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M Horowitz

Publications and source records attributed to M Horowitz.

At least 397 records · Page 22Linked to original sources
PubMed1990

Evaluation of patterns of human antral and pyloric motility with an antral wall motion detector.

We have examined the hypothesis that isolated pyloric pressure waves occur in the absence of even low-amplitude antral contractions. Antropyloroduodenal motility was recorded in seven healthy adult volunteers. A sleeve/side-hole manometric assembly was positioned across the pylorus with the aid of measurements of transmucosal potential difference. A new sensor consisting of an elliptical wire transducer 2.5 cm long and 1.5 cm in transverse diameter was incorporated into the assembly above the sleeve. This sensor was designed to detect nonlumen-occluding antral contractions. Motility was studied for 45 min under each of three conditions: 1) fasting, 2) after ingestion of a 100-g beef burger, and 3) during and after a 15-min intraduodenal infusion of 25% dextrose at a rate of 4 ml/min. Overall, only 51% of antral transducer deflections were associated with a change in antral side-hole pressures. Eighty-nine percent of antral side-hole pressure waves were associated with an indication of antral wall motion. Of the pressure waves recorded by the sleeve classified as isolated pyloric pressure waves, none was associated with antral transducer deflection during fasting, 1.1% after intraduodenal dextrose, and 18% after the solid meal. Antral contractions were detected by the wall motion detector with greater sensitivity than antral side holes, possibly reflecting the occurrence of nonlumen-occluding antral contractions. With some exceptions during solid gastric emptying, manometrically defined isolated pyloric pressure waves appear to represent truly localized contraction.

Adult↗
PubMed1990

The reproducibility of bone-related biochemical variables in post-menopausal women.

Seventeen measured and derived bone-related biochemical variables were determined in 60 postmenopausal women on two occasions from 1 to 35 months apart. The coefficients of determination (r2) between the first and second observations were highly significant in respect of all measured and calculated variables except for anion gap, calculated complexed calcium, fasting urinary sodium:creatinine ratio and urinary phosphate:creatinine ratio. The variables with coefficients of determination which ranked highest include plasma alkaline phosphatase, albumin, globulins, calculated ionized calcium and fasting urinary corrected calcium:creatinine and hydroxyproline: creatinine ratios. They also showed marked individuality suggesting that changes within the conventional population based reference range possibly indicate significant physiological changes in metabolism. The critical difference for two results to be significantly different (P less than 0.05) was calculated from the total variation for each variable. We conclude that most of the measured and derived bone-related biochemical variables in fasting plasma and urine samples are sufficiently reproducible in postmenopausal women to be clinically and physiologically meaningful but that urinary sodium and phosphate are inconstant and probably dependent on the previous day's dietary intake.

Aged↗
PubMed1990

The parathyroid hormone-related protein stimulates human osteoblast-like cells to secrete a 9,000 dalton bone-resorbing protein.

The mechanism by which parathyroid hormone-related protein (PTH-RP) stimulates bone resorption is not known. Like certain other resorbing agents it may act to release bone-resorbing cytokines from the osteoblast. To examine this hypothesis, we used serum-free conditioned media (CM) from SAOS II cells incubated with 10(-8) M h(1-74) PTH-RP for 48 h. Treated CM contained substantially more bone-resorbing activity (BRA) in the fetal-rat long-bone assay than CM from untreated cells (2.17 +/- 0.21 vs 1.38 +/- 0.16 fold stimulation over basal [f]; p less than 0.05]. After centrifugation and dialysis, 1 liter of treated CM contained a total BRA of 7102 ngeq b(1-34) PTH with a specific activity (SA) of 447 ngeq b(1-34) PTH/mg protein. Treated CM did not stimulate the ROS assay and the cytokines PGE2, TGF-alpha, EGF, GM-CSF and IL-1 were present in low concentrations. The BRA was heat sensitive. Ultrafiltration revealed that 97% of the BRA was in a 3-30 kD fraction. Further purification was achieved by sequential reverse phase HPLC and size exclusion-HPLC (SE-HPLC). A single fraction containing BRA from SE-HPLC was purified 277-fold to a SA of 123,810 ngeq b(1-34) PTH/mg protein and had an apparent MW of 9 kD. SDS-PAGE revealed 4 bands in this SE-HPLC fraction with 1 band at 9 kD unique to that fraction. PTH-RP may cause bone resorption in part by stimulating the release of a 9 kD protein from osteoblasts which is responsible for activating osteoclasts.

