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Biomedical subjects

B Benson

Publications and source records attributed to B Benson.

At least 19 recordsLinked to original sources
PubMed2001

Regional cerebral blood flow correlated with flashback intensity in patients with posttraumatic stress disorder.

BACKGROUND: Nuclear imaging studies have examined cerebral blood flow (rCBF) in subjects with posttraumatic stress disorder (PTSD) using symptom evocation paradigms. To date, no such studies have investigated rCBF as related to subjects' reports of flashback intensity. METHODS: Subjects with varying traumatic histories and longstanding PTSD were studied using [15O]-H2O positron emission tomography with an auditory script of their traumatic event. Eight subjects had three resting scans followed by their script and additional scans. Heart rate responses as well as the presence of flashbacks and their intensity were recorded. rCBF was correlated with flashback intensity in each subject's scan. Combined analysis of all subjects' data yielded common regions related to the flashback experience. RESULTS: rCBF correlated directly with flashback intensity in the brainstem, lingula, bilateral insula, right putamen and left hippocampal and perihippocampal, somatosensory and cerebellar regions. Inverse correlations with rCBF were found in bilateral dorsolateral prefrontal, right fusiform and right medial temporal cortices. CONCLUSIONS: This study correlated flashback intensity and rCBF in a group of patients with chronic PTSD suggesting involvement of brainstem, and areas associated with motor control, complex visual/spatial cues and memory.

Adult↗
PubMed1998

An essential role for ovarian inhibin in pineal gland-mediated anestrus in Syrian hamsters.

When transferred from long photoperiod (LP) to short photoperiod (SP), female Syrian hamsters exhibit depressions of follicle stimulating hormone (FSH) and follicular development, cessation of ovulation, and marked ovarian interstitial tissue hyperplasia. Pinealectomy prevents these effects of SP. The object of this study was to determine the role of inhibin in the regulation of FSH during SP-induced anestrus. Adult LSH/SsLak hamsters maintained in LP (LD 14:10 hr) were transferred to SP (LD 8:16 hr) on the day of estrus, and groups of animals killed at either 16.00 hr on proestrus or 08.00 hr on estrus during each of five consecutive 4-day estrus cycles after transfer. Groups of females that became anestrus in SP were killed either at 08.00 or 16.00 hr, 12 days after the last observed estrus discharge. Compared to LP controls, serum FSH levels on estrus increased significantly (P<0.01) during the first two cycles in SP before declining to concentrations that were significantly lower than control values (P<0.01). Serum inhibin levels increased significantly by the third, fourth, and five days of estrus in SP. Regression analysis revealed a significant inverse correlation between serum inhibin and FSH levels on estrus during SP exposure (P=0.021) but not on proestrus. Relative levels of inhibin alpha- and betaA-subunit mRNAs were lower in ovaries from SP proestrus and anestrus females killed at 16.00 hr as compared to those from proestrus LP controls; they were elevated in ovaries from SP estrus and anestrus females killed at 08.00 hr compared to those from estrus LP controls. The absence of antral follicles on estrus in the last cycles of SP and anestrus suggests that the increase in circulating inhibin and inhibin mRNAs may be derived from hyperplastic interstitium. These observations suggest that inhibin may play an essential role in suppressing FSH secretion during pineal gland-mediated anestrus in Syrian hamsters.

Anestrus↗
PubMed1997

Morphologic and molecular changes induced by recombinant human leptin in the white and brown adipose tissues of C57BL/6 mice.

