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Biomedical subjects

D M Phillips

Publications and source records attributed to D M Phillips.

At least 127 records · Page 7Linked to original sources

Factors influencing women's decision to undergo mammography.

Despite the consensus that mammography is a valuable screening tool for the detection of early breast cancer, it is underused by physicians, and most women remain unconvinced of its efficacy. We studied consecutively 735 women who underwent mammography at two rural midwestern hospitals to determine the factors that influence the decision to undergo mammography. Those who underwent mammography had significantly more education and higher household incomes than the general population. The decision to have mammography was influenced by many factors, the most important of which were encouragement by the doctor, influence of the media, and the cost of the mammogram. Women of higher socioeconomic status were most likely to be influenced by the media, particularly printed material, but were much less likely than women of lower socioeconomic status to report physician influence as an important factor. These data have implications for the methods physicians use in recommending mammography to individual patients.

Adult↗

Ethylene dimethanesulfonate destroys Leydig cells in the rat testis.

Ultrastructural changes in the interstitial cells of the adult rat testis were studied up to 45 days after administration of a single dose (100 mg/kg) of the antifertility compound ethylene dimethanesulfonate (EDS). Most Leydig cells showed degenerative changes 12 h after treatment. Twenty-four and 48 h after injection, all Leydig cells observed showed gross degenerative changes. At 4 and 14 days, intact Leydig cells could not be identified in the interstitial spaces. Twenty-one days after treatment with EDS, small Leydig cells were visible, and at 45 days, Leydig cells appeared normal. The seminiferous epithelium appeared morphologically normal until 4 days after injection of EDS, when slight abnormalities were observed. At 14 and 21 days, the seminiferous epithelium was grossly abnormal, but at 48 days, spermatogenesis appeared normal. Twelve, 24, and 48 h after treatment, large quantities of material, presumably from dead Leydig cells, were observed within the macrophage cytoplasm. The predominant cell in the interstitial space 4 and 14 days after EDS was the macrophage. Inclusions from the dead Leydig cells within the cytoplasm of the macrophages had almost disappeared. LH receptors (hCG binding) in testicular homogenates were consistent with the cytological changes in Leydig cells. Receptor concentration was low at 24 h and was almost zero at 4 days. This change was accompanied by a decrease in serum testosterone to castrate levels by 2 days. The responses of the endocrine system to destruction of the Leydig cell by EDS, as monitored by serum FSH, LH, and testosterone, were slower than those after castration, indicating that the response to EDS reflects the time required to kill the Leydig cell rather than direct impairment of the steroidogenic pathway. These experiments demonstrate that Leydig cells can be specifically destroyed by a cytotoxic drug. The availability of a specific cytotoxic agent for Leydig cells offers further opportunities to study the interrelationships between the Leydig cell and the seminiferous tubule.

Animals↗

Mammalian fertilization as seen with the scanning electron microscope.

For several years we have been looking at mammalian gametes and their interactions with the scanning electron microscope (SEM). Examining the images produced by the SEM has given us a three-dimensional view of sperm, eggs, and egg investments. We are particularly impressed with the structural variation among gametes of different mammalian species. In this short report we examine the structure of mammalian spermatozoa, eggs, zonae pellucidae, and cumuli. Our observations and those of others have led us to believe that variation in gamete structure and function may have evolved as a mechanism for reproductive isolation of mammalian species.

Animals↗

Unusual features of sperm ultrastructure in the musk shrew Suncus murinus.

The spermatozoon of the Musk shrew Suncus murinus displays unusual fine anatomical features. In the head, the equatorial segment of the acrosome is recessed within a waist in the sperm nucleus in a way that could afford some protection for this fusogenic region, perhaps during penetration of the egg vestments. The perinuclear material has distinctive inner and outer regions, the latter being arranged as a series of coxcomblike spikes. These structures in Suncus could serve to anchor its characteristically giant acrosome to the sperm nucleus. In the tail, small aggregations of electron dense material appear against some centriolar triplets and also, proximally, against some axonemal doublets. In the midpiece, prominent satellite material aggregates proximally over the inner border of the dense fibers. More distally, the material maintains a close relationship with and primarily lies between the corresponding axonemal doublets and dense fibers 5 and 6, the latter being positioned asymmetrically in relation to the remaining dense fibers.

Animals↗

Structural changes induced in rat leukemic basophils by immunological stimulus.

