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Biomedical subjects

P J Cohen

Publications and source records attributed to P J Cohen.

At least 19 recordsLinked to original sources
PubMed1992

Allopurinol administered prior to hepatic ischaemia in the rat prevents chemiluminescence following restoration of circulation.

Oxygen-derived free radicals produced during reperfusion may be responsible for the disturbed pathology which follows prolonged ischaemia. Measurement of hepatic chemiluminescence (low level light emission resulting from the energy released during chemical reactions of free radicals) allowed determination of whether allopurinol could prevent formation of oxygen-derived free radicals during reperfusion of the ischaemic liver. While control animals demonstrated a burst of light emission shortly after reperfusion, the rats pretreated with allupurinol showed no evidence of chemiluminescence during either ischaemia or reperfusion. It is concluded that allopurinol may modify reperfusion-induced free radical formation and possibly ameliorate the organ damage which can follow ischaemia.

Administration, Oral↗
PubMed1992

Cultured human Langerhans cells process and present intact protein antigens.

Epidermal Langerhans cells (LC) undergo profound phenotypic and functional alterations when cultured for 2 to 3 d. To determine whether the in vitro culture of human LC modulates their capacity to process and present intact protein antigens, we compared the ability of freshly isolated LC (fLC) and cultured LC (cLC) to stimulate in vitro T-cell proliferative responses to recall antigens. We found that human fLC and cLC were able to process and present recall antigens to primed T cells, inducing significant proliferative responses. For tetanus toxoid and Candida albicans extract, T-cell proliferative responses at 6 d to antigen-pulsed fLC were slightly greater than responses to antigen-pulsed cLC. For live influenza A virus, the T-cell responses induced by antigen-pulsed cLC were comparable or slightly greater compared with fLC. Allogeneic T-cell proliferation for both LC preparations were also comparable. The exogenous pathway of antigen processing was demonstrated by chloroquine inhibition.

Antigens↗
PubMed1992

Phorbol myristate acetate-induced lung injury: involvement of reactive oxygen species.

Using lucigenin-enhanced chemiluminescence, isolated rat lungs perfused with physiological salt-Ficoll solution were studied to test whether phorbol myristate acetate (PMA)-induced lung injury was mediated by reactive oxygen species (ROS). PMA (0.03 micrograms ml-1) caused small but significant increases in lung ROS levels and pulmonary arterial perfusion pressure (Ppa) but did not induce lung oedema. PMA (0.15 micrograms ml-1) induced lung oedema with large increases in ROS production and Ppa. Superoxide dismutase (SOD) inhibited the increases in ROS, Ppa, and lung oedema. Catalase and dimethylthiourea inhibited lung oedema but did not attenuate the increases in ROS and Ppa entirely. Indomethacin attenuated lung oedema partially but did not inhibit the increases in ROS and Ppa. These data indicate that PMA-induced lung injury is dependent on PMA concentration and ROS are responsible for such lung injury. Thromboxane plays a minor role for PMA-induced lung injury. The different effects of oxygen radical scavengers suggest that different radical species contribute to the increased pulmonary vascular response and lung injury.

Acridines↗
PubMed1990

Continuous in vivo measurement of hepatic lipoperoxidation using chemiluminescence: halothane and chloroform compared.

Hepatic necrosis, rarely occurring after administration of modern halogenated general anesthetics, has been ascribed to free radical-induced lipoperoxidation. As evaluation of hepatic chemiluminescence has been shown to provide a noninvasive assay for oxidative radical reactions, we have made continuous in vivo measurements of hepatic light output in the phenobarbital-induced halothane anesthetized rat and compared them with observations made during chloroform anesthesia. Chloroform produced a far more rapid and more profound increase in chemiluminescence, a phenomenon probably related to depletion of hepatic glutathione. These findings are consistent with significant differences in hepatic pathology associated with the two agents.

Animals↗
PubMed1990

Dysplastic nevi and malignant melanoma.

The incidence of melanoma has been steadily increasing, with a trend for this tumor to develop at younger ages. The only satisfactory treatment for melanoma is early intervention; therefore, routine screening for melanoma and dysplastic nevi during the general physical examination is important. The prevalence of dysplastic nevi is estimated to be 2 to 5 percent. Patients with dysplastic nevi appear to have at least a 6 percent lifetime risk of melanoma. In the most severely affected patients (those with a family history of dysplastic nevi and more than one melanoma), the lifetime risk may exceed 50 percent. Patients with dysplastic nevi merit periodic follow-up. Since these nevi tend to be familial, close relatives of affected patients may also benefit from a screening examination. Individuals at increased risk for melanoma may display one or more of the following risk factors: dysplastic nevi, freckling, tendency to sunburn and numerous common nevi. Such individuals may benefit most from education in sunburn avoidance, sunscreen use and self-examination for changing nevi. A better informed public and heightened physician awareness are the most effective means of reducing mortality from this virulent malignancy.

Diagnosis, Differential↗
PubMed1989

Hyperbaric pressure does not affect the analgesia produced by nitrous oxide in the mouse.

