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M Horowitz

Publications and source records attributed to M Horowitz.

At least 415 records · Page 23Linked to original sources
PubMed1989

Relationships between gastric emptying of solid and caloric liquid meals and alcohol absorption.

The effects of three variations in meal composition (a solid and a liquid meal consumed together, a liquid meal consumed alone, and a liquid meal consumed 90 min after a solid meal) on the rates and patterns of solid and liquid gastric emptying were examined in 13 volunteers. By including alcohol (0.5 g/kg body wt) in the liquid meal, the relationship between alcohol absorption and gastric emptying was also assessed. The lag phase and the initial emptying phase of the solid meal were prolonged (P less than 0.001) when the liquid meal was consumed with the solid meal, compared with when the liquid meal was consumed 90 min after the solid meal. In this latter situation, consumption of the liquid meal caused the cessation of emptying of solid food, and this second lag phase was followed by a slower (P less than 0.001) than initial emptying phase. Gastric emptying of the liquid meal was slower (P less than 0.005) when solid food was present and was slowest (P less than 0.05) when liquid was consumed 90 min after the solid meal. Alcohol absorption was fastest (P less than 0.05) when the liquid meal was consumed alone and slower (P less than 0.01) when alcohol was consumed with or after the solid meal. For all three meals there was a close correlation (r greater than or equal to 0.91; P less than 0.001) between alcohol absorption and liquid emptying. We conclude that gastric emptying of liquid may be influenced by solid food and that the rate and pattern of solid emptying may be modified by the presence of liquid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Osmoregulation and body fluid compartmentalization in dehydrated heat-exposed pigeons.

Osmoregulatory and volume-regulatory responses of heat-acclimated pigeons (Columba livia) were studied during normal hydration and dehydration combined with heat exposure. Dehydrated heat-exposed pigeons (exposure to 50 degrees C following 48 h of water deprivation; 16-18% mass loss) could recover 97% of their initial body mass within 30 min of free drinking at the end of heat exposure. At the end of heat exposure, body temperature increased by 3 degrees C and hematocrit increased by 12.5%. Serum electrolyte and protein concentrations increased by 33-53% (P less than 0.001). Serum osmolality reached an outstanding mean value of 436.7 +/- 28.5 mosmol/kg (n = 11), 30.5% higher than the normal mean value. Serum glutamic-pyruvic transaminase and glutamic-oxaloacetic transaminase concentrations did not change during dehydration, suggesting no impairment in circulatory function. Blood urea nitrogen increased sixfold, indicating a total shutdown of the kidney. Relative plasma volume was maintained during dehydration at the expense of extravascular spaces and with a decreased vascular permeability as indicated by the increase in Evans blue-labeled albumin half-life (control, 104 +/- 53 min; dehydration, approaching infinity). Altogether, extracellular fluid volume and intracellular fluid volume contributed 53 and 47% of the evaporative water loss, respectively. It is concluded that plasma volume regulation may play an important role in the effective thermoregulatory responses of heat-exposed dehydrated pigeons. This regulation is achieved by preferential shifts of body water reserves among the various body water compartments coinciding with a remarkable tolerance to high osmotic pressures.

Acclimatization↗
PubMed1989

Hearing loss in children and young adults receiving cisplatin with or without prior cranial irradiation.

One hundred seventy-seven children and young adults with various malignant neoplasms were prospectively tested for hearing loss after they had received cisplatin (n = 146), cranial irradiation (n = 18), or both (n = 13). Adequate renal function, no history of treatment with ototoxic drugs other than cisplatin, and availability for repeated audiometric testing were requirements for enrollment. Substantial hearing loss, defined as a hearing threshold of 50 dB or greater, was noted in only 11% of the cohort on tests conducted at the common speech frequencies (500 to 3,000 Hz). About half the patients had substantial deficits at higher frequencies (4,000 to 8,000 Hz). The probability of substantial hearing loss was directly related to the cumulative dose of cisplatin. In nonirradiated patients tested at the speech frequencies, there was a negligible risk of substantial deficits over the dose range of 90 to 360 mg/m2. As the dose increased to 720 mg/m2, the risk increased to 22%. In irradiated patients who later received cisplatin, cumulative drug doses as low as 270 mg/m2 were associated with a high probability of substantial hearing loss, suggesting potentiation of ototoxicity when these therapies are used together. Hearing acuity was either not affected or only minimally decreased in the irradiation-only group. Younger age, prior irradiation, and the presence of a CNS tumor each contributed significantly to the severity of hearing deficits at given cisplatin dose levels. We conclude that early increases in hearing threshold at a stimulus frequency of 4,000 Hz indicate probable subsequent deficits at lower frequencies, especially in young children with CNS tumors who have received cranial irradiation. The probability charts derived from this analysis should provide a useful tool for predicting hearing loss in the speech frequencies.

