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Biomedical subjects

J Kaplan

Publications and source records attributed to J Kaplan.

At least 271 records · Page 15Linked to original sources
PubMed1989

The effect of radiofrequency-generated thermal energy on the mechanical and histologic characteristics of the arterial wall in vivo: implications for radiofrequency angioplasty.

Abrupt reclosure of atherosclerotic vessels after percutaneous transluminal balloon angioplasty has been blamed on traumatic dissections and elastic recoil of the vessel wall. Thermal energy with compression produces fusion of separated arterial wall layers, and heat appears to alter the elastic recoil of the vessel wall. Radiofrequency (RF) thermal energy has been used to perform vascular anastomoses and thermal angioplasty. A simple in vivo experiment was designed to describe and quantitate vascular tissue weld strength produced by a range of RF thermal energy levels. Canine carotid arteries were compressed between a pair of modified bipolar forceps that applied RF energy, causing occlusive tissue welds between the apposed intimal surfaces. The strength of the welds was evaluated by measuring the perfusion pressure required to reopen the vessel lumen. A dosimetry range of 0 to 205 joules showed a typical dose-response curve for the relationship between energy applied and bond strength, plateauing at approximately 300 mm Hg. Light microscopy showed fusion of the inner surfaces of the vessel with preservation of vessel wall architecture. Additionally inflation of a bipolar RF balloon catheter in the normal canine carotid lumen produced an alteration of vessel profile angiographically and histologically. Results of these preliminary experiments suggest that balloon angioplasty with adjunctive RF thermal energy may have benefits in reducing the factors causing acute failure of conventional percutaneous transluminal balloon angioplasty.

Angiography↗
PubMed1989

Immunophenotyping in a multicenter study: the Transfusion Safety Study experience.

The Transfusion Safety Study (TSS) is a cooperative investigation of factors that determine the occurrence of and modify the expression of transfusion-transmitted infections. A major component of its data is derived from lymphocyte immunophenotyping using a large panel of monoclonal antibodies and two-color flow cytometric analysis. The multicenter longitudinal character of TSS necessitates a uniformity of instrumentation, reagents, and protocols, as well as an intensive quality control program. The baseline assessment of a cohort of males 10 years of age and over with congenital clotting disorders (CCD) exemplifies the approach and some of the flow cytometry results. A comparison of anti-HIV-1 positive and negative subjects shows that more of the loss of T4+ cells was attributable to a decrease in the T4+4B4+ subset than the T4+2H4+ subset. There was an overall increase in CD8 cells, with a significant increase in the I2+T8+ and Leu7+T8+ cells, but a fall in NKH.1+T8+ cells. Monocytes, MO2+I2+ cells, increased. In CCD patients under the age of 10, both anti-HIV-1 positive and negative, there were absolute elevations in immunocytes, including CD4. There was also a distinctly different distribution of CD4 subsets. The suppressor inducer subset, 2H4+T4+, was increased relative to the helper inducer subset, 4B4+T4+, in the younger subjects.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Thermal compression and molding of atherosclerotic vascular tissue with use of radiofrequency energy: implications for radiofrequency balloon angioplasty.

The combined delivery of pressure and thermal energy may effectively remodel intraluminal atherosclerotic plaque and fuse intimal tears. To test these hypotheses with use of a non-laser thermal energy source, radiofrequency energy was delivered to postmortem human atherosclerotic vessels from a metal "hot-tip" catheter, block-mounted bipolar electrodes and from a prototype radiofrequency balloon catheter. Sixty-two radiofrequency doses delivered from a metal electrode tip produced dose-dependent ablation of atherosclerotic plaque, ranging from clean and shallow craters with histologic evidence of thermal compression at doses less than 40 J to tissue charring and vaporization at higher (greater than 80 J) doses. Lesion dimensions ranged between 3.14 and 3.79 mm in diameter and 0.20 and 0.47 mm in depth. Tissue perforation was not observed. To test the potential for radiofrequency fusion of intimal tears, 5 atm of pressure and 200 J radiofrequency energy were delivered from block-mounted bipolar electrodes to 48 segments of human atherosclerotic aorta, which had been manually separated into intima-media and media-adventitial layers. Significantly stronger tissue fusion resulted (28.5 +/- 3.3 g) with radiofrequency compared with that with pressure alone (4.8 +/- 0.26 g; p less than 0.0001). A prototype radiofrequency balloon catheter was used to deliver 3 atm of balloon pressure with or without 200 J radiofrequency energy to 20 postmortem human atherosclerotic arterial segments. In 10 of 10 radiofrequency-treated vessels, thermal "molding" of both normal and atherosclerotic vessel wall segments resulted with increased luminal diameter and histologic evidence of medial myocyte damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗
PubMed1989

