Phototherapeutic keratectomy in the treatment of corneal scarring from trachoma.

Trachoma is still one of the world's major blinding diseases. Characteristically, trachoma causes deep scarring of the conjunctiva and tarsus that can result in tear deficiency, trichiasis, and entropion. Another common finding is a diffused corneal opacity that is the end stage of peripheral and central corneal infiltrates.

Identification of an epidermal growth factor receptor transcriptional repressor.

Identification of the factors controlling transcription of the epidermal growth factor (EGF) receptor gene is essential for understanding regulation of the EGF receptor and its overexpression in human carcinomas. In this study, we have identified a 60-base pair (bp) region (-919 to -860) relative to the AUG translation initiation codon in the EGF receptor 5' promoter that functions as a cis-acting EGF receptor transcriptional repressor (ETR). This fragment also acted as a repressor when linked to the thymidine kinase promoter.

Localization of immunoreactive epidermal growth factor receptor in neonatal and adult rat hippocampus.

The regional and developmental expression of epidermal growth factor (EGF) receptor in rat hippocampus was investigated utilizing immunocytochemical techniques at the light and electron microscopic levels. EGF receptor immunoreactivity in adult hippocampus was compared to that found at postnatal day 7 (P7). While the receptor was observed in P7 hippocampus, immunostaining was more prominent in the adult hippocampus, especially in the pyramidal CA2 field.

Adenovirus and protein kinase C have distinct molecular requirements for regulating epidermal growth factor receptor trafficking.

The ligand-activated tyrosine kinase receptor for epidermal growth factor (EGF) is down-regulated by an integral membrane protein coded for by the E3 early transcription unit of group C adenoviruses. The E3 protein appears to block recycling of constitutively internalized receptors, causing them instead to traffic to lysosomes where they are degraded. Expression of functional EGF receptors is also regulated by protein kinase C (PKC), which directly phosphorylates the EGF receptor at Thr-654.

Functional analysis of conserved residues in the active site of insulin-degrading enzyme.

Insulin-degrading enzyme (IDE), a nonlysosomal metalloprotease involved in metabolizing internalized insulin, has catalytic properties that have been strongly conserved through evolution. Two major properties distinguish IDE from the prototypic metalloprotease thermolysin. 1) It is inhibited by cysteine protease inhibitors as well as metalloprotease inhibitors; 2) it contains an inversion of the HEXXH active site motif of thermolysin, where the histidines coordinate zinc and the glutamate participates in catalysis.

Activation of mitogen-activated protein kinase by epidermal growth factor in hippocampal neurons and neuronal cell lines.

Epidermal growth factor (EGF) functions in a bimodal capacity in the nervous system, acting as a mitogen in neuronal stem cells and a neurotrophic factor in differentiated adult neurons. Thus, it is likely that EGF signal transduction, as well as receptor expression, differs among various cell types and possibly in the same cell type at different stages of development. We used hippocampal neuronal cell lines capable of terminal differentiation to investigate changes in EGF receptor expression, DNA synthesis, and stimulation of mitogen-activated protein (MAP) kinase by EGF before and after differentiation.

Activity of a novel quinoxaline derivative against human immunodeficiency virus type 1 reverse transcriptase and viral replication.

S-2720 [6-chloro-3,3-dimethyl-4-(isopropenyloxycarbonyl)-3,4- dihydroquinoxalin-2(1H)-thione], a quinoxaline derivative, was found to be a very potent inhibitor of both human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) activity and HIV-1 replication in tissue culture. Like other nonnucleoside RT inhibitors, S-2720 does not affect the HIV-2 RT. A S-2720-resistant virus was selected and shown to possess a mutation within the RT-coding region that has not previously been described.

Role of threonine residues in regulation of the epidermal growth factor receptor by protein kinase C and mitogen-activated protein kinase.

Epidermal growth factor (EGF) receptor tyrosine kinase activity is down-regulated by a number of growth-modulating agents that activate protein kinase C and/or mitogen-activated protein (MAP) kinases. Although the mechanism is unclear, it has been hypothesized that phosphorylation of specific threonine residues leads to inhibition of the EGF receptor tyrosine kinase. Two sites phosphorylated on the EGF receptor in response to phorbol esters are possible mediators of this effect: threonine 654, the target of protein kinase C, and threonine 669, the target of MAP kinase and the major site of phosphorylation on the EGF receptor.

Mitogen-activated protein kinase regulates the epidermal growth factor receptor through activation of a tyrosine phosphatase.

Epidermal growth factor (EGF) receptor tyrosine kinase activity is inhibited by growth factor-stimulated kinases involved in cellular signaling. Mitogen-activated protein (MAP) kinase is activated in response to a wide variety of growth modulating agents including EGF. To determine whether MAP kinase can inactivate the EGF receptor tyrosine kinase, we investigated the effect of pp42 MAP kinase on the EGF receptor.

Mutations in a zinc-binding domain of human insulin-degrading enzyme eliminate catalytic activity but not insulin binding.

Insulin-degrading enzyme is a nonlysosomal metalloprotease that initiates degradation of internalized insulin in some cells. We previously identified a potential catalytic site containing an inversion of the Zn(2+)-binding domain of the thermolysin family (Kuo, W.-L.