Biological Factors↗
PubMed1990

The relative contributions of age and years since menopause to postmenopausal bone loss.

We have estimated the relative contributions of age and menopause to forearm mineral density in 485 normal postmenopausal women up to age 75 yr. In 87 pairs matched for years since menopause, in which 1 member was below 61 yr and the other was 61 yr or older, the mean bone density was significantly lower in the older than in the younger subjects despite their identical years since menopause (P less than 0.001). Further analysis suggested a model for bone loss after the menopause which comprises a menopausal component of exponential type and an age-related component which is linear and starts in the mid-50s. According to this model, a 70-yr-old woman has lost 11% of her bone due to menopause and 18% as a function of age. Thereafter, the age-related function is dominant. Early menopause is associated with a self-limiting loss of bone which does not progress further until aging exerts its effect. The main conclusion is that the significance of early menopause as a risk factor for osteoporosis has been overstated.

Age Factors↗
PubMed1990

Acid beta-glucosidase: enzymology and molecular biology of Gaucher disease.

Human lysosomal beta-glucosidase (D-glucosyl-acylsphingosine glucohydrolase, EC 3.2.1.45) is a membrane-associated enzyme that cleaves the beta-glucosidic linkage of glucosylceramide (glucocerebroside), its natural substrate, as well as synthetic beta-glucosides. Experiments with cultured cells suggest that in vivo this glycoprotein requires interaction with negatively charged lipids and a small acidic protein, SAP-2, for optimal glucosylceramide hydrolytic rates. In vitro, detergents (Triton X-100 or bile acids) or negatively charged ganglioside or phospholipids and one of several "activator proteins" increase hydrolytic rate of lipid and water-soluble substrates. Using such in vitro assay systems and active site-directed covalent inhibitors, kinetic and structural properties of the active site have been elucidated. The defective activity of this enzyme leads to the variants of Gaucher disease, the most prevalent lysosomal storage disease. The nonneuronopathic (type 1) and neuronopathic (types 2 and 3) variants of this inherited (autosomal recessive) disease but panethnic, but type 1 is most prevalent in the Ashkenazi Jewish population. Several missense mutations, identified in the structural gene for lysosomal beta-glucosidase from Gaucher disease patients, are presumably casual to the specifically altered posttranslational oligosaccharide processing or stability of the enzyme as well as the altered in vitro kinetic properties of the residual enzyme from patient tissues.

Amino Acid Sequence↗
PubMed1990

Genotype assignment in Gaucher disease by selective amplification of the active glucocerebrosidase gene.

Genomic DNA prepared from human cells in culture was amplified by the polymerase chain-reaction technique using two primers specific for the active human glucocerebrosidase gene. The 1,036-bp amplified fragment derived from the active gene was tested for the existence of three mutations--designated "370," "NciI," and "HhaI"--by allele-specific oligonucleotide hybridization. The results obtained from the cell lines examined permitted a clear distinction between homozygous affected, heterozygous, and normal genotypes. However, 28% of the possible affected loci were normal with respect to the three mutations, indicating the presence of additional mutations that remain to be elucidated. While the NciI mutation could be found in both Ashkenazi Jewish and non-Jewish type 1 patients, the only homozygotes with this mutation had the neurological (type 2 or type 3) form of the disease. The 370 mutation, on the other hand, was only present in type 1 patients and was not identified among any of the patients with neurologic forms of the disease.

Base Sequence↗
PubMed1990

Relationship between forearm and vertebral mineral density in postmenopausal women with primary hyperparathyroidism.

Vertebral and forearm mineral density of 28 postmenopausal women with mild primary hyperparathyroidism was measured and compared with expected values on the basis of age and years since menopause. In these patients we found that the bone deficit in the distal forearm was greater than in the spine, and 8 patients had already suffered one or more peripheral fractures. This suggests that postmenopausal women with mild, asymptomatic hypercalcemia of primary hyperparathyroidism are likely to be relatively more predisposed to peripheral than vertebral fractures, which is clear evidence of the need for treatment to prevent bone loss in these patients.

Aged↗
PubMed1990

Treatment of postmenopausal hyperparathyroidism with norethindrone. Long-term effects on forearm mineral content.

