Biomedical subjects
Publications and source records attributed to D Parker.
CA 125 is an epithelial membrane marker which can be detected in the serum of patients with ovarian cancer and which may reflect tumour burden. In a group of 42 patients, the level of this marker has also been shown to be significantly related to survival.
The CA 50 levels in serum samples from 440 patients were estimated using a dissociated enhanced lanthanide immunofluorimetric assay. The distribution was similar to CA 50-RIA assays. Raised levels (greater than 14 U/ml) were present in 95% pancreatic cancer, 68% hepatoma, 54% advanced colorectal cancer, 58% advanced breast cancer and 48% lung cancer. High values were observed in adenocarcinoma of the lung, and were related to tumour mass in small cell lung cancer. CA 50 is independent of CEA. The marker is of considerable potential in pancreatic cancer where the majority of patients express the Can 50 Ag.
A recombinant bacteriophage containing the entire alpha-lactalbumin gene was isolated from a human genomic library constructed in bacteriophage lambda L47. Within this recombinant the 2.5 kb alpha-lactalbumin gene is flanked by about 5 kb of sequence on either side. The complete nucleotide sequence of the gene and its immediate flanking sequences were determined and compared with those of the rat alpha-lactalbumin gene. These studies showed that the size, organization and sequence of the exons have been highly conserved, whereas the introns have diverged considerably. In particular, the first intron of the human gene was found to contain an Alu repetitive sequence not present in the rat. A high degree of homology (67%) was also observed in the 5' flanking regions, extending as far as 655 nucleotide residues upstream of the transcriptional initiation site. Comparison of the 5' flanking sequences of these two alpha-lactalbumin genes with those of five casein genes has revealed the presence of a highly conserved region [consensus sequence: RGAAGRAAA(N)TGGACAGAAATCAA(CG)TTTCTA], extending from position -140 to -110 in all seven sequences examined, suggesting a possible regulatory role in the hormonal control or tissue-specific expression of milk protein genes in the mammary gland.
Sequential sera from 48 subjects infected with human immunodeficiency virus type I (HIV-I) were examined over 36 months for the presence of neutralising antibodies, and for specific anti-gag (p24) and anti-env (gp41) antibodies to HIV-I. Results were interpreted in terms of clinical outcome during the period 1982/3 to 1985/6. HIV-I-infected subjects who remained symptom-free, by comparison with those who manifested AIDS or AIDS-related complex (ARC), had a significantly higher titre of anti-p24 antibodies throughout the 3 years, as measured by competitive enzyme-linked immunosorbent assay and radioimmunoprecipitation. The symptomless subjects also showed a trend towards an increasing neutralising antibody titre with time. There was no relation between anti-gp41 titre and clinical outcome, nor an independent relation between anti-p24 and neutralising titre. A lower or falling titre of anti-p24 antibody was associated significantly with clinical progression, up to 27 months before development of AIDS/ARC.
Adriamycin (ADR), 4-hydroperoxycyclophosphamide (4-OOHCYP) and the new cyclophosphamide derivative AZ 7557 (AZ) were tested for their effects on the release of the Interleukins IL-2 and IL-1 from rat spleen cells and peritoneal exudate macrophages respectively. ADR was found to enhance IL-2 release and less effectively IL-1 release. 4-OOHCYP and AZ were found to inhibit IL-2 release but had no effect on IL-1 production. It is suggested that the modulation of IL-2 levels by these drugs is unlikely to be mediated by their effects on IL-1.
A patient with primary aldosteronism had bilateral adrenal tumours on computed tomography. Selenocholesterol scintigraphy showed uptake by the larger right adrenal gland and a tumour in the gland was also visualized by venography. In contrast, measurements of aldosterone concentrations in adrenal venous blood lateralized to the left side. At surgery the left adrenal gland contained an aldosteronoma and the right adrenal gland a large non-functioning adenoma. Thus, selenocholesterol scintigraphy incorrectly localized the functioning adrenal tumour.
