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Biomedical subjects

B Culver

Publications and source records attributed to B Culver.

16 recordsLinked to original sources

Impaired cardiac contractile function in ventricular myocytes from leptin-deficient ob/ob obese mice.

The level of the obese gene product leptin is often positively correlated with body weight, supporting the notion that hyperleptinemia contributes to obesity-associated cardiac dysfunction. However, a link between leptin levels and cardiac function has not been elucidated. This study was designed to examine the role of leptin deficiency (resulting from a point mutation of the leptin gene) in cardiomyocyte contractile function. Mechanical properties and intracellular Ca(2+) transients were evaluated in ventricular myocytes from lean control and leptin-deficient ob/ob obese mice at 12 weeks of age. Cardiac ultrastructure was evaluated using transmission electron microscopy. ob/ob mice were overtly obese, hyperinsulinemic, hypertriglycemic, hypoleptinemic and euglycemic. Ultrastructural examination revealed swelling and disorganization of cristae in mitochondria from ob/ob mouse ventricular tissues. Cardiomyocytes from ob/ob mice displayed reduced expression of the leptin receptor Ob-R, larger cross-sectional area, decreased peak shortening and maximal velocity of shortening/relengthening, and prolonged relengthening but not shortening duration compared with lean counterparts. Consistent with mechanical characteristics, myocytes from ob/ob mice displayed reduced intracellular Ca(2+) release upon electrical stimulus associated with a slowed intracellular Ca(2+) decay rate. Interestingly, the contractile aberrations seen in ob/ob myocytes were significantly improved by in vitro leptin incubation. Contractile dysfunction was not seen in age- and gender-matched high fat-induced obese mice. These results suggested that leptin deficiency contributes to cardiac contractile dysfunction characterized by both systolic and diastolic dysfunction, impaired intracellular Ca(2+) hemostasis and ultrastructural derangement in ventricular myocytes.

Animals↗

Technique of, and complications attributable to, repeated hyperosmotic blood-brain barrier disruption in dogs.

OBJECTIVE: To design a repeatable technique for reversible, hyperosmotic blood-brain barrier disruption (BBBD) in dogs and evaluate clinical effects of multiple BBBD. ANIMALS: 10 healthy adult dogs. PROCEDURE: Using fluoroscopic guidance, an arterial catheter was directed into the internal carotid artery via the femoral artery of 10 dogs. Blood-brain barrier disruption was achieved in 5 dogs, using intracarotid infusion of mannitol. Five control dogs received only saline solution. After recovery, dogs were monitored for clinical signs of disease before a second, nonsurvival procedure was performed 2 to 3 weeks later. BBBD was estimated, using computed tomographic (CT) densitometry values, as well as Evan's blue dye staining on necropsy specimens. RESULTS: Seven dogs completed the entire study. Two treatment dogs were lost after the first infusion because of deteriorating neurologic function attributed to CNS edema and increased intracranial pressure. One control dog was lost because of vessel wall damage during catheterization. The remaining dogs had only transient neurologic, ocular, and vasculature injuries. Successful BBBD was documented in all treated dogs by use of CT and Evan's blue dye evaluation. CONCLUSION: Repeated catheterization of the internal carotid artery and disruption of the blood- brain barrier is possible in dogs. CLINICAL RELEVANCE: Refinement of this technique would be useful not only for improved delivery of chemotherapeutic agents in patients with brain tumors, but also would allow further investigation of new treatments involving genetically engineered retroviruses and monoclonal antibodies.

Animals↗

Vaginal fluid adenosine 3',5'-cyclic monophosphate (cAMP) in the rat: interaction with sperm cAMP-dependent protein kinase regulatory subunits.

Cyclic AMP (adenosine 3',5'-cyclic monophosphate) concentrations were determined in rat vaginal fluids throughout the estrous cycle. Radioimmunoassay results demonstrated that estrus and early metestrus vaginal fluids had significantly (p less than 0.01) elevated cAMP concentrations compared to proestrus, late metestrus, and early and late diestrus. Ovariectomy reduced RIA-detectable cAMP in vaginal fluid. When cauda sperm were preincubated for 5 min with vaginal fluids from each stage of the estrous cycle, results demonstrated that only estrus- and early metestrus-stage vaginal fluids caused a decrease in [32P]-8N3cAMP (8-azido photoaffinity analogue of cAMP) photolabeling of sperm cAMP-dependent protein kinase regulatory subunits RI and RII. To examine if this reduction in [32P]-8N3cAMP photoincorporation by sperm RI and RII could be due to endogenous cAMP, vaginal fluids were boiled, trypsinized, and/or incubated with EGTA or phosphodiesterase. Only phosphodiesterase-treated vaginal fluids restored sperm regulatory subunit photoincorporation of [32P]-8N3cAMP. It is suggested that cAMP is present in rat vaginal fluids during the estrous cycle in a concentration sufficient to bind the regulatory subunits of rat sperm cAMP-dependent protein kinase.

Animals↗

Changes in plasma proenkephalin peptide F and catecholamine levels during graded exercise in men.

Proenkephalin peptide F immunoreactivity, epinephrine, and norepinephrine were measured in the plasma of endurance-trained and untrained male subjects riding on a bicycle ergometer at 28%, 54%, 83%, and 100% of maximum oxygen consumption (VO2). At rest the trained group had peptide F levels almost twice the level of the untrained group, whereas all other variables measured were the same. The maximum epinephrine and norepinephrine levels were found at 100% exercise intensity, with a precipitous drop in the levels at 5 min of recovery. In contrast, the peptide F immunoreactivity reached a maximum at 5 min of recovery and was still substantially above the initial level after 15 min of rest. In addition, the trained subjects showed another peak of peptide F immunoreactivity at 54% VO2max. Possible explanations for the different patterns of catecholamine and peptide F levels are presented.