We have examined morphological events in RBL-2H3 basophilic leukocyte-derived cells following stimulation to secrete with specific antigen. Following stimulation, the cell surface undergoes a rapid and pronounced ruffling concomitant with an overall flattening. Secretory granules which are located in one area before stimulation becomes rapidly dispersed throughout the cytoplasm. Since secretion has been shown to be a relatively slow process in the RBL-2H3 cell line our observations suggest that ruffling and flattening precede the secretion process.

Animals↗

Intralimb coordination of the paw-shake response: a novel mixed synergy.

Intralimb coordination of the paw-shake response (PSR) was studied in five normal and eleven spinal adult cats. Representative extensor and flexor muscles that function at the hip, knee, and ankle joints were recorded, and in six spinal cats the kinematics of these joints were determined from high-speed cinefilm. The PSR was characterized uniquely by mixed (flexor-extensor) synergies. Knee extensor (VL) and ankle flexor (TA) coactivity constituted one synergy, while the second synergy included hip extensors (GM, BF), knee flexors (BF, LG), and ankle extensor (LG). Joint displacements reflected the mixed synergy. Motions at the knee and ankle were out of phase, while motions at the hip were in phase with movements of the knee. Electromyographic burst durations and onset latencies were similar for normal and spinal cats, and in all cycles of a given PSR, the recruitment pattern was consistent for all muscles, except VL. High variability and missing bursts marked the activity of VL in some spinal cats. In PSRs with missing VL bursts, oscillations at the knee joint were not coordinated with cyclic actions at the hip and ankle. From the kinematic records three distinct phases of the PSR were identified: start-up consisted of the initial four to six cycles during which hip, knee, and ankle actions progressively became organized; steady-state included the middle three to five cycles that were characterized by consistent displacement at all three joints; and slow-down comprised the last three to four cycles during which the rate of oscillations slowed, and joint excursions decreased. During steady-state cycles, muscle contractions acted to reverse joint motions at the knee and ankle joints. Thus, knee and ankle extensor recruitment coincided with joint flexion, while joint flexors were recruited during joint extension. Muscle activity at the hip, however, was in phase with displacement. While neural input to muscle is consistent throughout the three phases of the PSR, segment motions can become progressively organized during start-up to achieve stable oscillations. Whether the PSR attains steady-state or not may hinge on the sensitive interplay that occurs between muscle activities and intersegmental mechanical interactions. That kinetic interplay is detailed in the following paper.

Animals↗

Antigen challenge and canine tracheal mucus.

Tracheal mucus hypersecretion was demonstrated in 7 dogs with cutaneous sensitivity to extracts of Ascaris suum when the dogs were exposed to aerosols of the same antigen. There was a correlation between antigen skin sensitivity and the aerosol dose at which hypersecretion first occurred. In addition to hypersecretion, antigen challenge led to significant alterations in mucus viscoelasticity. The dose-response pattern was similar to that seen with methacholine and histamine aerosol administration in dogs employing the same methodology. The antigen-induced hypersecretion was blocked or substantially reduced by pretreatment with atropine, H1-antagonists, and thiazinamium chloride. These observations suggest that mucus hypersecretion associated with A. suum challenge in dogs involves histamine release and proceeds at least in part via a cholinergic mechanism.

Aerosols↗

Characterization of the maturational changes induced by a GnRH analogue in the rat ovarian follicle.

The GnRH analogue [D-Ser(t-Bu)6]des-Gly10-GnRH-N-ethylamide (GnRHa, 2 micrograms/rat) or hCG (4 i.u./rat) was administered to hypophysectomized, PMSG-primed immature female rats. Oocyte maturation was initially detected by 2 h after GnRHa administration but the response to hCG was observed only after 4 h. Initiation of GnRHa-induced ovulation also preceded the response to hCG by 2 h. Maximal response to both these hormones was obtained at 10 and 14 h after hormone administration for oocyte maturation and ovulation respectively. The number of oocytes ovulated after GnRHa was significantly lower than that with hCG (29 +/- 4 and 50 +/- 7 per rat respectively; P less than 0.05). Expansion of the cumulus mass and secretion of mucoid material, which are characteristic responses to LH, were also observed after GnRHa administration. However, while the action of 5 micrograms ovine LH/ml on the cumulus cells was mediated by cAMP, no accumulation of the nucleotide could be detected in follicles exposed to GnRHa (10(-7) M). We conclude that even though GnRHa and LH/hCG seem to elicit similar responses in the ovarian follicle they differ in their kinetics, their efficiency and the mediator of their action.

