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Biomedical subjects

T Tucker

Publications and source records attributed to T Tucker.

50 records · Page 3Linked to original sources

Disseminated or localized growth of a human B-cell tumor (Daudi) in SCID mice.

A human Burkitt lymphoma (Daudi) has been grown in the mutant mouse called C.B-17 SCID. Twenty-eight days after s.c. injection of Daudi cells, a palpable tumor grew only at the site of injection in all injected mice. In contrast, after intravenous (i.v.) or intraperitoneal (i.p.) injection, macroscopic, disseminated tumors developed. Following i.v. inoculation, tumors grew in the lungs, kidneys, ovaries and adipose tissue, and microscopic tumor infiltrates were observed in the spleen, bone marrow, spinal column and femur, whereas after i.p. injection, the tumors were localized in the abdomen, liver, spleen, ovaries and muscular tunics of the gut, but did not disseminate into the lung or bone marrow. The growth pattern and phenotype of the Daudi cells were similar whether the inoculated tumor cells were derived from the in vitro cell line or from in vivo passaged tumors. The survival time of the tumor-bearing animals was dependent on the dose of i.v.-administered Daudi cells; as few as 100 cells caused death. All mice injected i.v. showed paresis or paralysis of the hind legs just prior to death. This was associated with the presence of neoplastic nodules within the spinal canal. Two surface antigens on Daudi cells (CD19 and CD22) were stably expressed in all the neoplastic lesions. Radiolabelled anti-CD22 antibodies localized in organs infiltrated with tumor, but did not penetrate primary s.c. tumors. This model of disseminated vs. solid tumor should prove useful for evaluating the efficacy of different types and doses of therapeutic antibodies, immunoconjugates and immunotoxins prepared from anti-human B-cell antibodies.

Animals↗

Central nervous system AIDS.

The retrovirus that causes the acquired immunodeficiency syndrome (AIDS) has two targets: the immune system and the nervous system. Central nervous system (CNS) manifestations of AIDS are protean. This review describes the opportunistic infections and malignancies that affect the nervous system in AIDS, and discusses the syndromes resulting from primary infection of the CNS by the AIDS virus. Possible mechanisms of CNS injury are cited as well as potential predictors of neurologic expression of AIDS.

Acquired Immunodeficiency Syndrome↗

Frontier hospitals: endangered species and public policy issue.

Frontier hospitals are the most geographically remote acute care facilities in the United States, and they are rapidly becoming and endangered species. Like other small rural hospitals, especially those under 50 beds, they are experiencing considerable distress and more and more are facing the possibility of closure (American Medical Association 1985; Mullner and McNeil 1986; Van Hook 1985; Cordes and Wright 1985). Frontier hospitals play a key role in acute care, serve an important function in the recruitment and retention of physicians and health personnel, and contribute to the community's economic development. However, the local economy surrounding them may be inadequate to prevent socially undesirable facility closures. Present public policy, which is primarily based on a market approach, is incapable of addressing the problems faced by frontier hospitals. A reexamination of this does not mean that the only other option is to follow the patterns of highly regulated states such as Massachusetts, New York, and Connecticut. United States health care has both competitive (market-driven) and regulatory aspects. Several other options or approaches between the extremes are explored.

Data Collection↗

Thoracic surgical implications of the yellow nail syndrome.

Idiopathic lymphedema associated with yellow discoloration of the nail beds constitutes the yellow nail syndrome. Pleural effusions and chronic sinusitis are also frequently present. This report describes a case of yellow nail syndrome in a 65-year-old woman.

Aged↗

Cytomegalovirus and herpes simplex virus ascending myelitis in a patient with acquired immune deficiency syndrome.

Progressive ascending myelitis was the presenting feature of the acquired immune deficiency syndrome (AIDS) in a homosexual man who also had Kaposi's sarcoma, Pneumocystis pneumonia, and disseminated cytomegalovirus (CMV) infection. Neuropathological studies showed profuse cytomegalic cells throughout the brain and spinal cord, but no inflammatory response. At postmortem examination, CMV and herpes simplex virus, type 2 (HSV-2), were recovered from multiple sites throughout the central nervous system (CNS). HSV-2 was isolated from the anus, but from no other extraneural site; in contrast, pathology typical of CMV was also seen in the liver, gastrointestinal tract, adrenals, and lungs. Although histopathological evidence suggesting prior CMV infection has been seen in the brains of AIDS patients, the virus has never been cultured from the CNS in these immunosuppressed hosts, nor has it been known to infect the spinal cord. The absence of an inflammatory response suggests that the pathogenesis of CNS viral infections is altered in AIDS patients. Evidence for CMV infection of the CNS in AIDS patients is no longer circumstantial.