Adolescent↗
PubMed1989

Gastric and oesophageal emptying in obesity.

Gastric and oesophageal emptying were evaluated in 31 obese patients and 31 control subjects. A double-isotope technique was used to measure gastric emptying of a mixed solid/liquid meal, and oesophageal emptying was measured as the time taken for a bolus of the solid meal to enter the stomach. Gastric emptying of the solid (p less than 0.001) and the liquid (p less than 0.02) meal and oesophageal emptying (p less than 0.001) were delayed in the obese patients compared with the control subjects. There were no significant relationships among gastric emptying, oesophageal emptying, and upper gastrointestinal symptoms in the obese patients alone, but in the total group of 62 subjects there were significant correlations between body mass index and both gastric (r = 0.44, p less than 0.01) and oesophageal (r = 0.45, p less than 0.001) emptying. These results indicate that delayed gastric and oesophageal emptying occurs frequently in obesity and that these abnormalities relate to body weight.

Adolescent↗
PubMed1989

Characterization of mutations in Gaucher patients by cDNA cloning.

Mutated cDNA clones containing the entire coding sequence of human glucocerebrosidase were isolated from libraries originated from Gaucher patients. Sequence analysis of a mutated cDNA derived from a type II Gaucher patient revealed a C-to-G transversion causing a substitution of an arginine for a proline at residue 415. This change creates a new cleavage site for the enzyme HhaI in the mutated cDNA. Allele-specific oligonucleotide hybridization made it possible to show that this mutation exists in the genomic DNA of the patient. From a cDNA library originated from a type I Gaucher patient, a mutated allele was cloned that contains a T-to-C transition causing a substitution of proline for leucine at residue 444 and creating a new NciI site. This mutation is identical to that described by S. Tsuji and colleagues in genomic DNA from type I, type II, and type III patients. Since the new NciI site generates RFLP, it was used to test the existence of this mutated allele in several Gaucher patients by Southern blot analysis. This allele was found in type I (Jewish and non-Jewish), type II, and type III Gaucher patients. These findings led us to conclude that the patient suffering from type II disease (denoted GM1260) carried both mutations described above. Any one of the amino acid changes described reduces the glucocerebrosidase activity as tested by transfection of COS cells with expression vectors harboring the mutated cDNAs. The base changes in the two mutated cDNAs do not affect the electrophoretic mobility of the corresponding polypeptides on an SDS polyacrylamide gel.

Alleles↗
PubMed1989

Human sphingolipid activator protein-1 and sphingolipid activator protein-2 are encoded by the same gene.

Mixed oligonucleotide primers complementary to the translation product of the sphingolipid activator protein (SAP)-2 were used to generate a 144-base pair (bp) complementary DNA (cDNA). This cDNA probe was used to isolate a 2,649-nucleotide-long cDNA that was sequenced and found to contain coding sequences for two known activators of lysosomal enzymes, namely, the sphingolipid activator protein (SAP)-1 and SAP-2. The cDNA contains an open reading frame of 1,482 nucleotides and 1,167 nucleotides of 3'-nontranslated region, followed by a stretch of 24 residues of adenylic acid. At 20 nucleotides upstream from the poly(A) tail there is a consensus AATAAA polyadenylation signal that is preceded by another potential polyadenylation signal. The cDNA, designed SAP-1/SAP-2 cDNA, hybridizes with two human mRNA species of approximately 3 kb in length, which most probably arise from polyadenylation at different sites. There are higher amounts of steady-state RNA levels of the SAP-1/SAP-2 mRNA in skin fibroblasts in comparison to B cells. The steady-state SAP-1/SAP-2 mRNA levels in Gaucher B cells are higher than in their normal counterparts. There is one human SAP-1/SAP-2 gene that has been cloned and is localized on two approximately 5 kb BamHI fragments.

Amino Acid Sequence↗
PubMed1989

Concordance between different measures of small sensory and autonomic fibre neuropathy in diabetes mellitus.

