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Biomedical subjects

G Price

Publications and source records attributed to G Price.

At least 55 records · Page 3Linked to original sources
PubMed1988

T-cell depletion with ricin A-chain T101 in allogeneic bone marrow transplantation to prevent severe graft-versus-host disease.

Bone marrow cells from 10 marrow transplant donors were treated with an immunotoxin, which couples A-chain of ricin with a monoclonal anti-T-cell antibody T101 to prevent graft-versus-host disease by the elimination of mature T-cells. Marrow cells treated with the anti human T-cell immunotoxin (IT101) were cultured for erythropoietic colonies, granulocytic colonies, and multilineage hematopoietic colonies (CFU-GEMMT) containing myeloid cells and T-cells, and optimal conditions were defined for the elimination of T-cells present in the harvested donor marrow prior to marrow transplantation. Marrow samples purged with IT101 were examined for residual T-cells by fluorescence activated cell sorting, using anti-T-cell antibodies, [3H]-thymidine incorporation after PHA stimulation, and an assay for clonogenic T-cells. The number of T-cell colonies observed in the treated marrows was less than 5% of the number in comparable unpurged donor marrows. Treatment with IT101 did not alter the plating efficiency of hematopoietic colonies compared to untreated donor marrow cells. These data suggest that multilineage progenitors responsible for the reconstitution of the recipient hematopoietic system are not affected by marrow IT101 purging. The clinical data on 10 patients indicate that the depletion of T-cells in the donor marrow with IT101 is effective in decreasing the severity of acute graft-versus-host disease in allogeneic marrow transplantation and warrants continued investigation.

Adult↗
PubMed1988

Gastrointestinal arterial fibromuscular dysplasia of childhood.

An unusual case of a progressive, noninflammatory stenosing vasculopathy, arterial fibromuscular dysplasia is presented. The distinctive features of this particular case include onset in early childhood with a predominant involvement of the gastrointestinal system, sparing of the renal arteries, lack of hypertension, and no cutaneous features of progressive systemic sclerosis. We discuss the clinical history over a decade and the pathologic features, including routine and electron microscopic findings of biopsy and autopsy tissues, and review the literature.

Adolescent↗
PubMed1987

Cytotoxic effects of tumour necrosis factor and gamma-interferon on acute myeloid leukaemia blasts.

We have studied the cytotoxic effects of recombinant tumour necrosis factor and recombinant gamma interferon on primary cultures of leukaemia cells. The agents were added alone or in a combination to cells from 17 patients. Eleven had acute myeloblastic leukaemia (6 at presentation, 5 at relapse), 4 had acute lymphoblastic leukaemia, one had hairy cell leukaemia, and 2 had chronic myeloid leukaemia--one of whom was in myeloid blast transformation. Cells from patients with lymphoid malignancies or from the patient with chronic phase CML were not affected by either agent in any dose combination. In contrast, reduction of viability of myeloid blasts was weakly accelerated by TNF and gamma-interferon individually. Combination of the agents invariably produced enhanced killing and additive or synergistic effects were seen when 20-500 IU ml-1 of each cytokine was present. This sensitivity was also shown by blast cells from 5 patients with relapsed AML. We therefore suggest that trials of such combination therapy may be indicated in drug resistant or relapsed AML.

Cell Survival↗
PubMed1986

Stop ourselves smoking: a smoking cessation programme.

The stop ourselves smoking (SOS) pilot programme, designed for those who want to stop smoking, is based on a self-help approach. It was developed in Christchurch to supplement existing smoking cessation programmes in the community. Of the 142 participants, 118 finished the course. Of these, 80 (68%) were not smoking at the end of the eighth week and 61 (52%) were still not smoking at the end of the 15-month followup period. The success of this programme exceeds that of any reviewed in the literature. The format of the programme is readily adaptable to other lifestyle programmes.

Humans↗
PubMed1985

Adenosquamous carcinoma of the colon.

Two cases of primary adenosquamous carcinomas of the sigmoid colon and rectum are presented. Clinical features and pathologic findings of both primary and metastatic lesions are reported (including immunohistochemistry and electron microscopy). We emphasize that the presence of a metastatic squamous tumor in a patient with an unknown primary does not exclude the possibility of colonic carcinoma. Comparison with other reports in the American medical literature indicates that these are very aggressive tumors that may have a worse prognosis than the more common form of colonic adenocarcinoma. Furthermore, the squamous component, in particular, may have a greater potential for metastasizing and can do so as an undifferentiated-appearing carcinoma. In view of this, the authors suggest that very poorly differentiated areas within colonic adenocarcinomas should be very carefully evaluated by means of immunoperoxidase stains and/or electron microscopy in an attempt to identify squamous features.

