Gonadotropic and luteotropic cells in chickens treated with estrogen after hatching

IgA concentrations were determined in saliva from epileptic patients taking phenytoin and in saliva from healthy controls, by single radial immunodiffusion technique. Mean salivary IgA in epileptic children was 7.23 mg/ml; in healthy children, 16.44 mg/ml. Corresponding values for adults were 13.53 and 19.48 mg/ml, respectively. In 14 out of 84 samples, salivary IgA levels were too low for quantitative analysis. Salivary IgA levels were normal in untreated patients and fell during treatment with phenytoin. Gingival inflammation was commonly accompanied by an increase of salivary IgG and serum-derived IgA, whereas compensatory increase of IgM was infrequent. Phenytoin-induced deficiency of salivary IgA can result in increased susceptibility to gingival inflammation, which is considered one of the predisposing factors for subsequent development of gingival hyperplasia.     

Characterization of insulin receptor substrate 4 in human embryonic kidney 293 cells

We recently cloned IRS-4, a new member of the insulin receptor substrate (IRS) family. In this study we have characterized IRS-4 in human embryonic kidney 293 cells, where it was originally discovered. IRS-4 was the predominant insulin-elicited phosphotyrosine protein in these cells. Subcellular fractionation revealed that about 50% of IRS-4 was located in cellular membranes, and immunofluorescence indicated that IRS-4 was concentrated at the plasma membrane. Immunoelectron microscopy conclusively established that a large portion of the IRS-4 was located at the cytoplasmic surface of the plasma membrane in both the unstimulated and insulin-treated states. IRS-4 was found to be associated with two src homology 2 (SH2) domain-containing proteins, phosphatidylinositol 3-kinase and Grb2, the adaptor to the guanine nucleotide exchange factor for Ras. On the other hand, no significant association was detected with two other SH2 domain proteins, the SH2-containing protein tyrosine phosphatase 2 and phospholipase Cgamma. Insulin-like growth factor I acting through its receptor was as effective as insulin in eliciting tyrosine phosphorylation of IRS-4, but interleukin 4 and epidermal growth factor were ineffective.     

Macrophage growth factors introduced into the kidney initiate renal injury

BACKGROUND: CSF-1 expression precedes renal injury in autoimmune MRL-lpr mice and is responsible for macrophage (M phi) proliferation and survival in the kidney. By comparison, C3H-lpr mice do not express CSF-1 in the kidney, and despite the lpr mutation, kidneys remain normal. The purpose of this study was to test the capacity of local and systemic expression of M phi growth factor, CSF-1 to initiate renal injury in normal (C3H-(++), MRL-(++) and autoimmune (C3H-lpr, MRL-lpr) mice. MATERIALS AND METHODS: We designed a gene transfer system to deliver cytokines into the kidney by transducing renal tubular epithelial cells (TEC) using retroviral vectors expressing CSF-1 or another M phi growth factor, GM-CSF. We placed transduced syngeneic cytokine-TEC under the renal capsule of normal and autoimmune prone mice prior to renal injury and evaluated renal pathology at 3, 7, 14, 28, and 90 days postimplant. RESULTS: CSF-1-TEC and GM-CSF-TEC, but not uninfected TEC, caused extensive local renal injury in strains with the lpr mutation. At 3-7 days the infiltrating cells were mainly M phi, and by 28 days they were predominantly lymphocytes. By comparison, the kidneys of MRL-(++) and C3H-(++) mice remained normal. Implanted genetically modified TEC caused a sustained increase of CSF-1 or GM-CSF in the circulation which did not modify the contralateral kidney. CONCLUSIONS: Gene transfer of M phi growth factors into the kidney initiates severe local renal injury in autoimmune prone mice with the lpr mutation, but does not compromise the kidney in nonautoimmune hosts. Of note, introduction of M phi growth factors into the kidney of C3H-lpr mice which do not spontaneously develop renal injury incites renal damage. These studies offer a gene transfer approach to explore the impact of local and systemic cytokine production on renal injury.     

Extensive cutaneous-subcutaneous infiltration as a side-effect of interferon-beta injection

Twenty years ago, a concept of psoriasis pathogenesis was proposed in which epidermal proliferation of psoriatic lesions was the consequence of immunological abnormalities. This concept has subsequently been supported by the remarkable efficacy of immunosuppressive drugs. Moreover, recent experimental data indicate that activated psoriatic lymphocytes are capable of inducing keratinocyte proliferation. However, we have still to explain the mechanism by which lymphocytes act on keratinocytes and to find out what antigenic material could be responsible for their activation.     

Brain nucleic acid composition and fractional rates of protein synthesis in response to chronic ethanol feeding: comparison with skeletal muscle

Soybeans were treated with proteases to reduce allergenicity. By immunoblotting with a monoclonal antibody against a major soybean allergen (Gly m Bd 30K), two of eight proteases so far tested were selected to achieve a reduction in allergenicity. Both antigenicity to the monoclonal antibody and allergenicity to the sera from soybean-sensitive patients proved to be markedly reduced by processing with either protease. Thus, soybeans treated with an appropriate protease may possibly be supplied as a hypoallergenic foodstuff for patients.     

Reversal of pulmonary capillary ischemia-reperfusion injury by rolipram, a cAMP phosphodiesterase inhibitor

Isoproterenol (ISO) and forskolin, agents that increase adenosine 3',5'-cyclic monophosphate (cAMP) via adenylyl cyclase activation, reverse lung injury associated with increased microvascular permeability. We studied the role of rolipram, a relatively isozyme-selective cAMP phosphodiesterase (PDE) inhibitor, in reversing increased capillary permeability due to ischemia-reperfusion (I/R), a form of oxidant injury in the lung, by using the isolated perfused rat lung model. Rolipram (2 microM) administered after 45 min of ischemia and 45 min of reperfusion reduced I/R-increased permeability as measured by the capillary filtration coefficient to control lung values. Computer image analysis of air space edema and perivascular cuffing, as well as wet-to-dry weight ratios, confirms the permeability reversal by rolipram administration. Rolipram inhibition of cAMP PDE in the lung was assessed by using [3H]adenine prelabeling adapted for the whole lung and perfusate [3H]cAMP accumulation. Rolipram failed to increase perfusate cAMP alone but dramatically increased perfusate cAMP above ISO alone. Dose-response relationships of ISO or rolipram show a close correlation of the half-maximal effective dose (ED50) for injury reversal and perfusate cAMP production. The combination of rolipram and ISO produced synergistic reversal of I/R injury. We conclude that reversal of I/R-induced increased microvascular permeability can be achieved with rolipram and that the mechanism of action of rolipram is probably through PDE isozyme-selective inhibition. The similarity of the ED50 values for cAMP efflux and reversal of permeability increases also supports a close coupling between cAMP accumulation and endothelial cell permeability.