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Biomedical subjects

M Horowitz

Publications and source records attributed to M Horowitz.

At least 19 recordsLinked to original sources

Systemic lupus erythematosus patients with central nervous system involvement show autoantibodies to a 50-kD neuronal membrane protein.

An antibody was detected in the sera from patients with systemic lupus erythematosus (SLE) and central nervous system (CNS) involvement that reacted with a 50-kD antigen in the plasma membrane of brain synaptic terminals. The 50-kD antigen was solubilized with Triton X-100 from preparations enriched with synaptic plasma membranes, and was partially purified by molecular sieve filtration column chromatography. The sera of 19 of 20 CNS-SLE patients showed strong to moderate immunoreactivity with the 50-kD protein in Western blots. Immunoreactivity with the 50-kD protein was also detected in the cerebrospinal fluid of CNS-SLE patients. Control sera from healthy individuals did not react with the 50-kD protein. Low to background reactivity was detected in 35% of a group of SLE patients without CNS manifestations, and in 3% of patients displaying other connective tissue diseases. A total of 100 individuals were tested in this study. Purified autoantibodies to the 50-kD protein from CNS-SLE patients were used for immunofluorescent labeling of neuroblastoma cells. The immunofluorescent staining revealed a distinct macular distribution pattern on the surface of the cell membrane. Taken together, the data suggest that the 50-kD protein may be an important target for autoantibodies, preponderantly found in CNS-SLE patients, and that the antigen may play a role in the pathogenesis of some neurological manifestations in SLE.

Adolescent

Hemopoietic functions of marrow-derived osteogenic cells.

Osteoblasts, members of the marrow stromal cellular network, may play an active role in the hemopoietic microenvironment as well as in bone remodeling. In this study, we examined the extent to which marrow-derived osteogenic cells (MBA-15) possess various stromal functions. This marrow stromal-derived cell line was shown by us to exhibit osteoblastic characteristics in culture and to form bone in vivo. These cells are shown here to constitutively produce and secrete cytokines identified as M-CSF, GM-CSF, and IL-6. MBA-15 cells modulate growth of normal and malignant myeloid and lymphoid cells as well as leukemia cell lines in vitro. Cell-cell interactions were studied in co-cultures with adherent MBA-15 cells and the target hemopoietic cells. Growth inhibition effects, observed under various experimental conditions, can be attributed to the presence of different soluble and membrane-bound inhibitory activities produced by MBA-15 cells. Thus, MBA-15 cells spontaneously produce both stimulators and inhibitors that can affect myeloid and lymphoid cell growth. Marrow osteogenic cells may therefore participate in the stromal regulation of hemopoiesis.

Alkaline Phosphatase

Ambiguous genitalia: diagnosis, evaluation, and treatment.

The pediatric radiologist plays a significant role in the evaluation and the treatment of infants with ambiguous genitalia. On the first day of life, an investigation should be initiated that includes studies, in particular a sonogram, to demonstrate the presence or absence of a uterus, and a genitogram to define the presence of a vagina. Once gender assignment has been made, information regarding the size of the vagina and its position in regard to the urogenital sinus becomes essential to the pediatric urologist when planning a course for reconstruction. Herein we break down intersex states into four major categories: female pseudohermaphroditism, male pseudohermaphroditism without müllerian structures, and male hermaphroditism with müllerian structures and true hermaphroditism. The role of the radiologist in each of these states is discussed.

Disorders of Sex Development

Intravenous erythromycin overcomes small intestinal feedback on antral, pyloric, and duodenal motility.

The retardation of gastric emptying caused by intraduodenal lipid is associated with suppression of antral contractions and stimulation of localized pyloric contractions. Similar patterns of motility have been described in patients with gastroparesis. The effect of erythromycin on the antropyloroduodenal motor responses to intraduodenal lipid was investigated. In 17 volunteers an intraduodenal lipid infusion (10% Intralipid) was given at 1 mL/min for 50 minutes. Either erythromycin (3 mg/kg) or saline was administered IV for 15 minutes, beginning 20 minutes after the start of the intraduodenal lipid infusion. Antral, pyloric, and duodenal motility were measured with a sleeve/sidehole manometric assembly. Intraduodenal lipid stimulated localized pyloric contractions. Erythromycin suppressed localized phasic (P less than 0.003) and tonic (P less than 0.002) pyloric pressure waves and stimulated antral (P less than 0.003) and duodenal pressure waves (P less than 0.02). After erythromycin antral pressure waves were usually of high amplitude (greater than 50 mm Hg) and often associated with duodenal pressure waves. It was concluded that erythromycin overcomes the effects of intraduodenal lipid on antral, pyloric, and duodenal motility. These effects probably contribute to the gastrokinetic properties of erythromycin.

