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Biomedical subjects

P Chang

Publications and source records attributed to P Chang.

At least 253 records · Page 14Linked to original sources

Effects of clonidine on renal sympathetic nerve activity and norepinephrine spillover.

The antihypertensive action of clonidine (CLO) depends mainly on decreased release of the sympathetic neurotransmitter, norepinephrine (NE), at vascular neuroeffector junctions. The decreased release can be due to stimulation of alpha-2 adrenoceptors or other receptors in the brain or due to stimulation of presynaptic inhibitory alpha-2 adrenoceptors on sympathetic nerve endings. To compare central and peripheral contributions to the depressor action of CLO, renal sympathetic nerve activity (RSNA) and renal spillover of NE (RNEs) were measured at baseline and during reflexive increases in RSNA evoked by nitroprusside-induced hypotension (27, 50 and 105 micrograms/kg/min) before and after CLO treatment in adrenal-demedullated, anesthetized rats. Administration of CLO decreased RSNA by 52 +/- 8% and RNEs by 32 +/- 13% (means +/- S.E.M.). At levels of RSNA less than 50% above control, there were no significant changes in RNEs; above this level of activity RNEs increased, regardless of CLO treatment. CLO treatment did not alter significantly the relationship between increases in RSNA and in RNEs during nitroprusside-induced hypotension. The results suggest that in neurologically intact, anesthetized animals, CLO decreases renal NE release mainly by inhibiting sympathetic outflow, with little if any peripheral presynaptic action.

Adrenal Medulla↗

Loss of NGF receptor immunoreactivity in basal forebrain neurons of aged rats: correlation with spatial memory impairment.

Nerve growth factor (NGF) has recently been implicated as a trophic agent in the survival and maintenance of basal forebrain cholinergic neurons. To test the hypothesis that NGF may play a role in the age-related decline of cerebral cholinergic function and loss of cognitive ability, we investigated the possible correlation between the loss of basal forebrain neurons that stain for NGF receptor, and impairment of spatial reference memory performance in aged rats. Our results suggest that NGF receptor-positive basal forebrain neurons undergo marked cell atrophy and loss of neuropil staining in aged rats exhibiting impaired spatial learning and memory performance. Conversely, numerous, densely immunoreactive perikarya and a profuse neuritic plexus within the basal forebrain nuclei was consistently observed in behaviorally intact rats. Overall, the mean number of NGF receptor-positive basal forebrain neurons both in the nucleus of the diagonal band and nucleus basalis correlated with retention of the spatial task (r = 0.84 and r = 0.67, respectively; P less than 0.01). Our results support the view that progressive failure of retrograde trophic support due to the age-related loss of NGF receptors may promote degenerative changes in basal forebrain cholinergic neurons, and contribute to deterioration of cognitive ability in senescence.

Aging↗

Improved neonatal heart preservation with an intracellular cardioplegia and storage solution.

The optimal conditions for preservation of the neonatal heart for transplantation remain uncertain. An isolated, working neonatal piglet heart model was used to compare a standard extracellular-like cardioplegic solution followed by storage at 4 degrees C in normal saline for 12 hr (n = 8) to cardioplegia and storage at 4 degrees C for 24 hr in an intracellular-like solution (n = 7). Seven of eight hearts in the 12-hr Extracellular Group failed to regain function, with a maximum stroke work index (SWI), developed at a left ventricular end-diastolic pressure (LVEDP) of 9 mm Hg of 0.91 +/- 0.30 x 10(3) erg/g (mean +/- standard error of the mean), 7.1% of nonpreserved control hearts. In contrast, all hearts arrested and stored for 24 hr in the intracellular solution regained function with a maximum SWI, again at a LVEDP of 9 mm Hg of 9.51 +/- 1.98 X 10(3) erg/g, 73.7% of control (P less than 0.05). Ultrastructural changes seen by electron microscopy paralleled the functional results. We conclude that an intracellular arrest and storage solution may be superior to conventional solutions for extended preservation of the neonatal heart.

Animals↗

Cell-cycle radiation response: role of intracellular factors.