Adult↗

Glial cells: modulators of neuronal environment.

Studies of glial cells in neural tissue culture systems suggest that glial cells subserve different functions during development and aging of the central nervous system and that they may help modulate the neuronal environment by virtue of their responsiveness to hormones and other intrinsic factors. There is a marked proliferation of glial cells during early stages of brain development, probably reflecting the involvement of glial cells in myelination and other growth processes. Studies in culture suggest that proliferation of glial cells can be induced by steroid hormones. The migration rate of glial cells from cerebellar explants of embryonic chick brain grown in organotypic culture was measured in control and hormone-treated explants. Treatment with cortisol, corticosterone, estradiol, and progesterone significantly elevated glial cell migration from the tissue explants. The influence of steroid hormones on glial cells may be mediated via a steroid intracellular mechanism. In C-6 glioma cells and in chick embryo dissociated brain cell cultures consisting predominantly of glial cells, 3H-corticosterone was shown to accumulate by a saturable but non-specific retention mechanism. In contrast, the accumulation of 3H-corticosterone by predominantly neuronal cultures was both saturable and specific. Glial cells in culture exhibit certain age-related changes, including changes in resting membrane potentials and in cellular responses to hormone treatment, as measured by changes in incorporation of 3H-leucine into protein and incorporation of 3H-uridine into RNA. The possibility that glial cells in vivo may likewise exhibit differential responses to hormones throughout the lifespan suggests that hormones may markedly influence cellular aging.

Aging↗

Variability in interpretation of pulmonary function tests.

We asked 26 pulmonary physicians to interpret results of ten consecutive pulmonary function tests from one laboratory. There was frequent disagreement in their assessment of respiratory impairment. This is likely due to the variety of criteria for grading the severity of obstructive and restrictive defects. Since the narrative interpretation of pulmonary function data may influence patient care, physicians should consider the numerical magnitude of the derangements, as well as the descriptive terms applied.

Humans↗

A Golgi analysis of caudate neurons in rats exposed to carbon monoxide.

Interneurons of the caudate nucleus have been reported in the literature to respond to deafferentation by reduction in dendritic spines. In the studies reported here, caudate interneurons have been examined using the Golgi technique and increased numbers of spines were found in adult rats exposed to carbon monoxide as neonates. The development of spines on the caudate neurons was delayed for several days after an acute anoxic episode in 5-day-old rats exposed to carbon monoxide to the point of respiratory arrest. By the time the rats were 6 weeks old the caudate neurons had recovered to the point where they had essentially normal numbers of spines. At later ages (2- and 7-months old) the number of spines was greater in rats exposed perinatally to carbon monoxide than in control rats of the same age. The development of abnormal numbers of spines coincided with the time of recovery of rats from behavioral hyperactivity induced by carbon monoxide. The increased spines on the caudate neurons of the adult rats (7-months old) can be explained as a compensatory response to increased afferent flow to the caudate during the period of juvenile hyperactivity which reaches a peak at 6 weeks of age. It is proposed that the return to normal activity in the adult may be a consequence of increased activity of the caudate nucleus.

Age Factors↗

Comparison of the structure of hyperactive behavior in rats after brain damage from x-irradiation, carbon monoxide and pallidal lesions.

Nocturnal hyperactivity, as measured by photocell counts of locomotion in a residential maze, was produced in rats by 3 different kinds of brain damage, X-irradiation at gestational day 14 or 15, exposure to carbon monoxide on the fifth day of postnatal life, or bilateral stereotaxic lesions of the globus pallidus in adult rats. These brain-damaged rats and their controls were photographed at 1 frame/sec during their first exploratory experience in a simple cage. Frequency of 15 motor acts, duration of each occurrence and associations of pairs of acts were calculated. The 15 motor acts were divided into 3 clusters of acts labeled grooming, exploratory and attention behaviors. Hyperactivity was associated with shortened durations and increases in frequency of exploratory acts, while grooming and attention behaviors tended to decrease in duration and frequency. Sequences of behavior acts were less structured in hyperactive animals than in controls. In spite of the marked differences known to be produced on brain structures by the 3 different kinds of damage, no changes in behavior structure were found which were uniquely associated with one kind of brain damage. Hyperactivity appeared to be a continuum in that the intensity of effects produced on behavior as measured by the photographic technique correlated well with the amount of increase in photocell activity.

Animals↗

Primary meningococcal pericarditis presenting with tamponade.

An unusual case of a patient with primary meningococcal pericarditis presenting with tamponade is reported. tdespite repeated aspiration and appropriate antibiotic therapy with eradication of group C Neisseria meningitidis, pericardial effusion continued to reaccumulate. Institution of high-dosage corticosteroid therapy resulted in rapid resolution of the effusion. Only six other cases of primary meningococcal pericarditis have been reported in the English literature. Early manifestations of this disease are due to bacterial invasion of the pericardium. The later phase of intensive reaccumulation of sterile pericardial fluid may conceivably be related to meningococcal endotoxin and appears to be responsive to corticosteroid or salicylate therapy. Recognition of this phenomenon may obviate the necessity for a pericardiectomy.

Adult↗

Measurement of the effects of drugs on activity of permanent groups of rats.

The diurnal light-dark cycle, grouping of animals and spatial organization of the environment may affect the behavioral responses of animals to psychoactive drugs. A method of working with these factors experimentally is described, using a residential maze equipped with photocells for recording activity of groups of animals. Preliminary results show reliable activity measurements are produced which are sensitive to modification by drugs.

Amphetamine↗