Carcinoid tumour of breast diagnosed by FNA.
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Biomedical subjects
Publications and source records attributed to G R Armstrong.
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In conflict with a previous report, we find that phenolic inhibitors of lipid peroxidation (butylated hydroxytoluene [BHT] and butylated hydroxyanisole [BHA]) do not have significant inhibitory effect on galactosemic cataract formation. This is consistent with the lack of enhancement of stable products of lipid peroxidation (measured by the thiobarbituric acid assay) in the lenses of galactosemic rats. This does not imply that oxidative stress plays no role in galactosemic cataract formation (indeed, we find that galactosemic lens homogenates contain increased amounts of an Fe2+ oxidant, possibly a peroxide), but rather that BHT- and BHA-inhibitable lipid peroxidation specifically has no role to play. In instances where drugs appear to inhibit galactosemic cataract formation, other effects caused by the drugs, e.g., inhibition of feeding or induction of general detoxification pathways, must be considered.
Rats fed 1% paracetamol in the diet failed to grow and a dose-dependent inhibition of growth was observed and found to be independent of hepatoxicity. Addition of 0.5% D- or L-methionine, or L-cysteine to a diet containing 1% paracetamol restored growth. Addition of L-methionine to the drinking water was equally effective. Feeding D-cysteine or sodium sulphate were ineffective. Acute paracetamol toxicity was also prevented by D- as well as by L-methionine. It is concluded that the inhibition of growth was due to depletion of sulphur amino acids in the course of paracetamol metabolism. This was sometimes followed by episodes of liver cell injury. Since the normal human dosage of paracetamol is up to 4 g/day, which is equivalent to 1% of the diet, the possibility of induction of amino acid deficiency by chronic use of paracetamol in normal dosage is raised.
Expression of the pro-opiomelanocortin (POMC) gene was examined in normal human lymphocytes and lymphocyte cell lines infected by lymphotropic viruses. POMC gene transcripts were detected in human lymphocytes using stringent RNA-RNA hybridizations. Low transcript levels were found in normal phytohemagglutinin-stimulated peripheral blood mononuclear cells and in tonsillar T and B cells. The highest levels were found in cells infected with Epstein-Barr virus (EBV). However, T cell lines infected with human T lymphotropic viruses did not have increased levels of transcripts. The transcript levels in an EBV-transformed B lymphocyte line were not affected by dexamethasone or corticotropin-releasing hormone, known regulators of anterior pituitary POMC gene expression. Therefore, it is possible that EBV infections could result in abnormal POMC expression.
An immunological study of B cells in patients with colitis that was associated with Hirschsprung's disease was undertaken and compared with that in patients with ulcerative colitis and in normal controls. There was an appreciable increase in IgA and a decrease in IgG in both disease groups. Humoral reaction in colitis associated with Hirschsprung's disease seems to be indistinguishable from that in ulcerative colitis and possibly in other inflammatory bowel diseases.
A large mass in the popliteal fossa was found to be a leiomyoma of the popliteal vein with portions of tumour both inside and outside the vein. This is only the second recorded case of a benign smooth muscle tumour of a peripheral vein.
We present a case of diffuse malignant peritoneal mesothelioma, initially misdiagnosed as benign. Electron microscopy and immunocytochemistry proved helpful diagnostically. Using monoclonal antibodies against cytokeratin and vimentin, we compared neoplastic with normal and reactive mesothelia and we found coexpression of these two intermediate filaments in the reactive and neoplastic mesothelial but not in the normal mesothelia, supporting the suggestion that surface mesothelial cells are derived from multipotential submesothelial cells.
Seventy-two new cases of Hirschsprung's disease were seen between 1980 and 1985. Twenty-six patients (36%) developed the clinical features of enterocolitis and, of nine patients who died, colitis was the immediate cause of death in six. Histologic material was available from 20 patients with colitis; this showed nonspecific inflammation typical of Hirschsprung's colitis in 13 cases but seven had pseudomembranous colitis (PMC). Five of the patients with PMC had not recently been exposed to antibiotics. PMC was responsible for three of the six deaths from colitis. All patients with Hirschsprung's disease who develop signs of colitis should have stool testing for Clostridium difficile toxin and should be treated with an antibiotic active against Clostridium difficile.
