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Biomedical subjects

M Horowitz

Publications and source records attributed to M Horowitz.

At least 433 records · Page 24Linked to original sources
PubMed1988

Structural analysis of the human glucocerebrosidase genes.

Two different genomic clones containing the entire coding sequence of human glucocerebrosidase were isolated from a fetal liver library using a cDNA probe previously cloned by us. These clones correspond to two human glucocerebrosidase genes, designated 6-1 and 10-2. Clone 6-1 contains sequences homologous to the cDNA we cloned previously. The promoter regions of the genes were identified by S1 analysis and sequenced. They contain TATA- and CAAT-like boxes, but lack a GGCGGG motif. When coupled to the bacterial gene coding for chloramphenicol acetyl transferase (CAT) and transfected to Gaucher skin fibroblast lines, both promoter fragments enhanced CAT activity. The promoter of gene 6-1 was eight times more efficient than the promoter of gene 10-2. Northern blot analysis revealed three human glucocerebrosidase RNA species of 6, 2.6, and 2.2 kb in size. The 6-kb transcript is probably a nuclear transcript whereas the 2.6-kb and 2.2-kb transcripts are cytoplasmic species which emerge from polyadenylation at different sites.

Base Sequence↗
PubMed1988

Glucagon antagonism of calcium channel blocker-induced myocardial dysfunction.

Calcium channel blockers (CCBs) may produce profound myocardial depression. Glucagon antagonized verapamil-induced hypotension and bradycardia in rats; however, glucagon's ability to antagonize other CCBs is unexplored. This study determined: a) if glucagon reverses verapamil-induced depression by a direct cardiac effect, b) if myocardial depression induced by diltiazem and nifedipine (representing different classes of CCBs) is also reversed by glucagon, and c) the glucagon concentration needed to reverse myocardial depression. Isolated rat hearts were perfused at a constant flow rate in a Langendorff preparation. Developed pressure (dP), contractility (+dP/dtmax), relaxation (-dP/dtmax), heart rate, and coronary vascular resistance were recorded. A CCB (n = 6, each blocker) was infused until greater than 50% depression of contractility was achieved. Glucagon was then simultaneously infused (perfusion concentration of 0.6-1.1 x 10(-7) M), and repeat cardiac variables were recorded. In a separate group of 36 hearts, glucagon dose response was determined. After producing a greater than 50% depression in dP/dtmax with 3 mumol of diltiazem, a single concentration of glucagon was infused simultaneously into each heart (perfusion concentrations between 10(-6) and 10(-9) M) and percent recovery of baseline function was determined. Glucagon restored baseline contractility and dP with all three CCBs. Complete reversal of diltiazem-induced myocardial depression occurs at glucagon concentrations greater than or equal to 5 x 10(-7) M. We conclude that a) glucagon directly reverses myocardial depression from three classes of CCBs at concentrations achieved in vivo, and b) glucagon may be useful in the treatment of CCB-induced myocardial toxicity.

Animals↗
PubMed1988

Open reduction and internal fixation of volar lip fractures of the distal radius.

Fractures of the volar lip of the distal radius are relatively uncommon injuries. However, controversy exists concerning the treatment of these fractures. We reviewed our experience with open reduction and internal fixation through a volar approach using buttress plates. Sixteen patients with 17 fractures were treated by this method. Their ages ranged from 16 to 65 years (average 38 years). Eight fractures occurred secondary to motor vehicle accidents, while the remaining patients sustained falls. Mean follow-up time was 19.5 months. All fractures healed with no infections. Sixteen of the fractures were treated primarily with open reduction and internal fixation, while one patient was treated 6 weeks after injury for a malunion. Ranges of motion averaged 71 degrees dorsiflexion, 60 degrees palmar flexion, 79 degrees pronation, 78 degrees supination, 22 degrees radial deviation, and 32 degrees ulnar deviation. Analysis of results demonstrated 12 excellent, 2 good, and 3 fair results. Two patients with fair results had nonanatomic restoration of the joint surface at surgery, while the other patient with a fair result was treated late. We recommend early open reduction and internal fixation of displaced or unstable volar lip fractures of the distal radius. Accurate anatomic alignment and stable fixation are achieved with the volar buttress plate. Motion can begin 2-3 days after surgery to aid in obtaining excellent functional results.

