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Biomedical subjects

J D Kennedy

Publications and source records attributed to J D Kennedy.

12 recordsLinked to original sources
PubMed1992

Extrathymic T cell maturation. Phenotypic analysis of T cell subsets in nude mice as a function of age.

T cell maturation in an extrathymic environment has been studied using as a model the congenitally athymic nude mouse. Phenotypic analyses as a function of age were conducted on lymphocytes obtained from the spleens and lymph nodes of nude mice through use of mAb recognizing T cell surface markers and multiparameter flow cytometry. The data show that nude mice accumulate increasing numbers of lymphocytes bearing Thy-1, CD3, CD4, and CD8 with age characterized by a progression from heterogeneous dim to more homogeneous bright expression. In contrast, the expression of heat-stable Ag (HSA), a marker of immature thymocytes, decreases with age. By analogy to intrathymic maturation, spleens and lymph nodes in nude mice contain T cells defined as immature, transitional, and mature based on the expression of these markers. Although the proportion of CD4+ and CD8+ T cells associated with bright CD3 expression increases with age, at no age are significant numbers of CD4+8+ cells observed, in contrast to intrathymic T cell maturation. In addition to the frequently observed inversion in the ratio of CD4 to CD8, the CD8 T cell subpopulation in older nude mice contains mainly mature cells (CD8+, CD3+, HSA-) whereas only 50% of CD4+ T cells express the mature (CD4+, CD3+, HSA-) phenotype. At any age, the spectrum of phenotypes observed indicates that lymph nodes contain more mature T cells than spleen, suggesting a role for environmental Ag in driving extrathymic maturation, a process occurring most efficiently among CD8+ T cells. Because extrathymic maturation mirrors some but not all aspects of the intrathymic pathway, we propose that the nude mouse may be a useful model for further dissecting those interactions crucial to establishing the T cell repertoire in euthymic individuals as well as elucidating the contribution of extrathymically derived T cells to the peripheral immune system.

Age Factors↗
PubMed1991

CD8+ alpha/beta or gamma/delta T cell receptor-bearing T cells from athymic nude mice are cytolytically active in vivo.

Phenotypic analysis of lymphocytes that mature extrathymically in congenitally athymic nude mice has revealed a large population of CD3+ CD8+ T cells that express gamma/delta-TCR. In euthymic mice, significant numbers of cells with this phenotype are found only in the intestinal epithelium. Intestinal intraepithelial lymphocytes have been shown to be cytolytically active in vivo, as measured by the redirected lysis assay. In this communication, freshly harvested T cell subsets obtained from pooled nude mouse spleen and lymph nodes and separated by flow cytometric cell sorting were assayed for their ability to lyse FcR+ P815 targets in the presence of mAb to the epsilon-chain of the CD3 complex. CD8+, but not CD4+ or CD4- CD8-, T cells in nude mice were cytolytically active. CD8+ alpha/beta- and gamma/delta-TCR-bearing T cells from the spleen and lymph nodes of nude mice demonstrated similar cytolytic activity. No cytolytic activity of purified cell subsets was apparent in the absence of anti-CD3 mAb, even when NK-susceptible target cells were used. These data indicate that, in contrast to euthymic mice, a large proportion of CD8+ cells from the spleen and lymph nodes of nude mice are cytolytically active in vivo. In addition, these results suggest that the intestinal epithelium is not the only anatomical location where constitutively cytolytic CD8+ alpha/beta- or gamma/delta TCR-bearing T cells may be found.

Animals↗
PubMed1991

T cell receptor expression by T cells that mature extrathymically in nude mice.

The expression of TCR by T cells that mature extrathymically in nude mice was determined by staining Ig- cells from B10 nude mice that were 5 months of age or older with mAbs specific for CD3, alpha/beta or gamma/delta TCR. Although the majority of Ig- cells in older nude mice express TCR, the distribution of alpha/beta and gamma/delta TCR in relation to CD4 and CD8 expression is markedly different compared to T cells from euthymic mice. Approximately half of the CD3+ T cells found in the spleen and lymph nodes of nude mice express gamma/delta TCR that is equally distributed between CD4-8- double-negative and CD8+ single-positive T cells. These data provide the first quantitative measure of the expression of TCR by T cells that mature in the absence of a thymus and suggest that the extrathymic environment, although not efficient, is permissive for the maturation of T cells that express alpha/beta and gamma/delta TCR.

Animals↗
PubMed1990

Intralesional immunotherapy of brain tumors with combined Corynebacterium parvum and recombinant interleukin-2 in mice.

Clinical observations and experimental work suggested that inflammatory cells attracted to the brain exert a nonspecific antineoplastic effect. Intralesional treatment of implanted malignant murine brain tumors (KHT sarcomas) with killed Corynebacterium parvum produced an inflammatory cell infiltrate and increased survival in C3H mice relative to that in untreated control C3H mice. This antitumor effect was enhanced when recombinant interleukin-2 was sequentially added as a second intralesional immunomodifier. A high percentage of mice so treated were cured. Inflammatory cells in the brains of treated mice divided for 1-2 weeks, and metabolic activity of astrocytes increased. These findings form the basis for a recently initiated immunotherapy protocol in patients with recurrent glioblastoma multiforme.