Leptin is a 16-kd protein synthesized and secreted by adipose tissue, which regulates adiposity and body weight. To investigate the peripheral effects of recombinant human leptin, lean C57BL/6 mice were treated with subcutaneous injections of vehicle or 20 mg/kg/day leptin for 1 to 14 days. Groups of animals were killed on Days 1, 2, 3, 4, 7, or 8 and 15 to evaluate the time course of clinical chemistry, morphologic, and molecular changes in white (WAT) and brown adipose tissue (BAT) depots. There was a progressive daily reduction in the body weight of mice receiving leptin. By Day 15, the body weight of leptin-treated groups decreased by 6% to 8% relative to base-line weight. Clinical chemistry changes in treated mice included decreased cholesterol and triglyceride levels. At necropsy, the mice had rapidly progressive atrophy of subcutaneous, intra-abdominal, and retroperitoneal WAT and interscapular BAT depots, with complete depletion of fat stores by Days 3 to 4 in most females and by Days 7 to 14 in male mice. Histologically, white and brown adipocytes underwent marked atrophy with loss of lipid droplets and activation of BAT cells in WAT depots. Ultrastructurally, white and brown adipocytes contained numerous, enlarged mitochondria. Molecular analysis of key adipose tissue genes in brown and white fat depots revealed a rapid, selective increase in the mRNA expression of thermogenic proteins and lipolytic enzymes, including uncoupling proteins 1 and 2, lipoprotein lipase, and hormone-sensitive lipase, with decreases in the lipogenic enzyme fatty acid synthase, endogenous leptin, and cytochrome c oxidase. These data suggest that the peripheral effects of leptin include increased thermogenesis and lipid oxidation in brown fat coupled with increased lipolysis and decreased fat synthesis in white and brown fat, which lead to a rapid reduction in the body weight and adiposity of mice.

Adipose Tissue↗
PubMed1996

Chronic lateral ventricle infusion of a pineal gland-derived decapeptide alters pulsatile secretion of LH in rats.

The object of this investigation was to determine whether chronic lateral ventricle infusion of a pineal gland-derived antigonadotropic decapeptide (AGD) would affect pulsatile luteinizing hormone (LH) release in conscious, unrestrained male rats. Adult male Harlan SD rats were bilaterally orchiectomized and maintained under conditions of controlled photoperiods and temperature. After three (Experiment one) or four (Experiment two) weeks each was fitted stereotaxically with a stainless steel cannula for infusion into the right lateral ventricle. Each cannula was attached to a subcutaneous osmotic minipump filled either with artificial cerebrospinal fluid (CSF) or AGD in CSF (0.5 microgram/microliter). CSF (1.0 microliter/hr) or the AGD (0.5 microgram/microliter hr) was infused over a period of four days. Blood samples for determined of LH by radioimmunoassay were obtained at five minute intervals from a Tygon microbore cannula inserted via a femoral artery into the abdominal aorta. LH pulses were defined and identified with a computerized deconvolution algorithm designed to determine spontaneous LH secretory events. Although mean LH levels were not significantly reduced, LH secretory pulse frequency and nadirs were significantly decreased by ADG infusion (p<0.01). Additionally, LH secretory pulse amplitude and LH secretory response to LHRL administration were significantly increased (p<0.01) by AGD treatment. These results confirm initial reports of depressive effects of the AGD on LH secretion and support its hypothesized central site of action.

Activity Cycles↗
PubMed1996

Lung function in premature rabbits treated with recombinant human surfactant protein-C.

We report the activity of recombinant human surfactant apoprotein-C (rSP-C[Cys]2) and various phospholipids in a preterm rabbit model of respiratory distress syndrome (RDS). Mixtures of rSP-C(Cys)2 and certain phospholipids had similar activity (lung compliance and lung pressure-volume behavior) to rabbit surfactant in this model. The activity of rSP-C(Cys)2 was maximal at 1 mol% protein and varied significantly with the phospholipid composition. Chemically synthesized SP-C had similar activity to rSP-C(Cys)2. Deletion of six amino-terminal residues did not affect function. Substitution of cysteines and cysteine6 with adjacent serines (rSP-C[Ser]2) by site-specific mutagenesis minimized aggregation of rSP-C but did not affect activity. Palmitoylation of cysteine5 and cysteine6 in rSP-C (rSP-C[C16]2) did not enhance the activity of rSP-C(Cys)2. We conclude that bacterial expression is a practical source of functional SP-C, and that nonacylated forms of SP-C may be useful adjuvants to phospholipids in the treatment of RDS and possibly other forms of acute lung injury.