Effects of various doses of sodium dichloroacetate on hyperlactatemia in fed ischemic rats.

In shock, the presence of hyperlactatemia is prognostic of a failure to survive. An experimental model of stroke that combines bilateral carotid ligation and bleeding to a mean arterial pressure of 50 mm Hg induces hyperlactatemia like that associated with tissue hypoperfusion of hemorrhagic shock. In previous nonsurvival studies with this model, post-ischemic treatment of fed rats with 25 mg/kg of sodium dichloroacetate (DCA) was effective in lowering brain tissue lactate but did not significantly affect the ischemia-induced increase in serum lactate measured after 30 minutes of ischemia followed by 30 minutes of reperfusion. Investigators using other animal models treated hyperlactatemia associated with tissue hypoperfusion successfully with a DCA dose of more than 25 mg/kg. Our goal was to determine the effect of a higher dose of DCA on serum lactate in the model of cerebral ischemia with systemic hypotension that we had used in previous studies. The previously unstudied dose-response also was evaluated in our study. Rats that had been fed ad libitum were assigned randomly to either a real or sham (control) ischemic group. Immediately after 30 minutes of ischemia and subsequent reinfusion of blood or after 30 minutes of sham ischemia, rats received DCA (0, 25, 50, 100, 200, or 300 mg/kg). Comparisons were made of blood values measured at the end of equilibration before ischemia, after 30 minutes of ischemia, and after 30 minutes of reperfusion. All ischemic rats were hyperlactatemic. Serum lactate levels were not correlated to blood glucose elevation during ischemia. After treatment in both control and ischemic rats, the percentage decrease in serum lactate varied as a logarithmic function of the DCA dose administered. Glucose levels and pH were not affected by DCA treatment at any dose. Because acidemia decreases lactate uptake by the liver, values for acidotic rats were compared with those for nonacidotic rats. Whereas lactate in acidotic rats decreased significantly only when treated with DCA, nonacidotic rats evidenced this decrease regardless of whether they received DCA. We discuss the relationship of these findings to the peak levels of lactate achieved, the resolution of hyperlactatemia, and factors that affect the interpretation of data in therapeutic studies using DCA.

Acetates↗
PubMed1989

Effects of sodium dichloroacetate dose. Brain metabolites associated with cerebral ischemia.

Excessive brain lactate, as may develop in cerebral ischemia, has been implicated as a major cause of irreversible cell damage. With an experimental model that produces cerebral ischemia by bilateral carotid ligation combined with systemic hypotension, previous studies have shown that treatment with 25 mg/kg sodium dichloroacetate (DCA) is effective in reducing brain lactate more quickly than no treatment at all. Because higher doses of DCA may be more effective, the main objective of our study was to examine the dose-response of brain tissue lactate to DCA. In addition, other metabolites that may be indirectly affected by this response (eg, glucose, glycogen, ATP, and phosphocreatine) also were measured. Adult male Wistar rats were assigned to experimental and treatment groups, and real or sham ischemia was induced as described in our previous article. After 30 minutes of reperfusion, rats were euthanized by in situ freezing of the brain. Cerebral cortex, hippocampus, and cerebellum were analyzed bilaterally. There was no effect of DCA dose on glucose or glycogen. When compared with hippocampus, lactate was higher in the cerebral cortex after ischemia, and DCA was more effective in reducing those levels. This is evidence of a lower metabolic rate in hippocampus than in cortex. Cerebellum did not exhibit an increase in lactate; therefore, it can serve as an in situ tissue control for that metabolite. Significantly different levels of metabolites in one hemisphere of some DCA-treated ischemic rats appeared to reflect a dose effect of DCA on lactate and a significant change in ATP and phosphocreatine at the higher doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1989