Adult↗
PubMed1988

Keratinocyte derived T-cell growth factor (KTGF) is identical to granulocyte macrophage colony stimulating factor (GM-CSF).

Keratinocyte derived T-cell growth factor was initially described as a product of cultured neonatal keratinocytes and keratinocyte cell lines that induced the proliferation of HT-2 cells, a murine T-cell line that responds to IL-2 and IL-4 by incorporating 3H-Thymidine. Subsequently, KTGF has been purified to high specific activity and found to be distinct from IL-2 and IL-4 by a variety of biochemical, immunologic, and immunochemical criteria. Because it was found that certain HT-2 cell lines also proliferated in response to GM-CSF, the present study asked whether KTGF was related to GM-CSF. In this study, we demonstrate that antibodies to recombinant murine GM-CSF completely neutralize the capacity of KTGF to induce HT-2 proliferation without interfering with IL-2 or IL-4 induced HT-2 proliferation. Furthermore, poly-A+ RNA homologous to murine GM-CSF cDNA as judged by S1 nuclease analysis was detected in Pam 212 cells, and protein serologically homologous to GM-CSF was found in Pam 212 conditioned medium. We conclude that KTGF is identical to GM-CSF. The T-cell activating properties of GM-CSF require further exploration.

Colony-Stimulating Factors↗
PubMed1988

Stimulation of pyloric motility by intraduodenal dextrose in normal subjects.

Recent studies suggest that the pylorus may play an important role in the regulation of the gastric emptying of nutrient liquids in man. Dextrose solutions in the range 5-25 g/dl have been reported to empty from the human stomach at a constant caloric rate of 2.1 kcal/min. This study examined, in 12 healthy volunteers, the effects of intraduodenal dextrose on pyloric motility. Dextrose solutions, 5, 10, 15, and 25 gde/dl and saline solutions, 0.9 and 2.7 g/dl were infused into the duodenum at 4 ml/min for 10 minutes. Antral, pyloric, and duodenal motility were monitored with sideholes and a sleeve sensor positioned across the pylorus. Significant increases in the rate of isolated pyloric pressure waves and in basal pyloric pressure were seen with 15 and 25 g/dl dextrose (p less than 0.02) and 2.7 g/dl saline (p less than 0.05). The intensity and duration of the phasic and tonic pyloric motor responses to intraduodenal dextrose were dose dependent and correlated directly with the rate of calorie delivery (p less than 0.005 for each parameter). Intraduodenal delivery of dextrose at a rate in excess of 2.1 kcal/min stimulates both phasic and tonic pyloric contraction. These changes in pyloric motility may contribute to the close regulation of the emptying of dextrose from the stomach.

Adolescent↗
PubMed1988

Effect of ICS 205-930 (a specific 5-HT3 receptor antagonist) on gastric emptying of a solid meal in normal subjects.

The effects on gastric emptying of a solid meal of the specific 5-HT3-receptor antagonist ICS 205-930, 10 mg and 20 mg intravenously were assessed with a scintigraphic technique in 12 normals. The 50% emptying time was less, the lag phase was shorter and the post lag emptying rate was faster after 20 mg ICS 205-930 (p less than 0.02). After 10 mg ICS 205-930 the lag phase was significantly shorter compared with placebo (p less than 0.04). These results suggest that 5-HT3 receptors may be involved in the regulation of gastric emptying in man.

Adult↗
PubMed1988

Antropyloroduodenal motor responses to intraduodenal lipid infusion in healthy volunteers.

