twenty-five of 140 (17%) had a reduction of total dose, 26/140 (18%) had exclusion of the small intestine by shrinking fields, or patient positioning and 13/140 (9%) had displacement of the small intestine by distention of the bladder. No patient developed small intestine injury. The disease free survival for cervix cancer was 27/33 (82%), corpus cancer 68/79 (86%) and ovarian cancer 5/11 (45%). Pelvic failure was observed in 19/123 patients who received definitive or adjunct irradiation. One patient with corpus cancer and three patients with ovarian cancer might have benefited from the use of a larger treatment volume or a higher total dose.

Adult↗
PubMed1983

Reassessment of radiation therapy for the management of lung cancer in patients with chronic pulmonary disease.

Surgery has remained the mainstay of definitive treatment for lung cancer. Radiation therapy has been advocated when the location of the lung cancer precludes resection or the severity or the cardiopulmonary impairment indicates that the patient cannot withstand the proposed resection. Extended field irradiation has been shown to improve tumor control and survival. However, in patients with chronic pulmonary disease, extended field irradiation may exacerbate pulmonary insufficiency and compromise survival. Between 1975 and 1980, 29 patients with lung cancer and chronic pulmonary disease were treated by involved field irradiation (IFR). This was compared to the experience of 41 patients who had been treated prior to 1975 by extended field irradiation (EFR). The frequency of subjective response and tumor control were comparable in each group. One patient treated by IFR developed a marginal recurrence. Radiation pneumonitis was observed in 7/41 (17%) EFR patients versus 2/29 (7%) IFR. Treatment related death occurred in 2/41 (5%) EFR versus 1/29 (3.3%) IFR. One year disease free survival was 8/41 (19%) EFR versus 12/29 (41%) IFR. Two of 14 (14%) IFR patients at risk five years are alive without evidence of disease.

Aged↗
PubMed1983

Chemically synthesized peptides of hepatitis B surface antigen duplicate the d/y specificities and induce subtype-specific antibodies in chimpanzees.

Synthetic peptides, predicted from the nucleotide sequence of the S gene of hepatitis B virus were analyzed in terms of the established specificities of the hepatitis B surface antigen. The analysis indicated that the group-specific alpha antigen is composed of at least three nonoverlapping sequences and that a relatively hydrophilic region of the surface antigen protein, spanning amino acid residues 110-137, specifies the major d and y subtype system. The d/y subtype appears to depend on changes in one or more variable amino acids at positions 127, 131, and 134 of the hepatitis B surface antigen protein. Peptide 49 (consisting of amino acid sequences of the y subtype for the region 110-137), coupled to a carrier protein and mixed with an adjuvant, stimulated a brisk anti-y response in chimpanzees, the relevant model of human response to hepatitis B virus immunization and infection. Experimental challenge with homologous hepatitis B virus resulted in a pattern of partial protection. The results offer promise for the application of chemically synthesized peptides as vaccines in the prophylaxis of hepatitis B virus disease.

Amino Acid Sequence↗
PubMed1983

Synthetic peptide immunogens as vaccines.

Synthetic peptide immunogens have been shown to elicit antibodies that can react with full-length proteins containing that peptide. Such antibodies are directed against a specific region of the protein chosen in advance by the investigator and so have a predetermined specificity. In basic research, these antibodies are useful in identifying the protein product of an open reading frame, localizing the gene product to particular cells or subcellular organelles, identifying the enzymatic function of a protein product, following the fate of particular regions of a product through protein maturation processes, analyzing the expression of exons following DNA rearrangements and RNA splicing, and purifying the protein by immunoaffinity chromatography techniques. In medicine, such antibodies may provide reagents for passive vaccination, antitoxin therapy, and targeted immunotherapy of neoplasia. The peptides themselves may be used as synthetic vaccines. The immediate future of the synthetic peptide immunogen in medicine is clear--the promise demonstrated in the laboratory must be reduced to safe application in the hospital. Two barriers to this are the selection of precisely the best peptide and the selection of the proper adjuvant. Currently, a brute force approach is utilized to find the best peptide for eliciting the desired antibodies. This is clearly a problem when the pathogenic organism is assayable only in man. Possibly, by combining studies on the antigenicity of the pathogenic organism with an analysis of naturally occurring variants that alter its immunogenicity, peptide selection will be made easier. Also, since the adjuvants and carriers used in the laboratory are in general too harsh for widespread use in humans and animals, much work needs to be done to find suitable adjuvants and carriers. Nonetheless, now that the major conceptual hurdle to synthetic peptide vaccines has been cleared (that is, it is not necessary to reproduce conformation exactly), it should be relatively straightforward to solve the remaining problems.