Twenty-four hour variation of transferrin saturation in treated and untreated haemochromatosis homozygotes.

We studied 43 haemochromatosis homozygotes and seven normal individuals to test the hypothesis that there is an almost continuous relative deficiency of apotransferrin in treated and untreated homozygotes. Transferrin saturation was measured at 2-h intervals for 24 h while all subjects ate their usual diet. Subjects with haemochromatosis were separated into four groups based on sex and whether or not they had been iron-depleted. Nineteen treated and 11 untreated male homozygotes had mean transferrin saturation values of 70 and 81%, respectively. Five treated and eight untreated female homozygotes had mean transferrin saturation values of 71 and 69%. Normal subjects had mean transferrin saturation values of 29% (3 males) and 21% (4 females). These data demonstrate continuously high transferrin saturation values, greater than 69% in most treated and untreated male and female homozygotes, resulting in hepatic iron accumulation of non-transferrin-bound iron from the portal circulation.

Bloodletting↗
PubMed1989

Taxol produces a predominantly sensory neuropathy.

Taxol, a plant alkaloid with promise as an antineoplastic agent, produced a predominantly sensory neuropathy in 16 of 60 patients treated in two phase I trials. This neuropathy occurred only at taxol doses greater than 200 mg/m2. Symptoms typically started 1 to 3 days following treatment, beginning in the hands and feet simultaneously in most patients. Electrophysiologic data suggests both axonal degeneration and demyelination. This previously undefined neurotoxic neuropathy most likely results from taxol's unique ability to produce microtubule aggregation in dorsal root ganglion cells, axons, and Schwann cells.

Adult↗
PubMed1989

Function, location, and regulation of the src protein-tyrosine kinase.

The physiological roles, precise locations, and relevant targets of the 60 kD protein-tyrosine kinase encoded by viral and cellular src genes p60src are not known, despite intensive study. We describe recent work that bears upon these unresolved problems: (i) p60c-src is phosphorylated during mitosis on threonine and serine residues by the protein kinase encoded by the mammalian homologue of cdc2, suggesting that c-src may contribute to the phenotype of mitotic cells; (ii) multiple regions in the amino-terminal portion of p60src are required for its proper intracellular localization--a short signal for myristylation and signals for association with cytoplasmic granules and with perinuclear and plasma membranes; and (iii) regions (called SH3 and SH2) upstream of the kinase domain modulate the behavior of p60src in complex ways, with some mutations in SH2 rendering p60 host-dependent for transformation. The latter mutants may prove to be powerful tools for identifying proteins that modify or serve as targets for src-encoded protein-tyrosine kinases.

Amino Acid Sequence↗
PubMed1989

Changes in the distribution of testosterone and estradiol serum fractions in hirsute women after administration of L-thyroxine.