The delivery of lipid to the duodenum has been shown to slow gastric emptying and to increase the resistance to gastric outflow. To investigate mechanisms responsible for these effects, we have recorded antropyloroduodenal motility in nine healthy volunteers during alternate intraduodenal infusions of normal saline and triglyceride emulsion (Intralipid 10%). During the lipid infusions there were reproducible, major changes in the patterns of motility. Pressure waves, apparently isolated to the pylorus, usually started within 10 min of initiation of the lipid infusion. After 20-25 min of lipid infusion these waves occurred at median rates of 2.4 and 2.8/min (1st and 2nd lipid infusions, respectively); these rates were significantly greater (P less than 0.05) than the median rates (all less than or equal to 0.4/min) observed during the equivalent period of the succeeding saline infusions. During 10 of 22 lipid infusions, isolated pyloric pressure waves were associated with sustained pyloric tone. Infusion of lipid into the duodenum suppressed antral pressure waves in all subjects and initiated brief periods of regular duodenal contractions during 11 of 22 infusions. These studies have demonstrated alterations of antropyloroduodenal motor patterns in response to changes in the duodenal luminal content. The effects on antral and pyloric motility are probably of importance in the regulation of transpyloric flow by nutrients in the duodenal lumen.

Adult↗
PubMed1988

Cardiac output distribution in thermally dehydrated rodents.

The effect of thermal dehydration (37 degrees C) on the integrated response of the circulation was studied in conscious laboratory rats and in the desert species Psammomys obesus, the latter being studied prior to and following acclimation to heat. Cardiac output (CO) and its distribution were measured using labeled microspheres with the reference organ technique. At low dehydration (7-9% body wt loss) rats showed peripheral vasodilation coincidentally with splanchnic vasoconstriction, whereas the desert species exhibited an increased CO and peripheral vasodilation with no change in splanchnic blood perfusion. At severe dehydration (10-18% body wt loss), closure of skin arteriovenous anastomoses together with splanchnic vasodilation was observed in both species. These changes were discussed in relation to plasma volume conservation mechanism and its deterioration. Acclimation to heat resulted in no change in CO, whereas blood flow to splanchnic and skin capillaries increased remarkably. Dehydration in heat-acclimated P. obesus (5-10% body wt loss) brought about a significant fall in CO. However, most organs maintained relatively stable blood flow. This might contribute to better survival during heat stress.

Adaptation, Physiological↗
PubMed1988

Proximal, distal and total stomach emptying of a digestible solid meal in normal subjects.

The gastric fundus and antrum probably play different roles in the emptying of solids and liquids in man, but there is little information about the intragastric distribution of food. We have used a new radionuclide technique to quantify proximal, distal and total stomach emptying of a digestible solid meal (100 g of 99Tcm-labelled liver/ground beef given with 150 ml of 10% dextrose) in 13 normal subjects. A proximal reservoir area was seen after consumption of the meal, and used to define the proximal stomach region. A line drawn immediately below this area divided the total stomach region into proximal and distal stomach. Emptying from the total stomach exhibited two phases--an initial lag period (median 41 min, range 21-57 min), followed by approximately linear emptying. Redistribution of food from the proximal to the distal stomach was a major component of the lag period in 11 of the 13 subjects. In the remaining two subjects, redistribution was rapid (proximal 50% emptying time of 4 and 10 min) and antral retention was the major component of the lag period. In seven subjects, a region of reduced activity (contraction band) was seen. The midpoint of this band closely approximated to the line used to divide proximal and distal stomach. We suggest that a contraction band may be responsible for the proximal gastric reservoir seen after meal consumption and plays an important role in the redistribution and emptying of digestible solid food from the stomach. There is considerable variation between normal subjects in the rate of transfer of digestible solid food from the proximal to the distal stomach.

Adult↗
PubMed1988

Pulmonary nodules resembling bronchioloalveolar carcinoma in adolescent cancer patients.

Pulmonary nodules morphologically indistinguishable from bronchioloalveolar carcinoma (BAC) were found in two adolescent cancer patients postchemotherapy. A solitary nodule was noted at thoracotomy for a single computerized tomography (CT) scan lesion in a 16-yr-old male, 6 yr after diagnosis of Ewing's sarcoma. A similar nodule was found in a 19-yr-old male coincident with resection of multiple lung metastases of a testicular germ cell tumor. Both lesions were discrete nodular masses (1 cm and 0.5 cm) consisting of atypical epithelial cells with a papillary and lepidic growth pattern and surrounded by histologically normal appearing lung. Immunohistochemistry of both cases was positive for laminoorganel (LO) antigen, which is found in normal type II pneumocytes, and one nodule showed carcinoembryonic antigen (CEA) staining. Quantitative DNA analysis in one case indicated aneuploidy. Thus the morphology, immunohistochemistry, and DNA content of these lesions suggest that they may represent early lung cancers despite the highly unusual clinical context. The extreme rarity of BAC in this age group makes this report significant in light of heightening concern about second malignancies in pediatric cancer patients and reports of chemically induced pulmonary adenomas in mice. It also underscores the importance of basing therapeutic decisions on a histologic diagnosis of lung nodules in cancer patients rather than assuming the presence of metastatic disease.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1988

