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Biomedical subjects

M Schwartz

Publications and source records attributed to M Schwartz.

At least 559 records · Page 31Linked to original sources

The neurological outcome following surgery for spinal fractures.

Sixty consecutive patients with spinal injuries and encroachment upon the spinal canal of greater than 20% were assessed for neurological outcome. The patients were divided into two groups, those undergoing posterior surgery alone, and those undergoing anterior surgery for formal decompression with or without anterior or posterior instrumentation. In those patients undergoing posterior surgery, an improvement rate in the neurological function of 83% was noted in patients with incomplete lesions, whereas an 88% improvement rate was found in those undergoing the anterior procedure. There was no statistical difference in outcome between these two groups. Positive correlations were found between the level of injury and Frankel grades. The cord lesions tended to demonstrate more severe neurological deficit, whereas the cauda equina lesions were associated with a lesser severity of neurologic deficit. A component of dislocation to the injury also resulted in a more severe neurological deficit. There was no apparent difference between the degree of bony encroachment of the spinal canal and the initial Frankel grade, nor was there a clear difference between those patients undergoing anterior versus posterior surgery.

Adolescent↗

Optic nerve regeneration--new aspects.

Injury to the optic nerve and its environment provokes a process of degeneration that leads to a degenerative process resulting in an irreversible loss of visual function. We succeeded in stimulating regeneration in injured optic nerves of adult rabbits. The stimulus to regeneration was achieved by implanting in injured optic nerves of adult rabbits substances originating from growing (regenerating) optic nerves of fish or developing optic nerves of neonatal rabbits, and by delaying the degenerative process by irradiating the injured optic nerve with a low energy laser. The effect was manifested by abundant growth of new fibers across the injury site and by other manifestation of regeneration characteristics.

Animals↗

Primary site of the huge increase in resistance upon inhibition of gastric acid secretion with hypotonic secretory solution.

In summary, in this paper previous as well as some new results are presented for analysis. It has been shown for the in vitro frog gastric mucosa, with secretory solutions hypotonic relative to the nutrient solution, that inhibition of acid secretion produces a large increase in the transmucosal resistance, Rt. We have shown on the basis of electrophysiological findings that the large increase in Rt is due to an increase in the resistance of the pit and tubular lumina and that the primary factor in this increase is a decrease in luminal area. We have shown that the low transmucosal resistance of the fundus (the acid-secreting portion of the stomach) under standard conditions is due to a low resistance of the lumen-tubular (acid-secreting) cell pathway and that the parallel pathways have high resistances. The latter conclusion is important in deciding among the various models for the mechanism of acid secretion. The histological findings are qualitatively predicted by the electrophysiological results. The limitations of present histological techniques for a quantitative determination of the area of the lumina have also been discussed.

Animals↗

Morphological response of injured adult rabbit optic nerve to implants containing media conditioned by growing optic nerves.

Adult rabbit retina can express regeneration-associated characteristics after optic nerve injury, provided it is supplied with appropriate diffusible substances originating from media conditioned by regenerating fish optic nerves or by optic nerves of a newborn rabbit [Hadani et al., Proc. Natl. Acad. Sci. U.S.A., 81 (1984) 7965; Schwartz et al., Science, 228 (1985) 600]. This was shown by applying the active substances to the injured axons in the form of 'wrap-around' implants, consisting of collagen-coated silicone tubes which had been soaked in the conditioned media (CM). The regeneration-associated response was manifested biochemically and by sprouting of nerve fibers in culture. The present work provides morphological evidence that the implantation prolongs survival of ganglion cells and optic nerve fibers and induces new growth. Light microscopic analysis (using horseradish peroxidase (HRP) for labeling the fibers) revealed, 1 week following optic nerve injury, labeled fibers and ganglion cells in both the implanted and control (injured only or injured and implanted with collagen-coated silicone tubes free of CM) nerves. However, from the second week after the injury, distinct differences in the appearance of viable ganglion cells and labeled fibers, were seen between experimental and control preparations. In sections taken through the optic nerve, at the region distal to the site of injury, HRP-labeled fibers were seen in the experimental nerves 1 week, 2 weeks and to a significantly lesser extent 1 month after injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Expression of differentiation-specific proteins in preneoplastic mammary tissues in BALB/c mice.

