PubMed HealthSearch

Biomedical subjects

J Adler

Publications and source records attributed to J Adler.

At least 19 recordsLinked to original sources

On the identity of the major postsynaptic density protein.

Increasing evidence suggests that the postsynaptic density (PSD) plays a critical role in synaptic communication and plasticity. The major PSD protein (mPSDp), a calcium/calmodulin-dependent protein kinase, appears to be central to PSD function. The mPSDp has long been considered identical to the alpha subunit of the soluble calmodulin kinase II (alpha-CKII). However, mPSDp and alpha-CKII do differ in solubility and antigenicity, raising the possibility that the two proteins are distinct. To further define the relationship between the two proteins, we purified the mPSDp to homogeneity from adult rat cerebral cortex and compared the proteins. In contrast to alpha-CKII, the purified mPSDp was insoluble in high concentrations of salt, various detergents, chelators of divalent cations, and the strong denaturant guanidine hydrochloride. The pI value of the mPSDp was 6.2, whereas that of alpha-CKII was 6.7-7.2. The purified mPSDp bound calmodulin in the presence of Ca2+ and was autophosphorylated in a Ca2+/calmodulin-dependent manner. Polyclonal antiserum raised against mPSDp (anti-mPSDp) recognized purified mPSDp or mPSDp in synaptic membrane, indicating immunologic specificity among the synaptic proteins. Anti-mPSDp did not recognize alpha-CKII, whereas anti-alpha-CKII antibodies reacted only weakly with mPSDp, suggesting that the proteins are distinct but structurally similar. Moreover, sequence analysis of protease V8-digested polypeptides revealed that there was at least an 8-amino acid sequence, MLKVPNIS, that is not present in alpha-CKII. Finally, HPLC analysis of V8-digested fragments of mPSDp and alpha-CKII in parallel revealed dissimilar peptide patterns. Thus our observations suggest that mPSDp and alpha-CKII are similar but not identical. The unique physicochemical and structural properties of the mPSDp may provide insights into molecular mechanisms mediating synaptic plasticity.

Amino Acid Sequence

Inoculation of C6 glioma cell suspension into the brain of adult rats: morphological study.

The C6 astrocytoma cell line was inoculated intracerebrally as suspension into the rat brain. Tumors were allowed to grow 2 to 60 days and their development was studied on coronal sections at these survival times. Tumor cells developed intraparenchymal solid tumor at the implantation site. C6 cells also filled out the needle track-area and spread into meninges. At 2 days postimplantation (2 DPI), tumor cells were observed to infiltrate recipient's brain directly from the implantation site or via perivascular spaces of adjacent cerebral blood vessels. Some cells escaped from the implantation channel during transplantation. They spread diffusely via cerebrospinal fluid (CSF) in leptomeningeal regions over the brain surface. At 10 DPI, the tumor mass invaded the adjacent brain parenchyma as well as cerebral ventricles (CV) and C6 cells could spread intraventricularly. At 30 DPI, tumor extremely increased its size and its growth was expansive. It exhibited areas of necrosis and later on, at 60 DPI, inoculated rat brains revealed large empty pseudocysts resulting from decay of necrotic tumor masses.

Animals

Methanol formation in vivo from methylated chemotaxis proteins in Escherichia coli.

Chemotactically wild type Escherichia coli were incubated with L-[methyl-3H]methionine to label the methyl groups of their methyl-accepting chemotaxis proteins. Cells were then treated to specifically demethylate these proteins. We have identified the end product of this demethylation as [3H]methanol in the cell-free medium from treated cells.

Bacterial Proteins

Effect of cyclic changes in environmental lighting and ambient temperature on the daily rhythm in melatonin excretion by rats.