Multiple components of the T cell antigen receptor complex become tyrosine-phosphorylated upon activation.

Triggering of the multicomponent T cell antigen receptor (TCR) complex results in several biochemical processes which are critical for the functional activation of T lymphocytes. One common process is the tyrosine phosphorylation of several proteins, including the TCR zeta chain. Here we show that in addition to TCR zeta, other subunits (CD3 gamma, CD3 delta, and CD3 epsilon) of the TCR complex can also be tyrosine-phosphorylated in response to antigen receptor stimulation.

Insulin-degrading enzyme is differentially expressed and developmentally regulated in various rat tissues.

Insulin-degrading enzyme (IDE), a cytosolic metalloendoprotease, can degrade insulin, insulin-like growth factor-II, insulin-like growth factor-I, and transforming growth factor-alpha. While IDE has been implicated in the cellular degradation of insulin, other physiological functions of this enzyme are not known. To assess the possible role of IDE in cellular growth and development, we determined the tissue and developmental distribution of the enzyme.

Corneal electrode for recording electroretinograms in rats.

The corneal contact lens electrode, because of its convenience, has replaced the cotton-wick electrode for recording electroretinograms from patients and animals such as dogs, rabbits, and cats. The cotton-wick electrode, however, remains popular for rat electroretinogram measurements because small contact lens corneal electrodes that fit rat eyes are difficult to fabricate. We prepared corneal electrodes from disposable needles for use in recording electroretinograms from rats.

Dose and temporal parameters in delaying injured optic nerve degeneration by low-energy laser irradiation.

Low-energy laser irradiation has been reported to postpone the degenerative processes in crushed optic nerves of rats, which are part of the nonregenerable mammalian central nervous system. In the present study, we evaluated the optimal irradiation parameters for this purpose. Optic nerves of 141 rats were subjected to crush injury and then irradiated through the eye, starting at different points of time before or after the injury, for different durations and periods, using various intensities of either helium-neon laser or noncoherent infrared light (904 nm).

Activation of MAP kinases by calcium-dependent and calcium-independent pathways. Stimulation by thapsigargin and epidermal growth factor.

In order to determine the effect of calcium mobilization on mitogen-activated protein (MAP) kinase activation, we have treated human foreskin fibroblasts (HSWP cells) and human epidermal carcinoma (A431) cells with thapsigargin. Intracellular free calcium was monitored by single cell image analysis using fura-2 and correlated with MAP kinase stimulation as assessed by immunoprecipitation, kinase renaturation assays and immunoblotting. Thapsigargin stimulated the 44- and 42-kDa MAP kinase isozymes in both cell types with kinetics that were slightly delayed relative to enzyme stimulated by epidermal growth factor.

Ultrastructural characteristics of the spleen in hairy cell leukemia.

Eighteen spleens derived from patients with hairy cell leukemia (HCL) were analyzed by correlative scanning and transmission electron microscopy. In 15 of the cases, the white pulp areas were markedly decreased or absent when compared to normal spleens, although few hairy cells were observed within this region. In only one case did the white pulp appear normal.

Therapeutic parameters of methylprednisolone treatment for retinal photic injury in a rat model.

Methylprednisolone (MP) has been prescribed for the treatment of solar retinopathy presumably because of its anti-inflammatory effect. Recently, high doses of MP have been shown to ameliorate light-induced photoreceptor degeneration, and the mechanism of action was suggested to be the inhibition of lipid peroxidation. In this study we examined the dose-response effect and the effect of delayed treatment with MP in an established rat model of retinal photic injury.

Evaluation of the Boehringer Mannheim ES 300 immunoassay analyzer and comparison with enzyme immunoassay, fluorescence polarization immunoassay, and radioimmunoassay methods.

The ES 300 (Boehringer Mannheim Diagnostics, Indianapolis, IN) is a new automated immunoassay analyzer intended for the quantitative determination of a wide range of analytes. We compared its performance to enzyme immunoassay (EIA), fluorescence polarization immunoassay (FPIA), and radioimmunoassay (RIA) methods for cortisol, digoxin, ferritin, prolactin, T4-uptake, total-T3, and TSH. The ES 300 methods showed excellent precision and the manufacturers' linearity claims were met in all cases.

Structurally different members of the okadaic acid class selectively inhibit protein serine/threonine but not tyrosine phosphatase activity.

The relative potencies of four main types of okadaic acid class compounds as inhibitors of the catalytic subunits of protein serine/threonine phosphatases 1 and 2A and the protein tyrosine phosphatase 1 were determined. These four types of compounds are okadaic acid, calyculin A, microcystin-LR, and tautomycin, which are isolated from different natural sources, a black sponge Halichondria okadai, a marine sponge Discodermia calyx, a blue-green alga Microcystis aeruginosa, and Streptomyces spirover ticillatus, respectively. While okadaic acid was a more effective inhibitor of protein phosphatase 2A (IC50, 0.

Oct-3 and mammalian development: correction of discussion.

The title of the 5 June report on page 1445 by R. C. deL.