This study presents concordance data from 3 different tests of small nerve-fibre function on the same diabetic patients and also examines the effects of hyperglycaemia. Thus the TTT-Glasgow automated thermal threshold test, EAR-Electrically evoked axon reflex flare, and GOE-Gastric emptying of a mixed sold/liquid meal and oesophageal emptying of a solid bolus were all measured on 25 diabetic patients. The TTT, EAR and GOE all gave values ranging from within the normal reference range for non-diabetics to markedly dysfunctional readings. Mean warm perception (WPT) on the foot dorsum averaged 0.73 degrees C +/- 0.93 for normal controls, but was 4.67 degrees C +/- 3.99 in the 25 diabetics. Cold perception thresholds (CPT) were 0.48 degrees C +/- 0.55 for normal subjects and 3.75 degrees C +/- 4.28 for diabetics. In the same normal subjects the mean EAR flare laser flux responses (for 8 and 16 noxious TENS pulses) was 2.8 V.min, while for diabetics the mean was 0.2 V.min. Solid and liquid gastric 50% emptying times and oesophageal emptying for non-diabetics were within normal range (mean 78 min and 18 min, 18 sec respectively) but for the 25 diabetics emptying times ranged from normal to very prolonged (mean 114 min and 30 min, 68 sec respectively). A plot of 3 measured variables (TTT, EAR and GOE) showed a high degree of correspondence between the gastro-oesophageal emptying delays and the presence of reduced electrical axon reflex and elevated thermal thresholds. Of 25 patients, 6 could be classed as within normal limits on all 3 variables, but 8 of 25 displayed objective evidence of C-fibre neuropathy--thermal perceptual impairment (C- and A-delta sensory fibres), reduced neurogenic inflammatory flare (peptidergic nociceptive afferents) and delayed gastro-oesophageal emptying (vagal afferent/efferent fibres).

Autonomic Nervous System↗
PubMed1989

The Dutch polymath.

Explore the source record for details and available documents.

History, 20th Century↗
PubMed1989

Effects of nandrolone decanoate and antiresorptive therapy on vertebral density in osteoporotic postmenopausal women.

Conventional antiresorptive therapy for osteoporosis can delay bone loss, but secondary inhibition of bone formation appears to prevent an increase in bone density. Recently, anabolic steroid therapy has been shown to increase total body calcium and forearm density in osteoporotic patients, perhaps by causing an increase in bone formation. It is not known if these agents affect vertebral density. We have measured vertebral mineral density in 71 postmenopausal osteoporotic women before and after treatment with either the anabolic steroid nandrolone decanoate or antiresorptive therapy. After a mean treatment period of 14 months, there was a mean increase of 20% in vertebral mineral density in the former group, and no significant change in the latter group. The difference in the time-weighted mean rates of change between the two groups was significant. The results suggest that nandrolone decanoate therapy increases bone formation.

Aged↗
PubMed1988

Differential expression of the human glucocerebrosidase-coding gene.

Gaucher disease is an inborn error of sphingolipid metabolism. It is due to decreased enzymatic activity of glucocerebrosidase (GCase) which causes accumulation of glucocerebrosides, mainly in cells of the reticulo-endothelial system. The disorder is clinically heterogenous and can include central nervous system signs. However, the manifestations of the disease in most cases are restricted to a limited number of cell types and organs. This could be explained by highly differential expression of the human gcs gene. To test this notion, the level of GCase-specific mRNA was determined in different human cell lines by hybridizing Northern blots to a human GCase-specific cDNA probe or by using the RNase protection method. It was found that epithelial cells exhibit high levels of GCase mRNA while skin fibroblasts and promyelocytes show intermediate steady-state levels of this RNA. Macrophages have low steady-state levels of GCase mRNA and in B-cells it is hardly detectable. Moreover, when B-cells or skin fibroblasts were transfected with a vector harbouring the bacterial cat gene coupled to the human gcs gene promoter, the levels of CAT expressed in each cell type were directly correlated to the amount of endogenous GCase RNA. Comparison of the GCase mRNA levels in Gaucher-versus non-Gaucher-derived cells revealed that in Gaucher cells this RNA is always more abundant than in the corresponding non-Gaucher counterparts, suggesting the involvement of a feed-back mechanism sensitive to the levels of actual enzymatic activity.

Blotting, Northern↗
PubMed1988

Bone resorption by isolated chick osteoclasts in culture is stimulated by murine spleen cell supernatant fluids (osteoclast-activating factor) and inhibited by calcitonin and prostaglandin E2.

The question of whether any of the agents known to activate bone resorption in vivo or in organ cultures acts directly on the osteoclast or via intermediate target cells that secondarily secrete locally paracrine factors is important for our understanding of bone remodeling. In an attempt to clarify this issue for some of the agents, we have taken advantage of the recent progress in obtaining and culturing relatively pure populations of osteoclasts. We performed an in vitro bone-resorbing assay in which isolated and partially purified chick osteoclasts were cultured on devitalized, paired and standardized bone disks prepared from rat calvaria prelabeled with both 45Ca and 3H-proline. Some of the isolated osteoclasts attached to the devitalized bone matrix, formed a ruffled border, and acidified the bone-resorbing compartment that they established with the matrix, thereby indicating that they resorbed bone in a physiologic manner. Salmon calcitonin added to these cultures (0.3 U/ml = 60 ng/ml) and prostaglandin E2 (PGE2) (10(-6) M) inhibited both basal and stimulated 45Ca and 3H-proline release. Neither parathyroid hormone (PTH) 1-34 (1 U/ml), 1,25-(OH)2-D3 (10(-8) and 10(-9) M), nor interleukin 1 (IL-1) (purified from P388D1 macrophage culture supernatant fluids or recombinant murine IL-1-alpha) (100 ng/ml) stimulated bone resorption in these cultures. In contrast, supernatant fluids from concanavalin A (Con-A)-activated murine spleen cell cultures (murine osteoclast-activating factor; OAF) consistently and significantly induced a 3- to 5-fold stimulation of bone resorption in this system.