Acquired Immunodeficiency Syndrome↗

In vivo reconstitution of ricin-like activity from its A and B chain subunits.

The capacity of highly purified preparations of ricin A and B chains to reconstitute ricin toxicity both in vitro and in vivo was studied. When the nontoxic A and B chain subunits were mixed and electrophoresed on sodium dodecyl sulphate-polyacrylamide gels (SDS-PAGE), reconstituted ricin was observed. The mixtures killed cells of the human Burkitt's lymphoma cell line Daudi in vitro and killed mice after i.v. injection. It was also shown that when mice were injected with one ricin subunit followed by administration of the complementary polypeptide up to 8 hr later, they died with lesions similar to those of ricin-induced death. This observation suggests that A and B chains recombine either in the serum or on the surface of cells. The rate of clearance of A and B chains from the blood of rats indicated that sufficient concentrations of either chain were present in the circulation 8 hr after injection to account for the observed toxicity. The above studies therefore suggest that the subunits of ricin have a very high affinity for each other and are capable of reconstituting biologically active ricin in vitro and in injected mice.

Animals↗

Controlled comparison of hemodialysis and peritoneal dialysis: Veterans Administration multicenter study.

We measured mortality and morbidity among 114 patients assigned randomly to home hemodialysis (HD) and home intermittent peritoneal dialysis (IPD). Data were collected during the time of home training and for 12 months after initiation of home dialysis. Training time was shorter for the IPD than for the HD patients (P less than 0.001) with median time 1.8 months for IPD and 3.9 months for HD. Switching to the alternative mode of treatment was more frequent for the IPD group (29/59 vs. 5/55, P less than 0.001). Survival time was not different, perhaps because of the modality change. More IPD patients were hospitalized in the first 6 months (20 for IPD vs. 9 for HD, P = 0.02), but they had fewer troublesome cardiovascular events in the first year (0 vs. 12, P less than 0.001). The HD patients maintained better nutritional status as reflected in body weight and arm muscle circumference and possibly in urea appearance rate. Thus, these data suggest that for most patients, IPD is a less satisfactory form of therapy than HD, but certain advantages of IPD did emerge. Applications of this information to the currently more popular mode of CAPD await further study.

Clinical Trials as Topic↗

Inhibition of cardiolipin synthesis following infection with herpes simplex virus.

The results of this study show that the synthesis of the inner mitochondrial membrane phospholipid, cardiolipin, is markedly inhibited following infection of human embryonic lung or hamster embryo fibroblast cells with herpes simplex virus type 1 or 2. The synthesis of other phospholipids, i.e., phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and phosphatidylinositol, is relatively unaffected.

Animals↗

Preparation and characterization of conjugates of recombinant CD4 and deglycosylated ricin A chain using different cross-linkers.

In a previous study, we have demonstrated that conjugates containing soluble, recombinant human CD4 (rCD4) and the deglycosylated form of ricin A chain (dgA) (rCD4-dgA) effectively kill a human T cell line infected with the human immunodeficiency virus (HIV) in vitro. In contrast, such conjugates are 100-1000-fold less toxic to uninfected cells. In order to use a rCD4-dgA conjugate effectively in vivo, it was important to demonstrate that (1) it binds to and kills HIV-infected, but not uninfected, human cells, (2) it is stable in the circulation, and (3) it has an optimal therapeutic index (toxicity to animals versus toxicity to target cells). A major factor affecting the efficacy of such conjugates in vitro and in vivo is the nature of the cross-linker between the ligand (rCD4) and the toxin (dgA). In this report, we have prepared rCD4-dgA conjugates using three different cross-linkers. Different methods of purification have been compared by determining the optimal yield, purity, and retention of biological activity (i.e., binding to gp120 and dgA chain activity). The structure of these conjugates as well as their cytotoxicity to target cells in vitro has been analyzed. Finally, we have compared their pharmacokinetics, tissue localization, and toxicity in mice.

Animals↗