摘要:

The inotropic responsiveness of the developing myocardium to dopamine and isoproterenol was evaluated using isolated, perfused ventricles and atrial strips from puppies ages 15 hr to 33 days. Responses were compared to those in adult animals.The maximum percentage of increase of left ventricular dF/dt increased from 12 ± 5 (mean ± SEM) at 0–7 days (n= 6) to 100 ± 40 at 21–33 days (n= 3) of postnatal age. At 7–14 days (n= 4) and 15–20 days (n= 5) of age the maximum percentage of increase of left ventricular dF/dt was 28 ± 10 and 39 ± 17, respectively. Puppy ventricle responded to isoproterenol at all ages equally (maximum percentage increase of left ventricular dF/dt = 46 ± 13).

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

Lysosomally compartmentalized cystine can be removed from cystinotic cells by the use of reducing agents. In further investigation of means for converting cystine to a form or forms capable of penetrating the lysosomal membrane, a number of chemical agents either enclosed in phospholipid vesicles (liposomes) or free in solution were presented to cystinotic cells in tissue culture. After a 2-hr incubation, cystine content of cultured cystinotic cells was generally reduced more effectively by such agents in liposomes than in the medium. The most effective combination was cysteamine (MEA) in liposomes: a 0.5 mM dose of MEA reduced the cystine content of cystinotic cells 86% more when enclosed in liposomes than when dissolved at the equivalent dose in the medium. This observation could not be repeated when serum was omitted from the incubation medium, indicating that serum binds or otherwise inactivates cysteamine and that the liposome-enclosed cysteamine is protected from this action. Other liposome-entrapped compounds tested showed little if any depletion of intracellular cystine beyond that caused by non-liposome-enclosed drug action. Some agents increased the intracellular cystine content. Others of low molecular weight proved to be poorly retained by liposomes, a factor which may have been responsible for their relative ineffectiveness. Cysteamine, which is positively charged at neutral pH, was retained effectively when enclosed in “negative” liposomes made by inclusion of phosphatidic acid in the lipid mixture.[35S]Cysteamine (2.5 μCi, 23 μg/g), both free and enclosed in liposomes, was injected intravenously into mice. Ratios of MEA uptake by phagocytic as compared to non-phagocytic tissues (e.g.,kidney/brain) were higher in liposome-injected than in control mice, indicating preferential uptake of liposome-enclosed MEA by selected tissues of mice corresponding to those exhibiting high levels of cystine accumulation in cystinotic patients. Cell fractionation of liver and kidney from MEA-liposome-treated mice showed a much higher proportion of radioactivity in the mitochondrial-lysosomal fraction than in control animals receiving the same drug dissolved in medium.SpeculationDrugs such as MEA and dithiothreitol (DTT) have been used in treatment of cystinotic patients, as they are effective in reducing intracellular accumulations of cystine in vitro. They are, however, toxic, particularly to brain tissue. Cyctine is known to accumulate in large amounts in certain actively endocytic tissues in cystinosis. The administration of liposomes containing drugs aimed at reducing or otherwise altering the accumulated cystine might prove advantageous as a therapeutic measure if selectivity of uptake into target tissues could be improved, particularly since these lipid carriers are nonallergenic and degradable by lysosomal enzymes after their uptake by phagocytic cells.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

Wilms' tumor contains approximately 1 mg hyaluronic acid and approximately 0.3 mg sulfated glycosaminoglycan per g tissue. Minced tumor and cells cultured from the tumor incorporate labeled acetate and glucosamine into hyaluronic acid and sulfated glycosaminoglycans. A particulate enzyme preparation derived from the tumor catalyzed the transfer of GlcUA or GlcNAc from UDP-GlcUA or UDP-GlcNAc at a rate of approximately 20 nmol/hr/mg protein to produce high molecular weight hyaluronic acid chains. The urine and plasma of a Wilms' tumor patient contained approximately 20 mg hyaluronic acid and 8 mg sulfated glycosaminoglycan/100 ml, respectively. It appears that this higher than normal level of circulating glycosaminoglycan is synthesized by the Wilms' tumor.SpeculationThe conversion of normal cells to malignant cells results in changes in regulation of glycosaminoglycan synthesis. Of special interest is the same qualitative change in hyaluronic acid synthesis in Wilms' tumor as observed in SV40-transformed human fibroblasts.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

In a case of dihydrolipoyl dehydrogenase deficiency, there was not only an elevation of lactate and α-ketoglutarate but also of branched chain amino acids. The levels of branched-chain amino acids varied from the normal range to three times the upper limit of normal during the patient's lifetime, and alloisoleucine was detectable at all times. Examination of postmortem tissues revealed that the activity of branched-chain keto acid dehydrogenases was between zero and 10% of that in control tissues. It is suggested that the multiple defects seen in oxidative decarboxylation in this patient is the consequence of a single genetic deletion of an enzyme common to pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and branched-chain keto acid dehydrogenases.SpeculationThe dihydrolipoyl dehydrogenase component of pyruvate, α-ketoglutarate, and branched-chain keto acid dehydrogenases is genetically and biochemically a single entity.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID