[Metalloproteinases and their inhibitors: the importance of extracellular matrix degradation in malignancy].
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Biomedical subjects
Publications and source records attributed to B Sela.
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Hypertension is one of the most important risk factors for cardiovascular morbidity and mortality. Recently it has been suggested that the amino acid homocysteine contributes to this process. This study evaluates whether elevated plasma levels of homocysteine in hypertensive patients are associated with increased risk for cardiovascular events. Fifty hypertensive patients with a documented history of cerebral or cardiac events were age and gender matched to 50 hypertensive patients with no evidence of any cerebral or cardiac event. Demographic details, duration of hypertension, presence of other risk factors, and use of antihypertensive medications were recorded for each patient. Plasma levels of homocysteine were measured by high-performance liquid chromatography technology. The two groups had similar demographic parameters, with a mean age of 64.6 +/- 9.4 years. Patients with cardiovascular events were more likely to be past smokers and to have been treated with calcium antagonists, aspirin, and nitrates. Homocysteine levels were 12.1 +/- 5.8 micromol/L in those with documented cardiovascular disease and 11.1 +/- 4.7 micromol/L in those without (P = NS). Levels of plasma homocysteine were higher in those with hypercholesterolemia (P = .03) and in smokers, and tended to be lower in those who used beta-blockers, angiotensin converting enzyme (ACE) inhibitors, diuretics, and nitrates. Thus, hyperhomocysteinemia is not a feature of hypertensive patients with atherothrombotic events and there is no support for additive or synergistic effects between these two independent risk factors.
OBJECTIVE: To investigate fibronectin levels in urine samples from patients with noninvasive transitional cell carcinoma (TCC) of the bladder immediately and for 4 weeks after transurethral resection of bladder tumour (TURBT), to determine whether soluble fibronectin within the bladder, which blocks the attachment of bacillus Calmette-Guérin (BCG), might lower the efficacy of BCG therapy over this period. PATIENTS AND METHODS: Urinary fibronectin was measured using an enzyme-linked immunosorbent assay in 25 patients with superficial bladder TCC who underwent TURBT for complete resection. Eight samples were collected for each patient, one before and seven during the 4 weeks after TURBT. RESULTS: High levels of urinary fibronectin were detected in 18 patients (72%) after TURBT. In 16 patients the fibronectin level returned to normal within 2 weeks of surgery. The other two patients showed elevated levels of fibronectin for > 4 weeks. CONCLUSIONS: These results show that urinary fibronectin concentration is significantly increased in most patients after TURBT and this should be considered in patients who receive BCG therapy. Treatment within the first 2 weeks after TURBT may be associated with a high failure rate, as urinary fibronectin levels were increased significantly in about three-quarters of these patients during that period. Indeed, the persistent elevation of fibronectin, occurring in two of the present patients, may be responsible for some of the failures of BCG therapy when it is administered 2-5 weeks after surgery.
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Nutritional sodium, potassium and calcium are considered to be important regulators of blood pressure (BP). The present study evaluates the effects of combined low-sodium (LS), high-potassium (HK), high-calcium (HCa) diet on BP in patients with mild essential hypertension. Thirty-six patients (26 M, 10 F), 24-67 years of age (mean 46 +/- 8), participated in the study. Patients were divided into three groups and given a diet consisting of three 1-month segments, which they followed in different order. Group 1 (n = 11) received LS diet followed by the addition of HCa and then HK. The order in Group 2 (n = 12) was HK-LS-HCa; and in Group 3 (n = 13) it was HCa-HK-LS. The third month of the study all patients were eating a combined LS, HK and HCa diet. Urinary electrolytes were measured to confirm compliance with the diets. After 1 month of the LS diet urinary sodium excretion decreased significantly by 25 mmols/day (95% CI, 1-48 mmols/day); (P < 0.05). Eighteen patients did not comply with the diet. Systolic BP (SBP) only slightly decreased, from 142 mm Hg (95% CI, 137-146 mm Hg) to 138 mm Hg (95% CI, 133-142 mm Hg); (P = 0.11). The change in SBP was related to the change in urinary sodium excretion (R = 0.46; P = 0.006). After 1 month of the HK diet, urinary potassium excretion increased by only 5 mmols/day (P = NS). BP was unaffected by HK and HCa diet. At the end of the study, urinary sodium excretion decreased from 183 mmols/day (95% CI, 155-211 mmols/day) to 148 mmols/day (95% CI, 131-165 mmols/day); (P < 0.05), urinary potassium excretion slightly increased from 75 mmols/day (95% CI, 68-82 mmols/day) to 85 mmols/day (95% CI, 76-94 mmols/day); (P = 0.09), and urinary calcium excretion remained unchanged. BP did not decrease. It is concluded that only the LS diet may be advantageous in patients with mild essential hypertension.
AIM: To evaluate the influence of the intravenous injection of iodine during cardiac catheterisation, and of topical iodine antiseptics during surgical procedures, on thyroid function in full term neonates. METHODS: Twenty one full term infants with major cardiac anomalies who survived for more than a month were studied. Thyroxine and thyrotropin concentrations were measured (by radioimmunoassay) before each procedure, 24 hours after the procedure, and every week thereafter until the age of 1 month or until normal. Thyroxine values less than 64.4 nmol/l were considered low, while thyrotropin values greater than 30 mU/l were considered high. RESULTS: Thyroid function tests before iodine exposure were within normal limits in all infants. Following catheterisation or surgery six infants had raised thyrotropin concentrations; three had low thyroxine concentrations. Two of those infants were treated with L-thyroxine. CONCLUSION: Iodine exposure during cardiac catheterisation or surgery may induce transient hypothyroidism in term infants.