Adenocarcinoma↗
PubMed1985

An antigen related to the phenotype of multi-drug resistance can be induced in vivo and used as a target for immunotherapy of rat leukemia.

Several laboratories have reported that new plasma membrane peptides appear in rodent and human cells after induction of in-vitro resistance to vinca alkaloids, anthracyclines and other anti-neoplastic drugs. Recently, murine monoclonal antibodies have been produced that recognize surface components of such drug-resistant cells. The work presented here describes the development of an in-vivo animal model of this phenomenon using a rat myeloid leukemia. Brown Norway rats were made leukemic with promyelocytes of the BNML line and subsequently were treated with 7.7 mg kg-1 of daunorubicin. After eight cycles of passage-treatment-regrowth, the resulting cells reacted with this antibody in immunofluorescence and cytotoxicity assays. Animals injected with cells that had been pre-incubated with antibody in the absence of complement survived significantly longer than did the controls. Further prolongation of survival occurred when the cells were treated with a second antibody of a different specificity. These results demonstrate that some of the changes associated with in-vitro drug resistance occur also in vivo and potentially may be exploited as a focus for immunotherapy.

Animals↗
PubMed1985

Control of zona glomerulosa function in the isolated perfused rat adrenal gland in situ.

The extent to which results obtained using in-vitro techniques can be taken to reflect in-vivo physiological responses in the study of adrenocortical function has not been subjected to systematic study. Some evidence suggests that in-vitro preparative methods may affect the secreted steroid profile. For this reason it seemed desirable to study adrenal function using an isolated perfused whole gland technique, and this study reports results obtained with known aldosterone stimulants. Angiotensin II, ACTH and potassium ions all stimulated aldosterone secretion in a dose-dependent manner. The stimulation thresholds of these substances were compatible with their normal circulating concentrations. For angiotensin II stimulation this preparation was two orders of magnitude more sensitive than any in-vitro preparation. Most importantly, the specific glomerulosa effectors, angiotensin II and potassium, selectively stimulated aldosterone output, and had no consistent effect on corticosterone secretion at any dose used. On the other hand, ACTH stimulated both corticosterone and aldosterone output at all effective concentrations. The actions of alpha-MSH were also studied using this preparation. Low doses of alpha-MSH selectively stimulated aldosterone secretion, while higher doses were needed to stimulate corticosterone. The onset of response to all stimulants was invariably seen within the first 10 min after administration of stimulants. Maximal aldosterone output was achieved within the first 10 min whereas corticosterone secretion usually peaked 10-20 min later. The amount of aldosterone produced by this preparation was much higher than the amount produced by dispersed cell preparations, and closely approximated to the levels of aldosterone obtained in adrenal vein blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1985

Electron microscopic diagnosis of cerebral toxoplasmosis. Case report.

Rapid and specific diagnosis of infections involving patients with acquired immunodeficiency syndrome (AIDS) is imperative. Toxoplasmosis is one of the most frequent causes of central nervous system disease in these patients. The authors present a case of cerebral toxoplasmosis in an AIDS patient, diagnosed by electron microscopy of brain biopsy tissue using rapid techniques.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Estimation of urine flow rate in mares.

To determine the rate of urine flow and thus urinary excretion in the horse from untimed urine samples alone, the flow rate, creatinine concentration, osmolarity, and refractive index of 228 quantitatively collected urine samples were determined in 53 experiments on 12 healthy Thoroughbred mares. Forty samples were collected after water-induced diuresis; 11 samples were collected after furosemide-induced diuresis. Flow rates, which ranged from 1.2 to 84.5 ml/min, could be predicted from the urinary creatinine concentration. Correlation of urinary flow with urinary creatinine concentration accounted for 94% of the variability in the urinary flow rates. Phenylbutazone was administered before collection of 168 urine samples. Urine flow rates that were predicted from urinary creatinine concentration were used to estimate phenylbutazone excretion. Urine flow could be estimated without quantitative urine collection.

Animals↗
PubMed1983

Effect of thymosin and phorbol ester on purine metabolic enzymes and cell surface phenotype in a malignant T-cell line (MOLT-3).