Hydrostatic pressure antagonizes some, but not all, of the phenomena associated with general anaesthesia. For example, while unconsciousness produced by general anaesthesia in a wide variety of species is reversed by compression, anaesthetic-induced inhibition of synaptic transmission is potentiated by application of pressure. To date, the effect of pressure on analgesia has not been evaluated. In this study, hyperbaric pressure of 75 ata did not antagonize analgesia which had been produced by exposure of mice to 1.2 ata of nitrous oxide. However, the same hyperbaric pressure restored righting in animals which had been anesthetized with 1.5 ata of nitrous oxide. These data add to the suggestion that the multiple effects of general anaesthetics may be mediated at different loci.

Analgesia↗
PubMed1989

The Muir-Torre syndrome: a disease of sebaceous and colonic neoplasms.

The Muir-Torre syndrome of sebaceous neoplasms of the skin, with or without keratoacanthomas, and multiple low-grade visceral malignancies with prolonged survival is a rare disorder. Colonic polyps are frequently present, and the syndrome appears to be familial. We report 2 unrelated patients with the Muir-Torre syndrome. Each case exhibited sebaceous adenomas. Gastrointestinal findings included colonic adenocarcinomas and a tubulovillous adenoma. Although an unusual disease, the Muir-Torre syndrome requires recognition because these patients are at risk for multiple primary malignancies and may have family members also at risk.

Adenocarcinoma↗
PubMed1988

Meningeal carcinomatosis in the VX2 rabbit tumor model: detection with Gd-DTPA-enhanced MR imaging.

Meningeal carcinomatosis developed in 14 of 14 New Zealand White rabbits after infusion of a VX2 tumor cell suspension into the cisterna magna. All died or were killed 7-15 days after inoculation. Within days of the tumor infusion, magnetic resonance (MR) imaging with gadolinium-diethylenetriaminepentaacetic acid (DTPA) at 0.5 or 1.5 T demonstrated enhancement of the cerebrospinal fluid (CSF) secondary to disruption of the blood-CSF barrier by plaquelike lesions along the meninges. Eventually, meningeal enhancement was observed along the base of the brain and cervical spine. Quantitative assessment of the contrast enhancement on T1-weighted images revealed an increase in mean signal intensity of 213% +/- 130%. Contrast enhancement was not observed in four control animals who received an infusion of cell culture medium. These results demonstrate in an animal model that contrast material-enhanced MR imaging can be used to detect meningeal carcinomatosis by revealing breakdown of the blood-CSF barrier.

Animals↗
PubMed1987

Immunopathological changes after multiple spider bites.

Utilizing a panel of immune complex assays, antigen-antibody complex formation in a 29-year-old man shortly after a spider bite was documented. The clinical picture and laboratory parameters were consistent with a serum sickness reaction. Immune hyperactivity was evidenced by a detectable autoimmune serological response. This constellation of findings may be a common attendant to arthropod envenomation.

Adult↗
PubMed1987

Ocular and cerebral metastases in the VX2 rabbit tumor model: contrast-enhanced MR imaging.

Ocular and cerebral metastases developed after the inoculation of a VX2 tumor cell suspension into the internal carotid artery of 15 rabbits. The hematogenous spread of tumor cells resulted in ocular metastases in 13 of 15 animals (86.7%) and cerebral system metastases in 14 of 15 animals (93%). Magnetic resonance (MR) imaging with Gd-DTPA demonstrated early disruption of the blood-ocular barrier and blood-brain barrier 5-7 days after infusion of tumor cells. Quantitative assessment of contrast enhancement revealed a mean increase in signal intensity of 145% +/- 51% in the anterior chambers, 102% +/- 70% for choroidal metastases, and 51% +/- 29% for central nervous system (CNS) metastases. These results indicate that contrast-enhanced MR imaging can be used to demonstrate a loss of blood-ocular barrier integrity that is similar to the breakdown of the blood-brain barrier associated with metastatic tumors to the CNS and eye.

Animals↗
PubMed1987

A reproducible model of metastatic brain and ocular tumor by hematogenous inoculation of the VX2 tumor in rabbits.

A metastatic brain-tumor model has been developed in rabbits by infusing the VX2 carcinoma into the internal carotid artery to simulate hematogenous dissemination of tumor. In a series of 25 New Zealand White rabbits, multiple metastases arose in the hemisphere of 24 (96%) and in the eye of 22 (92%); in all instances ocular metastases were ipsilateral to the site of infusion. Ocular metastases were visible in the anterior chamber in 80% of animals 3 to 12 days after the infusion of VX2 tumor cell suspension. All rabbits deteriorated neurologically or died by Day 15 after the inoculation. Multiple metastases were demonstrated by magnetic resonance imaging as early as 5 to 7 days after infusion of the tumor cells and were confirmed at autopsy. This technique models hematogenous metastases to the brain and eye and is useful in evaluating the response of metastases to chemotherapy and radiation therapy directed to the brain and eye.

