Biomedical subjects
Publications and source records attributed to D J Gross.
We recently had occasion to diagnose eruptive xanthoma. The significance of this cutaneous finding is that it is indicative of an underlying hypertriglyceridemic state. Appropriate dietary changes, correction of secondary factors, along with the addition of antihyperlipidemic drugs as required, will lower the plasma triglyceride level and allow the xanthomatous lesions to resolve.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A 27-year-old woman experienced hemorrhagic shock after delivery. One week later she was seen in an obtunded state of consciousness. The results of laboratory evaluation were consistent with the syndrome of inappropriate antidiuretic hormone secretion caused by hypopituitarism. Hydrocortisone rapidly corrected sodium levels. Syndrome of inappropriate secretion of antidiuretic hormone caused by Sheehan's syndrome should be considered in the differential diagnosis of postpartum hyponatremia.
The A431 epidermoid carcinoma cell line responds to epidermal growth factor (EGF) stimulation with a number of rapid changes, including alterations in free cytosolic calcium ion concentration ([Ca2+]i). At the single cell level, these changes in [Ca2+]i are known to proceed after a clear lag phase subsequent to EGF stimulus (Gonzalez et al., 1988). The present study explores the dependence on EGF concentration of this early [Ca2+]i signal. High levels of EGF (9.0-4.3 nM) produce a [Ca2+]i spike followed by an elevation of [Ca2+]i above basal levels. The time of initiation of the spike varies from 5 to 9 s at the high dose and from 8 to 32 s at the low dose in cells that respond. A lower level of EGF (1.5 nM) produces [Ca2+]i oscillations with no prolonged elevation over basal [Ca2+]i. The initiation of response at this [EGF] ranges from 20 to 410 s. Intermediate stimulus levels generate [Ca2+]i responses that are kinetic admixtures of these limiting responses. A simple model based on the enzymatically amplified signal cascade from ligand binding through Ca2+ release or influx is examined. The model predicts a prolonged lag phase followed by a rapid increase in the [CA2+]i signal that compares favorably with the data reported here.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
AtT20 (pituitary corticotroph) cells were transfected with either the native or a mutant [AspB10]rat insulin II gene, using a plasmid containing the insulin gene and a neomycin resistance gene under the control of independent constitutive promoters. The cellular immunoreactive insulin (IRI) content ranged from 0.8-440 ng/10(6) cells, with the highest value similar to that found for a rat insulinoma cell line (RIN) and corresponding to approximately 1% that of native pancreatic B-cells. There was a direct correlation between insulin mRNA levels and IRI content and no correlation between mRNA levels and rat insulin II gene copy number. Furthermore, in some lines the insulin II transgene was lost even though the gene encoding neomycin resistance was retained. IRI release was stimulated up to 4-fold by isobutylmethylxanthine in all lines transfected with the native rat insulin II gene, and HPLC analysis showed most IRI as fully processed insulin, with less than 5% as proinsulin. These cells, thus, directed most proinsulin to secretory granules for conversion and regulated release regardless of the absolute amount of IRI expressed. One of the lines transfected with the AspB10 mutant gene (line AA9) released nearly 50% of IRI as proinsulin under basal conditions, with stimulation of insulin, but not proinsulin, release by isobutylmethylxanthine. This confirmed our previous finding of partial diversion of this mutant proinsulin from the regulated to the constitutive pathway. A second line (IC6) expressing the same mutant gene at much higher levels appeared to direct all mutant proinsulin to the regulated pathway, suggesting that for this particular mutant proinsulin, the secretory pathway employed by the transfected cells can be affected by the amount of proinsulin synthesized.
A patient with psoriasis was found to have a large mass on his scrotum. He was at increased risk for the occurrence of skin cancer, both from the treatments he received for control of his psoriasis and from previous occupational exposure. We present his case and review the risk factors involved.
