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Biomedical subjects

J Hildebrand

Publications and source records attributed to J Hildebrand.

At least 127 records · Page 7Linked to original sources

Characterization of two gangliosides from human leukemic polymorphonuclear leukocytes.

Eight bands of gangliosides, from human polymorphonuclear leukocytes were demonstrated by thin-layer chromatography. Bands 4 and 5 were isolated and purified in sufficient amounts to allow their biochemical identification by thin-layer chromatography, gas chromatography and sequential action of glycosidases and neuraminidase. The major ganglioside was characterised as N-acetylneuraminylgalactosyl-beta-N-acetylglucosaminyl-beta-galactosyl-beta-glucosylceramide. A second ganglioside was tentatively identified as N-acetylneuraminyl-galactosyl-beta-N-acetylglucosaminyl-beta-(N-acetylneuraminyl)galactosyl-beta-glucosylceramide. Both gangliosides isolated were hydrolysed by neuraminidase. However, treatment of the intact cells with neuraminidase did not alter the ganglioside pattern.

Carbohydrates↗

Changes in regional cerebral blood flows produced by dexamethasone in patients with brain metastases.

Four patients suffering from brain metastases were studied by brain scintigraphy carotid angiography and rCBF measurement, before and after one week of treatment with dexamethasone. It was noted that the neurological signs and the blood perfusion around the tumor were improved but that the volume of the lesion, as judged from the angiogram was unmodified. It is suggested that the corticosteroids reduce tissue pressure before actually diminishing the volume of the brain oedema.

Adult↗

Potentiation of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea by amphotericin B in murine ependymoblastoma.

This paper reports the potentiation of the therapeutic effect of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) by amphotericin B (AMB) in s.c. transplanted murine ependymoblastoma 01B111. The rate of 2-month cures was 6% when tumors were treated 10 to 12 days after transplantation by a single 6 i.m. injection of 2.5 mg of CCNU per kg and reached 15% with 10 mg of CCNU per kg. When 25 mg of AMB per kg were given i.p. 10 hr prior to CCNU, the respective figures increased to 18 and 58%, the differences being significant at 5 and 1%. A single dose of 25 mg of AMB per kg given alone did not affect tumor growth. Radioactivity per g of tumor was measured 30, 60, and 120 min after injection of [14C]CCNU in total tissue, chloroform:methanol (2:1, v/v) extract, and CCNU isolated by thin-layer chromatography. No difference was found between animals treated with 25 mg of AMB per kg and controls. The inhibition of DNA synthesis, measured 24 hr after the administration of CCNU and 2 hr after the injection of [3H]thymidine, was almost optimal with 5 mg of CCNU per kg. The inhibition caused by 1 mg of CCNU per kg was not enhanced by AMB. Thus, the potentiation of CCNU by AMB does not seem attributable to an increased permeability of the tumor to CCNU or to an enhancement of the inhibition of DNA synthesis, at least in murine ependymoblastoma.

Amphotericin B↗

Early diagnosis of metastases in the epidural space.

Examination of the cerebrospinal fluid (CSF), and myelography, were performed in most of 89 consecutive patients with X-ray evidence of vertebral metastases to test the value of these examinations in the early detection of neoplastic involvement of the epidural space. Patients were divided into 3 groups. In 7 cases (group I), the vertebral metastases were asymptomatic. Fifty-nine (group II) had symptoms or signs of radicular lesions but not of spinal cord compression. Twenty-three showed various stages of spinal cord or cauda equina compression (group III). Involvement of the epidural space was demonstrated on myelography in almost 50% of patients from groups I and II by a partial (29%) or complete (19%) arrest of the opaque medium. In addition, five patients in group II with normal myelograms had increased levels of CSF protein. Leucocyte counts were within normal limits in all patients. Neoplastic cells were found in two cases. It is suggested that in patients with only radiological evidence of neoplastic involvement of the epidural space and complete myelographic blocks, laminectomy, followed by radiation therapy, should be performed. Patients showing partial blocks should receive radiation therapy only.

Breast Neoplasms↗

Alterations of rat liver lysosomes and somooth endoplasmic reticulum induced by the diazafluoranthen derivative AC-3579. III. Mechanism and site of action.

To elucidate the mode of action of AC-3579, a diazafluoranthen derivative, the effects of the drug were tested, in incubations with rat liver homogenates on three phospholipases: the endogenous microsomal phospholipase A and the exogenous phospholipases A2 and C. The rates of hydrolysis of phosphatidylcholine and phosphatidylethanolamine, the main liver phospholipids, were significantly decreased in liver of treated animals. This inhibition was more marked in experiments with exogenous phospholipase A than with phospholipase C. For phospholipid the difference observed may be due to the decrease in activity of endogenous phospholipase A in livers of treated rats. On the other hand, the addition to the incubation media of AC-3579 or of homogenates of AC-3579-treated rat livers did not modify the action of the three phospholipases on phospholipids from normal rat liver homogenates. It is concluded that AC-3579 forms with the hydrophobic moiety of the phospholipids of smooth endoplasmic reticulum a reversible complex less accessible to the activity of phospholipase A. This mechanism accounts for the decrease in phospholipid catabolism, previously observed in vivo, which leads to hypertrophy of smooth endoplasmic reticulum and to the formation of lamellate cytosomes.

Animals↗

Incorporation of [32P]-orthophosphate into total and individual plasma phospholipids in patients with polycythemia vera.

Incorporation of [32P]-orthophosphate into plasma phospholipids was investigated in 11 patients with polycythemia vera. The specific activity of phospholipid radioactive precursors (TCA-extract) was maximal 1 hour after the delivery of radioactive phosphorus and dropped to less than 20 per cent of maximal value after 24 hours. The peak of total phospholipid specific activity was observed 48 hours after the administration of [32P]-orthophosphate in 10 patients, and after 24 hours in one, and decreases regularly afterward. The half-life of the lipid-bound phosphorus in the plasma of investigated patients, determined during the decrease of their specific activity was 252+/-60 hours. Concentration of total plasma phospholipids and the pattern of individual phospholipid found in patients with polycythemia vera were similar to those reported for normal individuals. The rate of incorporation of the labeled phosphorus into phosphatidylethanolamine and phosphatidic acid was much more rapid than into lysophosphatidylcholine, sphingomyelin, or phosphatidylcholine.

Chromatography, Thin Layer↗

Lipid composition of plasma membranes from human leukemic lymphocytes.

The specific activity of adenosine 5'-monophosphatase and the concentrations of cholesterol, glucosylceramide, lactosylceramide, and phospholipids were compared in the whole homogenates and in plasma membrane fractions in four preparations of human leukemic lymphocytes taken over a 1-yr period from a patient with chronic lymphocytic leukemia. There was a 69.5-fold enrichment of the specific activity of adenosine 5'-monophosphatase in plasma membrane fractions. This enzyme appeared to be the best plasma membrane marker of all compounds studied. The increase in lactosylceramide concentration in the plasma membranes was 34.4-fold. It was significantly higher than that of glucosylceramide. The enrichment of glucosylceramide in the plasma membranes was similar to that of cholesterol and total phospholipids. The pattern of individual phospholipids in the plasma membrane fraction, as compared with the whole homogenate, was characterized by a decrease in phosphatidylcholine and an increase in sphingomyelin.

Adenosine Monophosphate↗

Effects of the diazafluoranthen derivative AC-3579 (NSC-170561), a new experimental antitumour drug, on rat hepatoma.

The effects of AC-3579 (NSC-170561), a new experimental antitumour drug which depresses phospholipid catabolism in liver, were compared in rat aflatoxin-induced hepatoma and in non-neoplastic hepatocytes surrounding the tumour. Ultrastructural lesions, characterized by the hypertrophy of the smooth endoplasmic reticulum and the presence of lamellate cytosomes appeared in both tissues. They were less marked in hepatoma than in non-neoplastic cells. As in control livers, they were related to an invrease in pohspholipid concentration due to the decrease of phospholipid breakdown. In addition, chemical analysis demonstrated differences between hepatoma, non-neoplastic aflatoxin-treated liver and control liver: total and free cholesterol were decreased, relative concentration of sphingomyelin increased and that of phosphatidylethanolamine decreased by about 50%, in both hepatoma and non-neoplastic liver. Phospholipid concentration was decreased by 50% in tumour cells. After AC-3579 treatment total cholesterol was increased 3.2 fold in non-neoplastic liver and 2.5 fold in hepatoma but not in control liver.

Aflatoxins↗