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Biomedical subjects

J Weinstein

Publications and source records attributed to J Weinstein.

At least 73 records · Page 4Linked to original sources
PubMed1989

Tissue-specific expression of sialyltransferases.

Three sialyltransferases which attach terminal sialic acids to glycoprotein sugar chains are shown to exhibit striking differential expression in seven tissues of the rat. Using cDNA probes for the Gal beta 1,4GlcNAc alpha-2,6-sialytransferase which forms a NeuAc alpha 2-6Gal beta 1-4GlcNAc sequence on N-linked sugar chains, three different sized mRNAs are detected, two of which (4.7 and 4.3 kilobases (kb] have high homology along the full length, and a third (3.6 kb, in kidney) which is missing the 5' region corresponding to 45% of the NH2-terminal coding sequence. The 4.7- and 4.3-kb mRNAs exhibit differential expression of over 50-fold with the highest levels in liver and lowest in brain and heart. Assays for enzyme activity in tissue homogenates show high correspondence to the levels of mRNA. Evidence of tissue-specific expression was also obtained for two other sialyltransferases which form the NeuAc alpha 2-3Gal beta 1-4/3GlcNAc and NeuAc alpha 2-3Gal beta 1-3GalNAc sequences on N-linked and O-linked sugar chains, respectively. Comparison of the ratios of the three enzymes in several tissues suggests that they are expressed independently. The results are discussed for their relevance to cellular control of terminal glycosylation sequences on glycoproteins and glycolipids.

Animals↗
PubMed1989

Optic atrophy, hearing loss, and peripheral neuropathy.

Here we report on two families with a previously apparently undescribed, autosomal dominant disorder resulting in optic atrophy and subsequent development of hearing loss and peripheral neuropathy. This disorder differs from previous syndromes resulting in this triad of effects both in the severity and early onset of the optic atrophy and in its mode of transmission. Review of published cases of optic atrophy + hearing loss + peripheral neuropathy suggests that there are at least three such specific disorders; classification of these published cases by first-appearing symptom also results in a clean division by most-likely inheritance.

Adult↗
PubMed1989

The Wiltse pedicle screw fixation system. Early clinical results.

Ninety-nine patients were studied prospectively after spine fusion augmented with the Wiltse pedicle screw fixation system. Follow-up ranged from 12 to 34 months, averaging 20 months. There were 33 men and 66 women. Their ages ranged from 20 to 86, with the average age of 52. This was the first spine surgery in 23 patients. Seventy-six patients had had prior spine surgery. Spine fusion was attempted at one to four levels of the lumbosacral spine. Major perioperative complications were seen in seven patients (7%). Hardware failure was seen in seven cases (7%). Union was assessed by radiographs at 1 year or more after surgery in 82 patients (85%). In those 82 patients, union was seen in 56 (68%) and nonunion in 26 (32%). Change in lordosis was measured in 54 patients. The average change was a loss of 1.7 degrees lordosis per level fused. A questionnaire was answered by 79 patients (81%). Overall, 55 (70%) stated that they had some benefit from surgery, ten (13%) had no change, and 13 (17%) were worse.

Adult↗
PubMed1988

Post-Golgi apparatus localization and regional expression of rat intestinal sialyltransferase detected by immunoelectron microscopy with polypeptide epitope-purified antibody.

During studies on the Golgi apparatus immunolocalization of beta-galactoside alpha 2,6-sialyltransferase in intestinal cells, immunostaining of a number of post-Golgi apparatus structures including mucus droplets and plasma membrane were observed. In order to determine if this labeling was in fact due to sialyltransferase and not carbohydrate-specific antibodies in the polyclonal antiserum preparation, fusion protein to sialyltransferase was used to epitope purify polypeptide-specific antibodies. The affinity purification was performed on a column containing a beta-galactosidase-sialyltransferase fusion protein expressed in Escherichia coli. Using such antibodies we present evidence that in intestinal cells sialyltransferase is not only present in the Golgi apparatus cisternal stack but also its transtubular network and various post-Golgi apparatus structures. In absorptive enterocytes, post-Golgi apparatus vesicles, the brush border and basolateral plasma membrane, multivesicular bodies, and lysosome-like structures were labeled. In goblet cells the limiting membrane and lumen of forming and mature mucus droplets as well as the plasma membrane exhibited label for sialyltransferase. The results provide evidence for "ecto-sialyltransferase" in the plasma membranes of these cells, and suggest that most of the sialyltransferase is released from the Golgi membranes and becomes secreted with the goblet cell mucus. In addition, the polypeptide epitope-purified antibody was also used to examine regional expression of sialyltransferase in the rat intestinal epithelium. Immunolabel was restricted to the large intestine and not found in duodenum, jejunum, and ileum. Direct measurement of the enzyme activity was found to correlate with the immunoelectron microscopic data. This observation suggests that there is regional specific expression of the beta-galactoside alpha 2,6-sialyltransferase.