Adult

Adaptive changes in the pyloric motor response to intraduodenal dextrose in normal subjects.

Gastric emptying of glucose is faster after dietary supplementation of glucose, suggesting specific adaptation to changes in nutrient intake. In the present study, the effects of a continuous long-term (0-120-minute) and two short-term (0-20- and 80-100-minute) intraduodenal infusions of dextrose (2.4 kcal/min) on antropyloroduodenal motility and blood glucose, plasma gastric inhibitory polypeptide, and insulin concentrations were evaluated in nine volunteers. In four volunteers, an intraduodenal infusion of triglyceride (2.4 kcal/min) was administered immediately after the long-term dextrose infusion. The long-term dextrose infusion initially increased isolated pyloric pressure waves (IPPWs) and basal pyloric pressure (P < 0.05 for both), but after about 30 minutes IPPWs and basal pyloric pressure decreased and returned to baseline within 80 minutes. Each short-term infusion increased IPPWs and basal pyloric pressure (P < 0.05 for both). Antral pressure waves remained suppressed during the long-term dextrose infusion. Intraduodenal triglyceride increased IPPWs and basal pyloric pressure (P < 0.05 for both). The long-term dextrose infusion was associated with a sustained increase, and both short-term dextrose infusions were associated with peaks in glucose, insulin, and gastric inhibitory polypeptide levels. There was no significant relationship between biochemical measurements and antropyloroduodenal motility. It is concluded that specific adaptive changes occur rapidly in the phasic and tonic pyloric motor response, but not the antral motor response, to intraduodenal dextrose.

Adaptation, Physiological

Screening for gene deletions and known mutations in 13 patients with ornithine transcarbamylase deficiency.

We analyzed DNA from 13 males with ornithine transcarbamylase (OTC) deficiency for gene deletions and known point mutations using the polymerase chain reaction (PCR), allelle-specific oligonucleotide (ASO) hybridization, and Southern blotting with full-length OTC cDNA and exon-specific probes. Three patients were found to have deletions: one was missing the whole OTC gene; a second patient had a deletion of both exon 7 and 8; and the third had a deletion of exon 9. Only one of the remaining 10 patients had a known point mutation consisting of a G-to-A change in nucleotide 422 of the sense strand resulting in a glutamine substitution for arginine at amino acid 109 of the mature OTC protein. This study describes the integration of various molecular methods to screen OTC-deficient patients for deletions and points mutations. Two new deletions within the OTC gene are described.

Base Sequence

An investigation of a workplace cluster of Bell's palsy.

We undertook a study to confirm the existence of an apparent cluster of Bell's palsy in an industrial plant ("W4"), and to test etiologic hypotheses regarding chemical exposures, immune suppression, and infectious etiologies. Cases were enumerated by questionnaire. Employees with a history of Bell's palsy ("cases") were invited to participate in a study that included medical history, T cell studies, viral and Lyme disease serologies, and blink reflex studies. Thirty-three unaffected volunteers from W4 and 32 from a comparison building were also tested. Extensive environmental studies were carried out in W4, evaluating infectious, chemical, and radiation exposures. The lifetime incidence of self-reported Bell's palsy was 11.6/10,000 person-years (P-Y) in W4 and 2.4 cases/10,000 P-Y in the comparison building (RR = 4.8, P < .05); the comparison rate was similar to that reported in previous population studies. When restricted to cases occurring after the onset of work, the W4 incidence was 29.2 cases/10,000 P-Y, compared to 4.8 cases/10,000 P-Y in the comparison building (RR = 6.1, P < .05). The cases and noncases did not differ with respect to clinical histories or infectious disease titers. The W4 noncases had small but significant decreases in T lymphocyte (1974 +/- 86 vs 2291 +/- 103) and CD4 (1083 +/- 318 vs 1459 +/- 494) counts compared to the remote noncases. The cases had significantly prolonged RR1, LR1, and LFC values compared to both groups of noncases. No medical or environmental factors were identified that could explain an excess of disease.

Age Factors

Osteoporosis and Klinefelter's syndrome.