In 15 postmenopausal women with mild primary hyperparathyroidism, the long-term effect of norethindrone therapy (5 mg/d) on forearm bone mineral content (FMC) was evaluated. The FMC rose from 810 +/- 39 (SEM) mg/cm at baseline to 841 +/- 41 mg/cm after 2 years of treatment, representing a mean bone mineral gain of 1.9% per year. The majority of this bone gain occurred during the first 6 months of treatment. The rate of increase in FMC in the first 6 months was +3.71 +/- 0.12 mg/cm per month compared with -0.35 +/- 0.51 mg/cm per month during the second year. Fat-corrected FMC was measured to determine whether the bone gain was real or reflected a decrease in fat mass. There was a similar rise in fat-corrected FMC (from 885 +/- 36 mg/cm at baseline to 909 +/- 39 mg/cm at 2 years). The difference between fat-corrected and uncorrected FMC, however, decreased slightly on norethindrone treatment (from 75.2 +/- 11.9 mg/cm at baseline to 67.8 +/- 11.8 mg/cm at 12 months), indicating a reduction in the subcutaneous fat layer. We conclude that norethindrone therapy in postmenopausal women with mild primary hyperparathyroidism produces a gain in bone mass that is sustained for at least 2 years.

Absorptiometry, Photon↗
PubMed1989

Gastric and oesophageal emptying in patients with type 2 (non-insulin-dependent) diabetes mellitus.

Gastric emptying of a digestible solid and liquid meal and oesophageal emptying of a solid bolus were measured with scintigraphic techniques in 20 randomly selected Type 2 (non-insulin-dependent) diabetic patients receiving oral hypoglycaemic therapy and 20 control subjects. In the diabetic patients, the relationships between oesophageal emptying, gastric emptying, gastrointestinal symptoms, autonomic nerve function and glycaemic control were examined. The percentage of the solid meal remaining in the stomach at 100 min (p less than 0.001), the 50% gastric emptying time for the liquid meal (p less than 0.05) and oesophageal emptying (p less than 0.05) were slower in the diabetic patients compared to the control subjects. Scores for upper gastrointestinal symptoms and autonomic nerve dysfunction did not correlate significantly (p greater than 0.05) with oesophageal, or gastric emptying. The 50% gastric emptying time for the liquid meal was positively related (r = 0.58, p less than 0.01) to the plasma glucose concentration at the time of the performance of the gastric emptying test and the lag period, before any solid food emptied from the stomach, was longer (p less than 0.05) in subjects with plasma glucose concentrations during the gastric emptying measurement greater than the median, compared to those with glucose concentrations below the median. These results indicate that delayed gastric and oesophageal emptying occur frequently in Type 2 diabetes mellitus and that delayed gastric emptying relates, at least in part, to plasma glucose concentrations.

Aged↗
PubMed1989

Pyloric motor response to intraduodenal dextrose involves muscarinic mechanisms.

The delivery of dextrose solutions to the duodenum is associated with the stimulation of phasic and tonic pyloric contraction. In this study, the effects of intravenous atropine on the antropyloroduodenal motor responses to intraduodenal infusions of 25% dextrose were assessed in 10 normal volunteers. Antropyloroduodenal pressures were recorded with a manometric assembly incorporating a sleeve sensor spanning the pylorus, and sideholes in the antrum and duodenum. In each experiment, three intraduodenal infusions of 25% dextrose were given at a rate of 4 ml/min, for a median duration of 19 min (range 17-20). During the second dextrose infusion, intravenous atropine was given as a bolus (15 micrograms/kg) followed by an infusion (4 micrograms/kg.min), which was continued until the end of each experiment. Before atropine was given, the pyloric motor response to the second dextrose infusion was not significantly different from the response to the first infusion, but after administration of atropine there was a rapid decrease in the rate of isolated pyloric pressure waves, from 0.8 to 0.1 per minute (p less than 0.05). The isolated pyloric pressure wave response to the third dextrose infusion was completely blocked, and there was a much smaller maximum increase in basal pyloric pressure compared with the first infusion (p less than 0.01). This study indicates that intraduodenal dextrose reproducibly stimulates isolated pyloric pressure waves and increases basal pyloric pressure by mechanisms that involve muscarinic receptors.

Adult↗
PubMed1989

Long-term heat adaptation results in an enhanced efficiency of muscarinically-induced water secretion in rat submaxillary glands.

