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Biomedical subjects

D S Gordon

Publications and source records attributed to D S Gordon.

At least 55 records · Page 3Linked to original sources

[Localization of histamine in uterine structures].

By means of luminescent-histochemical method of Cross, Even, Rost histamine is revealed in all uterine structures. Visual and fluorometric data demonstrate uneven distribution of histamine in the organ's structures. A high content of histamine is specific for macrophages and mast cells, less high--in tegmental epithelium and endometrial glands. A low level of histamine have endometrial stroma, smooth myocytes, cells of the serous membrane and vessels. Basing on the literature data, concerning various sensitivity of the uterine tissues to estrogens and regarding effect of the estrogens upon histamine metabolism in the uterine and regarding interconnection of the histamine receptors in the uterus and the estrogens, a suggestion is made that various contents of histamine in the uterine structures depend on various amount of the histamine receptors in them and on different abilities of the uterine tissues to inactivate histamine. The ability of macrophages to accept free forms of bioamines, as it is described in the literature, evidently can be spread to the uterine macrophages, where a high content of histamine is revealed.

Animals↗

Preparation of a monoclonal antibody to a melanoma growth-stimulatory activity released into serum-free culture medium by Hs0294 malignant melanoma cells.

Autostimulatory growth factors may contribute to the ability of malignant cells to escape normal growth controls. We have previously shown that Hs0294 human malignant melanoma cells release into culture medium an acid-soluble, heat-stable, trypsin-sensitive, autostimulatory monolayer mitogen which can be purified from acetic acid extracts of conditioned medium by gel filtration, reverse-phase high-performance liquid chromatography, and preparative electrophoresis. The majority of this melanoma growth-stimulatory activity (MGSA) resides in a 16-Kd moiety, though bioactivity is also associated with 24-26 and less than 14-Kd forms of MGSA (Richmond and Thomas: J Cell Physiol 129:375, 1986). In order to further characterize this growth factor, monoclonal antibodies were prepared against a partially purified preparation of the autostimulatory melanoma mitogen. Monoclonal antibody clones were selected based on supernate inhibition of 3H-thymidine incorporation in serum-free Hs0294 melanoma cultures. One of these, termed FB2AH7, slows, but does not completely block, the growth of Hs0294 cells in serum-free medium in a dose-dependent manner. This antibody does not slow the growth of normal rat kidney fibroblasts, which neither produce nor require this mitogen, in either serum-free medium or medium containing 0.8% calf serum. This monoclonal antibody also blocks the mitogenic effects of partially purified preparations of this melanoma growth stimulatory activity (MGSA) on both Hs0294 cells and normal rat kidney fibroblasts. The FB2AH7 antibody has been demonstrated to bind MGSA by Western blot and by immunoprecipitation procedures. Western blot analysis of reverse-phase high-performance liquid chromatography purified growth factor demonstrated that FB2AH7 antibody binds to the 16-Kd and approximately 13-14-Kd forms of MGSA. FB2AH7 antibody can be used in immunoprecipitation experiments to bind the approximately 13-16-Kd forms of MGSA. The specificity of the binding of FB2AH7 antibody for MGSA but not other growth factors has been demonstrated in a modified dot blot assay. These data thus support the hypothesis that MGSA is an autostimulatory melanoma mitogen distinct from other growth factors.

Animals↗

[Localization of catecholamines, serotonin and histamine in the cells and mucus of bronchial washings from apparently healthy subjects].

By means of luminescent-histochemical methods localization of catecholamines, serotonin, histamine has been studied in cells and mucus of bronchial washings of 30 practically healthy persons. Cytofluorometry is performed in mucus, pulmonary epithelium, alveolar macrophages, lymphocytes and neutrophils of the bronchial washings. In the alveolar macrophages a high level of the compounds studied is detected.

Adolescent↗

Audit of surgical audit.

