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Biomedical subjects

T J Stewart

Publications and source records attributed to T J Stewart.

At least 19 recordsLinked to original sources
PubMed2000

Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation.

Demyelination contributes to the loss of function consequent to central nervous system (CNS) injury. Enhanced remyelination through transplantation of myelin-producing cells may offer a pragmatic approach to restoring meaningful neurological function. An unlimited source of cells suitable for such transplantation therapy can be derived from embryonic stem (ES) cells, which are both pluripotent and genetically flexible. In this paper we show that oligodendrocyte cultures can be reliably produced from retinoic acid-induced ES cells and that these oligodendrocytes can myelinate axons in vitro. Methods were further developed for generating highly enriched cultures of oligodendrocytes through an additional culturing step, producing an intermediate "oligosphere" stage. To test whether ES cells can survive, migrate, and differentiate into mature myelin-producing cells in areas of demyelination in the adult CNS, ES cells were transplanted into the dorsal columns of adult rat spinal cord 3 days after chemical demyelination. In the demyelination site, large numbers of ES cells survived and differentiated primarily into mature oligodendrocytes that were capable of myelinating axons. Furthermore, when oligosphere cells were transplanted into the spinal cords of myelin-deficient shiverer (shi/shi) mutant mice, the ES cell-derived oligodendrocytes migrated into the host tissue, produced myelin and myelinated host axons. These studies demonstrate the ability of ES cell-derived oligodendrocytes to myelinate axons in culture and to replace lost myelin in the injured adult CNS. Transplantation of ES cells may be a practical approach to treatment of primary and secondary demyelinating diseases in the adult CNS.

Animals↗
PubMed1998

Th2-type CD4+ cells neither enhance nor suppress antitumor CTL activity in a mouse tumor model.

Many cervical cancers express the E7 protein of human papillomavirus 16 as a tumor-specific Ag (TSA). To establish the role of E7-specific T cell help in CD8+ CTL-mediated tumor regression, C57BL/6J mice were immunized with E7 protein or with a peptide (GF001) comprising a minimal CTL epitope of E7, together with different adjuvants. Immunized mice were challenged with an E7-expressing tumor cell line, EL4.E7. Growth of EL4.E7 was reduced following immunization with E7 and Quil-A (an adjuvant that induced a Th1-type response to E7) or with GF001 and Quil-A. Depletion of CD8+ cells, but not CD4+ cells, from an immunized animal abrogated protection, confirming that E7-specific CTL are necessary and sufficient for TSA-specific protection in this model. Immunization with E7 and Algammulin (an alum-based adjuvant) induced a Th2-like response and provided no tumor protection. To investigate whether a Th2 T helper response to E7 could prevent the development of an E7-specific CTL-mediated protection, mice were simultaneously immunized with E7/Algammulin and GF001/Quil-A or, alternatively, were immunized with GF001/Quil-A 8 wk after immunization with E7/Algammulin. Tumor protection was observed in each case. We conclude that an established Th2 response to a TSA does not prevent the development of TSA-specific tumor protective CTL.

Adjuvants, Immunologic↗
PubMed1998

Vaccine-induced Th1-type responses are dominant over Th2-type responses in the short term whereas pre-existing Th2 responses are dominant in the longer term.

The effect of adjuvant on induction of human papillomavirus type 16 E7 protein-specific cytotoxic T lymphocytes (CTL) and immunoglobulin G (IgG)2a antibody was studied in C57BL/6 J mice immunized with various adjuvants and E7 protein. Quil-A adjuvant, but not complete Freund's adjuvant (CFA) or Algammulin, induced a T-helper 1 (Th1)-type response to E7, which was characterized by CTL activity against a tumour cell line transfected with E7 protein and by E7-specific IgG2a. All tested adjuvants elicited comparable levels of E7-specific IgG1. The longest duration and greatest magnitude of CTL response was seen following two immunizations with the highest dose of E7 and Quil-A. Simultaneous immunization with a Th1 and a T helper 2 (Th2)-promoting adjuvant gave a Th1-type response. However, E7 and Quil-A were unable to induce a Th1-type response (as measured by the inability to generate anti-E7 IgG2a antibody) in animals with a pre-existing Th2-type response to E7. These results suggest that saponin adjuvants may be suitable for immunotherapy in humans where a Th1-type response is sought, provided that there is no pre-existing Th2-type response to the antigen.