Previous studies have shown that thymosin (fraction 5) is able to induce surface differentiation markers on normal murine bone marrow T-cell precursors. Phorbol ester (TPA) promotes differentiation of human leukaemic lymphoblasts as assessed by changes in phenotypic surface markers and terminal deoxynucleotidyl transferase (TdT) activity. Changes in levels of purine degradative enzymes occur during T-cell maturation with a fall in adenosine deaminase (ADA) and a rise in purine nucleoside phosphorylase (PNP) and 5'nucleotidase (5'NT) activities. We have now investigated the effect of both thymosin (fraction 5) and TPA on a human leukaemic T-cell line (MOLT-3) in expression of the surface antigenic markers NAI/34 (a marker of immature thymocytes) and OKT11 (which corresponds to the sheep erythrocyte receptor) and of TdT, ADA, PNP and 5'NT. Thymosin (after 96 h incubation) significantly reduced the number of cells positive for NAI/34 from 76.0 +/- 5.0% (mean +/- S.D.) to 51.3 +/- 9.3% (p less than 0.01) but caused no significant change in the percentage of TdT or OKT11 positive cells. ADA levels were significantly reduced (p less than 0.02) and 5'NT levels were significantly elevated (mean increase 303 +/- 142% of control, p less than 0.001) but the increase in PNP level (108 +/- 16.8% of control) was not significant (p greater than 0.05). On the other hand, TPA (after 96 h incubation) significantly reduced cells positive for NAI/34 from 76.0 +/- 5.0 to 30.0 +/- 9.8% and for TdT from 81.7 +/- 6.5 to 17.3 +/- 4.4% and increased OKT11 positive cells from 67.3 +/- 5.5 to 89.0 +/- 2.8% (p less than 0.001). TPA caused no significant change in 5'NT or ADA levels (p greater than 0.05), but an increase in PNP level to 158 +/- 12.9% of control (p less than 0.02). The present study demonstrates for the first time that the normal thymic hormone, thymosin is capable of inducing differentiation changes in thymic derived human leukaemic cells. In addition, it shows that different inducing agents may cause different patterns of differentiation changes in leukaemic cells.

5'-Nucleotidase↗
PubMed1983

Comparison of purine degradative enzymes and terminal deoxynucleotidyl transferase in T cell leukaemias and in normal thymic and post-thymic T cells.

Adenosine deaminase (ADA), ecto 5' nucleotidase (5'NT), purine nucleoside phosphorylase (PNP) and terminal deoxynucleotidyl transferase (TdT) were measured in the cells of patients with acute or chronic T cell leukaemia and compared with normal putative prothymocytes (large, blast-like cortical thymocytes), cortical and medullary thymocytes and peripheral blood T lymphocytes. Distinct patterns of enzyme activities were found in the individual types of T cell leukaemia. Mean ADA, TdT and 5'NT activities in thymic acute lymphoblastic leukaemia (Thy-ALL) were 41.9 u/10(8) cells, 31.1 u/10(8) cells and 4.7 u/10(6) cells respectively; in chronic T cell leukaemia they were 7.1 u/10(8) cells, 0.6 u/10(8) cells and 18.1 u/10(6) cells respectively. Mean PNP activity was similar between these two groups of leukaemia (68.6 u/10(6)cells in Thy-ALL and 77.9 u/10(6) cells in chronic T cell leukaemia). The activities of these four enzymes in OKT4+ chronic T cell leukaemia did not differ significantly from those in the OKT8+ chronic T cell leukaemia cases. The activities of TdT, ADA, PNP and 5'NT in Thy-ALL closely resembled those in normal immature thymocytes, and in the chronic T cell leukaemias showed a similar pattern of enzyme activities to that of mature T lymphocytes. These findings are consistent with surface phenotypic studies of T cell malignancies which suggest that different T cell leukaemias represent malignant proliferation of T cell clones arrested at different stages of T cell differentiation. They also demonstrate the value of biochemical markers in defining the different subtypes of acute and chronic leukaemia.

5'-Nucleotidase↗
PubMed1983

Biochemical and immunological differentiation of human thymocytes induced by thymic hormones.

