Search PubMed⌕ Search

Biomedical subjects

W A Smith

Publications and source records attributed to W A Smith.

At least 73 records · Page 4Linked to original sources
PubMed1985

Calcium-cyclic AMP interactions in prothoracicotropic hormone stimulation of ecdysone synthesis.

The calcium-dependence of ecdysone synthesis by the insect prothoracic glands was examined in vitro using glands from day 0 pupae of the tobacco hornworm, Manduca sexta. Stimulation of ecdysone synthesis by the cerebral neuropeptide, prothoracicotropic hormone (PTTH), requires extracellular calcium; peptide-stimulated steroidogenesis is blocked by omission of calcium or by addition of the calcium antagonist lanthanum. By contrast, basal synthesis of ecdysone is not calcium-dependent. A stimulatory, as opposed to simply a permissive, role for calcium is indicated by the ability of the calcium ionophore A23187 to mimic the steroidogenic effects of PTTH. Agents that act by increasing the intracellular levels of cAMP (dibutyryl cAMP, 1-methyl-3-isobutylxanthine, forskolin) enhance ecdysone synthesis equally well in the presence or absence of extracellular calcium, indicating that the site of action of the cation in the steroidogenic pathway occurs prior to that of cAMP. Both PTTH and A23187 enhance the formation of cAMP, as measured by the conversion of [3H]ATP to [3H]cAMP, in a manner absolutely dependent upon the presence of extracellular calcium. The results suggest sequential roles for calcium and cAMP in PTTH-stimulated steroidogenesis by the insect prothoracic glands. A model is presented in which the peptide stimulates cAMP formation in a calcium-dependent manner, with the cyclic nucleotide in turn enhancing ecdysone synthesis.

Animals↗
PubMed1985

Anatomicomechanical study for the hydraulic line of a thermal left ventricular assist system.

A thermal left ventricular assist system currently under development consists of two separate major components, i.e., a pump/actuator module and an engine/thermal battery module. The possible implantation site of the engine/battery module is tentatively determined to be the iliac fossa, which requires a flexible interconnecting line to the pump/actuator module. A quantitative and biomechanical study was done on the effect of the implanted hydraulic line on the bendability of the torso. It revealed that the semirigid interconnecting line would not severely restrict the movement of the patient provided it has the proper prebend configuration. The cadaver fitting study proved the anatomical feasibility of the retroperitoneal iliac fossa as the implant site of the Thermal Ventricular Assist System 8 (TVAS 8) engine/battery module. The location and configuration of the interconnecting line of the TVAS 8 were determined using biomechanical analysis so that the restriction of the body movement due to the line could be minimized. The main route of the line was the left side of the trunk, and the line is W shaped in configuration. The line elongation is the most critical resistive factor and accordingly there may still be rigidity during lateral flexion.

Assisted Circulation↗
PubMed1985

Anatomical considerations in the design of a long-term implantable human left ventricle assist system.

A permanently implantable left ventricle assist system (LVAS) is being developed and is planned to be implanted in the left chest cavity against the chest wall with the electrohydraulic energy converter placed in a resected rib space. The inflow and outflow pump ports are connected to the left ventricle (LV) apex and to the descending aorta, respectively. Three additional major components of this system consist of the transcutaneous energy transmission system (TETS) (Thermedics), the variable volume device (VVD), and the internal battery. To finalize the design of this integrated system, key anatomical information was obtained by a special radiographic and angiographic study of 31 adult men with a varying degree of coronary artery disease and myocardial dysfunction. These data were combined with the previous computed tomography study by using a standard vertical reference system. The resultant integrated data, which consist of the three-dimensional chest model, the LV apex and axis orientation, rib orientation, chest wall thickness, and the descending aorta location, were used to define the design and anatomical locations of the inflow and outflow pump ports, the VVD, the pump and energy converter orientation, the TETS, and the internal battery. The most critical component for the design was found to be the inflow system. With regard to the average coronary disease patient, an anatomically practical configuration was demonstrated to exist for the presently proposed LVAS. Design flexibility was allowed for some of the critical components in order to fit the system in a large number of patients regardless of the stage and type of the underlying disease.

Adult↗
PubMed1984

The role of cyclic AMP in the regulation of ecdysone synthesis.