Melatonin excretion was measured by radioimmunoassay in 6 h or 12 h urine specimens from individual control rats and from animals previously blinded by bilateral orbital enucleation. Among sighted rats, the rate of melatonin excretion was greatest during the daily 12 h of darkness (1.44 +/- 0.06 ng/12 h dark period vs. 0.53 +/- 0.07 ng/12 h light period; P less than 0.001). Moreover, greater quantities of melatonin were excreted in the latter half of the dark period than in the first half (e.g. 0.55 +/- 0.08 ng/first 6 h vs 0.97 +/- 0.05 ng/second 6 h; P less than 0.001). When the onset of the daily light period was shifted forward by 12 h, 5--7 days were needed for the daily rhythm in melatonin excretion to become re-entrained to the new light--dark cycle. Among blinded rats, the rate of melatonin excretion also varied rhythmically; however, the rhythm was neither synchronized with the light-dark cycle nor influenced by alterations in the lighting schedule. Similarly, artificial cycles in environmental temperature were not effective in entraining the daily rhythm in melatonin excretion among blinded rats.

Animals

Identification of a methyl-accepting chemotaxis protein for the ribose and galactose chemoreceptors of Escherichia coli.

The ribose and galactose chemoreceptors of Escherichia coli have previously been identified as the ribose- and galactose-binding proteins. We now report the discovery of a methyl-accepting chemotaxis protein that functions in the transfer of receptor signals from these two binding proteins to the flagella. This protein is distinct from previously described methyl-accepting chemotaxis proteins. Its level of methylation is influenced by D-ribose, D-galactose, and certain structural analogues of them. This methyl-accepting protein is required for chemotaxis toward those attractants; mutants in the trg gene, which do not methylate this protein, are devoid of taxis toward D-ribose, D-galactose, and their analogues. In addition, methylation of the methyl-accepting protein in response to each of these attractants requires the appropriate binding protein. The binding protein's chemoreceptor function is required for such methylation, but its transport activity is not. Because the function of this methyl-accepting chemotaxis protein involves two of the best-characterized chemoreceptors, the discovery of this protein represents a promising base for further study of the linkage between chemoreceptors and flagella in bacteria.

Bacterial Proteins

Attractants and repellents control demethylation of methylated chemotaxis proteins in Escherichia coli.

A group of methylated proteins, the methyl-accepting chemotaxis proteins (MCP), has been shown to play a central role in bacterial chemotaxis. Both methylation and demethylation of MCP occur continuously in the absence of added stimuli; these two processes are in balance such that a basal level of methylation is maintained. Attractants cause the methylation level to increase to a new value, whereas repellents bring about a decrease in level. Therefore, attractants and repellents must somehow perturb the balance between methylation and demethylation of MCP. In this report the effect of attractants on demethylation of MCP was monitored in two ways: (i) by following the disappearance of [methyl-3H]MCP and (ii) by measuring formation of [3H]methanol, the product of MCP demethylation. Both methods showed that addition of attractants causes a transient inhibition of MCP demethylation. Repellent addition has previously been shown to stimulate MCP demethylation. It is therefore concluded that control of demethylation plays a crucial role in changing the level of methylation of MCP in response to attractants and repellents.

Bacterial Proteins

Attractants and repellents influence methylation and demethylation of methyl-accepting chemotaxis proteins in an extract of Escherichia coli.

During bacterial chemotaxis, attractants and repellents alter the methylation levels of the methyl-accepting chemotaxis proteins (MCPs). These methylation levels represent a balance between two enzymatic processes: methylation and demethylation. In vivo experiments previously have shown that chemoeffectors influence the demethylation process; effects on the methylation system have not been reported. Here we show that in a cell-free extract of Escherichia coli both methylation and demethylation of the MCPs are affected by attractants and repellents. Attractants enhance methylation and inhibit demethylation. Repellents inhibit methylation and stimulate demethylation. The cell-free system provides an opportunity for further study of the mechanisms by which attractants and repellents influence the levels of methylation of the MCPs.

Bacterial Proteins

Glucagonoma, chronic recurrent peptic ulcer disease, and enhanced amylase-creatinine clearance ratio. Report of a case with review of the literature.