OBJECTIVE: We wanted to measure forearm mineral density and bone-related biochemical variables in patients with Klinefelter's syndrome. DESIGN: Measurements made in patients with Klinefelter's syndrome were compared to those obtained in age-matched normal male volunteers. PATIENTS: We studied 22 patients with Klinefelter's syndrome (12 of whom had received sex hormone therapy) and 22 control subjects. MEASUREMENTS: We measured forearm mineral density, forearm fat content, fat-corrected forearm mineral density, plasma calcium and ionized calcium, serum osteocalcin, testosterone and dehydroepiandrosterone sulphate, and urinary hydroxyproline/creatinine ratio. RESULTS: Forearm mineral density was lower in the Klinefelter's group than in the control subjects (P less than 0.05) and below the control range in 5 patients. The fat content of the forearm was greater in the Klinefelter's group (P less than 0.002). Serum osteocalcin and testosterone were lower, while ionized calcium and the urinary hydroxyproline/creatinine ratio were higher in the Klinefelter's group (P less than 0.002). Serum dehydroepiandrosterone sulphate and testosterone were significantly related in the Klinefelter's group (r = 0.64, P less than 0.001), but not in the controls (r = 0.22, NS). Forearm mineral density and fat-corrected forearm mineral density were significantly related to serum testosterone in the Klinefelter's group (r less than 0.63; P less than 0.01), but not in the control subjects (r less than 0.03, NS). CONCLUSIONS: Decreased bone density occurs in about 25% of patients with Klinefelter's syndrome and probably reflects both decreased bone formation and increased bone resorption.

Adult

Relative contributions of years since menopause, age, and weight to vertebral density in postmenopausal women.

Vertebral mineral density (VMD) was measured by quantitative computerized tomography (QCT) in 16 premenopausal and 243 untreated postmenopausal women without vertebral compression. The mean VMD in the premenopausal group was 157 +/- 10.1 mg/mL, which is close to previously reported values. In the postmenopausal women, VMD fell significantly with age and years since menopause (YSM) separately and together, but the relation to YSM was more significant than that to age. After logarithmic transformation of YSM, the fall in bone density with logYSM was highly significant (P less than 0.001), and that with age was not quite significant. In 36 pairs of women matched for YSM, there was no significant difference in VMD between the subjects up to and over 55 yr of age. In 32 pairs matched for age, VMD was significantly lower in those over 55 yr than in those up to 55 yr (P = 0.005). There was also a significant correlation between VMD and body weight. After this was allowed for, the correlation between VMD and logYSM remained highly significant, but the correlation with age was not significant. We conclude that the fall in vertebral body trabecular bone in postmenopausal women is self-limiting, amounts to about 35% bone loss in 25 yr (most of it in the first 5 yr), and corresponds to but is proportionately greater than the trabecular component in postmenopausal forearm bone loss.

Adult

Indium-111-leukocyte and gallium-67 imaging in acute sarcoidosis: report of two patients.

Two young women with acute sarcoidosis underwent (111)In-labeled autologous leukocyte imaging because of persistent fevers. Images of one of the women demonstrated faint thoracic lymph node uptake of labeled cells, but no discrete focus suggestive of infection was seen. Images of the second woman were normal. Gallium-67 imaging, performed 48 hr after the leukocyte studies, revealed multiple areas of abnormal radiotracer accumulation corresponding to regions of active sarcoid in both women. These cases suggest that leukocyte imaging is not useful for assessing the extent of disease in patients with sarcoidosis. This technique may be valuable, however, in excluding superimposed infection in these individuals.

Acute Disease

Appreciation of pain in the elderly.

Pain was evaluated in 333 duodenal ulcer patients, and 86 myocardial infarction patients by the verbal rating scale method. We compared older patients (greater than 65 years of age) to younger controls and found a highly significant association between old age with mild pain and young age with moderate or severe pain in both diseases. We investigated two totally different diseases and got similar results. Thus, it could be concluded that age itself might be the underlying reason for the association with pain severity and not the character or origin of the pain.

Adult

Vasopressin in thermoregulation--competitive demands: experimental evidence and theoretical considerations.

Previous studies have substantiated the antipyretic role played by extrahypothalamic limbic system (EXHY-LS) AVP during fever. Repeated attempts to elucidate other thermoregulatory functions of this hormone have failed. Circumstantial evidence, however, suggest central role for this hormone in thermoregulation under hypohydration. Hypohydration, hyperosmolarity and hypovolaemia induced upward shifts in temperature thresholds for activation of heat dissipating mechanisms. When hypovolaemia is superimposed on hyperosmolarity these shifts are additive. Analogously, these two stressors when combined, decrease the osmotic threshold for AVP release. In rats, the elevated temperature thresholds for evaporative cooling and peripheral vasodilation occurring with hypohydration are positively correlated with lower Hypothalamic/EXHY-LS AVP ratio. Reciprocal relations between limbic system and blood AVP contents suggest competitive interaction between central and peripheral demands. Hypothesis for the possible mode of action of central AVP in thermoregulation under hypohydration is discussed.

Animals

Gastric emptying and intragastric distribution of oil in the presence of a liquid or a solid meal.