Granuloma faciale is an uncommon cutaneous condition characterized by brownish-red macules, papules, nodules, and plaques. Separate areas of granuloma faciale involving the nasal skin of a 32-year-old man were treated using electrosurgery, carbon dioxide laser, and dermabrasion. All modalities provided good cosmetic and functional outcomes. The relative advantages and disadvantages of each technique are presented.
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.
The biological function of the connecting peptide (C-peptide) of proinsulin is unknown. Comparison of all known C-peptide sequences reveals the presence of a highly conserved peptide sequence, Glu/Asp-X-Glu/Asp (X being a hydrophobic amino acid), adjacent to the Arg-Arg doublet at the B chain/C-peptide junction. Furthermore, the next amino acid in the C-peptide sequence is also acidic in many animal species. To test the possible involvement of this hydrophilic domain in insulin biosynthesis, we constructed a mutant of the rat proinsulin II gene lacking the first four amino acids of the C-peptide and expressed either the normal (INS) on the mutated (INSDEL) genes in the AtT20 pituitary corticotroph cell line. In both cases immunoreactive insulin (IRI) was stored by the cells and released upon stimulation by cAMP. In the INS expressing cells, the majority of IRI, whether stored or released in response to a secretagogue, was mature insulin. By contrast, most of the stored and releasable IRI in the INSDEL expressing cells appeared to be (mutant) proinsulin or conversion intermediate with little detectable native insulin. Release of the mutant proinsulin and/or conversion intermediates was stimulated by cAMP. These results suggest that the mutant proinsulin was appropriately targeted to secretory granules and released predominantly via the regulated pathway, but that the C-peptide deletion prevented its conversion to native insulin.
Antibodies to insulin appear prior to the development of Type I diabetes and their concentration may correlate with the rate of autoimmune beta cell destruction. In order to study potential mechanisms involved in the production of antibodies to insulin, we transplanted different strains of mice with histoincompatible non-islet cells (AtT20-Ins and NIH-3T3-Ins) synthesizing homologous insulin, in contrast to immunization with non-transfected cells and insulin in Freund's adjuvant. The pituitary cell line (AtT20) and the fibroblast cell line (NIH-3T3) were transfected with the rat insulin-II gene (which encodes an insulin molecule identical to that of mouse insulin-II). No antibodies to insulin were found after subcutaneous injection of AtT20-control cells (without the integrated rat insulin gene) or after injection of rat insulin complete Freund's adjuvant. After subcutaneous injections of living AtT20-Ins or NIH-3T3-Ins cells producing insulin (40 to 60 ng insulin/10(6) cells per injection) in two strains (BALB/cJ, C3H/HeJ) but not in a third (SJL/J), antibodies to insulin rapidly appeared. In addition, when AtT20-Ins cells were transplanted into Wistar-Furth rats, insulin antibodies appeared in three out of four animals. The level of antibodies induced was similar to the concentrations of insulin antibodies of prediabetic NOD mice. This finding suggests that during the immune destruction of a cell synthesizing insulin, humoral 'tolerance' to insulin can be rapidly abrogated. Genetic control of this response is suggested by the difference between response of BALB/cJ and C3H/He vs SJL/J.
A patient with type II diabetes associated with hyperproinsulinemia has been shown to have a point mutation in one insulin gene allele, resulting in replacement of histidine with aspartic acid at position 10 of the B-chain. To investigate the basis of the proinsulin processing defect, we introduced an identical mutation in the rat insulin II gene and expressed both the normal and the mutant genes in the AtT-20 pituitary corticotroph cell line. Cells expressing the mutant gene showed increased secretion of proinsulin relative to insulin and rapid release of newly synthesized proinsulin. Moreover, the mutant cell lines did not store the prohormone nor did they release it upon stimulation with secretagogues. These data indicate that a significant fraction of the mutant prohormone is released via the constitutive secretory pathway rather than the regulated pathway, thereby bypassing granule-related processing and regulated release.
Explore the source record for details and available documents.