The effect of 1-thyroxine treatment on the distribution of testosterone and estradiol serum fractions was studied in 10 normal weight hirsute women with ages ranging from 18 to 25 years. Six of the patients had menstrual irregularities. Treatment consisted in one month of thyroxine (1-T4) at a dose of 2 micrograms/Kg body weight. Serum sex hormone binding globulin (SHBG) was measured by saturation analysis and serum testosterone (T), estradiol (E2), androstenedione (delta 4-A), dehydroepiandrosterone sulphate (DHAS), LH, FSH, PRL, T4, T3, by RIA. Serum T and E2 fractions were calculated by an equation derived from the law of mass action. Before and after T4 treatment serum SHBG was, respectively, (X +/- ES) 30.3 +/- 3.8 and 45.4 +/- 4.6 nmol/l (p less than 0.001), non-SHBG-bound T 25.7 +/- 8.1 and 18.8 +/- 6 ng/dl (p less than 0.001), free T 1.09 +/- 0.2 and 0.8 +/- 0.5 ng/dl (p less than 0.01), non-SHBG-bound E2 40.9 +/- 13.7 and 19.2 +/- 2.4 pg/ml (p less than 0.001). No significant changes were observed in total T and E2 or free E2. Serum DHAS and delta 4-A decreased significantly after treatment from 3977 +/- 601 to 3480 +/- 250 ng/dl and from 4.7 +/- 0.61 to 3.34 +/- 0.34 ng/ml respectively (p less than 0.001). Serum basal levels of FSH, LH, PRL, T4, T3 and TSH were normal. A significant increase of serum T4 was observed after treatment from 8.4 +/- 0.4 to 11.7 +/- 1.1 ng/dl (p less than 0.01). However, the post-treatment value was within the limits of the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Immunological effects of zinc deficiency in sickle cell anemia (SCA).

Zinc deficiency occurs frequently in SCA subjects. Our studies have shown that several parameters of cellular immune functions may be altered in SCA subjects and related to a deficiency of zinc. These include anergy to certain common antigens, which was reversible following zinc supplementation, decreased activity of natural killer (NK) cells, decreased production of interleukin (IL-2), decreased T4/T8 ratio and serum thymulin. Inasmuch as we have observed similar immunological changes in human volunteers (non-SCA) in whom we restricted only zinc intake and produced a mild specific deficiency of zinc, we conclude that the above changes in SCA were due to zinc deficiency. Although it is well known that susceptibility to infections is a common problem in SCA subjects, the pattern of infections related to cell mediated immune dysfunction has not been well documented. Whether or not supplementation with zinc will alter the pattern of infection and decrease morbidity in SCA on a long-term basis remains to be determined.

Adult↗
PubMed1989

A splicing defect in the mouse transferrin gene leads to congenital atransferrinemia.

We have analyzed the biochemical defect in a mutant line of mice that produces less than 1% of the normal level of serum transferrin. This mouse line (Hp) transcribes the transferrin gene in liver at the same rate observed in normal mice, but the steady state levels of transferrin mRNA sequences are less than 20% of normal. Further hybridization studies reveal that most of the transferrin mRNA sequences present in homozygous Hp mouse liver are in the form of a 5 kb nuclear precursor instead of the mature 2.5 kb transferrin mRNA seen in normal mice. Using several different exon and intron probes from the mouse transferrin gene, we have shown that the 5 kb RNA precursor retains the last two introns of the transferrin gene but that the 5' and middle introns have been removed by processing. The defect in transferrin mRNA processing also extends to nonhepatic tissues and we find the same lack of mature mRNA and increased precursor accumulation in brain RNA. Since Southern blot analysis does not reveal gross changes in the structure of the transferrin gene in Hp mice, we suggest that the Hp defect is due to a small deletion or point mutation that either disrupts splicing signals or uncovers cryptic splice signals that interfere with processing of the last two introns in the transferrin gene. This Hp mouse line provides an opportunity to study the effects of transferrin deficiency on development and iron homeostasis.

Anemia↗
PubMed1988

Role of lymphokine-activated killer cells as mediators of veto and natural suppression.