We have been studying variations of radiosensitivity and endogenous cellular factors during the course of progression through the human and hamster cell cycle. After exposure to low-LET radiations, the most radiosensitive cell stages are mitosis and the G1/S interface. The increased activity of a specific antioxidant enzyme such as superoxide dismutase in G1-phase, and the variations of endogenous thiols during cell division are thought to be intracellular factors of importance to the radiation survival response. These factors may contribute to modifying the age-dependent yield of lesions or more likely, to the efficiency of the repair processes. These molecular factors have been implicated in our cellular measurements of the larger values for the radiobiological oxygen effect late in the cycle compared to earlier cell ages. Low-LET radiation also delays progression through S phase which may allow more time for repair and hence contribute to radioresistance in late-S-phase. The cytoplasmic and intranuclear milieu of the cell appears to have less significant effects on lesions produced by high-LET radiation compared to those made by low-LET radiation. High-LET radiation fails to slow progression through S phase, and there is much less repair of lesions evident at all cell ages; however, high-LET particles cause a more profound block in G2 phase than that observed after low-LET radiation. Hazards posed by the interaction of damage from sequential doses of radiations of different qualities have been evaluated and are shown to lead to a cell-cycle-dependent enhancement of radiobiological effects. A summary comparison of various cell-cycle-dependent endpoints measured with low- or high-LET radiations is given and includes a discussion of the possible additional effects introduced by microgravity.

Cell Cycle↗

Hydrophobic interactions in human casein micelle formation: beta-casein aggregation.

The association of non-phosphorylated (0-P) and fully phosphorylated (5-P) human beta-caseins was studied by fluorescence spectroscopy and laser light scattering. The tryptophan fluorescence intensity (FI) level increased between 20 and 35 degrees C, indicating a change in the environment of that residue. A similar transition occurred when ANS was used as a probe. Transition temperatures were slightly lower in 10 mM-CaCl2 but were not affected by an equivalent increase in ionic strength caused by NaCl. The magnitude of the FI change was less for the 5-P than the 0-P protein but was increased for both by CaCl2 addition. These FI data were characteristic of a conformational change and this was supported by fluorescence polarization which indicated that with CaCl2, tryptophan and ANS mobility increased at the transition temperature even though the extent of protein association also increased. Light scattering suggested that protein association proceeded with the primary formation of submicellar aggregates containing 20-30 monomers which then associated further to form particles of minimum micelle size (12-15 submicelles), and eventually larger. The temperature of precipitation of the 5-P form in the presence of CaCl2 was lower than the conformational transition and suggested that both hydrophobic interactions and Ca bridges between phosphate esters on adjacent molecules are important in micelle formation.

Caseins↗

Polymorphic reticulosis: a malignant lymphoma of B-cell lineage.

Whether the pathogenesis of polymorphic reticulosis is from T cells, B cells, or histiocytes has been controversial. In this study, the Southern blot hybridization technique was used to analyze immunoglobulin and T-cell receptor beta-chain genes and to perform the conventional surface marker analysis in two patients with polymorphic reticulosis. The immunophenotype demonstrated the presence of predominantly mature, activated T-lymphocytes, minimal B-cells, and no natural killer cells or monocytes/granulocytes. The mature T-cell phenotype could be due to either inflammatory infiltrates or neoplastic cells of peripheral T-cell type, because the two coexist in polymorphic reticulosis tumors. The value of surface marker examination is limited in the analysis of PMR tumors. However, genetic analysis revealed that only Ig genes were rearranged, with no rearrangement of the TCR beta gene. Rearrangement of immunoglobulin genes occurs in B-lineage lymphoid neoplasms and is thought to be a criterion for diagnosis of lymphoid neoplasms. Based on genetic analysis and clinicopathologic information, this study concluded that polymorphic reticulosis is a malignant lymphoma of B-cell lineage.

Adult↗

Tumors of the pharyngomaxillary space.

A bulging of the soft palate should alert one to the possibility of a mass in the pharyngomaxillary space. Work-up includes CT scan or MRI and possible needle aspiration. Open biopsy should be avoided. Benign, mixed tumors are most commonly encountered. Surgical excision by external approach is generally advocated.

Adenoma↗

Prevention of reperfusion injury in the neonatal heart with leukocyte-depleted blood.

Activated leukocytes release oxygen free radicals and cause microvascular occlusion. This experiment tests the hypothesis that reperfusion with leukocyte-depleted blood reduces injury after extended ischemic preservation. An in vitro model consisting of an isolated, working neonatal piglet heart and an adolescent support pig was used. Hearts were arrested with a cold crystalloid cardioplegic solution, excised, and stored in 4 degrees C saline for 12 hours. Two groups were compared. In group 1 piglets (n = 8), reperfused with whole blood, the maximum stroke work index was 0.91 +/- 0.29 x 10(3) erg/gm (mean +/- standard error of the mean). Group 2 piglets (n = 6), reperfused with blood depleted of leukocytes by a polyester filter, had a maximum stroke work index of 11.6 +/- 1.0 x 10(3) erg/gm. This difference was highly significant (p less than 0.0001). Group 1 exhibited severe injury with myofibrillar necrosis, mitochondrial disruption, nuclear chromatin clumping, and moderate interstitial edema. Group 2 had normal ultrastructure on electron microscopic examination. We conclude that reperfusion with leukocyte-depleted blood prevents reperfusion injury and results in excellent myocardial function after long-term heart preservation.