Herpesviral infections and cellular immunity were studied in 19 patients with acquired immunodeficiency syndrome who were treated with human lymphoblastoid interferon for Kaposi's sarcoma. Before treatment, cytomegalovirus (CMV) and Epstein-Barr virus were isolated from 18 of 19 patients and 13 of 14 patients, respectively. Serum levels of interferon were measurable in all cases. Concanavalin A induced lymphocyte proliferation normally in 16 of 18 patients, but CMV induced proliferation in only nine of 18 patients. Natural killer cell activity was normal in 12 of 19 patients and was augmented in vitro by interferon in six of 19 subjects. CMV-specific HLA-restricted cytotoxic T cell activity was found in only two of 15 cases. With therapy, serum levels of interferon increased in 15 of 18 patients. There were two partial tumor remissions but no improvements in viral infections. Natural killer cell activity was decreased in 11 of 14 cases, and in vitro augmentation by interferon was absent in all five previous responders. CMV-specific T cell activity did not improve, but HLA-unrestricted cytotoxicity was increased in four of eight cases.
We report here the development of a fatal lymphoproliferative disease in a common marmoset (Callithrix jacchus) following inoculation of the Ag876 strain of Epstein-Barr virus (EBV) and of the tumor promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA). The marmoset showed antibodies against EBV capsid and early antigens (VCA, EA) but not against nuclear antigen (EBNA). EBNA was detected in impression smears from lymph nodes and liver, and the presence of the EBV genome was detected from the same organs by hydridization techniques. To our knowledge this is the first report of the oncogenicity of this strain of EBV. The need for further studies to assess the in vivo interaction between EBV and tumor promoting agents in the development of malignancies is stressed.
It is demonstrated in this study that a serum factor, a lymphocyte stimulation inhibitor (LSI), which inhibits Epstein-Barr virus (EBV)-induced lymphocyte stimulation, is a potentially useful tool in the diagnosis and monitoring of nasopharyngeal carcinoma (NPC). In a study of 25 patients with undifferentiated NPC, 20 healthy controls, and 20 patients with other head and neck tumors, LSI was found only in the NPC patients with active disease. In a more complete study of 8 patients longitudinally followed up for at least 20 months, a comparison of LSI with antibodies to a variety of EBV antigens including viral capsid antigen, early antigen, and nuclear antigen indicated that LSI levels provided a reliable and sensitive indicator of disease activity that should be added to clinical markers currently in use as monitors of disease activity in NPC.
A unique association of Epstein-Barr virus (EBV) with the undifferentiated nasopharyngeal carcinoma (NPC) is a well acknowledged phenomenon. We report here the detection of a factor present in the sera of NPC patients which inhibits the blastogenic response of lymphocytes from EBV seropositive individuals to EB virions or soluble antigens. This lymphocyte-stimulation inhibitor (LSI) was found to be associated with the IgA fraction of the serum immunoglobulins. No inhibitory activity was detected in the sera and their immunoglobulin fractions from healthy (both EBV-seropositive and seronegative) individuals and patients with other carcinomas of the head and neck region. Interestingly, the IgA-LSI was absent in the sera of NPC patients who were successfully treated and remained in remission, while it was readily detectable in the sera of NPC patients in relapse, LSI-positive IgA fractions did not inhibit mitogenic response of lymphocytes to phytohemagglutinin. Taken together, the data presented suggest that LSI is a specific inhibitor of the response of sensitized lymphocytes to EBV antigens and that it may indeed represent a marker of great clinical significance regarding undifferentiated nasopharyngeal carcinoma, particularly for its prognosis.