The involvement of cAMP in the steroidogenic action of the cerebral neuropeptide, prothoracicotropic hormone (PTTH), was examined in the tobacco hornworm, Manduca sexta. PTTH stimulates ecdysone synthesis by paired organs in the thorax, the prothoracic glands. The steroidogenic effect of PTTH on prothoracic glands of day 3 fifth instar larvae and day 0 pupae is mimicked in vitro by agents that act by increasing the intracellular levels of cAMP (1-methyl-3-isobutylxanthine, cAMP analogs and forskolin). In addition, partially purified big PTTH (Mr 28500 daltons) stimulates the formation of cAMP in both stages of glands in a rapid, dose-dependent manner. However, a significant accumulation of cAMP in response to PTTH occurs only in larval prothoracic glands. In pupal glands, effects of the neuropeptide on cAMP synthesis are seen only in the presence of a phosphodiesterase inhibitor. The results indicate that cAMP is involved as a second messenger in PTTH action, but that the developmental status of the prothoracic glands influences the degree to which cAMP accumulates in response to the neurohormone.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Human thoracic anatomy based on computed tomography for development of a totally implantable left ventricular assist system.

Human thoracic anatomy was studied using computed tomography (CT) for the development of a totally implantable electrohydraulic left ventricular system [Nimbus, Inc., and The Cleveland Clinic Foundation (CCF)]. To obtain statistical dimensional information for the chest wall, apex of the heart, and aorta, routine calibrated CT scans of 18 men and 17 women were analyzed. A special radiopaque vest was worn by the patient just prior to the scanning and X-ray procedures, so that each transverse scan could be assigned to a specific chest level after combination with a standard vertical referencing system set on the patient's radiogram. A polar coordinate system and direct measurement of transverse distances from the vertical column to points on the chest wall were employed to define collectively the shape and size of the intrathoracic surface of the chest wall. Locations of the aorta and apex were described by measuring their normalized distances from the midline and vertical column to the intrathoracic surface of the lateral and anterior chest wall. The radius of curvature of the intrathoracic wall lateral to the left ventricle was determined to be approximately 10.4 cm for the average adult male chest. The present CCF intrathoracic pump with this curvature fits fairly well in both the average and individual thoraxes of these adult males. The location of the aorta, particularly of the descending aorta, was used to determine the optimal outlet design. The most critical anatomical area was the apex location. For adult males, an average distance of 2.8 cm from the apex to the internal chest wall was found. Because of this small dimension, careful design of the inflow port is being performed to avoid anatomical mismatch.

Adult↗
PubMed1984

Microaggregation of the gonadotropin-releasing hormone-receptor: relation to gonadotrope desensitization.

Desensitization of the pituitary gonadotrope was examined using perifusion of immobilized dispersed cells. Specifically, a relatively brief (20 min) pulse of GnRH was shown to result in markedly reduced release of LH in response to subsequent administration of the releasing hormone. Derivatives of cAMP exerted neither an inhibitory nor a stimulatory effect on desensitization. Nonreceptor mediated secretagogues (phorbol dibutyrate and melittin) promoted gonadotropin release without desensitizing pituitary cells indicating that release and desensitization are dissociable. However, conditions that promote GnRH receptor-receptor cross-linking did lead to reduced GnRH-responsiveness, even when the receptor was occupied by an antagonist. Cells were perifused with a conjugate consisting of two dimers of a pure GnRH-antagonist (D-pGlu1-D-Phe2-D-Trp3-D-Lys6-GnRH) attached to cross-reacting antibody. The antagonist conjugate, now able to cross-link (microaggregate) GnRH receptors, is converted to an agonist. In the present work we show that the conjugate stimulates desensitization in addition to release of LH. This observation suggests that microaggregation is the final step common to both pathways, on the one hand leading to Ca2+ mobilization and release of LH, and on the other, leading to Ca2+ independent receptor-mediated desensitization.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1983

GnRH-mediated desensitization of the pituitary gonadotrope is not calcium dependent.

In the present work we describe homologous desensitization of gonadotropin release from pituitary cells in response to short-term exposure to GnRH. Like the release process itself, desensitization requires receptor occupancy by an agonist. In contrast, however, inhibition of LH release by chelation of extracellular calcium or blockade of the calcium ion channel does not inhibit desensitization. Further, stimulation of gonadotropin release by ionophore A23187 (which mobilizes calcium without GnRH receptor occupancy) does not lead to desensitization. These findings indicate that the decrease in pituitary sensitivity to GnRH due to an initial exposure to the peptide can be uncoupled from LH release. The data provide the first evidence of a calcium-independent biological effect of the releasing hormone in cultured pituitary cells.