The levels of milk-specific mRNAs (alpha-casein, whey acidic protein) and proteins (casein, alpha-lactalbumin) were examined in the DIM series of mammary preneoplastic outgrowth lines and tumors. The constitutive production of casein protein was variable among the preneoplastic DIM outgrowth lines maintained in virgin mice. Outgrowth line DIM-2 consistently expressed a very low level of casein mRNA and protein but no detectable alpha-lactalbumin protein. Outgrowth line DIM-4 expressed a high level of casein protein and no alpha-lactalbumin; however, by transplant generation 9, the levels of casein mRNA and protein were significantly decreased but remained greater than those found in DIM-2. Outgrowth line DIM-3 expressed high levels of casein protein during all transplant generations examined and sporadically exhibited detectable amounts of alpha-lactalbumin. The level of beta-casein mRNA in DIM-3 was 7 times greater than seen in DIM-4 outgrowths, but still only 2% of that measured in the normal mammary gland from lactating mice. The majority of tumors derived from the DIM outgrowth lines expressed very low levels of beta-casein mRNA and total casein protein, although occasionally tumors were observed with very high levels of casein expression. Immunoblot analysis of cellular extracts indicated that alpha, beta-, and gamma-caseins were expressed in the three outgrowth lines to varying degrees. Whey acidic protein mRNA attained barely detectable levels in the best of cases. Only outgrowth line DIM-3 responded to a normal lactogenic stimulus (lactating mouse) with significantly increased levels of milk-specific products. As determined by avidin-biotin peroxidase staining, the percentage of alveoli expressing beta-casein and alpha-lactalbumin proteins in lactating mice increased from 20 and 0%, respectively, in virgin mice to 85 and 40%, respectively, in lactating mice. Similarly, the levels of mRNA for beta-casein and whey acidic protein increased 8- and 5.5-fold, respectively. These results indicate that the cell populations selected by serial transplantation of preneoplastic mammary tissues fall into at least three categories with respect to expression of mammary-specific differentiation products: uninducible, inducible, constitutive. The DIM-3 outgrowth line appears to represent a highly inducible cell population. As concluded in earlier investigations, there was no correlation between secretory activity, morphology of the outgrowths, and tumor-producing capabilities in virgin mice. The effect of a normal lactogenic stimulus on the tumor potential of the DIM-3 line is currently under investigation.

Adenocarcinoma↗

Microelectrode studies of potential difference responses to changes in stromal K+ in bullfrog cornea.

The effects of changing stromal K+ were studied using microelectrodes in an in vitro preparation of frog cornea. The intracellular potential (V0) responded in two opposite ways under short-circuit conditions: (1) depolarization (normal response) when stromal K+ was increased from 4 to 20 or to 79 mM, about 30 mV per 10-fold K+ concn. change; (2) a hyperpolarization (anomalous response) of 10 mV maximum when stromal K+ was increased from 0 to 4 mM. The increase from 4 to 20 or 79 mM decreased or even reversed the short-circuit current (Isc). The transepithelial conductance (gt) increased when K+ was increased to 79 mM but no change occurred in the apical membrane fractional resistance (fRo). Increase of stromal K+ from 0 to 4 mM increased Isc and minimally changed gt and fRo. Ouabain (10(-3) M) abolished the anomalous responses, that is, the increases in V0 and Isc when stromal K+ was increased from 0 to 4 mM. These results are interpreted in terms of two K+ conductive pathways in the basolateral membrane of the corneal epithelium, a Nernstian conductance and an electrogenic (Na+ + K+)-ATPase pump transporting more Na+ than K+ ions per cycle. The normal or anomalous potential difference responses to changes in stromal K+ appear to depend on the relative resistance of the two pathways at the time stromal K+ is changed.

Animals↗

Inhibition of acid secretion of fundus of Rana pipiens with a high concentration of potassium on the secretory side.