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A 20-month old infant, who had short bowel syndrome following extensive surgery for a mid gut volvulus, developed hyperchloremic acidosis, with a large anion gap after enteral feeding was instituted. The organic acidosis was at least partly due to an increased concentration of D-lactic acid. This patient, as did five other pediatric patients, presented with a typical encephalopathy syndrome. Early recognition of this syndrome and treatment with an intestinal antibiotic and discontinuation of enteral feeding enabled prompt correction of the hyperchloremic acidosis and a rapid clinical recovery.
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Tumor progression, lung metastasis, and death occur in tumor-bearing BD IX syngeneic rats in a fashion similar to the course of patients with metastatic colon cancer. In an effort to establish a relevant model for monoclonal antibody (MoAb) therapy of tumors, we generated murine MoAb against DHD/TR, a dimethylhydrazine-induced rat colon carcinoma which has been adapted to cell culture. Murine MoAb 17B10 E4 (E4) reacts with the TR tumor and shows weak immunoperoxidase reactivity with normal rat tissues. Murine MoAb 5F7 D3 (D3) reacts with the tumor and a variety of normal rat epithelia. Both are IgG2a and mediate cytotoxicity by rat peripheral blood mononuclear cells. 18D5 F6 (F6) also reacts with the tumor and normal tissues but is an IgG2b and does not mediate cytotoxicity in the presence of rat effector cells. Iodinated E4 and D3 antibodies retained their immunoreactivity. E4 revealed 9.8 x 10(5) antigenic sites per TR cell, with an affinity constant of 9.35 x 10(7) M-1, while D3 demonstrated 2.5 x 10(6) antigenic sites and an affinity constant of 4.2 x 10(7) M-1. Immunoblotting showed that the antigens recognized by D3 and E4 are glycoproteins with molecular weights of 27,000 and 66,000, respectively. F6 failed to react with its antigen present in the blot. This rat colon carcinoma and the monoclonal antibodies described here may provide experimental data useful for implementing monoclonal antibodies in cancer therapy.
A morphological survey of the central nervous system of a NCTR-Balb/C mouse afflicted by neurovisceral storage disease was performed. It has been demonstrated that this mutant is characterized by primary dysmyelination, which is evident as early as 12 days of age. The failure of myelin formation in the CNS was shown by histochemical and ultrastructural methods. Inasmuch as neither lipid-containing macrophages nor infiltrating mononuclear cells were apparent, secondary demyelination could be excluded. The multiform ultrastructural appearance of the storage material in the various CNS cell types suggested heterogeneity of the accumulated substances. The storage materials which reacted positively with periodate-Schiff reagent, but not with other histochemical stains, are most likely the accumulated gangliosides and neutral glycosphingolipids identified previously in this mutant's brain. Considering the probable role of cholesterol ester in the early phases of myelinogenesis, in conjunction with the fact that the NCTR-Balb/C mouse carries a defect in the esterification of exogenously derived cholesterol, it is possible that the later metabolite is relevant to the impaired myelin formation.
The interaction of myelin basic protein with monosialoganglioside GM1 was investigated. It was found that the emission maximum of the tryptophan of the protein is blue-shifted due to the interaction. In mixtures of the monosialoganglioside with phosphatidylcholine, the myelin basic protein induces phase separation of the lipids as inferred from differential scanning calorimetry experiments.
Morphological and biochemical studies were performed on the CNS of neurologically affected NCTR-Balb/C mouse. Histological and electron microscopic techniques demonstrated severe myelin deficiency in the affected brains. Neither the presence of lipid-containing macrophages nor reactive gliosis was apparent. Analysis of myelin-associated lipids and proteins revealed prominent depletion of galactocerebroside, sulfatide, and proteolipid proteins. In contrast to the scarcity of myelin-specific constituents a marked accumulation of GM2 and GM3 gangliosides and several neutral glycolipids, i.e., glucocerebroside, lactosylceramide, gangliotriaosylceramide, and gangliotetraosylceramide were found in affected CNS. These abnormalities were already apparent in 12-day-old pups as well as in 65-day-old mice. A significant deficit in the proportion of long-chain fatty acids (C24), notable in both normal and alpha-hydroxy acids of cerebrosides from affected white matter, was measured. The lack of reactive gliosis, the observed depletion of galactocerebroside and sulfatide at the early age of 12 days, and the relative decrease in long-chain fatty acids in affected CNS strongly suggest a defect in myelinogenesis in this mutant rather than a secondary process of myelin breakdown.
The effect of various lipids such as cerebrosides, gangliosides and dipalmitoyl lecithin (DPPC) on the lowering of the melting temperature of water, was determined by differential scanning calorimetry (DSC). The lowering of the melting temperature, and the number of water molecules per lipid molecule which apparently do not undergo melting, increase with the increase of the size and charge of the polar group and with the unsaturation of the hydrocarbon chains. Freezing curves show supercooling to about -20 degrees C. It was found that the number of apparently unfreezable water molecules is about four for glucocerebroside from Gaucher's spleen and about eight or nine for galactocerebroside from bovine brain. In gangliosides from bovine brain the following number of water molecules/lipid molecule are apparently unfreezable: 22-30 in GM1, 33-40 in GD1a + GD1b while a fraction of gangliosides containing 75% GQ1b and 25% GT1b affects up to 60 molecules of water/molecule of lipid. A zwitterionic DPPC molecule removes apparently six to seven water molecules from freezing. There is no indication that the apparently unfreezable water molecules are in a distinct state. It is suggested that they freeze at very low temperatures producing a flat tail preceding the transition peak which cannot be discerned from the base line.