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Biomedical subjects

M Horowitz

Publications and source records attributed to M Horowitz.

At least 505 records · Page 28Linked to original sources
PubMed1985

Chromosome 1 abnormalities: a common feature of pediatric solid tumors.

Abnormalities of chromosome 1 were found in 32 of 46 pediatric solid tumors including Ewing's sarcoma, Wilms' tumor, rhabdomyosarcoma, primitive neuroectodermal tumor, and hepatoblastoma. Trisomy of 1q was the most common abnormality, and breakpoints were most frequent in the region 1cen to 1p22. Abnormalities of chromosome 1 are not specific to any type of tumor. However, their frequent occurrence indicates that they may endow a clonal advantage in the development of cancer.

Aneuploidy↗
PubMed1985

1,25-Dihydroxycalciferol and calcium therapy in osteoporosis with calcium malabsorption. Dose response relationship of calcium absorption and indices of bone turnover.

We have studied some effects of small doses of 1,25-dihydroxycalciferol (calcitriol) and calcium, either combined or separately, in 45 patients with osteoporosis and malabsorption of calcium. In 24 patients on 0.25 micrograms/d of calcitriol the hourly fractional rate of radiocalcium absorption rose from 0.37 +/- 0.02 to 0.55 +/- 0.04 (p less than 0.001) and in 21 patients on 0.50 micrograms/d it rose from 0.36 +/- 0.02 to 0.69 +/- 0.05 (p less than 0.001). These responses were seen within 5 days and were not increased further at 6 weeks to 3 months. The combined therapy significantly reduced the fasting urinary hydroxyproline/creatine ratio (OHPr/Cr) and plasma alkaline phosphatase activity (ALP) in 6-12 weeks, the smaller dose of calcitriol (0.25 micrograms/d) being as effective as the larger one (0.50 micrograms/d) in this respect. Calcium alone (1 g/d) had no effect and calcitriol alone (0.25 mcg/d) had a lesser effect on both OHPr/Cr and ALP than the combined therapy. The falls in OHPr/Cr and ALP tended to be greatest in the cases with the highest initial levels but constituted only partial suppression of these variables towards the theoretical non-bone components. These results suggest that treatment with calcitriol and calcium suppresses bone resorption in osteoporosis associated with malabsorption of calcium and is more effective than calcium or calcitriol given alone.

Alkaline Phosphatase↗
PubMed1985

Disorders of gastric emptying in humans and the use of radionuclide techniques.

Associated with the development of methods to quantify gastric emptying, there has been an increased understanding of the physiology of gastric emptying in normal subjects and the pathophysiology and pharmacological treatment of gastric emptying disorders. The measurement of gastric emptying, using radionuclide-labeled food markers and a scintillation camera, has widespread clinical and research applications.

Barium Sulfate↗
PubMed1985

New approaches to the problems of osteoporosis.

Professor Urist's contributions to the understanding of osteoporosis are worthy of reevaluation at this time, when interest in the field has reached unprecedented heights. Recent advances in technology have greatly increased our understanding of osteoporosis by showing that there is no loss of bone in normal premenopausal women, and that the loss which starts at the menopause can be attributed to an increase in bone resorption. It is suggested that the primary event is a rise in plasma calcium that leads to a rise in obligatory urinary calcium loss, which in turn increases the calcium requirement. The subset of the postmenopausal population who develop fractures (particularly in the spine) show additional risk factors, which include malabsorption of calcium (which further increases bone resorption) and reduced adrenal androgen production (which may produce a fall in bone formation). The treatment of established cases requires control of bone resorption by calcium supplementation and/or hormone therapy, with the addition of calcitriol if malabsorption of calcium is present. Stimulation of bone formation is more difficult, but there is a suggestion that this may be possible with the use of anabolic steroids.

17-Ketosteroids↗
PubMed1985

Regional measurements of [14C]misonidazole distribution and blood flow in subcutaneous RT-9 experimental tumors.