Inhibition of acid secretion of the frog fundus is generally accompanied by an increase in transmucosal resistance, Rt, and in potential difference, PD (nutrient normally positive). These results are predicted for the intact tissue by an electrogenic proton pump. It has been suggested that the increase in PD with inhibition can also be explained by a neutral proton pump. The latter model postulates a K+ diffusion potential across the secretory (lumen-facing) membrane tending to make the secretory side positive. Upon inhibition, the [K+] in the lumen is assumed to increase, which decreases the diffusion potential, resulting in an increase in the positivity of the nutrient side. To test this theory, we determined the effects of inhibition with a high [K+] on the secretory side. With a high [K+] in the lumina, inhibition would result in only a small change in the ratio of K+ in the cell to that in the lumina, and hence a small change in the diffusion potential. We found, however, that inhibition increased the PD essentially the same as in the controls. With inhibition the resistance also increased with high secretory K+. Elevating the secretory K+ during secretion produced a 44% decrease in Rt indicating a large increase in luminal K+. We conclude that the results are not compatible with the K+ diffusion potential model but are those predicted by the electrogenic concept.

Animals↗

Laminin-immunoreactive sites are induced by growth-associated triggering factors in injured rabbit optic nerve.

We have previously demonstrated that application of soluble growth-associated triggering factors (GATFs) from regenerating fish optic nerve or neonatal rabbit optic nerve to a non-regenerative crushed adult rabbit optic nerve provokes regeneration-like changes in the adult rabbit. In this study we show that the responses initiated by GATFs also include a change in pattern of appearance of an extracellular matrix component, laminin, known to play a role in neurite outgrowth and elongation. These findings suggest a mechanism whereby GATFs activate the adult rabbit glial cells to produce or to accumulate laminin and thereby allow partial compensation for the low inherent regenerative ability of the adult rabbit optic nerve.

Animals↗

Potential difference responses to secretory K+, Na+ and HCO3- changes in secreting and resting states of frog stomach in Cl(-)-free media.

The effects of changes in secretory concentrations of K+, Na+ and HCO3- on transmucosal potential difference (PD) and resistance in Cl(-)-free (SO4(2-)) solutions were compared for secreting fundus and resting fundus of Rana pipiens. In the resting fundus experiments, histamine was not present in the nutrient solution and cimetidine was primarily used to obtain acid inhibition. Increase of K+ from 4 to 80 mM, decrease of Na+ from 156 to 15.6 mM and decrease of HCO3- from 25 to 5 mM gave, 10 min after the change, in the secreting fundus delta PD values of 39.7, -11.9 and 3.2 mV, respectively. In the resting fundus, 1.5 to 2 h after the addition of cimetidine, the same changes in secretory ion concentration gave delta PD values of 12.2, -5.6 and 1.5 mV, respectively. Replacement of cimetidine with SCN and without histamine yielded a delta PD somewhat lower than that in cimetidine, namely 9 mV for a K+ change from 4 to 80 mM. Subsequent addition of histamine with SCN present gave a delta PD of about 21 mV. The change in PD was attributed to histamine increasing the secretory membrane area, leading to an increase in K+ conductance. Another possibility is that histamine increases the K+ conductance per se.

Animals↗

Estrogen receptor protein of breast cancer in patients with positive nodes. High recurrence rates in the postmenopausal estrogen receptor-negative group.

In 448 patients with positive axillary lymph nodes who were treated with mastectomy at Memorial Sloan-Kettering Cancer Center, New York, from 1973 to 1978, estrogen receptor (ER) status was associated with survival. With a median follow-up of 75 months, significant differences were noted in the 288 postmenopausal patients; ER-positive patients had better six-year disease-free survival than ER-negative patients (60% vs 45%), as well as better overall survival. These differences were true in subgroups with one to three and four or more involved nodes. The addition of adjuvant systemic therapy had no significant effect on either ER-positive or ER-negative patients. The need for new imaginative systemic programs in the subgroup of ER-negative postmenopausal patients with breast cancer with positive nodes is apparent.

Axilla↗

Effects of low-energy He-Ne laser irradiation on posttraumatic degeneration of adult rabbit optic nerve.

Axons of the mammalian peripheral and central nervous systems degenerate after nerve injury. We have recently found that He-Ne laser irradiation may prevent some of the consequences of the injury in peripheral nerves of mammals. In the present study, the efficacy of the laser in treating injured neurons of the mammalian CNS was tested. Optic nerves of adult rabbits were exposed daily for 8-14 days to He-Ne laser irradiation (14 min, 15 mW) through the overlying muscles and skin. As a result of this treatment, the injured nerves maintained their histological integrity, which is invariably lost in injured mammalian CNS neurons.

