Juvenile rheumatoid arthritis.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to C Weber.
Explore the source record for details and available documents.
The hepatitis B virus (HBV) genome carries an open reading frame of 462 bases, the X region, but the corresponding protein has yet to be identified as a natural product. In rodent cells cotransformed with the thymidine kinase gene of herpes simplex virus and HBV DNA, however, Gough [1983] identified a mRNA that hybridises uniquely with the X region of the HBV genome. A large fragment of the X region was inserted into plasmid pCL19 delta Y-T in order to produce, in Escherichia coli, the X gene product, HBxAg, as a polypeptide fused to the N-terminal part of the phage lambda cro gene product. Antisera raised against this fused polypeptide gave positive immunofluorescence reactions with the transformed rodent cells. This provides direct evidence for the expression of the HBxAg gene in eukaryotic cells transformed with HBV DNA. The approach used here should be generally applicable.
To determine if gastrin in hyperparathyroid glands is true gastrin or artifact and to determine the frequency of gastrin in parathyroid glands, 20 parathyroid glands from 11 patients with hyperparathyroidism but without MEA were extracted and analyzed for gastrin. The parathyroid glands from 4 out of 11 patients had measurable gastrin immunoreactivity (10.7 + 6 pg/mg tissue). Column separation chromatography confirmed that this was true gastrin (40% G-34; 50% G-17). Immunohistochemistry with ABC (avidin biotin complex) immunoperoxidase confirmed the presence of gastrin in cytoplasmic vesicles in scattered parathyroid cells. True gastrin does exist in some cells in some patients with hyperparathyroidism.
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.
A retrospective review of thyroidectomies to rule out cancer at Columbia Presbyterian Medical Center indicated that the maximum cancer incidence achievable in surgical specimens was only 57% if all microfollicular adenomas and thyroid cancers were removed. The size distribution of follicular cancer and microfollicular adenoma was similar and it does not appear to be useful in deciding which microfollicular lesions need to be surgically excised to exclude carcinoma. The incidence of thyroid cancer in patients undergoing thyroidectomy was not influenced by the introduction of fine-needle biopsy (FNB) at Columbia Presbyterian Medical Center. FNB did appear to increase the incidence of cancer at an affiliated community hospital. Coarse-needle biopsy definitely improved the incidence of cancer in patients undergoing thyroidectomy and was superior to FNB and clinical selection alone. A combination of FNB and coarse-needle biopsy when possible yielded a 41% incidence of cancer and appears to be the most useful technique for patient selection.
Major histocompatibility complex-linked immune response genes are thought to influence susceptibility to induction of both human insulin-dependent diabetes and murine streptozotocin-induced diabetes. To clarify this relationship, we administered streptozotocin intravenously in two doses (120 and 240 mg/kg body weight) on days 0 and 14, and monitored blood glucose until day 100 in young adult male mice of differing background genome and/or H-2 complex. In addition, we examined the effect of allogeneic whole blood transfusion on subsequent susceptibility to diabetes. B10 recombinant mice possessing the k allele at the centromeric H-2-K and I-A loci were most susceptible to diabetes induction. Variation in susceptibility of different inbred strains with the same major histocompatibility complex genotype suggested a rôle for non-major histocompatibility complex genes. Blood transfusion delayed the onset, but did not significantly reduce the incidence of, delayed hyperglycaemia. We conclude that, in this murine model, multiple genes within the outside the major histocompatibility complex influence multiple-dose streptozotocin-diabetes susceptibility, and that prior blood transfusion may modulate diabetes induction.
Explore the source record for details and available documents.
In vivo gap junctions (gj) are common in the subumbrellar plate endoderm of anthomedusa. When isolated and cultivated in artificial sea water the tissue, consisting of one cell type only, forms a spheroid in which all gap junctions disappear. Gap junction (gj) formation can, however, be induced by attachment and consecutive spreading of the endodermal tissue (spheroid) on stretched extracellular matrix (ECM) material isolated from the polyp stage (with Ca2+-Mg2+-free sea water, without EDTA). Formation, and loss of gj is reversible and strictly corresponds with the alteration from the monolayer 'spread' (on stretched ECM) to 'spheroid' arrangement (no ECM) of the endodermal cells. The functional competence of induced gj is ascertained by injection of Lucifer Yellow, and the transfer of the dye is used to map the pattern of communication. The experimental conditions that result in gj formation simulate the in vivo situation of the endoderm. The influence of the ECM on gj formation, and the structural organization of the isolated endodermal tissue in this well defined in vitro system are discussed.