Animals↗

Mechanisms of flagellar motility deduced from backward-swimming bull sperm.

Under certain conditions of cryopreservation, bull spermatozoa undergo an interesting structural alteration. The sperm tail becomes bent back on itself to form a hairpin shape. The bend in the tail occurs at a very precise point, 11 microns behind the neck, and it causes the tail to become kinked. Flagellar microtubules and dense fibers become broken and the ninefold symmetry of the flagellum is greatly distored. Although the portion of the flagellum between the kink and the sperm head does not propagate a wave, the distal portion of the flagellum propagates a base-to-tip wave, causing the spermatozoan to progress backward. These observations suggest that the mammalian spermatozoon does not need basal structures to propagate a flagellar wave.

Animals↗

Establishment of a peritubular myoid-like cell line and interactions between established testicular cell lines in culture.

Established cell lines and primary cultures derived from somatic cells of the testis have been used to study cell-cell interactions. Primary cultures of Sertoli cells or Sertoli-derived cell lines from the mouse (TM4) and rat (TR-ST) will aggregate when plated on monolayers of primary cultures of peritubular myoid cells or a rat (TR-M) cell line which has many properties of peritubular myoid cells. Time-lapse cinematography and scanning and transmission electron microscopy reveal that Sertoli cells formed aggregates after 1 day in coculture, display surface activity and move on the monolayer. When these aggregates touch one another, they rapidly combine. By the 4th day of culture, spherical aggregates are composed of 50 to 200 cells. They do not display surface activity or movement on the myoid monolayer. On the 5th and 6th day of culture most spherical aggregates have flattened to form dome-shaped aggregates in close association with the monolayer. Cells in the aggregates are characterized by long microvilli and some ruffles. In large aggregates, cells sometimes form close associations within the aggregates although junctions are seldom observed. Sertoli-derived cell lines will not aggregate on monolayers of Leydig-derived (TM3) or testicular endothelial-derived (TR-1) cell lines. Neither TM3 nor TR-1 cells will aggregate when plated on myoid monolayers. The TR-M cells produced an extensive extracellular matrix beneath the cells which contains collagen, an amorphous globular material resembling elastin and a fibrous noncollagenous component. Sertoli cells plated on this matrix will not aggregate. Thus the aggregation of Sertoli cells on myoid cell monolayers is cell type, but not species dependent and not determined solely by extracellular matrix components produced by TR-M cells.

Animals↗

Ultrastructure of Chlamydia trachomatis infection of the mouse oviduct.

Chlamydial inclusions were found in the luminal epithelium of all segments of the oviducts (ostium, ampulla, and isthmus) of mice experimentally inoculated with the mouse pneumonitis (MoPn) biovar of Chlamydia trachomatis. Electron microscopy of infected oviducts revealed chlamydial inclusions in both ciliated and nonciliated cells of the oviduct epithelium. Inclusions contained typical elementary, intermediate and reticulate bodies as well as numerous "miniature reticulate bodies" and membrane ghosts. Small, vesicle-like structures were observed in infected cells near inclusions but were not seen in apparently uninfected cells nor in the oviducts of mice inoculated with the control (sterile tissue culture supernate) suspension. Chlamydia-like particles were seen in vacuoles of polymorphonuclear leukocytes. Intracellular Chlamydia-like particles were not seen in any other cell type in the mouse oviduct. Infection of the mouse oviduct with MoPn is a convenient model for the study of C. trachomatis morphology in vivo.

Animals↗

Plasma morphine concentrations and clinical effects after thoracic extradural morphine or diamorphine.

Twenty-seven patients undergoing thoracotomy received either morphine sulphate 2 mg or diamorphine hydrochloride 2 mg by thoracic extradural injection for postoperative analgesia. Arterial plasma morphine concentrations were measured by specific radioimmunoassay, and the analgesic, respiratory and biochemical effects noted. The plasma morphine concentrations were significantly greater after extradural diamorphine than after extradural morphine in the first 30 min after injection. The maximum increase in plasma morphine concentration was significantly (P less than 0.02) greater after extradural diamorphine, and mean peak values occurred at 5 and 10 min for diamorphine and morphine, respectively. There were significant decreases in respiratory rate and plasma cortisol concentration with maximum effects between 90 and 180 min after the extradural injection. The analgesia produced by these doses was inadequate. The role of lipophilicity is discussed.