Animals↗

Interactions in human casein systems: self-association of nonphosphorylated human beta-casein.

Since caseins were originally defined as phosphoproteins, nonphosphorylated beta-casein, comprising nearly 5% of the total beta-casein in the isoelectric precipitate from human milk, appears to be unique. Despite the relatively small amount present, its properties suggest that it may play an important role in micelle formation and structure. It has a partial specific volume, v, of 0.749 +/- 0.008 and an absorbance, E1% 1 cm,280 nm of 6.2 +/- 0.2. Sedimentation and viscosity data yield a solvation of 3 g H2O/g protein and an axial ratio of about 5 for the monomer. This would be consistent with a prolate ellipsoid of 10 nm length and 2 nm width. Equilibrium in the system is attained quite slowly and the temperature-dependent polymerization was found to be reversible. With calcium, the solubility behavior reflects an increased hydrophobicity and lower electrostatic repulsion in the molecule. There is essentially no strong calcium binding to this protein but there is evidence which strongly suggests that calcium binds to nonphosphate groups at higher concentrations. Increasing the temperature from 4 to 37 degrees C causes an apparent conformational change and an increase in protein aggregation which is further increased by addition of NaCl at 37 degrees C until a limiting size is reached at about 0.1 M NaCl. This limiting size polymer contains about 75 monomers and is nearly spherical with a radius of about 12 nm and a solvation of 1.5 g H2O/g protein. Laser light scattering measurements on the solution in 0.25 M NaCl revealed a relatively homogeneous particle size with a corrected diffusion coefficient, D20,w, of 2.8 X 10(-7) cm2/s.

Calcium↗

An operating table for hand surgery.

The construction details for an inexpensive, easy-to-build operating table for hand surgery have been described. The table was specifically designed according to the needs of those working with it. It has been in daily use for over 2 years and has proved to be a popular product with all staff members.

Hand↗

Long-term neonatal heart preservation.

UNLABELLED: Donor availability is a major limiting factor in neonatal heart transplantation. Prolonging donor heart preservation would facilitate distant heart procurement. Forty-two neonatal (1 to 5 days) piglet hearts in seven groups were arrested with cold cardioplegic solutions, stored for 12 hours at 4 degrees C in storage solutions, and reperfused with blood from an adult support pig. The cardioplegic solutions used were a crystalloid solution with potassium chloride 30 mEq/L and bicarbonate (Stanford), the Stanford cardioplegic solution with the addition of calcium (1.2 mmol/L), or an intracellular solution (Sacks) with added glucose. Storage solutions were normal saline, Sacks II, or Sacks II with glucose 20 gm/L. Reperfusion was done with normal blood or modified blood for 20 minutes with superoxide dismutase, catalase, aspartate, glutamate, citrate-phosphate-dextrose, potassium, tromethamine, and 50% dextrose followed by normal blood. Evaluation of stroke work index after 60 minutes of recovery (as percent of control) was performed using the isolated, blood perfused, working heart preparation in all groups: Group I (Stanford cardioplegia, saline storage, normal blood reperfusion) had a recovery of 11%; group II (Stanford + calcium, saline, normal blood) 8%; group III (Stanford + calcium, saline, modified blood, superoxide dismutase 35,000 U/L, catalase 35,000 U/L) 37%; group IV (Stanford + calcium, Sacks II, modified blood, superoxide dismutase 35,000 U/L, catalase 35,000 U/L), 47%; group V (Stanford + calcium, Sacks + glucose, modified blood, superoxide dismutase 35,000 U/L, catalase 105,000 U/L) 89%; group VI (Stanford + calcium, Sacks + glucose, modified blood, superoxide dismutase 150,000 U/L, catalase 150,000 U/L) 107%; group VII (Sacks + glucose, Sacks + glucose, modified blood, superoxide dismutase 35,000 U/L, catalase 105,000 U/L) 115%. CONCLUSIONS: The neonatal heart stored hypothermically for 12 hours tolerates normal blood reperfusion poorly. Modified blood reperfusion markedly improves the recovery. Complete functional recovery was achieved by the intracellular Sacks plus glucose storage solution and modified blood reperfusion with oxygen-derived free radical scavengers (high catalase). Extended preservation of the neonatal heart is feasible.

Animals↗