The ontogeny of T lymphocyte maturation and function.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to C B Wilson.
Explore the source record for details and available documents.
To elucidate an involvement of mesangial cells in the regulation of glomerular hemodynamics, renal micropuncture techniques and glomerular morphometry were employed in Munich-Wistar rats with mesangial cell lytic or proliferative lesions induced by administration of an antibody reactive with Thy-1.1-like antigens on the mesangial cell surface. The antibody-induced mesangial cell lysis at day 1 resulted in a significant decrease in glomerular ultrafiltration coefficient, leading to reduction in single nephron glomerular filtration rate (SNGFR) in spite of a significant increase in both glomerular hydrostatic pressure and single nephron plasma flow (SNPF). During the antibody-induced proliferative lesion at day 6, glomerular ultrafiltration coefficient and SNGFR remained reduced; however, SNPF was now decreased. Morphometric analysis showed the enlargement of capillary luminal volume and the development of new open space in the mesangium accessible for blood flow in the mesangial cell-lytic glomeruli at day 1. An increase in mesangial cell volume was found in the proliferative glomeruli at day 6. The total area of peripheral glomerular basement membrane, presumed as the probable filtration area, was unchanged in these glomeruli. These results indicate that mesangial lesions decrease glomerular ultrafiltration coefficient, and suggest that mesangial cells participate in regulation of glomerular filtration rate.
Explore the source record for details and available documents.
Alveolar macrophages (AM) migrate less well in response to chemotactic ligands than do monocytes and neutrophils. The response of monocytes and neutrophils to chemotactic ligands is mediated at least in part by pertussis toxin-sensitive guanine nucleotide binding proteins (Gi proteins). Whether this is also true in AM is uncertain. We hypothesized that decreased chemotaxis by AM was due in part to diminished Gi protein and/or chemotactic receptor density in AM. G proteins are heterotrimers made up of alpha, beta, and gamma subunits; the predominant pertussis toxin-sensitive Gi proteins are those containing alpha i2 or alpha i3 subunits. Pertussis toxin pretreatment (0.5 microgram/ml) significantly reduced AM, monocyte, and neutrophil chemotaxis to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) and human zymosan-activated serum (P less than 0.05). However, as previously noted, AM chemotaxis was much less than that observed in monocytes and neutrophils. Immunoblots using antibodies that are specific for alpha i2 and alpha i3 showed that AM contained approximately 3-fold less alpha i2 and approximately 10-fold less alpha i3 per microgram of plasma membrane protein than did monocytes or neutrophils. Similar results were obtained in immunoblots made using antibodies to common alpha subunit determinants and to the beta 36 subunit. A comparable approximately 4-fold reduction in density of receptors for [3H]FMLP was found in AM compared to neutrophils. The diminished density of Gi proteins and FMLP receptors was not due to a generally decreased density of plasma membrane proteins in AM, since the density of the membrane-associated tyrosine kinase hck was similar in AM, monocytes, and neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)
The mechanisms by which T lymphocytes acquire the capacity to produce interleukin 4 (IL-4) and other lymphokines during intrathymic and extrathymic development are poorly understood. To gain insight into this process, we determined the capacity of human neonatal and adult T lineage cell populations to produce IL-4 after polyclonal activation. IL-2 and interferon-gamma (IFN-gamma) production were studied in parallel, since their production by neonatal T cells is known to be similar or diminished, respectively, compared to adult T cells. Production of IL-4 by neonatal CD4+ T cells and IFN-gamma by neonatal CD4+ and CD8+ T cells was markedly lower compared with analogous adult cell populations, whereas IL-2 production was similar. Transcription of IL-4, as determined by nuclear run-on assays, and IL-4 mRNA-containing cells, as determined by in situ hybridization, were undetectable in neonatal T cells, whereas both were detectable in adult T cells. IFN-gamma transcription and IFN-gamma mRNA-containing cells were reduced in neonatal T cells compared with adult T cells. Reduced lymphokine production by neonatal T cells correlated with their lack of a CD45R- (putative memory T cell) population; cells with this surface phenotype comprised 30-40% of the adult CD4+ T cells and were highly enriched for IL-4 and IFN-gamma, but not IL-2 production. IL-4, IFN-gamma, and IL-2 mRNA expression by neonatal CD4+CD8- thymocytes was similar to that found in circulating neonatal CD4+ T cells. Taken together, these findings suggest that the extrathymic generation of memory T cells during postnatal life may result in an increased capacity for IL-4 and IFN-gamma gene expression. In addition, IFN-gamma and IL-2 mRNA were significantly more abundant than IL-4 mRNA in activated neonatal CD4+CD8- thymocytes and CD4+ T cells, as well as adult CD4+ CD45R- T cells. Therefore, the capacity of T lineage cells to express the IL-4 gene may be more restricted compared to other lymphokine genes beginning in intrathymic development. This restricted capacity appears to persist during postnatal extrathymic maturation of T cells.