Adjuvants, Immunologic↗
PubMed1993

An unusual presentation of oat cell carcinoma.

A case is reported of oat cell carcinoma of the lung presenting with unusual sites of metastasis to the orofacial region. Distant metastases are common in oat cell carcinoma but a literature review did not reveal any reports of metastases either to the hard palate or to medial canthus of the eye.

Carcinoma, Small Cell↗
PubMed1992

Analysis of the complete sequence of a muscle calcium-binding protein of Schistosoma mansoni.

The complete sequence of the cDNA encoding a 20 kDa calcium-binding protein of Schistosoma mansoni (Sm20) has been determined. The predicted amino acid sequence contains 4 EF hand domains but examination of the predicted secondary structure of Sm20, together with the specific residues in each calcium-binding domain, suggests that only 1 EF hand (domain IV) is functional. Sm20 is most homologous to calmodulin, troponin C and the regulatory light-chain of myosin, particularly those of invertebrates. However, troponin C and the regulatory light-chain of myosin can be distinguished from Sm20 by size and by their differential levels of expression during the life-cycle. Sm20 also appears to be distinct from calmodulin but may be functionally equivalent to the soluble sarcoplasmic calcium-binding proteins of molluscs and crustacea which may act as a reservoir for calcium in muscle. Sm20 is encoded by a small multi-gene family whose members are clustered within a 15 kb region of the genome. A 20 kDa antigen, cross-reactive with Sm20, is expressed in Schistosoma haematobium, Fasciola hepatica and Paragonomus mexicanus.

Amino Acid Sequence↗
PubMed1990

Surgical treatment of glossopharyngeal neuralgia via the pharyngeal approach.

Idiopathic glossopharyngeal neuralgia is an uncommon disorder which often fails to respond to medical treatment. Surgical treatment most commonly consists of intracranial section of the glossopharyngeal nerve and upper vagal rootlets. We present three cases treated by the much simpler pharyngeal approach and argue that in appropriately selected patients this approach should receive more serious consideration.

Aged↗
PubMed1989

Fetal heart rate changes associated with general anesthesia.

Decreased fetal heart rate variability was noted 90 seconds after the induction of general anesthesia with sodium thiopentone and fentanyl in a patient undergoing basket extraction of a renal calculus at 30 weeks' gestation. The fetal sleep pattern lasted for 105 minutes after the anesthetic was discontinued, 45 minutes after the mother was fully awake.

Adult↗
PubMed1986

Tonsil flora in the very young tonsillectomy patient.

The tonsil flora of 20 children below the age of 4 years undergoing tonsillectomy, and a control group of 18 children were studied using tonsil swabs and core specimens. The study group had a significantly higher culture rate of anaerobic organisms, whereas there was no significant difference between the groups in respect of aerobic pathogens. Since most anaerobic organisms are relatively resistant to the antibiotics usually prescribed for recurring tonsillitis, the use of more appropriate antimicrobial therapy may be helpful in the prevention of early tonsillectomy.

Age Factors↗
PubMed1982

Effects of garlic on lipid metabolism in rats fed cholesterol or lard.

Effects of garlic on lipid metabolism were studied in three experiments using different aged male rats fed a diet containing 1% cholesterol or 15% lard. Lyophilized garlic was supplemented at 2% and 4% of the diet. Plasma glucose was not changed by dietary treatments. Rats fed cholesterol and lard diets increased plasma cholesterol and triglycerides compared to controls. Garlic decreased plasma cholesterol in cholesterol- and lard-fed rats, but decreased plasma triglycerides only in the lard-fed group. Garlic supplementation decreased very low density lipoprotein cholesterol and increased high density lipoprotein cholesterol. The liver weight, total liver lipid and cholesterol were increased in rats fed the cholesterol diet but a supplementation of garlic decreased those parameters by about 30%. Dietary cholesterol and lard decreased hepatic glucose-6-phosphate dehydrogenase and malic enzyme activities: the garlic supplementation further decreased these enzyme activities. Garlic feeding increased the excretion of the neutral steroids in both 16-week and 10-week-old rats and bile acids in only 16-week-old pair-fed rats. Garlic at the 2% level was similarly effective on lipid metabolism as at 4%. These results demonstrate that garlic increases the excretion of neutral and acidic steroids and exerts hypocholesterolemic effects in cholesterol-fed rats.