Animals↗
PubMed1996

Venlafaxine or bupropion responders but not nonresponders show baseline prefrontal and paralimbic hypometabolism compared with controls.

In this study, 11 unipolar depressed outpatients received baseline (medication-free) fluorine-18 deoxyglucose positron emission tomography scans prior to randomization to double-blind venlafaxine or bupropion monotherapy, with the option of a subsequent medication crossover. Based on Clinical Global impressions ratings, 6 of 11 responded to at least one medication. Regional cerebral glucose metabolic rate (rCMRglu) for these 6 responders was compared with 18 age- and gender-matched healthy controls; the 5 nonresponders were compared with 15 matched healthy controls. Compared with healthy controls, responders showed decreased (normalized > absolute) left middle frontal gyral, bilateral medial prefrontal, and bilateral temporal rCMRglu. In contrast, nonresponders showed decreased (normalized > absolute) cerebellar rCMRglu. These preliminary data suggest that among never-hospitalized unipolar depressed out-patients, those showing baseline prefrontal and paralimbic hypometabolism may be more likely to show a positive response to standard antidepressant treatments such as venlafaxine or bupropion.

Adult↗
PubMed1995

Immunoreactive inhibin decreases following bilateral ovariectomy and during the postovulatory rise of FSH in Syrian hamsters.

Inhibin is a heterodimeric glycoprotein which may regulate FSH synthesis and secretion as well as follicular development and maturation. The source and physiological role of inhibin have not been established for the hamster, although several investigators have suggested that this hormone may function in the regulation of FSH in this species. The major objectives of the present studies were to develop a radioimmunoassay (RIA) for the measurement of inhibin in hamster serum and tissue, to identify the primary source of inhibin and to examine the relationship between inhibin and FSH during the estrous cycle. A sensitive, accurate and specific RIA was developed and utilized to measure changes in circulating levels of immunoreactive inhibin (ir-inh-alpha) following bilateral gonadectomy and throughout the estrous cycle. Circulating ir-inh-alpha declined rapidly and significantly following bilateral gonadectomy in female hamsters suggesting a gonadal source. Serum FSH concentrations increased following the decline in serum ir-inh-alpha levels. In the adult female hamster circulating ir-inh-alpha increased gradually throughout diestrus, peaked at the time of the preovulatory gonadotropin surge, then declined to a nadir on the morning of estrus. Changes in ovarian inhibin subunit mRNAs were examined throughout the estrous cycle and correlated with changes observed in circulating ir-inh-alpha levels. Observed significant reductions in the relative amount of inhibin mRNAs and serum concentrations of ir-inh-alpha during early estrus may moderate the amount and duration of the secondary FSH rise and thus contribute to the regulation of follicle recruitment in the hamster.

Animals↗
PubMed1995

Delivery of superoxide dismutase to pulmonary epithelium via pH-sensitive liposomes.

Respiratory insufficiency, when treated with oxygen supplementation, or exposure to diverse pulmonary toxins can cause lung damage as a result of increased oxygen radical production. Enzymes such as superoxide dismutase (SOD) may attenuate this pathological process, but the intracellular delivery and antioxidant action of SOD is impeded by its inability to cross cellular membranes. One approach for facilitating intracellular delivery of macromolecules is to entrap SOD into liposomes. The delivery of SOD to lung cells was accomplished using pH-sensitive liposomes, made with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and 1-oleoyl-2-oleoyl-sn-glycero-3-succinate (DOSG), added to cultured fetal rat lung distal epithelial (FRLE) cells. FRLE cells, obtained from fetuses at day 19 gestation, expressed a high-affinity receptor for surfactant protein A (SP-A) with an apparent dissociation constant (Kd) = 3.6 +/- 0.2 micrograms/ml (5.5 x 10(-9) M) and a capacity of 130 +/- 3 ng/10(6) cells (125,000 +/- 3,000 binding sites/cell). This receptor was utilized for targeting liposomes to cells, after incorporating SP-A during liposome membrane formation. Liposomes were uniformly small (180 +/- 77 nm; mean +/- SD) and stable at 4 degrees C for 1 wk, entrapping 10 +/- 4% of initially added SOD. After incubation of pH-sensitive liposomes containing entrapped SOD with cultured FRLE cells, cell-associated SOD activity was increased 5.1-fold from 7.8 +/- 2.5 to 40.1 +/- 3.3 U SOD/mg cell protein. Incorporation of SP-A into liposomes increased by 6.2-fold the delivery of liposomal SOD to cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Survival after a severe iron poisoning treated with intermittent infusions of deferoxamine.