Animals↗

Response of peripheral nerve to He-Ne laser: experimental studies.

Low-energy He-Ne laser irradiation (LELI) was found to affect the electric activity and morphology in both intact and severely injured peripheral nerves in rats. Action potential (AP) in the healthy nerve increased by 33% following a single transcutaneous irradiation. Similar irradiation in crushed nerves caused AP to increase significantly over the AP of nonirradiated crushed nerve. Morphological observations revealed that a laser-irradiated injured nerve had diminished scar tissue as compared to an injured but not an irradiated nerve.

Animals↗

Linkage relationships and allelic associations of the cystic fibrosis locus and four marker loci.

The linkage relationships between the cystic fibrosis (CF) locus and four marker loci (MET-H, MET-D, D7S8 and D7S16), allelic associations between these loci and the extent of informativity at these marker loci were investigated in a sample of 206 families with at least one child affected by CF. The data were contributed by 11 laboratories from Europe and Israel. The maximum lod scores and recombination frequency estimates (luminal diameter) (and confidence limits of luminal diameter) were: 18.3 at luminal diameter = 0.007 (0.001-0.038) for CF vs. MET, 11.0 at luminal diameter = 0.016 (0.001-0.068) for CF vs. D7S8, and 5.7 at luminal diameter = 0.0 (0.0-0.064) for CF vs. D7S16. A gene order of CF-MET-D7S8 was best supported by the data, but its preference to the order D7S8-CF-MET is mainly based on one single family. There are significant allelic associations between CF, MET, D7S8 and D7S16; these allelic associations affect the risk of random individuals to be carriers of CF.

Alleles↗

A new HindIII restriction fragment length polymorphism in the hemophilia A locus.

Using a fragment of the cDNA for human coagulation factor VIII as a hybridization probe, we have detected a new polymorphic HindIII site in intron 19 of the factor VIII gene. The frequency of the minor allele is 0.30. This polymorphism shows strong linkage disequilibrium with a previously described BclI polymorphism in intron 18.

Alleles↗

The effects of polyoxyethylated cholesterol feeding on hepatic cholesterol synthesis and intestinal cholesterol absorption in rats.

Adduction of ethylene glycol moieties to the 3-hydroxy position of cholesterol produces polyoxyethylated cholesterol (POEC), a water-soluble compound that suppresses cholesterol synthesis and esterification in cultured human fibroblasts. Feeding Sprague-Dawley rats a diet containing 2% (wt/wt) POEC with 10 ethoxy groups resulted in a 3-fold increase in hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity compared to activity in rats pair-fed a diet of standard rat chow. POEC with an average of 20 ethoxy groups (POEC-20) caused comparable changes in hepatic [2-14C]acetate incorporation into non-saponifiable lipids under ad libitum feeding conditions, significantly reduced cholesterol absorption (18% vs 57%), and increased fecal excretion of neutral steroids (5.1 vs 2.0 mg/g food intake). POEC-20 also reduced cholesterol absorption in rats fed a diet enriched with 2% cholesterol (11% vs 31%). Histologic studies of intestinal mucosa and hepatic tissues from rats fed POEC showed no pathologic changes. These experiments indicate that POEC reduces cholesterol absorption and causes compensatory increases in hepatic cholesterol synthesis.

Animals↗

Patterns of polymorphism and linkage disequilibrium for cystic fibrosis.

Four polymorphic markers that map within 80 kb of an HTF island which is genetically very close to the cystic fibrosis locus have been identified. We have analyzed the linkage disequilibrium between each of these markers and the cystic fibrosis mutation in 89 families from four European countries, Denmark, Finland, Spain, and Great Britain. Strong linkage disequilibrium between three polymorphic sites and cystic fibrosis was observed. The markers on the J3.11 (D7S8) side of the HTF island show stronger disequilibrium than those on the met side. Linkage disequilibrium between markers and disease alters the probability that a person of a given haplotype is a carrier in some populations and helps to identify regions of a sequence that are most likely to contain the cystic fibrosis mutation.

Chromosome Mapping↗