The authors report the cases of three patients with epidermoid cysts which insinuated themselves into the brain stem. In all three patients, the tumor occupied the pons, although in one it was predominantly located in the medulla. The cyst contents and nonadherent tumor capsule were removed in all three patients, but no attempt was made to remove tumor densely adherent to the brain stem. One patient's cyst was removed in one operation, but maximal resection in the other two required two operations. After surgery, sixth nerve function completely returned in one patient; another patient had a stable pontine gaze palsy but developed new facial weakness; and the third patient had stable cranial nerve deficits with a diminished hemiparesis. The last patient developed a pseudomeningocele and communicating hydrocephalus, and required a lumboperitoneal shunt. In all three patients, computerized tomography scans demonstrated hypodense tumors not enhanced by contrast material. Magnetic resonance imaging was performed on two patients; in both, the tumors showed increased signal intensity relative to brain on T1-weighted images and decreased signal intensity relative to brain on T2-weighted studies. Magnetic resonance imaging, the most accurate modality for localizing these lesions and determining their extent, was also invaluable for postoperative monitoring and follow-up evaluation. Safe and adequate resection includes decompression of cyst contents and removal of nonadherent portions of the cyst capsule. Cyst wall adherent to the brain stem, however, should not be removed.
Dural arteriovenous (AV) fistulas are thought to be acquired lesions that form in an area of thrombosis within a sinus. If the sinus remains completely thrombosed, venous drainage from these lesions occurs through cortical veins, or, if the sinus is open, venous drainage is usually into the involved sinus. Among 105 patients with dural AV fistulas evaluated over the the past 5 years, seven had a unique type of dural AV fistula in the superior sagittal, transverse, or straight sinus in which only cortical venous drainage occurred despite a patent involved sinus; the fistula was located within the wall of a patent dural sinus, but outflow was not into the involved sinus. This variant of dural AV fistulas puts the patient at serious risk for hemorrhage or neurological dysfunction caused by venous hypertension. Three patients presented with hemorrhage, one with progressive neurological dysfunction, one with seizures, and two with bruit and headaches. A combination of surgical and endovascular techniques was used to close the fistula while preserving flow through the sinus.
A patient with trigeminal neuralgia and hemifacial spasm was evaluated using multiplanar magnetic resonance (MR) imaging with gadolinium enhancement. Preoperative images demonstrated massively ectatic vertebral and basilar arteries and their distortion of the brain stem and the trigeminal and facial nerves. Surgical manipulation included selective trigeminal rhizotomy, cushioning of the residual nerve at the point of maximal distortion by the underlying basilar artery, and microvascular decompression of the seventh nerve from the anterior inferior cerebellar artery which was being pushed dorsomedially by the vertebral artery. Postoperatively, the patient had neither trigeminal neuralgia nor facial spasm. Gadolinium-enhanced MR imaging not only excludes other etiologies such as tumor or arteriovenous malformation, but also demonstrates cranial nerve compression by ectatic vertebral and basilar arteries. The choice of preoperative imaging modality is discussed and the literature concerning the etiology of tic convulsif is reviewed.