Iron poisoning is the most common cause of overdose mortality in children under six years of age and there are no reports of survival with iron levels > 2687 mumol/L (> 15,000 micrograms/dL). A 22-month-old male was brought to the emergency department by his parents after ingesting an estimated 50 ferrous sulfate tablets (60 mg elemental iron/tablet) several hours earlier. Despite spontaneous emesis and gastric lavage his condition deteriorated and he was found to have a serum iron of 2992 mumol/L (16,706 micrograms/dL). During the first four days in the intensive care unit, he developed coma, metabolic acidosis, hypovolemic and cardiogenic shock, liver failure, coagulopathy and adult respiratory distress syndrome. He was treated with a unique deferoxamine dosage schedule (25 mg/kg/h for 12 h/d x 3 d), mechanical ventilation, Swan-Ganz catheter monitoring, dopamine/nitroprusside therapy, blood product, bicarbonate, electrolyte and volume replacement. After a prolonged hospital course complicated primarily by gastric outlet obstruction he was dismissed on full oral feedings, gaining weight, and neurologically intact. Swan-Ganz catheter monitoring guided the management of this patient's shock, iron-induced cardiac failure, and deferoxamine mesylate induced adult respiratory distress syndrome. Further experience and research is required to determine the most appropriate deferoxamine mesylate dosing schedule and our experience expands the range for possible survival after massive iron overdose.

Deferoxamine↗
PubMed1994

Infusion of a pineal gland-derived antigonadotropic decapeptide into the lateral ventricle depresses prolactin levels in male rats.

The primary structure of a pineal gland-derived antigonadotropic decapeptide (AGD) was determined recently, and a synthetic analog prepared by solid state methods. Adult male Harlan SD rats were maintained under controlled photoperiods. Each was fitted stereotaxically with a stainless steel cannula for infusion into a right lateral ventricle. Each cannula was attached to a subcutaneous osmotic minipump filled either with artificial cerebrospinal fluid (CSF) or the AGD in CSF (0.5 micrograms/microliters). Additional Tygon microbore cannulae were inserted through the femoral artery and placed in the abdominal aorta for blood sampling and the determination of prolactin (PRL) levels by radioimmunoassay. CSF (1.0 microliter/hr) or the AGD (0.5 microgram/hr) was infused into the right lateral ventricle over a period of seven days. Circulating PRL concentrations were significantly depressed by AGD infusion both in the morning and late afternoon; adenohypophysial concentrations were concomitantly elevated on infusion day seven. These results confirm previous observations of inhibitory effects of the AGD on PRL secretion, and further support its postulated central mechanism of action.

Adrenal Glands↗
PubMed1994

Structure of a pineal gland-derived antigonadotropic decapeptide.

An antigonadotropic decapeptide was extracted from bovine pineal glands, purified by ultrafiltration and Sephadex G-25 gel-filtration chromatography and isolated by serial semi-preparative high performance liquid chromatography. Its primary structure was determined by automated amino acid and microsequence analyses. A synthetic analog of the decapeptide, prepared by solid state methods, was observed to reduce circulating levels of luteinizing hormone and prolactin after intra-atrial injection in male rats.