Animals↗
PubMed1987

The immunopathology of sequential tumor biopsies in patients treated with interleukin-2. Correlation of response with T-cell infiltration and HLA-DR expression.

Sequential tumor biopsies from 9 patients with disseminated cancers were obtained before, during, and after treatment with interleukin-2 (IL-2) with or without the adoptive transfer of lymphokine-activated killer (LAK) cells. Infiltrating lymphoid and tumor cells were characterized in frozen sections by the use of monoclonal antibodies and the avidin-biotin complex (ABC) immunoperoxidase technique. Five patients had objective tumor regression (1 complete response of a follicular lymphoma, 4 partial responses of melanomas). Four patients (2 melanomas, 1 renal cell carcinoma, 1 breast carcinoma) were nonresponsive after treatment. After treatment, responsive tumors showed a pronounced infiltration of T cells, mainly Leu-2+ (CD8, primarily cytotoxic/suppressor) cells. Macrophages, although increased, were fewer than the T cells, and Leu-7+ or Leu-11+ (NK and K) cells were virtually absent. In nonresponders, there was no significant increase in lymphoid cells after therapy, and no differences were noted between groups before therapy. In 4 of 5 responders, tumor cells were positive for HLA-DR before therapy; and in the remaining responder, the tumor became positive during treatment. Tumor cells in all biopsy specimens from nonresponders were DR- before and after the start of therapy. It is concluded that the expression of HLA-DR by tumor cells may play a role in the response to IL-2 with or without LAK and that marked infiltration by T cells accompanies, and possibly mediates, such a response.

Adult↗
PubMed1987

Hepatic dysfunction after isoflurane anesthesia.

Four members of the Anesthetic and Life Support Advisory Committee of the Food and Drug Administration assessed the contribution of isoflurane (Forane) to 45 instances of hepatic dysfunction after isoflurane anesthesia reported to the FDA for 1981-1984. For 29 (64%) of the cases, at least three members concluded that nonanesthetic causes (e.g., hypoxia, sepsis, viral infection) explained the hepatic injury. For 16 cases (36%), two or more members concluded that isoflurane might be one of several possible causes of the hepatic injury. In the latter cases, patients tended to be younger, had undergone anesthesia of shorter duration for operations outside the chest and abdomen, had developed symptoms later, had higher plasma transaminase values but lower bilirubin values, and had a lower incidence of eosinophilia, anemia, transfusions, and congestive heart failure. The committee concluded that current evidence does not indicate a reasonable likelihood of an association between the use of isoflurane and the occurrence of postoperative hepatic dysfunction.

Adolescent↗
PubMed1986

Is chemiluminescence an index of hepatic lipoperoxidation accompanying chloroform anesthesia?

Hepatic lipoperoxidation by highly reactive metabolites produced during biodegradation of chloroform is believed to cause delayed hepatic necrosis. Chemiluminescence occurs during interaction of these metabolites with a lipid membrane. We have made continuous in vivo measurements of hepatic light output in the phenobarbital-induced rat breathing either air or chloroform vaporized in air. The data permitted direct estimation of the time course of chloroform-induced lipoperoxidation. These potentially toxic events began 15 min after initiation of anesthesia and continued for the duration of the study. Chemiluminescence did not occur with inhalation of isoflurane, an anesthetic undergoing minimal biodegradation.

Anesthesia↗
PubMed1986

Isolation of a rat liver delta-aminolevulinate dehydrase (ALAD) cDNA clone: evidence for unequal ALAD gene dosage among inbred mouse strains.

We have isolated several cDNA clones encoding delta-aminolevulinate dehydrase [ALAD; porphobilinogen synthase; 5-aminolevulinate hydro-lyase (adding 5-aminolevulinate and cyclizing), EC 4.2.1.24], the second enzyme in the heme biosynthetic pathway. We used a rabbit polyclonal antibody developed against the purified 35-kDa subunit of rat liver ALAD to screen a lambda gt11 cDNA expression library constructed from rat liver mRNA. A prototype clone (ALAD-1) contained a 680-base-pair insert and expressed a 140-kDa beta-galactosidase gene cDNA insert fusion protein immunoreactive with both polyclonal and monoclonal anti-ALAD. Identity of ALAD-1 was verified by hydridization to ALAD mRNA that had been enriched via immunopurification of rat liver polysomes with anti-ALAD. Intensity of such hybridization to a 1500-nucleotide-long mRNA was approximately equal to 200-fold greater than that realized with whole liver mRNA, a result consistent with the degree of immunoenrichment of ALAD mRNA found independently by analysis of cell-free translation products. A second ALAD cDNA clone (ALAD-3) was isolated when the rat liver cDNA expression library was rescreened with ALAD-1. The identity of both ALAD cDNA clones was established by correspondence between their nucleotide sequence and the reported amino-terminal protein sequence of bovine ALAD. Hybridization of ALAD cDNA to mouse genomic DNA indicates that the previously unexplained incremental differences in ALAD enzymatic activity among inbred mouse strains has arisen through alterations in ALAD gene dose.

Amino Acid Sequence↗