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Biomedical subjects

J Kaplan

Publications and source records attributed to J Kaplan.

At least 289 records · Page 16Linked to original sources
PubMed1988

Radiofrequency balloon angioplasty. Rationale and proof of principle.

Post-angioplasty restenosis (PARS) in atherosclerotic lesions of medium and small arteries occurs in about one-third of cases in the first year following percutaneous transluminal angioplasty (PTA) (early PARS). PARS includes acute spasm, dissection with reclosure, elastic recoil, fibrocellular proliferative response, and progressive atheromatous disease. Fibrocellular proliferation (possibly initiated by platelet derived growth factor) is felt to be culpable in many cases of early PARS (months). Pharmacologic regimens, stents, and thermal welding of the intimal-medial cracks of PTA are among the interventions being developed to deal with PARS. Radiofrequency (RF) current as a source of thermal energy may be useful in combination with balloon angioplasty to reduce PARS. Ideally, this combination would (1) weld intimal-medial cracks of PTA; (2) mold plaque and normal vessel to increase lumen diameters without creating intimal-medial cracks; and (3) destroy medial smooth muscle cells and multipotential cells (cellular substrate of PARS). Canine in vivo studies have established the feasibility of RF-mediated vascular tissue welding. Human aortic specimens (N = 28) were manually dissected into intima-media and media-adventitia layers. Bipolar RF energy (650 KHz, total 300 J) and mechanical pressure (1 atm) (experimental group, N = 24) or mechanical pressure alone (control group, N = 4) were applied to the reapposed specimen layers in a special chamber. The chamber was modified with a bipolar electrode designed to reproduce that planned for an RF balloon angioplasty catheter. Welding was demonstrated in normal and atherosclerotic treated specimens (23/24 or 96%) but not controls (0/4).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗
PubMed1988

Serum thymulin in human zinc deficiency.

The activity of thymulin (a thymic hormone) is dependent on the presence of zinc in the molecule. We assayed serum thymulin activity in three models of mildly zinc-deficient (ZD) human subjects before and after zinc supplementation: (a) two human volunteers in whom a specific and mild zinc deficiency was induced by dietary means; (b) six mildly ZD adult sickle cell anemia (SCA) subjects; and (c) six mildly ZD adult non-SCA subjects. Their plasma zinc levels were normal and they showed no overt clinical manifestations of zinc deficiency. The diagnosis of mild zinc deficiency was based on the assay of zinc in lymphocytes, granulocytes, and platelets. Serum thymulin activity was decreased as a result of mild zinc deficiency and was corrected by in vivo and in vitro zinc supplementation, suggesting that this parameter was a sensitive indicator of zinc deficiency in humans. An increase in T101-, sIg-cells, decrease in T4+/T8+ ratio, and decreased IL 2 activity were observed in the experimental human model during the zinc depletion phase, all of which were corrected after repletion with zinc. Similar changes in lymphocyte subpopulation, correctable with zinc supplementation, were also observed in mildly ZD SCA subjects. Inasmuch as thymulin is known to induce intra- and extrathymic T cell differentiation, our studies provide a possible mechanism for the role of zinc on T cell functions.

Adolescent↗
PubMed1988

[Genetic counseling in ornithine carbamoyltransferase deficiency].

Ornithine transcarbamylase (OTC) deficiency is an inborn error of urea cycle metabolism, responsible for lethal hyperammonemia in males and for severe symptoms in at least 20% of heterozygous females. The authors provide here additional data on the informativity of the protein loading test (PLT) for the detection of heterozygotes. They show that the risk of being a carrier for the mother of an affected boy falls from 2/3 a priori to only 1/8 if her PLT is negative. The risk for the mother of heterozygote girl falls from 1/2 a priori to 1/16 if her PLT is negative.

Amino Acid Metabolism, Inborn Errors↗
PubMed1988

[Genetic counseling in neurofibromatosis. Apropos of a study of 53 families].

Referring to a retrospective study of 53 families affected with neurofibromatosis and seen in genetic consultation from January 1977 to September 1987, the authors emphasize the difficulties of genetic counselling in this disease due to its variable expressivity with unforeseeable natural evolution and to the difficulty in detecting minor forms without biological markers. These results confirm previous studies (Carey 1979, Riccardi 1981): About half the cases are relevant to a neomutation and in these sporadic cases, the average paternal age is significantly increased (36.7 years). In familial cases, an intrafamilial variable expressivity is noted in 63.3% of families and no maternal effect is found. The penetrance of the disease, calculated from the familial cases, is estimated to 97% which confirmed the anterior data. The severe forms rate (grades III and IV) is about the same for familial cases, than in previous publications, but is higher for sporadic cases than the proportion described by Riccardi (25 to 30%) probably because of an ascertainment bias. Finally, If the risk for the offspring of an affected patient can be estimated at 1/2, however it is impossible to predict the severity of the disease. Before concluding to a neomutation (1st child of a couple) or to an absence of genetic risk (non affected person related to a familial case), a minor form must be searched by a careful physical examination, although the recent localization of the gene allows us to think of molecular biology for familial studies in a near future.