Animals↗
PubMed1983

Analysis of the antigen specificity of influenza haemagglutinin-immune human T lymphocyte clones: identification of an immunodominant region for T cells.

Human T lymphocyte clones specific for the haemagglutinin (HA) molecule of A/Texas/1/77 were maintained in long-term culture with T cell-growth factor. The clones were analysed for their viral antigen specificity using serologically defined type A influenza subtypes and chemically synthesized peptides of the HA-1 molecule. With the exception of one T cell clone that recognized only the HA molecule used for immunization, the clones responded to determinants that showed partial or complete cross-reactivity amongst the strain A subtypes. The cross-reactive population of T cell clones were specific for peptides distinct from the antibody binding sites of HA. Furthermore, one peptide located at the carboxyl terminus of the HA-1 molecule appeared to be immunodominant, although the critical residues for T cell antigen recognition within that could not be identified.

Antigens, Viral↗
PubMed1982

Lung cancer: retreatment of local recurrence after definitive irradiation.

Aggressive radiation therapy for the management of inoperable lung cancer has increased tumor control and survival. However, approximately 20% of patients continue to experience local recurrence as the sole manifestation of treatment failure. Seven hundred thirty-four patients were initially treated by radiation therapy for inoperable lung cancer, for recurrence after resection, or as adjunct postoperative therapy. Twenty-nine patients were referred for retreatment of cancer that recurred within the original treatment field. Following retreatment, 14 of 29 patients (48%) had a favorable subjective response, and 20 of 27 patients (74%) a favorable objective response. A favorable response was observed for all cell types and over a wide range of retreatment dosages. Symptomatic radiation pneumonitis developed in one patient, rib sclerosis and fracture developed in another. Th median survival after onset of retreatment was five months with a range of one month to 54 months. The clinically determined mechanisms of death were persistent intrathoracic disease in 14 of 25 patients (56%), intrathoracic disease and distant metastasis in 7 of 25 (28%), distant metastasis in 3 of 25 (12%), and unknown in 1 of 25 (4%).

Adult↗
PubMed1982

Immunogenic structure of the influenza virus hemagglutinin.

We chemically synthesized 20 peptides corresponding to 75% of the HA1 molecule of the influenza virus. Antibodies to the majority (18) of these peptides were capable of reacting with the hemagglutinin molecule. These 18 peptides are not confined to the known antigenic determinants of the hemagglutinin molecule, but rather are scattered throughout its three-dimensional structure. In contrast, antibody raised to intact hemagglutinin did not react with any of the 20 peptides. Taken together these results suggest that the immunogenicity of an intact protein molecule is not the sum of the immunogenicity of its pieces.

Amino Acid Sequence↗
PubMed1982

Differentiated function in cultured epithelia derived from thick ascending limbs.

Medullary thick ascending limbs were dissected from rabbit kidney and cultured on thin collagen membranes. The collagen membranes were supported by a special device that limited the exposed surface area to a disk 1 mm in diameter. The cells usually proliferated to form a confluent epithelial monolayer covering the collagen membrane within 8-10 days. Transepithelial voltage was measured between bridges immersed in the solutions bathing the bottom of the collagen membrane and the apical (upper) surface of the epithelium. The voltage typically was oriented positive toward the apical surface and persisted for a few weeks. Furosemide but not amiloride reduced the voltage reversibly. Both the orientation of the voltage and its reduction by furosemide are characteristic of thick ascending limbs. Therefore, the observed voltage supports the identification of the epithelial cells in culture and is evidence of differentiated function.