Animals↗
PubMed1990

Pseudo-Bartter's syndrome in cystic fibrosis.

Seven cases of cystic fibrosis complicated by chronic salt depletion and failure to thrive were studied. After replacement of the salt deficit, the metabolic abnormalities resolved, and weight gain was rapid. This should be considered as a differential diagnosis in children who have been diagnosed as having cystic fibrosis, but who fail to thrive despite standard treatment.

Alkalosis↗
PubMed1989

Effect of intracerebrally injected Corynebacterium parvum on implanted brain tumor in mice.

Experiments were performed to determine the effectiveness of Corynebacterium parvum on resistance to growth and development of tumor in the central nervous system. A syngeneic sarcoma was injected intracerebrally into C3H/HeN/MTV-negative female mice that had received intraperitoneal injections of C. parvum or saline prior to tumor inoculation or that received intraperitoneal C. parvum or saline after tumor inoculation. Groups then received an intracerebral injection of C. parvum or saline. Our results reveal that intracerebral C. parvum elicited an intracerebral inflammatory reaction which was enhanced by prior systemic priming with C. parvum. Any inflammatory reaction which was enhanced by prior systemic priming with C. parvum. Any inflammatory reaction produced by C. parvum retarded the growth of intracerebrally-implanted sarcoma and significantly increased the survival of mice bearing such tumors. These results suggest that C. parvum may be an effective therapeutic agent in the treatment of neoplasia of the central nervous system.

Animals↗
PubMed1989

Effect of intracerebrally injected Corynebacterium parvum on the development and growth of metastatic brain tumor in mice.

Using KHT tumor in a mouse metastatic tumor model, we examined the effect of intracerebral and/or intraperitoneal injections of Corynebacterium parvum on the growth of metastatic brain tumor and the development of an inflammatory response in the central nervous system (CNS). C. parvum given intraperitoneally had no effect on the development and growth of CNS tumor, but did prolong the survival of mice by inhibiting the growth of systemic metastatic tumor, which was the cause of death in our tumor model. Mice that received intracerebral injections of C. parvum exhibited significantly decreased growth of metastatic brain tumor, as compared with mice that received intracerebral injections of saline, whether or not they had received C. parvum intraperitoneally. In addition, the brains of mice that received C. parvum intracerebrally exhibited an inflammatory response that was minimal or absent in the brains of control mice. Our results suggest that if immunotherapeutic agents can be delivered to the CNS and cause an inflammatory response, they can be effective against CNS metastases.

Animals↗
PubMed1989

Effect of bracing on respiratory mechanics in mild idiopathic scoliosis.

The use of a corrective orthopaedic brace is an established form of management for patients with progressive idiopathic scoliosis. Thirteen patients with mild idiopathic scoliosis were studied with and without the corrective brace applied. Lung volumes and the pattern of chest wall and abdominal movement were measured during quiet breathing. Transdiaphragmatic pressures were measured in six of the patients and upper ribcage movement in seven patients. Application of the brace resulted in a significant reduction in vital capacity (14%), functional residual capacity (22%), and total lung capacity (12%). There was no effect on respiratory rate or minute volume. In the erect position the pattern of chest wall movement was altered with a reduction in lower ribcage movement of 46% and abdominal wall of 39% and an increase in upper ribcage movement of 43%. These changes were greater in the supine position. There was at least a twofold increase in end inspiratory and end expiratory gastric pressures during tidal breathing, but oesophageal pressures were not affected by the brace. Transdiaphragmatic pressures showed a similar twofold increase, which implies a substantial increase in the work of breathing. In view of the doubts concerning the influence of bracing on the natural history of idiopathic scoliosis and the substantial functional effect of bracing on the respiratory system, it is suggested that the current practice of bracing in this condition needs to be reviewed.

Adolescent↗
PubMed1979

Primary sarcoma of the heart: a light and electron microscopic study of two cases.

Two cases of primary malignant cardiac neoplasms are presented. The first, an angiosarcoma of the right atrium, developed in a 44-year-old housewife, who survived 23 days from the time of presentation; diagnosis was made at necropsy. The second, an embryonal rhabdomyosarcoma of the right ventricle, developed in a 17-year-old student; diagnosis was made by angiocardiography. He underwent surgery and cytotoxic and irradiation therapy and died 14 months later.

Adolescent↗
PubMed1978

Gastric neoplasm in the West of Ireland: an endoscopic survey.

The results of endoscopic examination, biopsy taken at endoscopy and cytology of brush smears and/or gastric lavage specimens in 100 patients with proven malignant gastric lesions are described. Overall, a correct pre-operative diagnosis was achieved in 98 cases. Endoscopic appearance was a more accurate criterion in cases of exophytic advanced carcinoma, malignant ulcer and lymphoma than in diffuse infiltrative carcinoma or in early carcinoma, where biopsy and cytology were more accurate. Nine per cent of neoplasms were malignant lymphomas, which is much higher than the usual reported incidence. Early carcinoma was found in 5% of cases. In spite of readily available facilities for endoscopic diagnosis, most cases of gastric neoplasm were already advanced at the time of examination.

Adolescent↗