A clinical audit, run by surgeons with modest clerical assistance, has been incorporated into the routine clinical practice of all hospitals in a large health authority. Data on operations and deaths are integrated into routine clinical recording, and feedback is by annual report containing statistical analyses and critical commentaries and by discussions with colleagues. The results of the first five years show statistically significant falls in the number of reoperations for intra-abdominal complications, retained gallstones, arterial grafts, and amputations and in operative mortality following surgery for benign biliary and pancreatic disease, resection of large bowel for benign disease, operations on aortic aneurysms, and arterial grafts except for aneurysms. Although the audit was designed originally for monitoring and improving quality of care, other uses include monitoring of increasing specialisation and changes in clinical practice, planning surgical services and postgraduate training, and showing the effects of changes in the availability of resources.

Clinical Competence↗

Vestibular nerve section and saccus decompression: an evaluation of long-term results.

The 1972 AAOO committee (Alford, 1972) guidelines brought some uniformity into the evaluation of therapy for Menière's Disease. We have adhered to its recommendations in this long-term follow-up report of 21 saccus decompressions and 29 vestibular nerve sections performed on 46 patients between 1968 and 1977. Comparisons between these and other groups have been possible with regard to: control of vertigo; hearing; tinnitus; and development of hydrops in the contralateral ear. All the vestibular nerve section group have enjoyed sustained relief from vertigo. Class D results (recurrent vertigo) account for 14 per cent of the saccus decompression group at one year and 29 per cent at eight to 10-year follow-up. Hearing levels in both groups deteriorated in parallel as time progressed but tinnitus became less noticeable. Nineteen per cent of the long-term review patients showed evidence of developing cochlear hydrops in the contralateral ear. Conservative surgical procedures should be employed whilst any useful hearing exists, though the emphasis remains on controlling vertigo. Saccus decompression, despite its controversial therapeutic basis, will remain the first-line surgical procedure for many otologists. However, in the fit young Menière's cripple or saccus decompression failure with serviceable hearing, vestibular nerve section remains the treatment of choice.

Adult↗

Cyclosporine.

Cyclosporine is a fungal metabolite increasingly used as an immunosuppressive agent in organ transplantation. It provides immunosuppression primarily through reversible inhibition of T-lymphocytes, without myelotoxicity. Cyclosporine appears to inhibit primary activation of helper cells and to decrease the production of lymphokines by these cells. Cyclosporine becomes widely distributed into tissue compartments and is metabolized primarily by the liver. Serum trough levels, measured by radioimmunoassay or high pressure liquid chromatography, are commonly monitored and sometimes used for dose adjustments. Cyclosporine has been used in human renal, cardiac, liver, bone marrow, and pancreatic transplantation, as well as in other experimental animal models. It has a narrow therapeutic index, with major complications arising from nephrotoxicity, hypertension, and hepatotoxicity. Cyclosporine also has some antischistosomal and antimalarial activity.

Animals↗

Cerebrospinal fluid rhinorrhea following surgery for acoustic neurinoma. Report of two cases.

In a series of 48 patients with acoustic neurinoma removed by the suboccipital route, one patient developed cerebrospinal fluid rhinorrhea and another patient had delayed-onset meningitis. Each complication was attributed to opening the posteromedial air-cell tract in the posterior wall of the internal auditory meatus. In operations requiring removal of the posterior meatal wall, it is important to look for the air-cell tract which may not be apparent on computerized tomography. If the tract is opened the cells should be occluded by bone wax.

Adult↗

[Possible causes of the heterogeneity of the histochemical properties of tissue basophils].

By means of a complex of histochemical staining techniques cytoplasmic biopolymeres of tissue basophils (TB) have been studied in the stomach of the men (64 observations), in that of the rat and dog (40 species each). The data obtained are compared to those of the literature on presence of histamin in the TB investigated. A hypothesis is formulated according to which heterogeneity of the TB histochemical properties at the level of the histophysiological microsystem is a reflection of the intertissue integration along the line: parenchymal cell-TB of the connective tissue stroma; at the cellular level TB heterogeneity is determined by presence or absence in them of histochemically determinated protein, its qualitative composition that, in its turn, depends on type and/or on set of bioamines, initiating the TB new formation.

Animals↗

Studies on the use of nonhuman primates to determine the DR status of the human hematopoietic stem cell.

Monoclonal antibodies that recognize monomorphic determinants of human DR are potentially useful for the in vitro elimination of malignant cells from marrow for use in autologous transplantation. While DR is expressed on normal hematopoietic progenitor cells and the cells of the majority of the hematologic and lymphoid malignancies, there is the possibility that DR may not be expressed on the hematopoietic stem cells responsible for marrow regeneration after transplantation. To resolve the uncertainty regarding the DR status of the human stem cell, we determined whether antihuman DR monoclonal antibodies recognized analogous antigens on nonhuman primate hematopoietic progenitor cells to determine an appropriate animal transplant model. We used antihuman DR plus C'-mediated lysis of marrow progenitor cells as an indicator of whether the analogous nonhuman primate cells express similar antigens. Using two potent C'-fixing anti-DR monoclonal antibodies separately (5F3, AMG-12), human progenitor cells are reduced by 90%-100%. The range of progenitor cell depletion varied more widely with the nonhuman primates studied: 80%-99% with cells from the chimpanzee, 48%-100% with cells from the orangutan, and 62%-100% with cells from the rhesus monkey. Despite this, the majority of animals yielded results identical to that seen with human cells. We concluded that autologous transplantation with DR-depleted rhesus bone marrow into a lethally irradiated animal would be a practical and expeditious means to determine the DR status of the cell responsible for marrow regeneration, and by inference the DR status of the human hematopoietic stem cell.

Adult↗

Phase I study of intravenous gamma globulin in multiple myeloma.

Seventeen patients with multiple myeloma were given intravenous immunoglobulin at doses ranging from 150 mg/kg to 500 mg/kg in a phase I study. The intravenous immunoglobulin was well tolerated with only three transient episodes of mild clinical toxicity during 27 infusions. In no instance was hepatic or renal toxicity seen. Marked biologic variability over the one month study period in total IgG levels in patients with non-IgG myeloma and IgG subclasses in many of the patients was observed, making intravenous immunoglobulin half-life determinations based on IgG or IgG subclass levels problematical. The decay of functional antibody to hepatitis B surface antigen was determined. Analysis of the hepatitis antibody data suggested that intravenous immunoglobulin half-life was in the range of seven to 20 days for the entire study group and was not related to the isotype of the myeloma paraprotein or to the baseline levels of IgG. No infections were observed in the study group during the study period, but the potential for infection prophylaxis by intravenous immunoglobulin in myeloma patients must be evaluated in a randomized, prospective, controlled phase III study.

Adult↗

Monoclonal antibody to human granulocytes: cellular specificity and functional studies.

Antigenic specificity and functional studies of G2, a monoclonal antibody to human granulocytes, prepared by fusing spleen cells from immunized Balb/c mice to the nonimmunoglobulin (Ig) secretor line SP2/0, are described. The antibody was reactive with the HL60 and K562 cell lines and with human peripheral blood granulocytes; and unreactive toward human lymphocytes, erythrocytes, a variety of T and B cell lines, as well as toward leukemic cells obtained from patients with acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and acute myelocytic leukemia (AML). The G2 monoclonal antibody identified cell surface antigens on cells from cases of acute myelomonocytic leukemia (AMMoL) and on cells from 2 of 12 cases of acute undifferentiated leukemia (AUL). G2 was capable of inhibiting oxygen consumption by human polymorphonuclear leukocytes (PMNL) stimulated with aggregated human immunoglobulin (IgG), opsonized zymosan, f-met-leu-phe (FMLP), and the calcium ionophore A23187. Inhibition of the PMNL response to phorbol myristate acetate (PMA) and digitonin was dependent upon the dose of the stimulant. G2 should facilitate elucidation of the mechanisms of granulocyte membrane perturbation and subsequent activation of various functions via a selective interaction with key cell surface antigens.