Changes in levels of purine degradative enzymes have been shown to occur during T-cell maturation in both rats and humans with a fall in adenosine deaminase (ADA) and a rise in purine nucleoside phosphorylase (PNP) and 5'-nucleotidase (5'NT) activities. We have investigated the effects of four thymic factors: thymosin fraction 5 (TMS-F5); thymosin alpha 1 (TMS-alpha 1); thymopoietin pentapeptide (TP-5); and thymic conditioned medium (CM) on TdT activity, purine enzyme levels and the phenotypic markers OKT3 (a marker for mature T cells) and NA1/34 (which reacts with immature cortical thymocytes) in human thymocytes and in the lymphoid leukaemic cell lines RPMI-8402 and JM1 (derived from Thy-ALL). All four thymic factors caused one or more maturation change in human thymocytes, e.g. TMS-F5 caused a significant increase in OKT3 expression, TMS-alpha 1 a fall in TdT and ADA activities and a rise in OKT3-positive cells, TP-5 an increase in PNP and CM a rise in 5'NT activity. TMS-F5 also caused a marked elevation of 5'NT in both the T lymphoblastic lines (P less than 0.001). On the other hand the non-physiological phorbol ester, 12-O-tetradecanoyl phorbol acetate (TPA), a tumour promotor with potency of inducing differentiation in some leukaemic cell lines, induced changes in both normal thymocytes and in the leukaemic line JM1 were inconsistent with maturation, e.g. a fall in the percentage of OKT3 cells. These observations suggest that maturation of normal thymocytes might proceed stepwise, each step requiring at least one of the thymic hormones. Although thymosin also induces differentiation changes in a malignant lymphoid line, the pattern of these differs from that induced in their normal counterparts.

Animals↗
PubMed1982

Acid phosphatase. I. Cytochemical localization in lenses of normal and galactose-fed rats.

In the present investigation we have examined the presence, distribution and probable role of acid phosphatase in lenses of normal and galactose-fed rats. Acid phosphatase was localized in lenses using two separate cytochemical procedures (Gomori and Barka-Anderson methods) and examined at the ultrastructural level. Both procedures, in general, provided similar sites of acid phosphatase activity, although with the Barka-Anderson method finer and larger amounts of well-defined reaction product were observable at the site of reaction. The reaction product was observed in lenses of both rats fed on regular laboratory chow and galactose-fed rats. The intracellular location of the reaction of this enzyme was primarily in lysosomes and occasionally in the endoplasmic reticulum cisternae. At the extracellular sites, it was near the epithelial cell membranes which abut each other and cortical fibers. However, in the cortical fibers the extracellular localization was at various sites on the entire intercellular space between neighboring fibers. The possible role of hydrolases in the lens tissue is discussed.

Acid Phosphatase↗
PubMed1982

Enzymes of purine metabolism in human peripheral lymphocyte subpopulations.

Ecto-5'nucleotidase (5'NT), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and deoxycytidine (CdR), deoxyguanosine (GdR), deoxyadenosine (AdR) and adenosine (AR) kinases have been measured in subpopulations of peripheral blood lymphocytes of eight healthy volunteers. The separation of B, T, T helper/inducer and T suppressor/cytotoxic cells was performed by means of density gradient centrifugation, E rosetting, passage through a nylon-wool column and antibody affinity chromatography utilising OKT8 and OKT4 monoclonal antibodies. ADA was significantly higher in T lymphocytes and 5'NT in B lymphocytes. Among T cell subpopulations, 5'NT activity was significantly higher (P less than 0 . 01) in T suppressor/cytotoxic (OKT8+) cells (32 . 9 units/10(6) cells than in T helper/inducer (OKT4+) cells (9 . 7 units/10(6) cells). Indeed, the 5'NT activity in T suppressor cells was similar to that in B cells. T helper cells tended, however, to have higher PNP and ADA activities than T suppressor cells but the differences were not statistically significant. No major differences were noted in kinase activities between any of the lymphocyte subpopulations.

5'-Nucleotidase↗
PubMed1980

In vitro generation from murine brow marrow cells of accessory cells with discrete antigen presentation capacity and ability to release lymphostimulatory molecules.

An investigation of the immunological accessory cell function of in vitro bone marrow derived colony forming cells has been made. Data are presented to show that such cells can present immunogenic stimuli to lymphocytes and release lymphostimulatory products that in turn replace certain macrophage functions in the immune response. The appearance of these two activities is not correlated. Considerable heterogeneity exists in terms of the ability of different populations of cells to present distinct carbohydrate antigens in immunogenic form. In addition, that different macrophage cell populations can alter the affinity of antibody produced by an optimally stimulated primed spleen cell population is reported.

Animals↗