1. Carbamylcholine-induced 86Rb+ and 36Cl- efflux, as markers of calcium mobilization and water secretion, respectively, were studied during 30 days of heat acclimation (at 34 degrees C) in rat submaxillary gland slices using perifusion techniques. 2. The fractional rate of 36Cl- efflux was markedly elevated with acclimation, reaching its maximal level on day 30, while that of 86Rb+, after an initial rise, returned to non-acclimated control levels. The total carbamylcholine-induced efflux of both ions markedly increased throughout the 30 days' acclimation. 3. The rapid increase in ion fluxes was accompanied by a transient increase in Na+ concentrations in the gland and a decrease in the saliva. 4. The data suggest that the acclimation-induced increase in secretory capacity is bi-phasic: initially, a rapid transient rise in ion fluxes accompanies a transient rise in muscarinic receptor density (Kloog et al., 1985). 5. Long term acclimation is characterized by increased efficiency of the cellular secretory mechanism(s), as demonstrated by the chronically increased efflux of ions.

Adaptation, Physiological↗
PubMed1989

The human glucocerebrosidase gene and pseudogene: structure and evolution.

We report the sequence of the entire human gene encoding beta-glucocerebrosidase and that of the associated pseudogene. The gene contains 11 exons extending from base pair 355 to base pair 7232 in the overall sequence. The gene promoter contains TATA- and CAT-like boxes upstream of the major 5' end of the glucocerebrosidase RNA. The two TATA boxes lie between nucleotides (-23)-(-27) and (-33)-(-39) and the two possible CAT boxes reside between nucleotides (-90)-(-94) and (-96)-(-99) in relation to the major 5' end of the mRNA. The functionality of the promoter region was monitored by coupling it to the bacterial gene coding for chloramphenicol acetyltransferase (CAT) and assaying the expression of the enzyme in cells transfected with this vector. The glucocerebrosidase promoter not only directs synthesis of the bacterial enzyme but also exhibits the same pattern of tissue-specific expression as that of the endogenous gene. An apparently tightly linked pseudogene is approximately 96% homologous to the functional gene. However, introns 2, 4, 6, and 7 have large "deletions" consisting of Alu sequences 313, 626, 320, and 277 bp in length, respectively. It is entirely possible that the ancestral gene lacks these sequences and that they have been inserted into the introns of the functioning gene. There is also a 55-bp deletion from a part of exon 9 flanked by a short inverted repeat. The sequence data should facilitate development of methods for diagnosis of Gaucher disease at the molecular level.

Base Sequence↗
PubMed1989

Cross-over study of fat-corrected forearm mineral content during nandrolone decanoate therapy for osteoporosis.

We have previously reported an increase in forearm bone mineral content (BMC) during therapy for osteoporosis with the anabolic steroid, nandrolone decanoate. However, it has recently been claimed that part of this increase is spurious, due to a decrease in forearm fat during the treatment. We have therefore analyzed the data from a cross-over study of the effects of this agent on 70 osteoporotic women, using the fat correction procedure supplied by the manufacturer of the forearm densitometer. There was a significant rise (p less than 0.001) in the mean fat-corrected BMC (BMC[fc]) on nandrolone decanoate (50 mg intramuscularly every 2 or 3 weeks) and a non-significant fall in mean BMC[fc] off the drug. The mean time-weighted rate of change in the fat-corrected value was +29 +/- 5 mg/cm/year on nandrolone decanoate and -5 +/- 5 mg/cm/year off nandrolone decanoate (p less than 0.001). Nandrolone decanoate produces a significant gain in forearm mineral content even after allowing for changes in forearm fat content during therapy.

Aged↗
PubMed1989

Cryosurgical treatment of endolymphatic hydrops.

Cryosurgery of the labyrinth, as a treatment of endolymphatic hydrops, was initially greeted with considerable enthusiasm, but has lately received little publicity. That it still has a valuable role is demonstrated by this study of 69 patients who underwent labyrinthine cryosurgery over a 16 year period. Complete relief from vertigo has been achieved in 71 per cent of cases and morbidity has been minimized by the precautions outlined. The literature is reviewed to demonstrate the superiority of the transmastoid approach, the evolution of the technique and experimental evidence for the supposed mode of action.

Adolescent↗
PubMed1989

Snake acetylcholine receptor: cloning of the domain containing the four extracellular cysteines of the alpha subunit.