Female↗
PubMed1988

[X-linked diseases and carrier detection].

Advances in molecular biology applied to the location of genes have generated a real evolution for the screening of women carrying X-related diseases. It is however imperative to first try to define the status of these women using classical methods: bayesian calculations taking into account genealogical data and direct screening which is partially reliable because of the inactivation of an X chromosome in women. The new genetic engineering techniques enable to locate the gene in an affected patient and follow its transmission in the families with the use of tracers linked to the gene of the disease. The difficulties of these studies are due to two phenomena. First, the risk of allele recombination because of a crossing over during the mitosis. This risk must be computed and specified. The second phenomenon is related to variations of information in the families which may either completely prevent identification of the carriers, or give less reliable results. The increasing number of molecular probes should enable to resolve this problem.

Bayes Theorem↗
PubMed1988

Genetic counselling, carrier detection, and prenatal diagnosis in hemophilia. A service experience.

Our experience over three years (1984-1986) is described in carrier detection and prenatal testing for hemophilia. We have analysed 50 families: 37 hemophilia A and 13 hemophilia B, 22 isolated cases and 28 familial. Eighty-three women belonging to this panel asked for a genetic risk. Pedigree and coagulation studies were performed to estimate genetic risks according to the Bayesian method. At this point, 40% of the females at risk were recognized carriers before the DNA analysis. Molecular biology allowed the detection of only 7% more carriers and the exclusion of 34%. In 19% of the cases, it was impossible to estimate the genetic risk because the families were uninformative for the DNA polymorphisms used. Twenty-two prenatal diagnoses were performed; 3 affected male fetuses were recognized by DNA analysis and pregnancies were terminated. Eleven healthy boys were born.

Blood Coagulation↗
PubMed1988

CFC syndrome: a syndrome distinct from Noonan syndrome.

We report two children with a common pattern of birth defects. Both have very sparse, curly hair, nystagmus and mental retardation. The first one has Noonan syndrome habitus associated with keratosis plantaris and nystagmus; the second one has a slightly Noonan-like face, macrocephaly, keratosis pilaris, and hypertrophic cardiomyopathy. They represent the extreme of a spectrum of congenital defects recently reported independently as CFC syndrome by Reynolds and as "Noonan-like short stature syndrome with sparse hair" by Baraitser and Patton. The clinical features are reviewed and the autonomy of the syndrome with regards to Noonan syndrome, is disputed, since every sign seems to occur independently in Noonan syndrome. The father of the second case probably has a minor syndrome expression, pointing to probable autosomal dominant inheritance.

Abnormalities, Multiple↗
PubMed1988

[Marfan disease].

After reviewing the main features of the Marfan syndrome (musculoskeletal, ocular, cardiovascular, pulmonary abnormalities), its autosomal dominant inheritance with high penetrance but variable phenotype and presence of "soft" conditions preventing an easy diagnosis, the authors report their own data relevant to 73 probands: ratio of each clinical manifestation, state of 34% of familial cases and display of a paternal age effect in the sporadic cases. The pathogenic defect is unknown as like the location of the gene. The difficulties of the genetic counseling are then approached: unpredictability of the severity and of the prognosis in the unborn children of an affected patient, benefit of the echocardiography in the management of people at risk.

Genetic Counseling↗
PubMed1988

[Evaluation of the risk in autosomal dominant diseases].

A lot of traps and difficulties complicate the estimation of a genetic risk in the autosomal dominant diseases. The authors recapitulate the notions of mutation, penetrance and variability and illustrate by some examples the part of each of them, isolated or associated together. The increasing of molecular biology allows to resolve some of these problems, but generate new dangers which are analysed and illustrated.

Genes, Dominant↗
PubMed1987

Phorbol esters and calcium ionophores inhibit internalization and accelerate recycling of receptors in macrophages.

Exposure of macrophages to phorbol esters or the calcium ionophore A23187 increases the number of several surface receptors due to recruitment of receptors from internal pools (Buys, S. S., Keogh, E. A., and Kaplan, J. (1984) Cell 38, 569-576). We have examined the mechanism by which these agents increase surface receptor number. Cells which were preloaded with either fluid phase or receptor-mediated ligands did not lose ligand following exposure to ionophore or phorbol ester. The rate of movement of ligands to the lysosome was also unaffected. These results suggest that A23187 does not induce the fusion of ligand-containing compartments with the cell surface. Ionophore treatment did, however, produce a severalfold increase in the rate at which unoccupied receptors reappear on the cell surface. These results suggest that the compartment of receptors affected by the ionophore formed subsequent to the dissociation of ligand from receptor. The altered rate of receptor reappearance was transitory (90 s), and the increase in receptor number was subsequently maintained by a decrease in the rate of internalization. Changes in the rate of receptor internalization did not correlate with changes in the rate of fluid phase pinocytosis, suggesting that the effect on receptor internalization was selective.

Animals↗
PubMed1987

Effect of phagocytosis on receptor distribution and endocytic activity in macrophages.