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A mouse anti-guinea pig monoclonal antibody, designated MSgp 1, was derived from a fusion between NS-1 myeloma cells and splenocytes hyperimmunised with guinea pig thymocytes. The MSgp 1 determinant is expressed by a subset of small thymocytes and lymph node T cells which participate in mixed leukocyte reactions. The determinant is modulated by antigen in vivo, and MSgp 1 antibody will prevent MHC class II driven proliferation in vitro. In addition, MSgp 1 reacts with a minor population of lymph node B cells, but not with a chronic B cell leukaemic cell line. Resident peritoneal macrophages express the MSgp 1 determinant, whereas chronic oil-induced peritoneal macrophages do not. The role of MSgp 1 defining guinea pig helper T cells is discussed by comparisons with other documented T helper cell reagents.
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Haptenated murine Langerhans' cells (LCs) have been reported to induce contact sensitivity when injected via the subcutaneous, intraperitoneal and, in some instances, the intravenous route. Similar studies were undertaken to elucidate the role of the LC in the induction of contact sensitivity in the guinea-pig. The subcutaneous injection of dinitrophenylated epidermal cells induced hapten-specific contact sensitivity in a dose-dependent fashion. This contrasts with the tolerance that was induced by the intravenous or intraperitoneal injection of similarly haptenated cells. Contact sensitivity by haptenated epidermal cells could be induced in syngeneic and allogeneic recipients and did not require the transfer of viable cells. Using the monoclonal antibody MSgp2, which detects LCs, LC-enriched and LC-depleted populations were prepared by an 'indirect antibody' panning technique. It was found that a haptenated LC-depleted epidermal cell population (0.1% LC) induced the same degree of contact sensitivity or tolerance, depending on the route of immunization, as a haptenated 'freshly isolated' epidermal cell population (1% LC). Whereas, a purified population of haptenated LC (85-90%) induced no significant degree of contact sensitivity or tolerance. These results confirm our previous conclusions based the in vivo depletions of Langerhans' cells, and suggest that the epidermal Langerhans' cell is not essential for the induction of contact sensitivity in the guinea-pig. However, this does not exclude the possibility that the LC is involved in the elicitation of contact sensitivity in a sensitized animal.
Exposure before flight to an environment that provides altered visual-vestibular relationships similar to those seen in weightlessness might facilitate adaptation to spaceflight. Fifteen normal subjects were exposed for 0, 5, and 20 min to an abnormal visual-vestibular environment in which the vestibular sensation of lateral tilt was associated with the visual impression of lateral translation. Lateral eye movement elicited by similar tilt in darkness was measured before and at intervals after the exposure. Of the 15 subjects, 12 showed increased VOR amplitude following the exposure, but this increase appeared unrelated to the duration of exposure to the visual stimulus and may be an effect of the VOR measurement procedure. Most subjects showed little shift in the phase relationship between tilt and eye motion. Three subjects showed changes in VOR and five reported changes in perception of motion which appear clearly related to the visual-vestibular exposure.
The hypothesis that the dexamethasone suppression test (DST) and rapid-eye-movement (REM) latency test are not biological markers for depressive illness but artifacts arising from dietary and sleep disturbances that accompany depression was examined in 28 normal volunteers. The restriction of calorie intake with moderate weight loss reproduced a pattern of response to dexamethasone closely resembling that claimed to be diagnostic of depressive illness. The shortened REM latencies claimed as a diagnostic marker were replicated in volunteers by mimicking the sleep pattern commonly found in depression. These changes could not be explained by the induction of mood disorder in the subjects. The results put in question the diagnostic value of the DST and REM latency tests in clinical practice, where sleep disorder and poor appetite, with reduced calorie intake, are the common accompaniments of depressive illness.
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To investigate the role of mononuclear cells in the meninges at all stages of chronic relapsing experimental allergic encephalomyelitis, juvenile guinea pigs were inoculated with isogeneic spinal cord in Freund's complete adjuvant (FCA) in parallel with animals inoculated with FCA alone as age-matched controls. Cytospins were prepared of the meningeal inflammatory cells obtained by washing the brains of these animals. These cytospins were stained by indirect immunoperoxidase, using a panel of monoclonal antibodies (Mabs) recognizing "activated" macrophages (M phi s), Ia antigen, total T cells and a putatively T-cell-suppressor subset, and an antiserum against immunoglobulins. The inflammatory response was quantitated and the proportions of the different cell types were determined. It was found that the total number of infiltrating cells correlated with the neurological symptoms of the disease. "Activated" M phi s increased significantly during the disease, in line with clinical signs. The expression of the Ia antigen, found on both lymphocytes and M phi s, also appeared to correlate with the disease. There was no increase in putative T-suppressor-cells during remission but there was a significant rise in the proportion of both cells staining with anti-immunoglobulins and plasma cells during relapse.
The antineoplastic drug bleomycin, which has not been shown to have immunosuppressive activity, was tested for its effect on concanavalin A-induced interleukin-2 production. When the drug was added to splenocytes of Lewis rats or Balb/c mice in the presence of concanavalin A, in optimal conditions for interleukin-2 production, no detectable effects were seen. However, using a suboptimal dose of concanavalin A, bleomycin increased interleukin-2 release significantly. This effect was achieved using less than 1 microgram/ml bleomycin. In addition, bleomycin was tested for its ability to alter interleukin-1 production by peritoneal exudate macrophages. The drug seems to increase the release of interleukin-1 from peritoneal exudate macrophages of Lewis rats without any lipopolysaccharide added or with a suboptimal concentration of lipopolysaccharide. It is suggested that bleomycin, and probably other cytotoxic drugs, may modulate the immune response through its effects on the release of immunostimulating cytokines such as interleukin-1 and -2.
Levels of PGE, PGF2 alpha, 6-oxo-PGF1 alpha and thromboxane (TXB2) in spinal cords and cerebellums of guinea pigs at different stages of chronic relapsing allergic encephalomyelitis (CREAE) were compared with those in Freund's adjuvant-treated, age-matched controls. PGE and TXB2 levels were found to be increased in spinal cords during acute and relapse phases of the disease. The number of lesions in the spinal cord was similarly increased in acute and relapse stages. There was, however, no similar correlation between number of lesions and eicosanoid levels in the cerebellum with the clinical stages of the disease based on hind limb paralysis. In the acute phase and remission lesion numbers were low, and high levels, similar to those found in the spinal cord, were only found in the relapse phase. Eicosanoid levels were high in the acute phase and remission, and generally low in relapse. The spinal cord levels of eicosanoids in remission and relapse correlated well with previous data obtained from the CSF of patients with multiple sclerosis.
Surface markers on lymphocytes from the thymus, lymph node and spleen of the rat were examined in single cell suspensions using a panel of monoclonal antibodies. These were used particularly to investigate Pan T, TH (T-helper), TS/C (T-suppressor-cytotoxic) and Ia antigens. The expression of these markers in rats treated with a single dose of cyclophosphamide (100 mg/kg body weight) was followed for 3 weeks after treatment. Maximum changes were detected at 3 days and recovery took up to 3 weeks to near completion. Comparison was made with histological observations of the effect of CY on these organs. At 3 days, the thymus showed maximum weight loss and gross cortical depletion. This associated with significant drop in the expression of the TS/C marker on small and large lymphocytes. Regeneration of the cortex, beginning at 7 days, was associated with the presence of many large pyroninophilic cells. This was accompanied by an increase in the expression of the TS/C marker on both small and large lymphocytes. The mesenteric lymph node showed marked depletion of the B-cell areas at 3 days. There was also a significant drop in TS/C and Ia expression and a marked rise in Pan T and TH. TS/C expression recovered rapidly with a rebound at 7 days. However, the expression of Pan T and TH did not return to normal until 21 days. In the spleen there was a similar decrease in the lymphocytes populating the B-cell areas at 3 and 7 days with an increase in the expression of Pan T and TH, and a decrease in the expression of Ia.(ABSTRACT TRUNCATED AT 250 WORDS)
Surface markers on rat lymphocytes from thymus and T-cell areas of lymph node, spleen and Peyer's patches were examined in histological sections after one single dose of Cyclophosphamide (CY, 100 mg/kg body weight). A panel of monoclonal antibodies was used: W3/13, W3/25 and OX8 to investigate Pan T, TH and Ts/c marker expressions respectively. Ts/c marker expression showed a marked and significant reduction in both thymus and lymph node lymphocytes 3 days after CY treatment. This was followed by return to normal in the thymus and a significant rebound increase in the lymph node by day 7 after treatment. This Ts/c marker expression in both the spleen and Peyer's patches showed a significant increase on both day 3 and 7 after CY treatment. Mast cells were observed in large numbers in the thymus and lymph node but not in the spleen and Peyer's patches. TH marker expression was increased significantly in lymph nodes, spleen and Peyer's patches. No change was observed in Pan T marker expression in any of the tissues at any of the times examined.