Thymic neuropeptides and T-lymphocyte development.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to F Robert.
Explore the source record for details and available documents.
A total of 19 patients with advanced squamous-cell carcinoma of the head and neck who had not previously been exposed to chemotherapy were treated with brequinar sodium as first-line chemotherapy. Brequinar was given intravenously at a median weekly dose of 1,200 mg/m2. The toxicity was moderate, with 7 patients (37%) experiencing grade 3 or 4 toxicity. In all, 16 patients who were evaluable for efficacy showed no objective response. We conclude that brequinar given at this dose and on this schedule has no significant activity in advanced squamous-cell carcinoma of the head and neck.
CI-921, (9-[[2-methoxy-4-[(methylsulfonyl)amino]phenyl]amino]- N,5-dimethyl-4-acridinecarboxamide 2-hydroxyethanesulfonate (1:1)), an anilinoacridine derivative with activity in experimental solid tumors was studied in a multicenter phase II trial in patients with solid tumors. Eligible tumor types included cancers of the breast, stomach, pancreas, nonsmall cell lung, small cell lung, colon, head and neck area, and melanoma. Prestudy requirements included an ECOG performance status of < or = 2, no CNS metastases, and measurable disease. CI-921 was administered intravenously over 1-2 hours on days 1, 8, and 15 of a 35-day course at an initial dose of 270 mg/M2, with modification in subsequent courses based upon tolerance. Principal toxicities included leukopenia, marked phlebitis, and mild nausea and vomiting. One hundred fifty patients were entered of whom 132 were evaluable for response. There was one complete and one partial response among 19 patients with breast cancer, and two partial responses, one each among 14 head and neck and 36 nonsmall cell lung cancer patients.
Explore the source record for details and available documents.
The individual data for 424 acute myocardial infarction patients from 15 reperfusion studies conducted with anistreplase were reviewed to assess the correlation between the delay onset of symptoms to treatment and reperfusion of the coronary artery. The patients had a mean age of 56 years and 85.4% were male. All patients had a baseline angiogram showing an occluded coronary artery. Anistreplase was given in doses ranging from 3.75 to 35 IU (60% of patients received 30 IU). The mean delay between onset of symptoms to treatment was 3 h 29 min and reperfusion was observed in a total of 61.1% of patients. There was a highly significant correlation between reperfusion and the delay from onset of symptoms to treatment (p less than 0.001). A multivariate logistic regression was performed adjusting for age, sex, location of infarct, dose, and concomitant treatment. The only remaining statistically significant prediction factor for reperfusion was the delay between onset of symptoms to treatment (p less than 0.001). In conclusion, the ability of anistreplase to cause the lysis of coronary thrombi appears to be increasingly important as the delay from onset of symptoms to treatment is decreased. This may contribute to the lower mortality rate observed with early fibrinolytic treatment.
Explore the source record for details and available documents.
The merits of evaluating the parietal extension of lung cancers is emphasized by the new TNM classification. CT and MRI have added to the conventional radiological techniques. The authors successively analyze the contribution of these techniques to the assessment of extension of lung cancers to the wall, including the costal and phrenic compartments, to the pleura and to the apex. Lung radiographs show obvious lesions, such as extensive costal lysis and major pleural extensions. Computed tomography has better sensitivity and specificity than lung radiographs to establish pleuroparietal involvement; it is best performed in the inclined plane of the ribs and in the high-resolution mode. The presence of costal lysis means parietal involvement, while the integrity of the pleura can be established if the lesion remains at a distance from the wall. The persistence of an extrapleural fatty rim between the tumor and the wall allows ruling out parietal extension. MRI provides accurate details in case of doubtful CT findings for the extension to the costovertebral groove, to the intervertebral foramina, to the peridural space and to the diaphragm. Its major asset is to assess the vertebral, vascular and nervous extension of cancers of the apex pulmonis.
Explore the source record for details and available documents.
The thymic repertoire of neuroendocrine 'self' antigens has been previously described on the basis of the intrathymic expression of neurohypophysial (NHP)- and tachykinin-related peptide signals and receptors. According to that model, the cryptocrine signalling between thymic epithelial/nurse cells and thymocytes through NHP-related signals and receptors constitutes one accessory pathway in the process of T-cell differentiation and/or activation. A pharmacological manipulation of that novel type of cell-to-cell signalling was tested by the investigation of the immunomodulatory properties of novel cyclic hexapeptide oxytocin (OT) antagonists (MSD Research Laboratories). These compounds were found to significantly inhibit the productions of cytokines (mainly IL-1 beta and IL-6) elicited by anti-CD3 treatment of human whole blood cell cultures. Cytokine productions were more significantly reduced by OT antagonists in whole blood cell cultures derived from female volunteers than in those obtained from male donors, suggesting an influence of the gonadal steroid environment on the expression of NHP peptide receptors by immune cells. These observations support the concept of novel immunomodulating approaches through immune-specific neuropeptide antagonists, as well as the pharmacological value of such strategies in selective immunotherapy.