A 53-year-old white woman developed diabetes mellitus, migratory erythema, and anemia, clinical features suggesting the presence of a "glucagonoma." Ten years earlier, after laparotomy and pancreatic biopsy, she had been told that she had an inoperable pancreatic carcinoma. Review of that biopsy together with current hormonal assay now confirms the diagnosis of glucagonoma. The recurrent peptic ulcer in this patient despite high levels of glucagon, a gastric inhibitory agent, is noted but not explained. An enhanced amylase-creatinine clearance ratio supports the notion that glucagon increases the clearances of amylase.

Adenoma, Islet Cell

Pleiotropic aspartate taxis and serine taxis mutants of Escherichia coli.

Mutants that at one time were thought to be specifically defective in taxis toward aspartate and related amino acids (tar mutants) or specifically defective in taxis toward serine and related amino acids (tar mutants) are now shown to be pleiotropic in their defects. The tar mutants also lack taxis toward maltose and away from Co2+ and Ni2+. The tsr mutants are altered in their response to a variety of repellents. Double mutants (tar tsr) fail in nearly all chemotactic responses. The tar and tsr mutants provide evidence for two complementary, converging pathways of information flow: certain chemoreceptors feed information into the tar pathway and others into the tsr pathway. The tar and tsr products have been shown to be two different sets of methylated proteins.

Aspartic Acid

Venous calcifications associated with cavernous transformation of the portal vein: computed tomographic and angiographic correlations.

A case of rare venous calcifications involving cavernous transformation of the portal vein and spontaneous splenocaval shunt is presented. Findings were obtained with plain abdominal radiography, computed tomography, and angiography. Inflammation of the portal vein with subsequent occlusion could account for splenomegaly and hypertrophy of the splenic artery and vein with atheromatous calcifications due to turbulence and sclerosis. Angiography is essential prior to surgical intervention in order to select the appropriate shunt.

Aged

On the mechanism of sensory transduction in bacterial chemotaxis.

Sensory transduction in bacterial chemotaxis is beginning to be understood at the molecular level. At the receptor end, we have some considerable knowledge about the molecular properties of chemoreceptors. At the effector end, we know that flagella rotate and that the direction of rotation is determined by attractants and repellents, although we do not yet know the molecular features of the motor and the gear shift. Between the receptors and the effectors is a system for integrating the sensory transduction, which somewhow involves methylation of membrane proteins and possibly a change in membrane potential, but further details of how the mechanism works remain to be elucidated. It seems to us likely that the facts and concepts learned from a study of sensory transduction in bacteria can be applied to answering questions about transduction mechanisms in eukaryotic cells. Examples include the following: How do sensory stimuli produce their effects in sensory receptor cells? How do neurotransmitters act at receptors of postsynaptic cells to produce the variety of effects possible (changes in membrane potential, in secretion, in contraction, etc.)? How do hormones interact with their receptors to bring about various responses?

Carrier Proteins

The behavior of bacteria: on the mechanism of sensory transduction in bacterial chemotaxis.

The mechanism of bacterial chemotaxis is beginning to be understood. At the receptor end, we have considerable knowledge about the molecular properies of chemoreceptors. At the effector end, we know that flagella rotate and that the direction of rotation is determined by attractants and repellents, although we do not yet know the molecular features of the motor and the gear shift. Between the receptors and the effectors is a system for integrating the sensory information and transmitting a message to the flagella. This system, sensory transduction, somehow involves methylation of membrane proteins and probably a change in membrane potential, but further details of how the mechanism works remain to be elucidated.

Bacterial Physiological Phenomena

Attraction by repellents: an error in sensory information processing by bacterial mutants.

Normal Escherichia coli bacteria are repelled by acetate, benzoate, and indole and attracted by alpha-aminoisobutyrate. We have isolated mutants that are attracted to acetate, benzoate, and indole and may be repelled by alpha-aminoisobutyrate. These reversed-taxis mutants are defective in a central processing component: a set of methylated proteins known as MCP 1. The mechanism of reversal of taxis is discussed.

Acetates