Animals↗
PubMed1988

Changes in blood volume and vascular compliance during body heating in rats.

The effects of hyperthermia on blood volume and effective vascular compliance were studied in control and heat acclimated rats (three weeks at 32 degrees C and 50% R.H.). Experiments were performed on conscious rats whose abdominal aorta and both jugular veins were cannulated. Continuous changes in blood volume (BV) were monitored by measuring 51Cr tagged erythrocyte dilution, using an arterio-venous extracorporeal shunt passing through a gamma counter. Total vascular compliance was calculated from the relation between changes in BV and central venous pressure during 10 min of infusion of saline at a rate of 1.6% body wt/10 min. Hyperthermia induced a significant blood volume expansion. This expansion was more pronounced in non-acclimated rats. Effective vascular compliance was similar in the normothermic, both non-acclimated and acclimated rats. However, while hyperthermia did not affect the vascular compliance of non-acclimated rats, it was decreased significantly in the acclimated hyperthermic rats. The data suggest that changes in vascular compliance play a role when rapid blood volume changes take place, especially in acclimated hyperthermic animals. The relations between changes in vascular compliance and heat induced redistribution of cardiac output are discussed.

Acclimatization↗
PubMed1988

Relationship of the motor activity of the antrum, pylorus, and duodenum to gastric emptying of a solid-liquid mixed meal.

The postprandial motor activity of the antrum, pylorus, and duodenum in 15 healthy volunteers was compared with the profiles of emptying of the solid and liquid components of a meal. The liquid component of the meal emptied rapidly in an exponential manner, whereas the solid remained in the fundus of the stomach until approximately 80% of the liquid had emptied and then emptied in a linear manner. The onset of solid emptying was associated with an increase in the rate of occurrence of antral pressure waves (p less than 0.05), and the half-time for solid emptying (t1/2 - lag period) was inversely correlated (p less than 0.05) with the rate of coordinated contractions involving the antrum. The substitution of 25% dextrose in normal saline as the liquid component of the meal increased the half-time for liquid emptying from a median of 8 to 40 min (p less than 0.01), increased the lag period for solid emptying from 40 to 87 min (p less than 0.01), and increased the rate of occurrence of isolated pyloric pressure waves during the solid lag phase from 7 to 58/h (p less than 0.05), but did not affect the slope of solid emptying or the rate of coordinated contractions involving the antrum during the solid emptying period.

Adolescent↗
PubMed1988

The relation between forearm and vertebral mineral density and fractures in postmenopausal women.

Vertebral and forearm mineral density (VMD and FMD, respectively) were determined in 124 postmenopausal women with no crushed vertebrae or peripheral fractures, 51 who had sustained peripheral fractures only since the menopause, 62 with vertebral compression(s) only and 75 with both types of fracture. There was a very significant correlation between the two measurements in the whole set. The scatter could not be accounted for by methodological error but was partly accounted for by body weight, since VMD was related to body weight and FMD was not. Whatever criterion was used for the diagnosis of osteoporosis (whether fracture or density) the percentage of misclassified cases was very similar by the two methods. However, VMD was relatively more reduced than FMD in vertebral fracture cases and FMD was marginally more reduced than VMD in peripheral fracture cases. There is little to choose between vertebral and forearm density in the diagnosis of osteoporosis but vertebral densitometry is slightly superior to forearm densitometry in describing the severity of osteoporosis in vertebral fracture patients.

Body Weight↗
PubMed1988

Effects of arginine vasopressin on the sequestration of albumin in extravascular space in the rat.

1. The effect of Arginine-Vasopressin (AVP) and phenoxybenzamine on regional sequestration of albumin in the extracellular space was studied in anesthetized (Na-Thiopentone) rats using a dual albumin labelling technique. 2. Low AVP dose (400 microU/kg) resulted in increased albumin sequestration, particularly in cutaneous and skeletal muscle extravascular space. In higher AVP doses this effect was not pronounced. 3. Phenoxybenzamin resulted in increased albumin sequestration, mostly in cutaneous and skeletal muscle extravascular space. 4. The effect of AVP, a potent pressoric hormone, on albumin sequestration resembles that of a vasodilator drug and contrasts with its pressoric nature.

Animals↗