Amino Acid Sequence↗
PubMed1993

Lung surfactant proteins, SP-B and SP-C, alter the thermodynamic properties of phospholipid membranes: a differential calorimetry study.

The ability of the low molecular weight lung surfactant-associated proteins, SP-B and SP-C, to alter the thermotropic properties of synthetic multilamellar vesicles was tested using differential scanning calorimetry (DSC). The presence of either SP-B or SP-C in dipalmitoylphosphatidylcholine (DPPC) or dipalmitoylphosphatidylglycerol (DPPG) multilamellar vesicles broadened the DSC thermogram and reduced the enthalpy of transition in a concentration-dependent manner. With both proteins, the temperature at which the peak of the phase transition (Tm) was detected was shifted to a higher value. The increase in Tm caused by both proteins was greater with DPPG than DPPC. We have interpreted these results as implying the presence of a protein-perturbed domain of lipid. Both SP-B and SP-C were found to influence the surface activity of the phospholipids in a concentration-dependent fashion. We speculate that instability of lipid packing predicted to occur at protein-created lipid domain boundaries may be important for the expression of surface activity in pulmonary surfactant.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1993

Age-related changes in biogenic amines, opiate, and steroid receptors in the prepubertal bull calf.

Events leading to the increase in pulsatile LH secretion during prepubertal development in the bull calf may include removal of inhibitory or the development of stimulatory mechanisms affecting the hypothalamic release of GnRH. To examine possible contributing systems, serial blood samples were collected from Holstein bull calves at 2, 5, and 10 wk of age one day prior to receiving either no treatment (controls) or two injections of alpha-methyl-p-tyrosine (alpha-MPT), an inhibitor of catecholamine synthesis. Blood was sampled every 10 min for 5 h and serum was analyzed for LH by RIA. Following treatment, animals were killed and hypothalamic and pituitary tissues were removed for analysis of total opiate receptors, mu-opiate receptors, estrogen and androgen receptors and concentrations of monoamines: dopamine, the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DO-PAC), norepinephrine, serotonin, and its metabolite 5-hydroxyindole-3-acetic acid (5-HIAA). Pulses of LH increased from non-detectable at 2 wk to nearly 1.5 pulses per sampling period at 10 wk. Pulse height rose to 0.95 +/- 0.16 ng/ml at 10 wk. Total opiate receptor number as determined by binding to naloxone was unchanged in all tissues between 2 and 10 wk. In contrast, mu-opiate receptors (DAGO binding) increased 2-fold in the preoptic-anterior hypothalamic area between 5 and 10 wk. No age-related changes in estrogen receptor concentrations were observed in any tissue except the anterior pituitary in which binding increased 3.2-fold between 2 and 10 wk. A similar increase was not noted for androgen receptors in the pituitary; however, testosterone binding in the preoptic-anterior hypothalamic area was 4.6-fold higher at 5 wk compared to levels at 2 and 10 wk.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Cell-specific posttranslational processing of the surfactant-associated protein SP-B.

Pulmonary surfactant-associated protein B (SP-B) is a 9-kDa lung-specific protein expressed in alveolar epithelial type II cells and Clara cells. The protein markedly increases the surface activity of phospholipids and is an active component in some surfactants in clinical use. SP-B is produced from a 43-kDa precursor protein by proteolytic cleavage of flanking regions from both the NH2- and COOH-terminal ends of the active protein. In this study we have compared the nature of the posttranslational processing of the SP-B precursor in type II cells and in a heterologous cell line transfected with the SP-B precursor. We found that isolated type II cells produce the 9-kDa form of SP-B from the precursor through a series of intermediates detectable in the cell lysates. In contrast Chinese hamster ovary cells stably transfected with the full-length human SP-B precursor produce the precursor and a 26-kDa intermediate but not the 9-kDa protein. The precursor protein in both cell types is glycosylated with NH2-linked sugars. Our results suggest there is cell specificity in the posttranslational processing of the SP-B precursor.

Animals↗