Fresh bone marrow cells have veto activity but little if any NK activity. By contrast, lymphokine-activated bone marrow cells have potent natural suppressor as well as veto activity, and also have cytolytic activity characteristic of lymphokine-activated killer cells. Veto activity of fresh bone marrow cells is eliminated by 9 Gy irradiation and by depletion of cells expressing Qa-2, but is unaffected by removal of cells expressing Thy-1, Qa-5, Ly-5, or asialo GM1. By contrast, the veto and NS activities of lymphokine-activated bone marrow cells are both abrogated by C lysis depletion of cells expressing Qa-2, Qa-5, Thy-1, asialo GM1, NK1, and Ly-11, but are unaffected by depletion of cells expressing Ly-2. Bone marrow cells depleted of Qa2+ cells fail to generate veto or natural suppressor activity when cultured in Con A-conditioned medium, unlike bone marrow cells depleted of mature NK1.1+ NK cells. Cloned NK cell line F8 is able to mediate both natural suppression and veto. These findings indicate that bone marrow veto and natural suppression are not mediated by T or NK cells present de novo in the bone marrow, but are dependent on proliferating cells that phenotypically resemble pre-NK cells. The progeny of these cells have the phenotype and functional activity of lymphokine-activated killer cells, and are capable of directly mediating both veto and natural suppression.

Animals↗
PubMed1988

Effect of hypo-osmotic incubation on membrane recycling.

Incubation of alveolar macrophages in hypo-osmotic media causes a time-and temperature-dependent increase in the number of surface receptors for three different ligands. Exposure of cells to solutions of 210 mOsM or less, at 37 degrees C but not at 0 degree C, resulted in an increase in the number of surface receptors for diferric transferrin, alpha-macroglobulin-protease complexes, and mannose-terminated glycoproteins. Upon media dilution at 37 degrees C, surface receptor number reached a maximum within 5 min and returned to near-normal values by 30 min. The increase in surface receptor number was the result of a decrease in the rate of internalization of receptors, either occupied or unoccupied. The rate of receptor exteriorization was unaltered by hypo-osmotic incubation of cells. The rate of fluid-phase pinocytosis was also inhibited upon incubation in hypo-osmotic solution. In experiments in which both receptor-mediated endocytosis and fluid phase pinocytosis were measured on the same samples, inhibition of both processes occurred with the same kinetics and to a similar extent. The rate of receptor-mediated endocytosis recovered to normal rates after 60 min in hypo-osmotic solutions, whereas the rate of fluid phase pinocytosis did not recover to the same extent.

Animals↗
PubMed1988

Regulatory volume decrease in alveolar macrophages: cation loss is not correlated with changes in membrane recycling.

Alveolar macrophages regain their normal volume after swelling in hypo-osmotic solutions. This process, termed regulatory volume decrease (RVD), is initiated 3-5 minutes after exposure of cells to hypo-osmotic solutions, and by 30 min, near-normal volumes are attained. Volume decrease does not occur at 0 degrees C or in solutions in which Na+ has been replaced by K+, or Cl- by the impermeant anion gluconate. These results, as well as direct measurement of intracellular cations, indicate that decreases in cell volume result primarily from the loss of K+ and Cl- and are similar to RVD in lymphocytes. Kinetic analysis of cation loss, both by directly measuring changes in intracellular cation content and by assaying rubidium efflux, showed that cation loss occurred immediately upon media dilution. The rate of cation loss fit first-order kinetics and preceded both the initiation of volume decrease and the maximum increase in surface receptor number. These results suggest that the cation transporters responsible for RVD are located at the cell surface and that regulation of activity is not dependent on alterations in membrane movement.

Animals↗
PubMed1988

Increase in Leu 2+ Leu 7+ lymphocytes in HIV 1-seropositive patients with hemophilia repeatedly treated with clotting factor concentrates.

The fact that patients with hemophilia treated with clotting factor and HIV 1-seronegative subjects with congenital anemias given repeated blood transfusions both have decreased ratios of T4/T8 lymphocytes and diminished NK cell activity indicates that these immunological abnormalities can be due to repeated exposure to blood and blood products, and are not necessarily indicative of HIV 1 infection. To search for an immunological change specific for HIV 1 infection we tested 36 hemophiliacs (22 HIV 1-seropositive, 14 HIV 1-seronegative), and 27 normal subjects for peripheral blood lymphocytes which coexpress Leu 2, a marker associated with suppressor/cytotoxic cells, and Leu 7, an NK cell marker. Compared to normal subjects, seropositive hemophiliacs showed a 2.5-fold increase in Leu 2+ Leu 7+ cells. No increase in this population was seen in the seronegative hemophiliacs. An increase in the percentage of Leu 2+ Leu 7+ cells is therefore an immunological alteration associated with HIV 1 infection but not blood product exposure per se.