Animals↗
PubMed1988

Neuropharmacologic effects of vibration on the dorsal root ganglion. An animal model.

The neuropharmacologic effects of low frequency vibration on the dorsal root ganglion, a reported epidemiological cause of low-back pain, have only recently been described. This investigation was undertaken to validate the hypothesis that substance P and VIP, known to be produced in the dorsal root ganglion cell bodies, will be affected by low frequency vibration. Three New Zealand white rabbits were vibrated at discrete frequencies (2-10 Hz) to determine the resonant frequency of the rabbit spine. The resonating frequency was in the (3.5-5.0 Hz) range. The peak amplitude was at 4.5 Hz. Ten female New Zealand white rabbits were then paired into two groups of five. One group served as a control and had exactly the same procedures performed as the experimental group except for the vibration. The L4-5 and L5-6 dorsal root ganglia were removed bilaterally and prepared for substance P and VIP extraction by radioimmunoassay technique. The control rabbits mean immunoreactive substance P was 14.06 pg/ml tissue, whereas the experimental or vibrated rabbits had a mean of 8.40 pg/ml (P less than 0.003). The control rabbits mean immunoreactive vasoactive intestinal peptide was 9.58 pg/ml whereas the experimental or vibrated rabbits had a mean of 20.9 pg/ml, P less than 0.07. Substance P is only one of several dorsal root ganglion neuropeptides that may play a role in nociceptor transmission. VIP is a neuropeptide that plays a role in reorganization of the nervous system following injury. The effects of low frequency vibration on dorsal root ganglion transmitters are essential to the understanding of vibration as a cause of back pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The pain of discography.

Lumbar discography is a commonly employed diagnostic tool, but important questions about it remain unresolved. Why is an abnormal discogram painful in one patient and not in another? This study was performed to investigate the changes in Substance P (SP) and Vasoactive-Intestinal Peptide (VIP), found in the dorsal root ganglion, following discography in normal and abnormal canine lumber intervertebral discs. The data from this study suggest that dorsal root ganglion SP and VIP are indirectly affected by manipulations of the intervertebral disc. It may be that various neurochemical changes within the intervertebral disc are expressed by sensitized (injured) annular nociceptors, and in part modulated by the dorsal root ganglion. Therefore, the concomitant pain sometimes associated with an abnormal discogram image may in part be related to the chemical environment within the intervertebral disc and the sensitized state of its annular nociceptors.

Animals↗
PubMed1988

133Xe blood flow monitoring during arteriovenous malformation resection: a case of intraoperative hyperperfusion with subsequent brain swelling.

Measurement of regional cerebral blood flow (rCBF) using the i.v. 133Xe technique was carried out during resection of a right temporooccipital arteriovenous malformation (AVM) with ipsilateral middle and posterior cerebral arterial supply. Intraoperatively, a rCBF detector was in place over the right frontotemporal area, about 5 to 6 cm from the border of the AVM. Anesthesia was 0.75% isoflurane in oxygen and nitrous oxide. After dural exposure, the rCBF was 27 ml/100 g/min at a pCO2 of 29 mm Hg and a mean arterial pressure (MAP) of 90 mm Hg. The pCO2 was then elevated to 40 mm Hg, and the rCBF was increased to 55 ml/100 g/min at a MAP of 83 mm Hg. After AVM removal, the rCBF rose to 50 ml/100 g/min at a pCO2 of 27 mm Hg and a MAP of 75 mm Hg. The pCO2 was elevated to 33 mm Hg and the rCBF increased to 86 ml/100 g/min at a MAP of 97 mm Hg. During skin closure, the rCBF was 94 ml/100 g/min at a pCO2 of 26 mm Hg and a MAP of 97 mm Hg. The patient was neurologically normal postoperatively except for a mild, new visual field defect. After 2 to 3 days, the patient gradually developed lethargy, confusion, and nausea with relatively normal blood pressure. An angiogram revealed residual enlargement of the posterior cerebral artery feeding vessel. Computed tomography showed edema extending from the area of AVM resection as far as the frontal region, producing a significant midline shift anteriorly. Intraoperative rCBF monitoring revealed significant hyperperfusion after AVM resection, which was associated with signs and symptoms of the normal perfusion pressure breakthrough syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Primary structure of beta-galactoside alpha 2,6-sialyltransferase. Conversion of membrane-bound enzyme to soluble forms by cleavage of the NH2-terminal signal anchor.

This report describes the primary structure of a rat liver beta-galactoside alpha 2,6-sialyltransferase (EC 2.4.99.1), a Golgi apparatus enzyme involved in the terminal sialylation of N-linked carbohydrate groups of glycoproteins. The complete amino acid sequence was deduced from the nucleotide sequence of cDNA clones of the enzyme. The primary structure suggests that the topology of the enzyme in the Golgi apparatus consists of a short NH2-terminal cytoplasmic domain, a 17-residue hydrophobic sequence which serves as the membrane anchor and signal sequence, and a large lumenal, catalytic domain. NH2-terminal sequence analysis of a truncated form of the enzyme, obtained by purification from tissue homogenates, reveals that it is missing a 63-residue NH2-terminal peptide which includes the membrane binding domain. These and supporting results show that soluble forms of the sialyltransferase can be generated by proteolytic cleavage between the NH2-terminal signal-anchor and the catalytic domain.

