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Biomedical subjects

D Morgan

Publications and source records attributed to D Morgan.

At least 271 records · Page 15Linked to original sources

Furazolidone versus ampicillin in the treatment of traveler's diarrhea.

Ninety-four U.S. students who acquired diarrhea in Mexico were treated with furazolidone (47 subjects) or ampicillin (47 subjects) on a double-blind random basis. Of 47 students, 26 (55%) who received furazolidone (100 mg four times daily for 5 days) recovered from illness within 48 h after initiation of therapy, in contrast to 15 of 47 (32%) who received ampicillin (500 mg four times daily for 5 days) (P less than 0.05). Altogether, 74% of students treated with furazolidone and 49% of those receiving ampicillin were well within 72 h (P less than 0.05). When furazolidone was compared with ampicillin, clinical illness was shortened on the average from 65 to 61 h for enterotoxigenic Escherichia coli diarrhea, from 83 to 58 h for shigellosis, from 82 to 51 h for diarrhea unassociated with a detectable agent, and from 72 to 57 h for all cases irrespective of etiology. Although not dramatically effective in the current trial, the broad spectrum of activity of furazolidone is of interest. Because of in vitro activity against Campylobacter strains and known effectiveness in treating giardiasis, furazolidone should be considered in therapy for diarrhea of unknown etiology in certain settings when laboratory processing of stools for etiological agent is not feasible.

Ampicillin↗

Human normal CTL clones: generation and properties.

This study reports the production of clones of human killer T cells grown in the presence of TCGF4 following sensitization in MLC against (1) allogeneic cells, (2) autologous Bebv+ lymphocytes, or (3) autologous lymphoma cells. Sensitization against the tumor cells required the addition of macrophages. The expression of the cytotoxic activity of the cloned T lymphocytes required re-stimulation with the specific stimulator cells. The cytotoxic activity seemed to be MHC-restricted, since (1) cloned allosensitized CTL lysed their corresponding allogeneic targets, but did not lyse autologous Bebv+ cell or K562 cells; (2) cloned CTL sensitized against autologous Bebv+ cells lysed their autologous targets but not allogeneic Bebv+ targets or K562 cells; and (3) cloned CTL sensitized against autologous Burkitt lymphoma cells lysed their corresponding lymphoma targets or autologous Bebv+ targets but did not lyse allogeneic lymphoma cells or Bebv+ cells from the same allogeneic lymphoma cells or Bebv+ cells from the same allogeneic donors. The cloned CTL were homogeneous in expressing the OK T8 molecules and in being negative for T4, T10 or M1. At any given time, 25-45% of the cloned cells manifested lytic activity. The ultrastructural properties and cell surface OK T markers were different from those of cloned human NK cells. Emphasis is focused on the differences between the structural, functional and culture characteristics of CTL clones produced by direct isolation of MLC responder cells forming conjugates with specific target cells and those of clones from transformed T-cell lines or from T hybridomas.

Antigens, Surface↗

Thirst, resetting of the osmostat, and water intoxication following encephalitis.

A young man developed pathological thirst and hyperdipsia, hyperphagia, disordered temperature regulation, a lowered threshold for aggressive behavior, apathy, impaired memory, and seizures following encephalitis. He had marked hyponatremia. Bouts of water drinking produced water intoxication and precipitated status epilepticus. Studies of water handling with measurements of plasma osmolality and arginine vasopressin (AVP) revealed a very low thirst threshold (below 242 mOsm/kg) with resetting of the osmostat to a new level (255 mOsm/kg) but normal control of plasma osmolality at that level with adequate AVP release.

Adult↗

Psychomotor performance in the senescent rodent: reduction of deficits via striatal dopamine receptor up-regulation.

In order to determine the relationship between striatal dopamine (DA) receptor density and psychomotor performance in senescent animals, two experiments were carried out. In the first, the age-related motor deficits were characterized using a battery of four psychomotor tests (rod walking, wire hanging, inclined screen, plank walking). These tests were administered to three groups of male Fischer rats (mature, 6-8 months; middle aged, 12-18 months; and senescent, 25 months) and performance measured. Age-related differences were observed on all the tasks, with the oldest animals showing the poorest performance. These animals were then used in a second experiment in which one-half of the group of animals from each age was administered 1.86 mg/kg/day of haloperidol for 14 days (via surgically implanted Alza Minipumps. Control groups of animals from each age were given pumps which contained only the vehicle (HCl diluted with distilled water, pH = 2.9). Following the 14 day drug administration, the pumps were surgically removed and 3 days later all the groups were retested on the psychomotor tests. Stereotypy (to 0.5 mg/kg of apomorphine, sniffing, licking, grooming and cage crossings) was also re-examined. Results show that haloperidol-treated animals from all three age groups display greater response times (i.e., better performance) than vehicle-treated animals on the battery of four motor tests and, the haloperidol-treated old animals exhibit more sniffing and grooming than the vehicle-treated old animals. Parallel increases in [3H]spiperone binding seen in all haloperidol-treated groups suggest a relationship between increases in the density of striatal DA receptors and improvement in motor performance.

Aging↗

Assay of anticancer drugs in tissue culture: cell cultures of biopsies from human astrocytoma.