Adult↗
PubMed1988

Comparison of sodium bicarbonate with dichloroacetate treatment of hyperlactatemia and lactic acidosis in the ischemic rat.

Serum lactic acidosis is characterized by a pH less than 7.25 and lactate greater than 5 mEq. Although sodium bicarbonate (NaHCO3) is standard treatment for this condition, clinical and experimental studies suggest that high doses of NaHCO3 may be ineffectual or even detrimental to brain, cardiovascular, and respiratory function, as well as survival. For this reason, low dose therapy with NaHCO3 has been recommended. Sodium dichloroacetate (NaDCA) has been used successfully to treat clinical and experimentally-induced lactic acidosis. The present study was designed to compare the effects of low dose NaHCO3 with NaDCA on blood pressure, blood chemistries and brain metabolites in rats with a low flow-induced (Type A, the most common type) lactic acidosis. Fasted male Wistar rats were subjected to cerebral ischemia and systemic hypotension for 30 min at which time, if the pH or HCO-3 fell to 7.2 or 10, respectively, the rat was treated with NaHCO3, NaDCA, or an equal volume of sterile water. Over the 30 min of recirculation that followed ischemia, treatment had no effect on blood pressure or glucose or on brain glucose or glycogen. NaHCO3 had no effect on lactate but appeared to stabilize pH and increase HCO3- more than in sham- or NaDCA-treated rats. Although NaDCA caused a greater increase in HCO3- than sham treatment, pH continued to decline. However, lactate decreased more in NaDCA- than in sham- or NaHCO3- treated rats. These results suggest that low dose NaHCO3 is not detrimental in this model; however, although NaHCO3 stabilized pH, it did not rapidly correct the acidosis. NaDCA at this dose had no effect on the acidosis but was effective in decreasing lactate. Since serum lactate has previously correlated with survival and since higher doses of NaDCA have corrected lactic acidosis in other studies, future evaluation of postischemic treatment with higher doses of NaDCA is warranted.

Acetates↗
PubMed1988

Control of perioperative hypertension during coronary artery surgery. A randomised double-blind study comparing isosorbide dinitrate and nitroglycerin.

A reduction in the causes of myocardial ischaemia remains of prime importance during coronary artery surgery. Hypertension with the ensuing increase in myocardial oxygen demand is a major factor in the aetiology of perioperative myocardial ischaemia. Nitroglycerin (NTG) has long been used beneficially to reduce myocardial oxygen demand by its effects on the systemic and peripheral vascular resistances. An alternative nitrate, isosorbide dinitrate (ISDN) is now available as an intravenous preparation, and may offer technical advantages, both due to its stability in solution and also its longer in vivo half-life. We designed and carried out a multi-centre study to compare and evaluate the efficacy of ISDN and NTG in the management of perioperative hypertension in 85 patients undergoing elective coronary artery surgery. A total of 288 events in which the systolic blood pressure (SBP) exceeded a predetermined trigger value were observed. ISDN was successful in treating hypertension in 63% of the events, whereas NTG had an 83% success. The SBP was significantly lowered after treatment with either ISDN, 155 mmHg to 138 mmHg, or NTG, 160 mmHg to 130 mmHg. The mean successful dose rate for ISDN was 6.5 micrograms kg-1 min-1, whereas for NTG this was 3.8 micrograms kg-1 min-1. In the ISDN group less events took place possibly due to the longer duration of this drug. In many previous studies NTG has been found to be effective in controlling hypertension; ISDN offers and alternative approach in reducing hypertension.

Coronary Artery Bypass↗