The effect of ultraviolet (UV) irradiation on the immunogenicity of rat pancreatic islets was examined in allograft and xenograft models. Direct UV irradiation (900 J/m2) of Lewis islets, isolated and hand-picked, does not alter pancreatic islet endocrine function in isograft experiments and results in indefinite islet allograft survival in streptozocin diabetic ACI rats without chronic immunosuppression. Direct UV irradiation, at an appropriate dose, also leads to indefinite islet xenograft survival of Lewis islets in B10-BR diabetic mice and prolonged survival of rat islets in Balb/C mice. When direct UV irradiation of islet allografts did not result in indefinite islet allograft prolongation [Wistar/Furth (W/F) to diabetic Lewis], the addition of brief peritransplant immunosuppression with cyclosporine (days 0, +1, and +2) resulted in permanent acceptance of islet allografts, a result not achieved by cyclosporine alone. The effectiveness of UV irradiation in abrogating islet allograft rejection in several experimental models is supported by in vitro studies showing that UV irradiation of stimulator cells, peripheral blood lymphocytes, splenocytes, and isolated rat dendritic cells abolishes any significant stimulation by such cells of totally histoincompatible thoracic duct responder lymphocytes. In vitro nonreactivity of mixed lymphocyte culture (MLC) with UV-irradiated stimulator cells and in vivo permanent allograft acceptance are reversed by the addition of a small number of untreated donor-type dendritic cells to either the MLC or the recipient bearing the permanent graft. The authors suggest that the primary effect of UV irradiation on immune alteration of islet allografts and xenografts is due to induction of a major metabolic change in the dendritic cells in the graft. This then leads to defective antigen presentation and results in either permanent or prolonged allograft and xenograft acceptance, depending on the degree of MLC stimulation between the islet donor and the diabetic recipient.
The activity of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) was determined radiometrically in heart and skeletal muscle (M. semitendinosus) of 21 fetuses of the last third of gestation (80th-112th day), 17 piglets from birth until the 9th day of life and 7 fattening pigs. Simultaneously the activity of the enzymes glucose-6-phosphatase (G6Pase) and fructosebisphosphatase (FDPase) was measured colorimetrically in heart and skeletal muscle of piglets and in skeletal muscles of fattening pigs. Heart and skeletal muscle have only a low PEPCK activity. During the last third of gestation PEPCK in heart remains on a constant level, which can be demonstrated also in fattening pigs, but doubled immediately after birth. During the last two weeks of gestation, at birth and during the first days of life the PEPCK activity in the skeletal muscle is 3-fold higher than at the 80th day of gestation and in fattening pigs. G6Pase and FDPase activity of the heart remains at a constant level during the first days of life. It was impossible to detect G6Pase in the skeletal muscle of piglets. The specific FDPase activity of the skeletal muscle remains constant also postnatally. In fattening pigs skeletal muscles with different types of fibres have the same FDPase and PEPCK activity.
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.
L cells were infected with lymphocytic choriomeningitis virus (LCM virus). They were subcultivated and infectious virus and interfering virus were quantified at intervals. Both entities fluctuated in perfect parallelism. Superinfection with LCM virus revealed a pattern of interference that bore no simple relationship with the quantity of interfering virus present. We explain the oscillating pattern of virus replication, which characterizes this type of LCM virus carrier cultures, as being due to spontaneous shutdown of virus synthesis in conjunction with the action of a resistance factor produced by cells coinfected with infectious virus and interfering virus.
Knowledge of protective effects of corticosteroids on traumatized cells prompted us to test the potential benefit of islet cryopreservation in the presence of hydrocortisone. Neonatal murine islets were isolated by collagenase, followed by 2- to 3-day tissue culture. Precryopreservation glucose-stimulated (50-500 mg/dl) insulin release was 25-388% above basal (mean = 113%) in 18/20 fresh islet preparations. Subsequent freezing was done in RPMI 1640 medium plus 10% (v/v) heat-inactivated fetal calf serum and 10% (v/v) Me2SO with or without 1 mg/ml hydrocortisone at 0.25 degrees C per minute in a programmed freezing system, to -80 degrees C, and stored for greater than 60 days at -196 degrees C. Thawing, by transfer to room air, was followed by dilution, 4x (v/v), in 4 degrees C RPMI plus 10% protein, after which glucose-stimulated insulin release was reassessed, showing 56-280% response over basal in 3/8 steroid-treated preparation and 20-220% response in 3/10 control preparations. Basal insulin release was 0.72 ng/microgram protein/hr in fresh islets (N = 20) and 0.22 ng/microgram protein/hr after freeze-thawing. We conclude that functional islet survival by this method is approximately 30% and that hydrocortisone did not improve viability.
Media from cultures of normal and abnormal human parathyroid fragments were assayed for parathyrin (PTH) and pancreatic polypeptide (PP) using sensitive radioimmunoassays. PP immunoreactivity was present in media (Day 6-7 in vitro) from cultures of 3/10 adenomas and 6/6 3 degrees hyperplastic glands (mean = 126. fmole/mg protein/day) (range = 6.-675.), and was not suppressed by 0 leads to 3 mM calcium challenge. PP was undetectable in media from cultures of one parathyroid carcinoma, one 1 degree hyperplasia, and one normal parathyroid. Medium C-terminal PTH levels were quite variable (26.-2,545,000. pg/mg protein/day). Presence of PP immunoreactivity in media from cultures of some hyperplastic parathyroids and some parathyroid adenomas suggests that PP may be released from these tissues in vitro. The significance of elevated PP levels in the MEA syndromes may be of special clinical relevance to this observation.