Amino Acid Sequence↗
PubMed1987

Codistribution of galactosyl- and sialyltransferase: reorganization of trans Golgi apparatus elements in hepatocytes in intact liver and cell culture.

The intracellular distribution of galactosyl- and sialyltransferase was investigated in rat hepatocytes of intact liver, primary monolayer cultures of freshly isolated hepatocytes, in a nontumorigenic hepatocyte cell line and in a hepatoma cell line. The two glycosyltransferases were detected by immunofluorescence using affinity-purified rabbit antibodies. Indirect double immunofluorescence showed that both terminal glycosyltransferases were identically codistributed in the same cell. This codistribution was always observed regardless of the cell type investigated, and in both stationary and migrating cells. The immunofluorescence pattern for both galactosyl- and sialyltransferase was found to be different in hepatocytes in vivo compared to hepatocytes grown in vitro. In hepatocytes of intact liver a spot-like cytoplasmic fluorescence was observed, whereas in cultured normal hepatocytes a perinuclear fluorescence from which an extensive tubular network radiated far into the cytoplasm existed. Cultured hepatoma cells also exhibited an extensive cytoplasmic fluorescence, which in contrast to the normal hepatocytes was rather diffuse. We conclude that (a) galactosyl- and sialyltransferase are codistributed in rat hepatocytes, and (b) a reorganization of (trans) Golgi apparatus elements containing both terminal glycosyltransferases occurs under conditions of in vitro growth and malignant transformation.

Animals↗
PubMed1986

Differential subcompartmentation of terminal glycosylation in the Golgi apparatus of intestinal absorptive and goblet cells.

Two terminal glycosyltransferases, a sialyltransferase and the blood group A alpha 1,3 N-acetylgalactosaminyltransferase, were found to exhibit differential subcompartmentation in the Golgi apparatus of intestinal goblet and absorptive cells. As expected from their role in terminal glycosylation, the two glycosyltransferases and their products, sialic acid residues and blood group A substance, were localized in the trans cisternae of the Golgi apparatus of goblet cells. In contrast, however, they were found throughout the Golgi apparatus stack of adjacent absorptive cells, with the exception of the fenestrated first cis cisterna. The results are in contrast to the general view that enzymes in the glycosylation pathway are arranged in a cis to trans gradient across the Golgi apparatus and that such polarized distributions may instead be cell type-specific.

ABO Blood-Group System↗
PubMed1986

Report of the 1985 ISSLS Traveling Fellowship. Mechanisms of spinal pain. The dorsal root ganglion and its role as a mediator of low-back pain.

The dorsal root ganglion as a mediator for low-back pain in an animal model was investigated. Low-frequency vibration, a known mechanical cause of low-back pain, was investigated. Quantitative results suggest a significant reduction effect on substance P, one of several neurotransmitters located in the dorsal root ganglion. The functional results of these changes are currently under investigation.

Animals↗
PubMed1986

Lumbar disc herniation. A comparison of the results of chemonucleolysis and open discectomy after ten years.

Using data obtained by questionnaire in a retrospective review of patients with low-back and sciatic pain (eighty-five treated by injection of chymopapain and seventy-one, by open discectomy), the results at one and ten years after treatment were analyzed. For this analysis we used six measures of pain relief, six measures of the patients' course during the ten-year period since primary treatment, and four measures of the patients' history of employment or work since initial treatment. Validity studies demonstrated that the pain-outcome measures reflected the patients' condition adequately and that all six measures were significantly related to each other (Pearson's r, p less than 0.003). The chymopapain and discectomy groups were not distinguishable on the basis of the pain-outcome measures. However, body mass was directly related to the presence of pain ten years after discectomy but not after injection of chymopapain. Analysis of the progress measures (indicators of the course of the patients' pain during the ten-year period) showed that the rates of reoperation in the two treatment groups did not differ significantly, but the discectomy patients tended to have had a higher rate of reoperation at both one and ten years after initial treatment. These measures did not show unequivocal superiority of one treatment compared with the other. Using the work measures (assessments of the patients' history of employment since initial treatment), it was found that in both treatment groups the patients who returned to work six to twelve weeks after treatment despite persistent symptoms had significantly more pain at ten years (p less than 0.04). Also, the patients who returned to work less than six weeks after treatment, while still symptomatic, showed a similar trend. On the other hand, among the patients who were still symptomatic at twelve weeks, it made no difference in the final results whether they returned to work at twelve weeks or thereafter. These findings support the notion that after either discectomy or chemonucleolysis, patients should return to work only after complete symptomatic recovery or a minimum convalescence of twelve weeks.

Adult↗