Adipose Tissue↗
PubMed1982

Physician communication with children and parents.

The way physicians communicate with patients has been shown to affect physiologic measurements, adherence to therapeutic regimens, and satisfaction with medical care. The purpose of this study was to document the content of medical interviews in routine pediatric visits and to identify demographic and situational characteristics that influenced the extent of communication between doctor and child. One hundred fifteen office visits to 49 physicians were videotaped and analyzed. Children studied were 4 to 14 years old with a mean age of 8.5 years. Verbal transactions were coded according to direction of communication, transaction type, and content category. Coder reliability for this system was 0.84. A considerable amount of the total communication, 45.5%, was between doctor and child. Doctors interacted differently with parents and children. More information about the current problem was obtained from children; physicians provided feedback primarily to parents. Parents received 4.4. times as much information as children about the nature and prognosis of a condition. The extent to which doctors talked to children in "substantive" areas was primarily associated with a child's age (r = .52, P less than .001) but was partly influenced by family size (r = .20, P less than .05) and family utilization (r = .22, P less than .02). Race, socioeconomic status, type of problem, and previous encounter with the examining physician did not alter communication patterns. Boys were given more information than girls (6.5% vs 4.0%, P less than .01). We suggest a theoretical framework for future investigation and teaching that identifies the child as an active participant in the medical process.

Adolescent↗
PubMed1981

Surgical anatomy and pathology of the round window.

A study of the surgical anatomy and pathology of the round window was performed on a total of 292 serially sectioned temporal bones. The surgical approach to the round window is discussed with consideration of the anatomical findings. In the pathological study obliteration of the round window niche occurred as a congenital anomaly, in otosclerosis, chronic otitis media and as an end result in suppurative labyrinthitis. Clinical reports seem to indicate that obliteration of the window is associated with significant hearing loss, contrary to the findings in experimental animals. In chronic otitis media the round window is a pathway for spread of infection to the labyrinth, but also the finding of perilymphatic precipitates to the window in some ears suggests that certain inflammatory products may enter the scala tympani through the round window and so lead to high tone sensorineural hearing loss.

Adolescent↗
PubMed1981

Children as patients: a communications process study in family practice.

To determine how family physicians divide their attention between children and parents, 115 videotaped pediatric encounters of children (aged 4 to 14 years) and parents with family physicians in a family medicine center were analyzed. It was learned that physicians tended to involve children actively in the diagnostic stages of interviews but much less so in discussions of treating or dealing with their problems. Physicians did not alter this pattern as they advanced in training. Older children were more likely to receive direct communication from physicians in all phases of office encounters. Though the family physicians in this sample had more direct communication with children than reported in previous research, it is argued that greater involvement of children in all phases of pediatric visits is warranted. A developmental framework indicates that children gradually evolve their attitudes, concepts, and behaviors around illness and health. Family physicians and family medicine programs are in an excellent position to explore and utilize the practice of actively incorporating a child in a medical interview.

Adolescent↗
PubMed1979

The pneumococcal vaccine. Immunization at a crossroad.

A new polyvalent pneumococcal vaccine (Pneumovax) was released in February 1978. In an effort to chronicle the dissemination of the vaccine to high-risk patients, we prospectively followed up a single clinic population and conducted a telephone survey of three neighborhood health centers, two private practices, and a university hematology clinic. Three months after notification of the vaccine arrival, physicians in the prospectively chronicled clinic had immunized six of 12 patients with sickle cell disease, five of 80 patients with chronic obstructive pulmonary disease, three of 225 patients with diabetes, and three of 45 patients older than 80 years. Immunization policy in the other clinics surveyed varied greatly. As an attempt to curb low-prevalence, high-severity illness in a small target population, the pneumococcal vaccine presents a new set of problems in the systematic implementation of an immunization.

Anemia, Sickle Cell↗