Adult↗

Tracheal mucus clearance in high-frequency oscillation. II: Chest wall versus mouth oscillation.

We compared the tracheal mucus clearance rate (TMCR) in anesthetized dogs during spontaneous breathing (SB), ventilation by high-frequency oscillation at the airway opening (HFO/AO), and ventilation by high-frequency oscillation of the chest wall (HFO/CW). The HFO/AO was carried out by using a piston pump with a high impedance transverse flow at the proximal end of the endotracheal tube; HFO/CW was effected by creating rapid pressure oscillations in an air-filled cuff wrapped around the lower thorax of the animal, causing small tidal volumes at the mouth. The TMCR was measured by observing the rate of displacement of a charcoal marker in the lower trachea; a fiberoptic bronchoscope was used to deposit the marker before each experiment and to relocate it after a 5-min run. In 7 dogs, mean TMCR during control (SB) was 8.9 +/- 3.5 mm/min. At 13 Hz with an oscillatory tidal volume (VTO) of 1.5 ml/kg, mean TMCR was 240% of control with HFO/CW (p less than 0.001) and 76% of control with HFO/AO (NS). During HFO/AO at 20 Hz and a VTO of 3 ml/kg, mean TMCR was 97% of control. We conclude that high-frequency ventilation by rapid chest wall compression enhances tracheal mucus clearance when compared with spontaneous breathing, whereas high-frequency oscillation at the mouth does not.

Animals↗

Effect of an LHRH agonist on pituitary and testicular function in rhesus monkeys.

Male rhesus monkeys were given 100 micrograms [(imBzl)-D-His6,Pro9-NEt]-LHRH (LHRH-A), a potent LHRH agonist, s.c. daily for 40 weeks. The first dose of LHRH-A caused acute increases (2-4 h after injection) in serum LH (50-fold), FSH (2 X 5-fold) and testosterone (15-fold) concentrations. Chronic treatment led to a 95% decrease in LH and FSH responses. In spite of a marked decrease in LH response the effect on testosterone response was less evident. Administration of 50 i.u. hCG to control and LHRH-A-treated animals showed that the testicular steroidogenic response was unimpaired by the chronic treatment. Evaluation of the electroejaculated semen at regular intervals showed that there was no consistent reduction in the sperm count of LHRH-A-treated monkeys. Testicular biopsies showed that normal spermatogenesis was occurring in all treated animals, but testicular volume was significantly decreased. These results suggest that, in rhesus monkeys, the pituitary is more susceptible to desensitization by chronic LHRH agonist treatment than are the testes, and that LHRH agonists do not have direct antitesticular effect in rhesus monkeys.

Animals↗

Identification of stage-specific proteins synthesized by rat seminiferous tubules.

Experiments were conducted to determine how the cycle of the seminiferous epithelium influenced synthesis and secretion of proteins by seminiferous tubules. Tubular segments were treated with collagenase and then cultured with [35S]methionine. These myoid cell-depleted tubules isolated from different stages of the epithelial cycle exhibited, at Stages VI and XII, two distinct peaks of secretion of total radiolabeled proteins. Two-dimensional gel electrophoresis indicated that the patterns of secreted proteins from these two stages were remarkably different, while those from other stages were intermediate between those at the peaks. At least 15 proteins were secreted cyclically, many of them previously unrecognized products of the seminiferous epithelium. One product, designated Cyclic Protein-2 (CP-2), exhibited a pronounced cycle of secretion, its peak at Stage VI being 30-fold greater than at its nadir at Stages XII-XIV. Further investigation indicated that CP-2 did not appear to originate from myoid cells or dispersed germ cells but could be recovered from Sertoli cell-enriched cultures prepared from Stage VI tubules. Protein secretion by tubular segments was also characterized by immunoprecipitation with two polyspecific antisera directed against Sertoli cell products. Five secretory proteins were identified which had cycles different from one another and from CP-2. In contrast to secreted products, the synthesis of most cellular proteins by tubular segments remained relatively constant throughout the cycle. It is concluded: 1) segments of the seminiferous epithelium secrete proteins into the culture medium which are distinct from cellular proteins; 2) the synthesis of many of these proteins varies with the epithelial cycle; and 3) several of the secreted proteins are of Sertoli cell origin, including a newly identified protein, CP-2. This indicates that the morphology and the protein synthetic capacity of the seminiferous epithelium are coordinated over space and time.

Animals↗