Animals↗

A randomized comparison of postremission therapy in acute myelogenous leukemia: a Southeastern Cancer Study Group trial.

The Southeastern Cancer Study Group conducted a post-remission induction randomized trial in adult acute myelogenous leukemia to assess the efficacy of alternate drug therapy during consolidation and of immunotherapy during maintenance. Of 508 evaluable patients entered into the study, 335 (66%) achieved a complete remission treated with a 7-day infusion of cytosine arabinoside at a dose of 100 mg/sq m/day and 3 days of daunorubicin at a dose of 45 mg/sq m/day. Those in remission were randomized to receive 3 courses of 1 of 3 consolidation regimens: (A) a continuous infusion of 5-azacytidine, 150 mg/sq m/day for 5 days; (B) 5-azacytidine plus beta-deoxythioguanosine, 300 mg/sq m/day for 5 days; or (C) cytosine arabinoside, 100 mg/sq m/day intravenously, and thioguanine, 100 mg/sq m orally every 12 hr, plus daunorubicin, 10 mg/sq m every 24 hr daily for 5 days. There was no difference in relapse rate among the 3 arms. Those completing consolidation and remaining in remission were randomized to 1 of 3 maintenance regimens: (D) chemotherapy, 5-day infusion of cytosine arabinoside and 2 days of daunorubicin (same doses as induction) given every 13 wk for 1 yr; (E) BCG given twice weekly for 1 mo and then monthly for 1 yr; or (F) the combination of regimens D and E. The median duration of remission was significantly better on regimen D (17.4 versus 9.4 and 9.5 mo), and median survival was 29 mo compared to 21 mo for the other regimens. Those given different drugs during consolidation than used for induction (regimens A and B) and subsequent chemotherapy for maintenance (regimen D) had the longest remission durations and survival. Immunotherapy was not as good as intensive chemotherapy for maintenance.

Adolescent↗

[Localization of catecholamines, serotonin, histamine and acetylcholinesterase in human peripheral blood structures].

By means of various histochemical methods localization of biologically active compounds in structure of peripheral blood of 66 practically healthy persons have been studied. In the blood structures studied (plasma, erythrocytes, neutrophilic granulocytes, lymphocytes) catecholamines, serotonin, histamine and acetylcholinesterase are distributed unevenly. In leucocytes their content is the greatest.

Acetylcholinesterase↗

Inhibition of adenosine deaminase leads to enhanced antibody responses in the mouse.

Inhibition of adenosine deaminase activity leads to decreased cellular immunity. The effect of deoxycoformycin (DCF), a potent inhibitor of adenosine deaminase, on the ability of mouse spleen cells to generate antibody responses in vitro has been examined. With either continuous exposure to or pretreatment of the cells with deoxycoformycin, there was a decrease in cell survival and an increase in antibody-producing cells in the surviving cell population. To identify the cell population most susceptible to the inhibitor, the spleen was separated into B-cell, and T-cell, and macrophage components and each population was pretreated with deoxycoformycin before combination with its complementary treated or untreated population. Deoxycoformycin pretreatment had no effect on macrophages or B cells; however, pretreatment of the T cells resulted in increased antibody responses. When T cells and B cells were both pretreated and combined, there was a synergistic increase in the antibody response. In addition, supernatants from cultures in which both B cells and T cells had been pretreated with DCF were capable of enhancing antibody responses in cultures containing DCF-treated T cells. Though adenosine was increased in the stimulatory culture supernatants, adenosine alone did not enhance antibody responses in either untreated or DCF-treated cultures.

Adenosine Deaminase Inhibitors↗