Five groups of Hereford steers were monitored for 293 days. One group of 3 was not given selenium supplementation; the other 4 groups of 3 steers each were given 2, 4, 6, or 8 reticulorumen selenium pellets. Health, body weight, and blood selenium concentration were monitored during the study. At the finish, steers were slaughtered, and various tissues from the carcasses were analyzed for selenium content. Initial blood selenium concentration did not differ significantly among groups. However, significant (alpha = 0.01) difference among means was detected during the early period of rapid increase in blood selenium concentration in steers of supplemented groups. Means of maximal blood selenium concentration also differed among groups; however, even the highest value, 0.253 micrograms/g, was lower than the 3 micrograms/ml reported in chronic clinical cases of toxicosis in the literature. Carcass analysis indicated significant (alpha = 0.05) differences in selenium concentrations among treatment groups for almost all tissues tested. Only kidney samples (7.9 micrograms/g) from steers of the 8-pellet treatment group exceeded published normal values (7.6 micrograms/g). Health variables for most dates were not significantly different among groups, and selenium toxicosis was not evident in any steer. Analysis did not indicate risk to human beings consuming tissues from these steers.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Ninety-six patients with intracranial meningiomas and two with hemangiopericytic variants received a 30-min intravenous infusion of bromodeoxyuridine (BrdUrd), 200 mg/m2, before tumor removal. Excised tumor specimens were stained by the indirect immunoperoxidase method to determine the BrdUrd labeling index (LI), or percentage of cells in DNA synthesis. The BrdUrd LI was less than 1% in 63 (86.3%) of 73 nonmalignant meningiomas and less than 1% in 20 (87%) of 23 malignant meningiomas. Of 23 malignant meningiomas 11 were recurrent tumors; 8 patients had recurrence 3 to 33 months after the study. The recurrence rate was 100% (five of five) in patients whose tumors had a BrdUrd LI greater than 5%, 44% (11 of 25) in those with a BrdUrd LI 1% to 5%, and 6.1% (4 of 66) in those with an LI less than 1%. Thus, meningiomas with a BrdUrd LI greater than 1% may grow faster and recur more frequently. Among patients with malignant meningiomas, the mean time to recurrence after the study was 7.5 months in those with a BrdUrd LI greater than 5% and 20.2 months for those with an LI 1% to 5%. The mean time to recurrence was 97.8 months in patients with nonmalignant meningiomas. Both hemangiopericytic variants were recurrent and showed LIs of 0.5% and 4.1%; the former tumor recurred 8 years after complete resection, while the latter recurred three times in 3.5 years. Thus, the proliferative potential of intracranial meningiomas as reflected by the BrdUrd LI appears to be a prognostic variable that can help to elucidate the biological behavior of individual meningiomas.
We report the cases of two patients with untreated pituitary adenoma who presented with cerebrospinal fluid rhinorrhea. The surgical treatment and mechanisms involved in this rare condition are discussed.
Data from Northern California Oncology Group protocol 6G61, which was closed in February 1983, were reanalyzed in December 1988. The protocol called for a randomized trial that compared the effects of following 60 Gy radiation/oral hydroxyurea treatment with either carmustine (BCNU) or the combination of procarbazine, lomustine (CCNU), and vincristine (PCV) for two histologic strata: glioblastoma multiforme and other anaplastic gliomas. PCV produced longer survival and time to tumor progression than BCNU for both histologic groups, although the difference was statistically significant only for the anaplastic gliomas. With PCV treatment, time to progression and survival doubled for anaplastic glioma patients in the 50th and 25th percentiles.
Explore the source record for details and available documents.
Explore the source record for details and available documents.