Brain tumor growth results from the relative proportion of cells contained in three populations: a) cycling/proliferative; b) quiescent (GO)/static, and c) terminally differentiated/dying. The cycling compartment can be detected by the mouse monoclonal Ki-67 antibody, an available, rapid, safe, sensitive, and specific method for immunostaining of proliferative cells. We report the Ki-67 labeling index (LI) in 48 brain tumors. Malignant brain tumors have elevated LIs, ranging from 6.0% to 56.9%: anaplastic astrocytoma, 8.0 +/- 7.3; glioblastoma multiforme, 10.1 +/- 4.2; germinoma, 11.7; medulloblastoma, 13.1 +/- 6.6; metastases, 40.3 +/- 13.1. By contrast, slow-growing tumors showed lower values (P less than .001), approaching 1%: acoustic schwannoma, 0.4 +/- 0.6; pituitary adenoma, 1.3 +/- 1.9; meningioma, 1.2 +/- 1.2; low-grade astrocytoma, less than 1; pilocytic astrocytoma, 5.6. Human brain tumors can therefore be ranked according to the percentage of cycling cells with the acoustic schwannoma among the least proliferative and the metastatic carcinoma among the most proliferative. Within a given histotype, the Ki-67 LI may have prognostic and therapeutic implications for the individual patient. Already important for neuro-oncology research, the Ki-67 labeling index should be added to the armamentarium of the clinical neuropathologist to complement the standard histopathologic diagnosis with a cytokinetic analysis of cellular proliferation.
Explore the source record for details and available documents.
The lymphocyte composition of the thymus and spleen from weaned (4 month old) hypopituitary dwarf Snell-Bagg mice were compared to those of their phenotypically normal littermates and of hormone (somatotropic hormone plus thyroxine)-treated individuals. Detection of cells bearing receptors for peanut agglutinin, physical analysis and measurement of in vitro reactivities to phytohaemagglutinin and concanavae intra-thymic lymphocyte population of dwarf mice. Examination of spleen-cell suspensions demonstrated a slightly higher frequency of T lymphocytes (Thy 1-2+ alpha-Naphthyl esterase+, high electrophoretic mobility) and lower frequency of B lymphocytes (surface immunoglobulin+, low electrophoretic mobility) in dwarf mice than in control mice. The degree of splenocyte responsiveness to T- and B-cell mitogens, however was similar in the two mouse types. High mobility (T) splenic cells were found to exhibit a smaller modal volume in dwarf mice (110 micron3) than in control mice (122 micron3) but this difference was not corrected by hormone administration. More pronounced were the quantitative differences between the spleens of hormone-deficient and normal mice. Thus, when expressed as a function of body weight, the numbers of splenic T and B lymphocytes in untreated dwarf mice were about half the corresponding values in hormone-reconstituted or normal littermates. These data suggested that in adult life, developmental hormones exert little direct effect on the thymus lymphocytes but influence the size of the pool of both peripheral T and B lymphocytes.
An ascitic tumor (SEWA) induced by polyoma virus in A.SW mice was analyzed in vivo as well as in vitro with regard to the electrophoretic mobility (EPM) which may be considered as a reliable criterion of surface charge. After the i.p. transplantation of 10(5) cells, the EPM decreased up to 14th day. Then, the mobility gradually increased with the age of the tumor. In the first phase of tumor growth, we have considered the possibility that immunoglobulin cell coating may be responsible for the decrease in EPM. In the late phase of SEWA growth, the progressive increase in EPM might be due to a rearrangement of sialic acids on the outer part of the cell membrane.
An attempt was made to classify human pituitary cell types by electron microscopic immunohistochemistry. The immunoperoxidase technique involving the use of the peroxidase-antiperoxidase complex was applied to thin sections of human pituitaries removed surgically for breast cancer or diabetic retinopathy. Using specific antibodies against human PRL, GH, beta-FSH, beta-LH, beta-TSH, and porcine ACTH, the localization of each hormone was studied. Identification of 5 human pituitary cells was possible: 1) The PRL-secreting cell contains round or slightly ovoid secretory granules of a diameter of 275-350 nm. 2) The GH-secreting cell is densely granulated with granule diameters ranging from 350-500 nm. 3) The gonadotrophic cell, which stains for both beta-FSH and beta-LH, is characterized by the presence of a varying number of secretory granules ranging from 275-375 nm. 4) The cortico-lipotrophic cell has numerous granules of about 375-550 nm in diameter. 5) The TSH-secreting cell contains small secretory granules of about 125-200 nm in diameter. Another cell type of which the small secretory granules of about 100 nm in diameter could not be stained by any of the antisera was also observed. This ultrastructural identification of human pituitary cells should contribute to a better understanding of the pathophysiology of the human pituitary.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Twenty-two pituitary adenomas in Cushing's disease were removed by transsphenoidal surgery. In six patients the pituitary tumor had become manifest following adrenalectomy (Nelson's syndrome). Sixteen tumors were microadenomas measuring from 2 to 9 mm, while two were diffuse invasive adenomas verified at postmortem examination. Light microscopy showed that the tumors were made of basophillic cells containing PAS-positive granules that stained blue with Herlant tetrachrome and lead hematoxylin. Immunocytochemical studies showed that the granules stained positively with antiserum to adrenocorticotrophic hormone (ACTH) or to beta-lipotropic hormone (beta-LPH) and the peroxidase-antiperoxidase complex. Electron microscopic study of the tumor cells showed ACTH and beta-LPH containing granules varying in size, shape, and amount. Perinuclear bundles of 70 A microfilaments constituted a specific ultrastructural finding.
In 45 patients without spontaneous breathing or cranial reflexes, and in whom blood pressure had to be supported, spinal reflexes were obtained in 60% and polysynaptic spinal reflexes in 33%. In all cases angiography showed cerebral circulatory arrest and/or repeated EEG recording gave an isoelectric line. The presence of spinal reflexes, appearing most frequently 6-36 h after death (which we defined as a sudden fall in blood pressure below 80 mm Hg with absence of spontaneous breathing) is not in contradiction with the assumption of brain death. 9 patients without signs of intoxication showed, in addition, a fall in body temperature below 34 degrees C. Such a fall in body temperature also in agreement with the diagnosis of brain death.