A method has been developed for measuring the drug sensitivity of human gliomas in short-term culture, using scintillation counting or autofluorography. Cell cultures prepared from malignant astrocytomas were treated with anticancer drugs whilst in exponential growth in microtitration plates. After drug treatment and a recovery period, residual viability was measured by [3H] leucine incorporation followed by scintillation counting or by [35S] methionine incorporation and autofluorography in situ. In 5 glioma cell lines tested against 6 drugs, the microtitration method correlated well with monolayer cloning. Although replicate samples of the same tumour showed little variation in chemosensitivity, there was marked variation between the chemosensitivities of cultures derived from the tumours of different patients. However, as variability between replicates was apparent during drug exposure or shortly after, it is important to allow the assay to run as long as possible after drug removal. It is hoped that this assay may provide the basis of a method for the prediction of in vivo chemosensitivity or the screening of potential chemotherapeutic drugs.

Antineoplastic Agents↗

Successful treatment of spinal arachnoiditis due to coccidioidomycosis. Case report.

An unusual case is reported of a patient with spastic paraparesis who was found to have severe spinal arachnoiditis due to Coccidioides immitis. Despite an obstructive hydrocephalus and a spinal subarachnoid block, the patient was treated effectively with surgery (shunting) and antifungal therapy (amphotericin and ketoconazole). He remains asymptomatic 3 years after diagnosis. Aggressive surgical and medical treatment of coccidioidal infection of the central nervous system can be beneficial, even in patients with the worst prognosis.

Adult↗

[Polyenzymatic activation of cellular hydrolases induced by interferon; its role in cytolysis and other cellular manifestations induced by interferon].

Interferon (IFN) treatment of human effector T cells activates CMC directed against K562 targets. An increase of the activity of the different hydrolytic enzymes tested (hexosaminidase and acid-phosphatase) measured in the effector cell population parallels cytolysis activation. IFN and IFN inducers (PIC) treatment of cultured murine L-929 cells generate molecular mediated cytolysis. An increase of hydrolytic enzyme activity (hexosaminidase; B-glucuronidase, acid and alkalin phosphatases) precedes cell lysis. Thus, in both cytolytic systems, IFN induced a polyenzymatic activation of hydrolases. This activation is similar to coordinate enzyme induction discovered by Hosli [16] in pathological and experimental instances, when absorbed substrates cannot be hydrolyzed by lack of specific enzymes. Activation of hydrolytic enzymes induced by IFN which determines its enhancing effect on CMC and on fibroblast autolysis [17] could speculatively explain other effects of IFN such as antiviral action, diminution of cell protein synthesis, inhibition of cell division or molecular alterations of cell surface.

Alkaline Phosphatase↗

Control of cell proliferation in human glioma by glucocorticoids.

Survival and proliferation of cell cultures from human anaplastic astrocytomas were shown to be enhanced by glucocorticoids with an optimal concentration of approximately 2.5 x 10(-5)M (10 micrograms/ml). The stimulation of proliferation was only observed in a clonal growth assay and was reversed as the size of individual colonies reached approximately 50 cells. Above this size, and in regular monolayer cultures, glucocorticoids were found to inhibit cell proliferation as measured by direct cell counting and incorporation of [3H] thymidine. Cultures grown to maximum cell densities in non-limiting medium conditions reached a lower terminal cell density, and had a reduced labelling index with [3H] thymidine in the presence of glucocorticoids. Although there was little difference between the actions of beta-methasone, dexamethasone and ethyl prednisolone, methyl prednisolone was found to be more effective, both in terms of stimulation of clonal growth and inhibition of growth at high cell densities. There was no evidence of cytotoxicity with glucocorticoids up to 5 x 10(-5)M (20 micrograms/ml) and it is suggested that glucocorticoids act via a normal regulatory process, perhaps enhancing cell-cell recognition.

Astrocytoma↗

Chemical carcinogenesis studies in mouse epidermal cell cultures.

Studies of tumor induction on mouse skin have provided insight into the basis biology of chemical carcinogenesis, but molecular mechanisms have been more difficult to elucidate. Mouse epidermal cell cultures have proven to be a valuable model for performing mechanistic studies. Previous data have indicated that such cultures proliferate and differentiate in a manner highly analogous to epidermis in vivo. In addition, carcinogen metabolism, DNA repair, and responses to tumor promoters are quite similar in mouse skin in vivo and in vitro. Recent data have extended these observations toward defining the biological characteristics of initiated cells and elucidating the mechanism of action of promoters and antipromoters. When mouse epidermis is cultured under conditions of low extracellular Ca++, proliferation is enhanced and terminal differentiation is inhibited. Addition of Ca++ induces terminal differentiation. If cells are treated with carcinogens under low Ca++ conditions and subsequently switched to standard Ca++, cell colonies which do not terminally differentiate evolve. Such colonies continue to synthesize keratin, are subculturable, and may represent preneoplastic cells. In other experiments, epidermal cells derived from mouse skin treated with carcinogens in vivo also demonstrate prolonged in vitro survival and subculturability while controls have a limited lifespan. Such studies suggest that biological alterations can be detected in epidermal cells exposed to carcinogens well before and the phenotypic expression of neoplasia. Exposure of epidermal cells to phorbol-ester tumor promoters induces ornithine decarboxylase (ODC). This induction is enhanced by corticosteroids and markedly inhibited by retinoids. Ultraviolet light also induces ODC in epidermal cells, but kinetic studies suggest that the early pathway of induction (afferent to the nucleus) is different from that of phorbol esters. The later pathways (efferent from the nucleus-i.e., transcription and translation) appear to be similar. Retinoids have only a minor suppressive effect on ODC induction by UV while corticosteroids enhance UV induction to the same extent as seen with phorbol esters These results suggest that the site of retinoids is in the afferent pathway while steroids act on the efferent pathway.

Animals↗