Animals↗
PubMed1982

Ultrastructural changes accompanying secretion and cell death in the molting glands of an insect (Oncopeltus).

During the fifth (last) larval instar of Oncopeltus fasciatus, morphological changes in the molting glands associated with ecdysone secretion include a increase in cytoplasmic volume relative to that of the nucleus, increased amounts of rough endoplasmic reticulum and mitochondria, and the formation of deep infoldings of the plasma membrane. On the sixth day of the fifth instar large electron-lucent areas become apparent beneath the basement membrane; however, the glands remain intact until the seventh (last) day of the instar when a dramatic fragmentation of the cytoplasm, and condensation and fragmentation of the nucleus are observed. It is likely that such changes occur rapidly, just prior to the time of ecdysis to an adult. Cell death in the molting glands of Oncopeltus is markedly different from that described for the molting glands of other insect species in that autophagic vacuoles are not observed prior to a complete loss of cellular integrity.

Animals↗
PubMed1982

Altered pituitary responsiveness to gonadotropin- releasing hormone in middle-aged rats with 4-day estrous cycles.

We employed a perifusion system to compare the GnRH responsiveness of pituitaries removed from young (3-6 months old) and middle-age (10-14 months old) female rats with 4-day estrous cycles in order to determine whether changes at this locus may contribute to alterations in LH secretion which precede a loss of regular estrous cycles. Pituitaries were removed and halved on each day of the 4-day cycle; one hemipituitary was retained for measurement (by RIA) of LH content. The second half was perifused for 2.5 h with medium 199 plus BSA, then stimulated for 6 h with 10(-7) M GnRH in medium 199 plus BSA. Results were as follows. 1) Within young and middle-aged groups, the magnitude of GnRH-stimulated LH release varied with stage of the estrous cycle (proestrus, diestrous day 2 greater than estrus, diestrous day 1). General patterns of LH release were similar between age groups; however, pituitaries removed from middle-aged females released significantly less LH on proestrus and diestrous day 1 than did those removed from young females. 2) The time required to reach maximal response to GnRH also varied with the estrous stage; response times were shortest on proestrus and estrus in both age groups. The time to maximal response was significantly longer in the middle-aged vs. the young group on all days of the estrous cycle except diestrous day 2. 3) Within age groups, pituitary LH content varied with the estrous cycle in a pattern similar to that of GnRH responsiveness. Between groups, LH content in middle-age females was equivalent to or greater than that in young females on all days of the cycle. These results indicate that reduced pituitary responsiveness to GnRH may contribute to the delayed attenuated proestrous LH surge that precedes reproductive senescence in the female rat.

Aging↗
PubMed1976

Arachnoid cysts of the middle cranial fossa.

Arachnoid cysts of the middle cranial fossa may present clinically in several different ways. They may remain asymptomatic throughout life, or may cause only local bulging of the skull, with or without exophthalmos. Expansion of the cyst may occur through a ball-valve mechanism of its membrane in communication with the general subarachnoid space leading to increased intracranial pressure with or without localizing neurological deficits. Finally, such cysts are associated with increased vulnerability to the effects of head injury, resulting in hemorrhage either into the cyst or external to the cyst to form a subdural hematoma. Recognition of these various manifestations is essential to proper treatment.

Adult↗
PubMed1976

Early posterior ankle release in the treatment of congenital clubfoot.

Eighty-one patients (116 clubfeet) underwent posterior ankle release before the age of two years, following unsatisfactory responses to serial corrective casts applied according to the technique of Kite. Seventy-three per cent of these feet showed no or only mild talar flattening at an average follow-up of 7.5 years. Four years, following posterior ankle release there was a none-mild talar flattening rate of 69 per cent in this group compared to a 40 per cent none-mild rate in ankle release reduces the incidence of recurrent equinus deformity and the necessity for subsequent surgery in comparison to the results obtained with serial plaster casts or with tendo Achillis lengthening alone. Recent trends in clubfoot management have favored increasingly early operative intervention. Denham stated that "In the infant hard tissues (bone and cartilage) should be regarded as soft, and the soft tissues (tendon and ligament) as hard." Our operative experience with posterior ankle release supports this philosophy and indicates that early aggressive surgical management is the treatment of choice for the resistant clubfoot.

Age Factors↗