There is little information about gastric emptying of extracellular fat. A marker for liquid fat, 99mTc-(V)-thiocyanate, was used to compare gastric emptying and intragastric distribution of oil to that of aqueous liquid and solid meal components. Eight volunteers consumed 60 ml of 99mTc-labeled oil and 290 ml of 113m-In-labeled soup (total 505 kcal) on one day and 280 g 113mIn-minced beef (500 kcal), 60 ml 99mTc-labeled oil and 290 ml nonlabeled soup (505 kcal) on another day. In the oil/soup meal, gastric emptying of oil was slower than soup (50% emptying time 139.1 +/- 16.5 min versus 47.9 +/- 4.5 min, p less than 0.01). There was retention of oil in the proximal stomach (p less than 0.01) and retrograde movement of oil from distal into proximal stomach. In the oil/soup/beef meal, there was no difference in emptying of oil and beef from the total stomach (retention at 180 min 71.4% +/- 3.4% versus 58.3% +/- 7.6%, ns), but more oil was retained in the proximal stomach and more beef was retained in the distal stomach (p less than 0.01). The emptying rate of oil in the oil/soup meal was about twice that for oil consumed in the other meal. There was no difference between the two meals in the number of calories emptied in the first 180 min. These results demonstrate major differences in the intragastric distribution of oil compared to solid and aqueous liquid meals.

Adult

Cigarette smoking and rate of gastric emptying: effect on alcohol absorption.

OBJECTIVE: To examine the effects of cigarette smoking on alcohol absorption and gastric emptying. DESIGN: Randomised crossover study. SETTING: Research project in departments of medicine and nuclear medicine. SUBJECTS: Eight healthy volunteers aged 19-43 who regularly smoked 20-35 cigarettes a day and drank small amounts of alcohol on social occasions. INTERVENTIONS: Subjects drank 400 ml of a radiolabelled nutrient test meal containing alcohol (0.5 g/kg), then had their rates of gastric emptying measured. Test were carried out (a) with the subjects smoking four cigarettes an hour and (b) with the subjects not smoking, having abstained for seven days or more. The order of the tests was randomised and the tests were conducted two weeks apart. MAIN OUTCOME MEASURES: Peak blood alcohol concentrations, absorption of alcohol at 30 minutes, amount of test meal emptied from the stomach at 30 minutes, and times taken for 50% of the meal to leave the proximal stomach and total stomach. RESULTS: Smoking was associated with reductions in (a) peak blood alcohol concentrations (median values in non-smoking versus smoking periods 13.5 (range 8.7-22.6) mmol/l v 11.1 (4.3-13.5) mmol/l), (b) area under the blood alcohol concentration-time curve at 30 minutes (264 x 10(3) (0-509 x 10(3)) mmol/l/min v 140 x 10(3)) (0-217 x 10(3) mmol/l/min), and (c) amount of test meal emptied from the stomach at 30 minutes (39% (5-86%) v 23% (0-35%)). In addition, smoking slowed both the 50% gastric emptying time (37 (9-83) minutes v 56 (40-280) minutes) and the intragastric distribution of the meal. There was a close correlation between the amount of test meal emptied from the stomach at 30 minutes and the area under the blood alcohol concentration-time curve at 30 minutes (r = 0.91; p less than 0.0001). CONCLUSION: Cigarette smoking slows gastric emptying and as a consequence delays alcohol absorption.

Adult

Relationships between oesophageal transit and solid and liquid gastric emptying in diabetes mellitus.

In 87 randomly selected diabetic patients (67 type 1, 20 type 2) and 25 control subjects, gastric emptying of digestible solid and liquid meals and oesophageal transit of a solid bolus were measured with scintigraphic techniques. Gastrointestinal symptoms, autonomic nerve function and glycaemic control were evaluated in the diabetic patients. Gastric emptying and oesophageal transit were slower (P less than 0.001) in the diabetic patients compared with the control subjects, and each was delayed in about 40% of them. There was a relatively weak (r = 0.32; P less than 0.01) relationship between solid and liquid gastric emptying, and no significant correlation (r = 0.11, NS) between oesophageal transit and gastric emptying of the solid meal. Scores for upper gastrointestinal symptoms and autonomic nerve function correlated weakly (r = 0.21; P less than 0.05) with both oesophageal transit and gastric emptying. Gastric emptying of the liquid meal was slower (P less than 0.05) in patients with blood glucose concentrations greater than 15 mmol/l. These results indicate that gastric emptying in patients with diabetes mellitus should be assessed by liquid as well as by solid test meals and that oesophageal transit should not be used as a predictor of generalised diabetic gastroenteropathy.

Diabetes Mellitus