Biomedical subjects

J D Weissman

Publications and source records attributed to J D Weissman.

27 records · Page 2Linked to original sources

PubMed1991

Lateral deviation of the eyes on forced lid closure in patients with cerebral lesions.

We examined 35 patients with unilateral cerebral lesions to determine the incidence of lateral deviation of the eyes under forcefully closed lids and the reliability of this sign in predicting the side of the lesion. Only patients with radiologically confirmed unilateral lesions were studied. Over 70% of patients had contralateral ocular deviation (Cogan's "spasticity of conjugate gaze"), 20% had ipsilateral deviation, and less than 9% of the patients had no deviation. Lateral ocular deviation was as sensitive, but not as specific, as a unilateral Babinski plantar response in determining the side with the lesion. Contralateral deviation was more common with parietotemporal localization, suggesting that the phenomenon reflects an underlying disturbance of attentional mechanisms.

Aged↗

PubMed1991

A complex regulatory DNA element associated with a major histocompatibility complex class I gene consists of both a silencer and an enhancer.

A novel regulatory element which contributes to the regulation of quantitative, tissue-specific differences in gene expression has been found between -771 and -676 bp upstream of the major histocompatibility complex (MHC) class I gene, PD1. Molecular dissection of this element reveals the presence of two overlapping functional activities: an enhancer and a silencer. Distinct nuclear factors bind to the overlapping enhancer and silencer DNA sequence elements within the regulatory domain. The levels of factors binding the silencer DNA sequence in different cell types are inversely related to levels of class I expression; in contrast, factors binding the enhancer DNA sequence can be detected in all cells. In cultured cell lines, inhibition of protein synthesis leads to the rapid loss of silencer complexes, with a concomitant increase in both enhancer complexes and MHC class I RNA. From these data, we conclude that a labile silencer factor competes with a constitutively expressed, stable enhancer factor for overlapping DNA-binding sites; the relative abundance of the silencer factor contributes to establishing steady-state levels of MHC class I gene expression.

Animals↗

PubMed1991

Striking similarities between the regulatory mechanisms governing yeast mating-type genes and mammalian major histocompatibility complex genes.

Expression of a mammalian major histocompatibility complex (MHC) class I gene is in part regulated by a silencer DNA sequence element which binds a complex of silencer factors. This negative regulatory system is shown to be strikingly similar to the yeast alpha 2 mating-type repression system. A moderate DNA sequence homology exists between the MHC class I silencer DNA element and the yeast alpha 2 operator. Mammalian silencer factors specifically bind to the yeast alpha 2 operator DNA and also specifically interact with a yeast alpha 2-binding protein. Furthermore, the alpha 2 operator functions as a silencer element in mammalian cells when placed upstream of a MHC class I promoter.

Animals↗

PubMed1991

Cervical magnetic stimulation: the role of the neural foramen.

Magnetic stimulation of cervical nerve roots is a promising new technique, limited in part by uncertainty about the site of nerve depolarization. We used a modified "butterfly" stimulus coil with an easily defined excitation field to activate the C-8/T-1 nerve roots, recording over abductor digiti minimi. Locating both the lowest threshold for stimulation and the points of maximum stimulation, we determined the optimum rostral-caudal position and orientation for the stimulus coil over the posterior neck and upper trunk. The most favorable positions corresponded to the C-8/T-1 neural foramina, and the most favorable orientations to the roots within them. Additional measurements of depth and electric field suggested that the stimuli used should have been insufficient to activate nervous tissue in a homogeneous medium. A simple model indicates that the induced current is intensified where it passes through a bony foramen and explains preferential excitation of the nerve root at this site.

Electrophysiology↗

PubMed1989

Pontine myelinolysis and delayed encephalopathy following the rapid correction of acute hyponatremia.

We describe a case of pontine myelinolysis associated with hyponatremia and hyperammonemia resulting from bladder irrigation during a transurethral prostatic resection. Following the procedure the patient exhibited seizurelike activity. He underwent rapid correction of the hyponatremia, he initially recovered but developed encephalopathy 19 days later. Magnetic resonance images showed symmetrical lesions in the white matter of the cerebellar peduncles. A relatively small pontine lesion was also noted. The patient later recovered. This case demonstrates that myelinolysis associated with rapid correction of hyponatremia may be greater in the cerebellar peduncles than in the central pons.

Aged↗

PubMed1987

Expression patterns of MHC class II genes in rabbit tissues indicate close homology to human counterparts.

Genomic clones corresponding to five distinct major histocompatibility complex class II alpha-chains have been described for the rabbit; four of these encode complete, potentially functional alpha-chains. Hybridization analysis and preliminary sequence analysis indicate that one of these clones is structurally related to HLA-DP alpha, one to -DR alpha, one to -DQ alpha and one to -DZ alpha. Probes specific for the four class II genes were used to screen RNA samples from normal rabbit tissues to determine which of these genes are transcribed and whether expression of any particular gene is tissue specific. All four of the genes are transcribed, but there are variations in the levels of expression, in tissue distribution, and in transcript size. The highest levels of RLA-DR alpha, -DQ alpha, and -DP alpha transcription were found in lymphoid tissues. Lower levels of transcription were also detectable in several nonlymphoid tissues. Transcripts observed were about 1.3 kb, a size expected for these class II alpha-chain genes based on experience with their human homologues. The RLA-DZ alpha probe corresponding to HLA-DZ alpha hybridized weakly with a band of 3.6 kb; its expression could be detected only in lymphoid tissues. The size of the DZ alpha transcript, its tissue distribution, and partial sequence data confirm its homology with the human gene DZ alpha. In blots of total cellular RNA, a probe for a recently described human beta-chain, DO beta, hybridized to a transcript of about 1.3 kb in lymphoid tissues. These data indicate that RNA transcripts corresponding to all HLA class II loci described to date can be detected in rabbit tissues.

Animals↗

PubMed1987

Sequence determination of a transcribed rabbit class II gene with homology to HLA-DQ alpha.

The human HLA-DQ alpha probe was used to screen genomic and cDNA libraries constructed from a rabbit T-cell line. Clones containing highly homologous sequences were obtained from both libraries and their sequences were determined. The organization of the RLA-DQ gene was determined by comparison of the nucleotide sequences of the genomic clone to that of the corresponding cDNA clone. This analysis allowed assignment of the complete structure of the RLA-DQ alpha chain. Comparisons with human and mouse class II products revealed that RLA-DQ is more closely related to HLA-DQ/DX than to H-2A. In contrast to the DQ/DX region of man, which contains at least two distinct alpha genes, the rabbit genome contains a single DQ gene which is equally distant from the HLA-DQ or -DX genes. The rabbit DQ alpha gene, like human HLA-DQ, is transcribed in T cells.

Amino Acid Sequence↗

PubMed1984

Maximal flux responses after multiple challenges with vasopressin.

Antidiuretic hormone (ADH) increases transepithelial flux of water and particular solutes across the amphibian urinary bladder and mammalian collecting duct by increasing the permeability of the apical surface. We find that if each challenge with ADH is ended by replacing the medium bathing both the mucosal and serosal surfaces of the toad bladder, then rechallenge with the same supramaximal dose of ADH 36-100 min later produces flux equivalent to or greater than the original response, but rechallenge after 15 min produces only 68% of the original response. If the medium bathing the mucosal surface is neither replaced nor returned to its original volume, complete recovery of the osmotic flux response to ADH does not occur. Maximal restimulation by ADH occurs with transepithelial osmotic gradients between 119 and 180 mosmol/kg during both challenges (the serosal bath is always isotonic amphibian Ringers). In addition, ADH-containing serosal baths that have maximally activated transport across bladders for 30-60 min can be reused and again produce maximal activation of ADH responses in fresh bladders or in the original bladders after washing. These results are in contradistinction to reports of desensitization of transepithelial flux upon rechallenge with ADH after an initial stimulation under many conditions. Our findings suggest that desensitization in vitro may result from experimental design rather than intrinsic biological characteristics of the system.

Animals↗

PubMed1982

DPN-linked sn-glycerol-3-phosphate dehydrogenase. Cyclopentanoid analogues mimic the active rotameric state of the natural substrate.

Five diastereoisomeric cyclopentane-1,2,3-triol monophosphate analogues of sn-glycerol 3-phosphate have been studied as substrates and inhibitors of sn-glycerol-3-phosphate dehydrogenase (EC 1.1.18) of rabbit skeletal muscle. Of the five analogues, only two were substrates, DL-1,2,3/0-1P (analogue I) and DL-1,2/3-1P (analogue II). The rest were weak competitive inhibitors of the enzyme. Initial rate kinetic studies of the substrate-active analogues analyzed by a rapid equilibrium random-order mechanism showed that Ks (I) = 4.6 +/- 2.6 mM; Ks (II) = 2.2 +/- 0.6 mM compared with Ks (DL-glycerol-3-P) = 2.4 +/- 0.9 mM. Correlation of the structures of the five analogues with their activities indicates that the enzyme requires a syn orientation of the carbon-oxygen bonds about C-2 and C-3 for activity, which is optimized by an anti relationship between the hydroxyl groups at C-1 and C-2 of the cyclopentanetriol monophosphates. These results are used to deduce the conformation of sn-glycerol-3-P as it is bound in the active site of the enzyme.

Binding Sites↗