Amiloride↗
PubMed1982

Clinical experience with malignant pheochromocytomas.

In a 30 year period at Vanderbilt University Hospital, the affiliated Nashville General Hospital and the Nashville Veterans Administration Hospital, 64 patients with pheochromocytoma have been observed. In eight of these, the tumor proved to be malignant. Retrospective review of biologic characteristics of pheochromocytomas in this series included clinical, diagnostic imaging, chemical and histopathologic data. Aside from presence of distant metastases, none of these features had predictive value in indicating the biologic malignant nature of the primary tumor. One patient has been cured by radical surgical resection for 16 years. Three others have died with metastatic tumor and three patients are alive with metastatic tumor.

Adolescent↗
PubMed1981

Response of lymph node metastasis to sequential estrogen and radiation therapy in prostate carcinoma.

Increasingly sophisticated diagnostic studies have shown a high incidence of tumor spread to the regional lymph nodes. The status of the lymph nodes has been evaluated by noninvasive diagnostic procedures such as lymphangiography and computerized axial tomography. The applicability of these procedures has been enhanced by the use of stringent criteria. Gross lymph node metastasis can be diagnosed with considerable confidence. Serial observations of lymphangiograms and computerized axial tomograms before and two months after the administration of estrogens provide an added dimension to the interpretation of lymph node metastasis. The nature and range of the response of lymph node metastasis were observed. Survival of patients with gross lymph node metastasis treated by sequential estrogen and radiation therapy was evaluated. A total of 11/18 (61 per cent) of patients remained free of symptoms, 8/11 (74 per cent) with a favorable lymph node metastasis responsive to estrogen therapy, and 3/7 (42 per cent) with lymph node metastasis refractory to estrogen therapy. Follow-up computerized axial tomograms of the lymph nodes done at one and two years after irradiation showed a persistent favorable response. Five patients are alive with disease, and 2 patients died of the disease.

Aged↗
PubMed1981

Sequence-specific antibodies show that maturation of Moloney leukemia virus envelope polyprotein involves removal of a COOH-terminal peptide.

We followed maturation of the glycosylated envelope polyprotein Pr80env of a murine retrovirus by using antisera specific to subregions of the protein, including an antiserum directed against a synthetic peptide corresponding to the COOH-terminus of Pr80env. Shortly after synthesis and glycosylation, Pr80env is cleaved into two species, gp70 and Pr15E, that are found associated, perhaps through disulfide bonds, in infected cells. Pr15E is further cleaved at the time of virus maturation to form virus protein p15E. NH2-Terminal protein sequence analysis showed that Pr15E had an NH2 terminus in common with p15E. Pr15E, but not p15E, is precipitated by antibody against the COOH-terminal peptide; hence, p15E is missing a peptide at the COOH-terminus. Our data indicate that Pr15E is the predominant species in cells and p15E is the major species in virus.

Amino Acid Sequence↗
PubMed1981

Chemically synthesized peptides predicted from the nucleotide sequence of the hepatitis B virus genome elicit antibodies reactive with the native envelope protein of Dane particles.

Thirteen peptides corresponding to amino acid sequences predicted from the nucleotide sequence of the hepatitis B surface antigen were synthesized chemically. The free or carrier-linked synthetic peptides were injected into rabbits, and 7 of the 13 elicited an antipeptide response. Antisera against four of the six soluble peptides longer than 10 amino acids were reactive with native antigen and specifically precipitated the 23,000- and 28,000-dalton forms from Dane particles. As the hepatitis molecule had not been chosen for study because of any structural feature suggesting unique opportunities for success, these results suggest that the strategy is general and should work for any protein as long as enough domains are studied. Peptides such as these could prove to be ideal vaccines.

Amino Acid Sequence↗