Biochemical effects of calcium supplementation in postmenopausal osteoporosis.

Although calcium supplements are widely used in the treatment of osteoporosis their beneficial effect is not conclusively established. The biochemical effects of a calcium supplement (1 g/d) given for between 6 and 36 months were studied in 20 postmenopausal osteoporotic women who had normal calcium absorption. The mean fasting urinary hydroxyproline/creatinine ratio decreased from 0.024 +/- 0.002 to 0.016 +/- 0.001 (P less than 0.005) indicating a significant reduction in bone resorption. The mean plasma alkaline phosphatase fell from 85 +/- 4 U/l to 73 +/- 3 U/l (P less than 0.005), probably representing a secondary reduction in bone formation following the inhibition of bone resorption. There was no significant change in calcium absorption. These results support the concept that calcium supplementation is useful in the treatment of postmenopausal osteoporosis.

Alkaline Phosphatase↗
PubMed1988

Radiation enteritis.

Damage to the intestine occurs frequently as a result of abdominal or pelvic radiation treatment, and chronic radiation enteritis is a cause of significant morbidity and mortality. This review focuses on advances in knowledge which may be applied to the treatment and prevention of radiation enteritis.

Acute Disease↗
PubMed1987

Autocrine growth of T cells independent of interleukin 2: identification of interleukin 4 (IL 4, BSF-1) as an autocrine growth factor for a cloned antigen-specific helper T cell.

Interleukin 4 (IL 4), formerly known as B cell stimulatory factor 1 (BSF-1), has recently been described as a growth factor for T cells. The role of IL 4 in the putatively IL 2-independent growth of certain cloned T helper cells is unclear. D10.G4.1 (D10) is a conalbumin-specific helper T cell that has been employed extensively in the analysis of T cell activation and as an assay for the detection of IL 1. Previously, it was thought that IL 1 induced the expression of IL 2 receptors on D10 cells, thereby permitting D10 to proliferate in response to endogenously produced IL 2. However, we cannot detect IL 2 mRNA or protein in D10 cells or their supernatants as determined by the following criteria: monoclonal antibodies that neutralize the in vitro activity of murine IL 2 do not block the IL 1-dependent proliferation of D10 cells; no competitive binding for high-affinity IL 2 receptors with 125I-labeled IL 2 can be detected with medium conditioned by activated D10 cells; and Northern blot analysis and S1 nuclease protection assays, performed with cDNA probes for IL 2, do not detect mRNA for IL 2 under a variety of different activation conditions that foster autocrine growth of D10 cells. In contrast, activated D10 cells produce both IL 4 mRNA and protein as judged by similar criteria. Purified IL 4 has significant TCGF activity as measured by proliferation of HT-2 cells. This activity can be blocked completely by a monoclonal antibody to IL 4 (11B11). The proliferation of D10 cells in the presence of 3D3 (a clonotype-specific monoclonal anti-T cell receptor antibody) and IL 1 can be blocked completely by 11B11 antibody. Highly purified IL 4 alone cannot induce the proliferation of resting D10 cells; however, equivalent amounts of IL 4 in the presence of recombinant IL 1 induce significant D10 proliferation. Therefore, IL 1 appears to render D10 cells responsive to their autocrine growth signal. These data indicate that IL 4 serves as the autocrine T cell growth factor for D10 cells, and that exogenous IL 1 is required for the transduction of this growth signal. This may represent a more broadly applicable mechanism for the growth of certain subsets of T helper cells.

Animals↗