Fischer F 344/CRBL female rats were injected intravenously with 10(6) syngeneic 13,762 adenocarcinoma cells, and daily doses of either 10 micrograms, 100 micrograms or 1 mg Staphylococcus aureus protein A were administered intraperitoneally on days 1 through 11. The animals were sacrificed on day 12, their lungs infused with Bouin's solution, and lung metastases counted. A significant reduction in the number of visible metastatic nodules was observed in the animals given 100 micrograms and 1 mg of Staphylococcus aureus protein A daily.
Four steroids and one protease inhibitor were evaluated for their effects on 12-O-tetradecanoyl phorbol 13-acetate (TPA)-induced and Epstein-Barr virus-induced early antigens (EBV-EA) in Raji cells. Continuous treatment with dexamethasone, prednisolone, hydrocortisone and cortisone inhibited TPA-induced EBV-EA to varying degrees, but the protease inhibitor N-alpha-p-tosyl L-lysine chloromethyl ketone-HCl (TLCK) had no significant effect. None of the agents tested inhibited EBV- induced EA. In addition, the effect of the steroids was reversible since the removal of these agents resulted in recovery of the percentage of EBV-EA-positive cells in TPA-treated cultures. These results were in agreement with the in vivo experiments of other investigators, who demonstrated inhibition of tumor promotion with steroids. Since TLCK failed to inhibit TPA-induced EA, it is unlikely that induction of EA by TPA is the result of production of proteases.
One of six white-lipped marmosets inoculated with cell-free B95-8 virus developed diffuse malignant lymphoma. Epstein-Barr virus (EBV) DNA was detected in a pathologically enlarged mandibular lymph node by DNA-DNA hybridization. The affected animal at the time of killing had EBV antibody titers of 1:320 for viral capsid antigen (VCA) and 1:20 for early antigen (EA) while all non-diseased animals had less than or equal to 1:80 VCA antibody and no detectable EA antibody. This is the first report of lymphoma development in a white-lipped marmoset following EBV inoculation.
The in vitro sensitivity of oncogenic herpesviruses, Epstein-Barr virus (EBV), and Herpesvirus saimiri (HVS) to human interferon produced by normal human leukocytes (Le), lymphoblastoid cell lines (LYI), and diploid fibroblasts (Fi) was studied. Four virus strains were used: HVS S295C, the highly oncogenic HVS S396-O, the transforming B95-8 strain of EBV, and the nontransforming P3HR1 strain of EBV. All interferons were active when applied to the cells after absorption of HVS and P3HR1-EBV, although different amounts were required to achieve 50% inhibition of HVS-induced cytopathic effect or EBV-induced early antigen (EA) expression. Transformation of human umbilical cord blood lymphocytes (HCBL) by the B95-8 strain of EBV was prevented only by Le and LYI. In these experiments, the most effective inhibitor of the oncogenic herpesviruses was Le, and the least effective was Fi. The effect of polynucleotides poly(I).poly(C) and the complex of poly(I).poly(C) with poly-L-lysine and carboxymethylcellulose on HVS and EBV was also studied. Their inhibitory action was proportionate to the ability of herpesvirus-infected cells to produce interferon. Thus owl monkey kidney cells, which produce relatively high levels of interferon, required nanogram quantities of polynucleotides to become resistant to HVS. Transformation of HCBL by B95-8-EBV was also prevented by poly(I).poly(C). In Raji cells superinfected with P3HR1-EBV, polynucleotides failed to stimulate interferon, and higher EBV-induced EA expression was observed. The percentage of P3HR1 and Raji cells spontaneously expressing EBV-associated antigens remained unchanged after exposure to either interferon or polynucleotides.
Human peripheral mononuclear cells treated with tumor promoting agent, 12-O-tetradecanoyl phorbol 13-acetate (TPA), released a soluble lymphocyte mitogenic factor (MF). The MF was found to be a protein capable of eliciting a proliferative response in normal human lymphocytes within 40-46 hours. The MF was detected in the culture supernatant fluid as early as 12 hours after TPA treatment and reached maximum at 48 hours. The biochemical characterization of MF is under active investigation.
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