Phagocytosis requires the internalization of a significant fraction of the plasma membrane and results in the intracellular deposition of large particles. We evaluated the effect of phagocytosis on the cellular distribution of recycling receptors and uptake of ligand to determine whether phagocytosis affects receptor behavior. Phagocytosis of zymosan, latex particles, or IgG-coated red blood cells by rabbit alveolar macrophages did not decrease the number of cell surface receptors for transferrin, alpha 2-macroglobulin X protease complexes, maleylated proteins, or mannosylated proteins. The number of surface receptors for transferrin was also unaltered in J774 cells, a macrophage-like cell line. In both cell types extensive phagocytosis did not affect the rate of receptor-mediated endocytosis or the distribution of receptors between the endosome and the cell surface. However, fluid phase pinocytosis was reduced by phagocytosis. The major reduction appeared to be not in the rate of internalization but rather in the delivery of fluid to the lysosome. These results demonstrate that internalization of a significant amount of the plasma membrane during phagocytosis does not diminish the number of receptors on the cell surface and has no effect on receptor-mediated ligand uptake.

Animals↗
PubMed1987

Mechanisms of ischemic cerebral injury.

Normal compensatory mechanisms protect the central nervous system (CNS) from moderate hypoxia and ischemia; however, after more severe ischemia progressive brain hypoperfusion ensues and irreversible damage occurs. Ischemic brain injury remains greatly significant clinically and elucidating the determinants of ischemic neuronal injury and death continues to challenge researchers. Although altered perfusion and decreased energy charge may contribute to the production of irreversible damage, the distribution of lesions seen after insult does not correspond with the degree of ischemic blood flow impairment, nor can neuronal energy deprivation explain the cell damage. Other factors, such as derangements in astrocyte function, calcium homeostasis, free radical metabolism, acid-base regulation and excitatory neurotransmitters also probably mediate ischemic neuronal death. Continued investigation to establish the cellular pathophysiology of cerebral ischemia can guide rational research and therapeutic strategies.

Acid-Base Equilibrium↗
PubMed1987

Dichloroacetate treatment of ischemic cerebral lactic acidosis in the fed rat.

Despite advances in cardiac resuscitation, ischemic brain injury remains generally untreatable. Animal studies of brain ischemia associate brain lactate levels of more than 18 mumol/g with irreversible neuronal injury. Lowering brain lactate therefore may prevent or minimize ischemic brain necrosis. Earlier studies in our laboratory using fasted rats demonstrated that sodium dichloroacetate (DCA) decreases ischemic brain lactate when given either before or immediately after partial global ischemia (PGI). Other investigators have shown that fed animals have more glucose and generate higher lactate levels by anaerobic metabolism during PGI. We evaluated the ability of DCA to lower brain lactate in fed male Wistar rats subjected to PGI. Four groups (n = 6 each) were studied--PGI and control rats with either placebo or DCA treatment. PGI was induced for 30 minutes by combining bilateral carotid artery occlusion with hemorrhagic hypotension. This was followed by release of carotid occlusion, reinfusion of shed blood, and immediate treatment with either DCA (25 mg/kg, IV) or placebo. Thirty minutes later brains were frozen in situ with liquid nitrogen for extraction and measurement of tissue glucose, glycogen, and lactate. Blood glucose and serum lactate were monitored throughout the experiment. No significant differences were found between the two PGI groups in brain glucose, brain glycogen, or ischemia-induced elevations in blood glucose and serum lactate. However, brain lactate was significantly lower in DCA-treated (12.5 mumol/g) than in untreated (22.8 mumol/g) PGI rats (P less than .001). In addition, all untreated PGI rats had levels of more than 18 mumol/g, and therefore were at high risk for neuronal necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1987

Tissue distribution and clearance kinetics of non-transferrin-bound iron in the hypotransferrinemic mouse: a rodent model for hemochromatosis.

Genetically hypotransferrinemic mice accumulate iron in the liver and pancreas. A similar pattern of tissue iron accumulation occurs in humans with hereditary hemochromatosis. In both disorders, there is a decreased plasma concentration of apotransferrin. To test the hypothesis that nontransferrin-bound iron exists and is cleared by the parenchymal tissues, the tissue distribution of 59Fe was studied in animals lacking apotransferrin. Two groups of animals were used: normal rats and mice whose transferrin had been saturated by an intravenous injection of nonradiolabeled iron, and mice with congenital hypotransferrinemia. In control animals, injected 59Fe was found primarily in the bone marrow and spleen. In the transferrin iron-saturated animals, injected 59Fe accumulated in the liver and pancreas. Gastrointestinally absorbed iron in hypotransferrinemic or transferrin iron-saturated mice was deposited in the liver. This indicates that newly absorbed iron is released from mucosal cells not bound to transferrin. Clearance studies demonstrated that transferrin-bound 59Fe was removed from the circulation of rats with a half-time of 50 min. In transferrin iron-saturated animals, injected 59Fe was removed with a half-time of less than 30 s. Analysis of the distribution of 59Fe in serum samples by polyacrylamide gel electrophoresis demonstrated the presence of 59Fe not bound to transferrin. These results demonstrate the existence of and an uptake system for non-transferrin-bound iron. These observations support the hypothesis that parenchymal iron overload is a consequence of reduced concentrations of apotransferrin.

Animals↗