Regional [14C]misonidazole-derived radioactivity (MISO*) was measured by quantitative autoradiography in s.c. RT-9 experimental tumors 0.5, 2, and 4 h after an i.v. bolus (25 mg) and constant infusion (10 mg/h) in rats. Misonidazole (MISO) concentration in plasma, tumor, and other tissues was also measured by high-pressure liquid chromatography. The distribution of MISO* in the tumors always resulted in a characteristic pattern with high peripheral and low central values. The high-activity regions in the tumor rim achieved tissue: plasma MISO* activity ratios of 0.97 and 2.2 by 0.5 and 4 h, respectively; for central tumor regions, this ratio was 0.20 and 0.32 for the same periods, respectively. The limited distribution of MISO* to central tumor regions could be correlated to low values of blood flow (measured with [131I]iodoantipyrine) and to diffusion from peripheral tumor regions. Low blood flow in the central regions of these tumors will significantly limit the distribution of MISO and other drugs to viable-appearing cells in these areas and could account in part for the failures of chemotherapy in certain solid tumors. Pharmacokinetic modeling indicates that 1 to 9 h may be necessary for MISO concentrations in some tumor regions to reach 50% of that in plasma.

Animals↗
PubMed1985

Combination of dacarbazine and doxorubicin in the treatment of childhood rhabdomyosarcoma.

The combination of dacarbazine and doxorubicin was given to 26 children with untreated rhabdomyosarcoma to determine its efficacy as front-line chemotherapy. A treatment course consisted of 250 mg/m2 of dacarbazine given iv on Days 1-5 and 60 mg/m2 of doxorubicin given iv on Day 1. After three courses of therapy, 17 patients (65%) achieved partial response and nine failed to respond. The side effects of treatment consisted of nausea, vomiting, flu-like symptoms, neutropenia associated with fever, mucositis, and thrombocytopenia (rarely). Although the response rate is comparable to other drug combinations, the lack of complete responses to the combination indicates that it is less effective as front-line therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Mechanism of activation of the mouse c-mos oncogene by the LTR of an intracisternal A-particle gene.

In the mouse myeloma XRPC-24 the DNA of an intracisternal A-particle (IAP) is inserted within the coding region of c-mos. This insertion splits the c-mos into a 3' rc-mos and a 5' rc-mos separated by approximately 4.7 kb of IAP DNA. The insertion is in a head-to-head orientation and brings the 5' LTR of the IAP in juxtaposition to the 3' rc-mos such that the IAP and the 3' rc-mos are transcribed in opposite directions. The intact c-mos gene is usually dormant, whereas the 3' rc-mos is actively transcribed and is capable of transforming NIH3T3 cells. In an effort to understand the nature of this activation we mapped the 5' ends of the 3' rc-mos mRNA present in XPRC-24. We found two main mRNA start sites, one mapping to the junction of the 3' rc-mos and the 5' LTR, and the other located 10 nucleotides upstream to this junction, within the 5' LTR. This result indicates that the 3' rc-mos in XRPC-24 was activated by insertion of a promoter provided by the LTR of an IAP genome. Furthermore, the 5' LTR appears to possess promoter activities in two directions. This conclusion was confirmed by the fact that this 5' LTR, in both orientations, was able to activate the bacterial gene coding for chloramphenicol acetyltransferase (CAT) in the modular vector pSVOCAT.

Acetyltransferases↗
PubMed1984

Gastric emptying after gastroplasty for morbid obesity.

Gastric emptying was studied in 11 patients who had undergone gastroplasty for morbid obesity 6 to 8 months previously and in 22 normal controls without gastrointestinal disease. A dual isotope technique for measuring solid and liquid emptying was used. Liquid emptying was slower in patients than controls. The emptying of solid was initially faster, but was followed by a prolonged slow rate of emptying indicating retention of solid food in the proximal partitioned pouch. There was no correlation between the weight loss produced by the operation and rates of solid or liquid emptying. Unlike gastric bypass, the changes in gastric emptying produced by gastroplasty were relatively small and gastric emptying rates in patients overlapped considerably with the range of emptying rates found in control subjects. The success of the procedure may depend on the induction of satiety by the filling of the partitioned pouch.

Adult↗
PubMed1984

Effect of plasma volume on thermoregulation in the dog.

Panting thresholds, plasma volume (PV) changes and cardiac filling pressure were studied during thermal dehydration in control, water deprived (WD) and hypovolemic (PEG) dogs. WD and PEG dogs showed a delayed panting threshold, apparently due to hypovolevoia. Initiation of heat stress however resulted in a transient plasma expansion in all dogs. Cardiac filling pressure did not change.

Animals↗
PubMed1984

Changes in gastric emptying rates with age.

A dual isotope technique which measures simultaneously the emptying of solids and liquids by the stomach was used to study gastric emptying in 35 subjects in the age range 21-84 years, who were all fit, mobile volunteers and were not taking any drugs. Solid and liquid emptying were significantly slower in older subjects, but this finding is unlikely to be of clinical significance because the changes were small and emptying rates were usually within the normal range for younger subjects.

Adult↗
PubMed1984

Thymus-derived lymphocytes and their interactions with macrophages are required for the production of osteoclast-activating factor in the mouse.

A bone-resorbing factor, comparable to the osteoclast-activating factor (OAF) produced from peripheral blood leukocytes, is shown to be produced by murine spleen cells activated with the T-cell mitogen Con A. Murine OAF is demonstrated here as being a product of the interaction between thymus-derived T lymphocytes and macrophages. Activation of T cells in the presence of macrophages with Con A yields culture supernatants with OAF activity. This OAF activity is not dialyzable and is not extracted by lipid solvents. Purified B cells in the presence or absence of macrophages and cocultured with Con A or activated with the B-cell-specific mitogen lipopolysaccharide yield culture supernatants with no detectable OAF activity. Similarly, macrophages cocultured with Con A or activated with lipopolysaccharide fail to yield culture supernatants with bone resorbing activity. These types of immune cell interactions are similar to that required for the production of lymphokines. These data support the hypothesis that one aspect of regulation of bone remodeling is through cells of the immune system.

Animals↗
PubMed1984

Effect of calcium supplementation on urinary hydroxyproline in osteoporotic postmenopausal women.

Although calcium supplements are widely used to reduce bone resorption in osteoporosis, their beneficial effect is not conclusively established. We studied the effect of a calcium supplement (1 g/day for 8 days) in 14 postmenopausal osteoporotic women. The fasting urinary hydroxyproline/creatinine ratio decreased from 0.022 +/- 0.001 to 0.017 +/- 0.001 (p less than 0.005) indicating a significant reduction in bone resorption. Both the tubular maximum for phosphate reabsorption (1.12 +/- 0.06 to 1.34 +/- 0.07, p less than 0.005) and plasma phosphate concentration (1.04 +/- 0.04 to 1.14 +/- 0.04, p less than 0.01) increased, consistent with suppression of parathyroid hormone activity. These results support the concept that calcium supplementation is useful in the treatment of postmenopausal osteoporosis.

Aged↗
PubMed1984

The effect of omeprazole on gastric emptying in patients with duodenal ulcer disease.

The effect of a single oral dose of omeprazole (90 mg) on gastric emptying was assessed with a dual isotope scintigraphic technique in eight patients with a history of duodenal ulcer disease. Omeprazole had no significant effect on solid or liquid gastric emptying. The bioavailability (AUC0-2 h) of omeprazole in all patients was greater than that required for total suppression of acid secretion. No adverse clinical or laboratory effects were observed.

Adult↗
PubMed1984

Hypopituitarism associated with myalgia.

A patient with panhypopituitarism who presented with muscle pain and stiffness is described. These symptoms responded rapidly to treatment with thyroxine and cortisone acetate. The association between muscle disease and hypopituitarism is briefly reviewed.

Humans↗
PubMed1984

Immobilization hypercalcaemia with severe bone mineral loss and hypogonadism.

Moderate hypercalcaemia occurred in a 17-year-old male who was immobilized with abdominal and right hip sepsis for 9 months after a motor vehicle accident. The hypercalcaemia was due to bone resorption, with a urine hydroxyproline:creatinine ratio of 0.203 (normal less than 0.017) and a urine calcium loss of 22.9 mmol/24 hr, associated with impaired renal function. There was radiological evidence of severe bone demineralization in the pelvis over 42 weeks. Radiocalcium absorption, using 47Ca, was decreased (0.17, normal range 0.35-1.30), renal tubular maximum for calcium reabsorption was decreased (1.61 mmol/1 glomerular filtrate, normal range 1.8-2.2), the serum parathyroid hormone concentration was in the low normal range (3.2, 3.6 u/l, normal range 2-6) and the plasma 1,25-dihydroxy-vitamin D concentration was decreased despite a normal 25-hydroxy-vitamin D concentration, indicating suppression of the parathyroid, 1,25-dihydroxy-vitamin D axis. The patient was found to be hypogonadal at 41 weeks after admission and testosterone therapy was begun, with associated improvement in mobilization and a reduction of the hypercalcaemia.

Adolescent↗