The acetylcholine receptor (AcChoR) at the neuromuscular junction of elapid snakes binds cholinergic ligands but unlike other muscle AcChoRs does not bind alpha-bungarotoxin. Numerous studies indicate that the ligand-binding site of the AcChoR includes cysteine residues at positions 192 and 193 of the alpha subunit. We have previously shown that a synthetic dodecapeptide corresponding to residues 185-196 of the Torpedo AcChoR alpha subunit contains the essential elements of the ligand-binding site. In an attempt to elucidate the structural basis for the precise binding properties of snake AcChoR, we sequenced a portion of the snake AcChoR alpha subunit. First, a mouse AcChoR alpha-subunit cDNA probe was used to screen a size-selected snake (Natrix tessellata) genomic library. A genomic clone was isolated and was found to contain sequences homologous to the exon including the first two cysteines (Cys-128 and -142) of AcChoR alpha subunit. The domain of the alpha subunit from Natrix and cobra AcChoR (amino acid residues 119-222), which contains the four extracellular cysteines (128, 142, 192, and 193), was amplified by reverse transcription of mRNA and the polymerase chain reaction and then sequenced. The deduced amino acid sequence showed that the snake alpha subunit contains the two tandem cysteines at positions 192 and 193, resembling all other AcChoR alpha subunits. Sequence comparison revealed that the cloned region of the snake alpha subunit is highly homologous (75-80%) to other muscle AcChoRs and not to neuronal AcChoR, which also does not bind alpha-bungarotoxin. In the presumed ligand-binding site, in the vicinity of Cys-192 and Cys-193, four major substitutions occur in the snake sequence--at positions 184 (Trp----Phe), 185 (Lys----Trp), 187 (Trp----Ser), and 194 (Pro----Leu). In addition, Asn-189 is a putative N-glycosylation site, present only in the snake. These changes, or part of them, may explain the lack of alpha-bungarotoxin-binding to snake AcChoR.

Amino Acid Sequence↗
PubMed1989

The influence of fibronectin administration on the incidence of sepsis and septic mortality in severely injured patients. The Medical College of Georgia Fibronectin Research Group.

Eighty-five trauma patients between the ages of 18 and 55, with American College of Surgeon's (ACOS) trauma scores greater than or equal to 7 were entered into a double-blind, randomized, placebo-controlled study to assess the efficacy of prophylactic fibronectin (Fn) administration on clinical course, sepsis development, and septic mortality. Patients were randomized on admission to receive purified human virus-inactivated Fn or placebo control (human serum albumin, HSA). Fn or HSA was administered on a daily basis if and when the patient was Fn deficient (less than 75% normal). When a Fn deficiency was not evident, the patient received saline. Seventy one patients developed Fn deficiencies during their initial clinical course: 36 received Fn, 35 received HSA. Fourteen patients did not develop a Fn deficiency after trauma and thus received only saline. Analysis of admission data demonstrated no significant differences between the three groups with respect to extent of injury (injury severity score, ACOS trauma score) or physiologic assessments of organ function (serum creatinine, bilirubin, lactic acid). On day 1 after trauma, Fn levels were shown to correlate with other plasma proteins and cellular components (range of r values, 0.24 to 0.75; all p less than 0.05), but not with organ function parameters. Eighteen of 85 patients became septic as judged by clinical criteria. Ten of these patients had received Fn (10 of 36), five had received HSA (5 of 35), and three had received only saline (3 of 14) before the development of sepsis (differences not significant). When septic, nine of 17 patients developed Fn deficiencies. Six patients received Fn while septic, three received albumin, and eight received saline. Seven patients died: 5 of 6 Fn patients, 1 saline, and 1 HSA recipient. Our data suggest that exogenous Fn repletion in states of deficiency does not alter clinical course, the development of sepsis, or septic mortality.

Adolescent↗
PubMed1989

Duodenal ulcer in the elderly.

Of 333 duodenal ulcer (DU) patients 75 (22.5%) were aged 65-93 years (study group). Ninety-two percent (306 patients) of the entire group were diagnosed endoscopically, and all were followed prospectively. In the study group of the older patients there were fewer smokers, but more patients used steroids and other nonsteroidal antiinflammatory drugs (NSAIDs) and had more arteriosclerotic heart disease than the younger control group. Presenting signs and symptoms were similar in both age groups, although painless upper gastrointestinal bleeding was more common in the elderly, and pain, when present, tended to be milder. Bleeding episodes were more prevalent in the older age group. Another difference between the groups was the larger incidence of concurrent gastric ulcer and DU observed endoscopically in the study population. Steroids and NSAIDs could be etiologically connected to bleeding in the older patients, as well as to their relative lack of pain. We conclude that DU in the elderly tended to present atypically and that pain was not the major symptom of activity. This places a different emphasis on diagnostic and therapeutic criteria.

Adult↗