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Biomedical subjects

L Beck

Publications and source records attributed to L Beck.

At least 19 recordsLinked to original sources

Phenotypic evidence for a common pathogenesis in X-linked deafness pedigrees and in Xq13-q21 deletion related deafness.

A structural cochlear abnormality has been observed by high resolution CT scanning in some families where X-linked deafness is segregating. We now present evidence that the same abnormality is present in a deaf patient who has a deletion within Xq21. This observation provides phenotypic evidence that the genotypic basis of deafness is the same in both patient groups. It is also likely that the perilymphatic fluid "gusher" abnormality may be common to both.

Child

Serum-free culture of stromal and functionally polarized epithelial cells of guinea-pig endometrium: a potential model for the study of epithelial-stromal paracrine interactions.

Stromal and glandular epithelial (GE) cells were isolated from guinea-pig endometrium and growth to near confluency (6-8 days) in primary culture on plastic surfaces in a serum-supplemented medium (SSM). The stromal cells were subcultured on plastic dishes and maintained for 72 h in SSM. Then SSM was replaced by a chemically defined medium (CDM) and the stromal cells grown to confluency (5-7 days). The GE cells were subcultured in CDM, on a basement membrane matrix (Matrigel) applied to permeable Millicell-PC filters, and grown to confluency (5 days). Homogeneity of the subcultured endometrial cell populations was ascertained immunocytochemically. The filter-cultured GE monolayers were polarized morphologically, and displayed epithelial-specific specialized structures. These monolayers had functional tight junctions as verified by a measurable transepithelial resistance. The subcultured cell populations were distinguished by an analysis of their cellular and secretory proteins after labelling with [35S]-methionine and analysis by polyacrylamide gel electrophoresis. The filter-cultured GE monolayers allowed identification of the proteins released vectorially in the apical or the basal secretory compartment, thus demonstrating the functional polarization of GE cells in this bicameral culture system. Within the defined conditions of this culture system, the paracrine factors released by the two endometrial cell populations as well as the interplay of stromal-epithelial interactions and ovarian hormones could be investigated.

Animals

Progesterone stimulates sulfate uptake in subcultured endometrial epithelial cells.

The effect of progesterone was studied on the sulfate entry in glandular epithelial cells of guinea-pig endometrium subcultured in bicameral chambers on matrix-coated filters in a chemically defined medium. At post-confluency (8 days of subculture), cells were treated with 10 nM estradiol alone or in association with various concentrations of progesterone. Optimal progesterone action was at a 16 h incubation time and a 10 nM hormonal concentration. Progesterone increased in a dose-dependent fashion the sulfate uptake specifically in glandular epithelial cells, preferentially from the basal surface. Progesterone effect on the sulfate uptake occurred only in estradiol-primed epithelial cells and was inhibited by the antiprogestin steroid RU-486. The progesterone-dependent increase in sulfate uptake was inhibited by the inhibitor of anion exchange, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). At physiological sulfate concentrations, progesterone essentially induces a high-affinity DIDS-sensitive transport system.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid

[Forensic aspects of bladder and ureteral injuries in standard gynecologic operations].

Damage to the efferent urinary passages during abdominal or vaginal hysterectomy cannot always be prevented no matter how carefully one may proceed preoperatively and intraoperatively. However, all possibilities of avoiding complications or at least of recognising and eliminating them before surgery, must be explored. Nevertheless, formation of vesicovaginal or ureterovaginal fistulas or of a congested ureter will be rare. In such cases, one cannot jump to the conclusion of mismanagement or a therapeutic error from the mere occurrence of damage. In each individual case, there must be an expertise and a legal judgment as to whether there has been any infringement of the legal requirement to exercise all possible medical care lege artis. Claims for damages are justified only if the conditions of an individual case show, on close examination, that such care had not been exercised.

Documentation

Progesterone control of fibronectin secretion in guinea pig endometrium.

Immunohistochemistry with a polyclonal antibody raised against human plasma fibronectin (Fn) was used to determine the localization of Fn in endometrial sections of guinea pig uteri isolated at the first, fourth, sixth, or tenth day of the estrous cycle. Immunoreactive Fn was constantly visualized in the endometrial stroma but absent from the epithelial layer. Fn was detected in the uterine lumen on the first or fourth day of the estrous cycle and was absent from the other sections. To determine the origin of this luminal Fn the ability of subcultured endometrial cells to produce Fn was tested, and the hormonal regulation of Fn secretion was studied. Cells were treated by estradiol alone or in association with progesterone, progesterone alone, or untreated. Whatever the hormonal treatment, stromal cells constantly secreted immunoreactive Fn into the culture medium. In the same way, the amount of Fn synthesized and basally secreted by epithelial cells was not affected by any hormonal treatments. However, Fn was found in the apical secretions of the untreated or estradiol-treated epithelial cells but was undetectable in the apical compartment when the epithelial cells were treated by progesterone alone or in association with estradiol. These results indicate that Fn is constitutively secreted by stromal cells and that subcultured epithelial cells of guinea pig endometrium secrete Fn from both their basal and apical membrane domains. However, the apical secretion of Fn is specifically suppressed by progesterone.

Animals

Head-down tilt bedrest. HDT'88--an international collaborative effort in integrated systems physiology.

An international collaborative project, initiated by the DLR-NASA Life Sciences Working Group, led to the performance of a head-down tilt bedrest (HDT) study at the DLR Institute for Aerospace Medicine. Scientific and operational questions were addressed in preparation for the D-2 Spacelab mission. Principal areas of interest were cardiovascular regulation and fluid/electrolyte metabolism. The results are detailed in a series of 13 reports to which the present paper serves as an introduction.

Adaptation, Physiological

The effects of a 10-day period of head-down tilt on the cardiovascular responses to intravenous saline loading.

We tested the hypothesis that adaptation to microgravity, simulated by a 10-day period of head-down tilt (HDT), alters the responses to an intravenous fluid load by causing a larger fraction of the infused volume to be retained and magnifying the acute hemodynamic effects. HDT caused a significant (p less than 0.01) decrease in blood volume (-0.72 liters) and weight (-1.6 kg). Rapid infusion (22 ml/kg over 20 min.) of isotonic saline before, during, and after HDT produced a transient blood volume expansion with 18% of the infusate retained intravascularly after 2 hours. HDT had no effect on this response. Control hemodynamics were significantly different with lower cardiac output and higher total peripheral resistance (TPR) during and after HDT. Saline caused significant increases in cardiac output, heart rate, and stroke volume and a decrease in TPR. The magnitude and time course of these changes were not altered by HDT. The results refute the hypothesis and suggest that during HDT new set points or operating points were established for the control of intravascular volume and hemodynamic state.

Adult

Cardiopulmonary function during 10 days of head-down tilt bedrest.

Pulmonary and cardiovascular responses to simulated weightlessness, i. e. 6 degrees head-down tilt bedrest (HDT) were investigated in six healthy male volunteers (mean age 26 yrs). Pulmonary diffusing capacity, functional residual capacity, pulmonary capillary blood flow, and lung tissue volume were measured by inert gas rebreathing. Heart rate and mean arterial blood pressure were obtained from finger blood pressure readings using a plethysmographic technique (Finapres). The short-term (20 min) response to HDT consisted of a 22% increase in pulmonary blood flow, and 13% and 31% falls in blood pressure and heart rate relative to standing. Functional residual capacity fell by 33%, while lung tissue volume increased insignificantly. Subsequent measurements during 10 days of HDT and 5 days of recovery revealed no further changes in lung volume, lung tissue volume, or blood pressure. However, diffusing capacity fell gradually and remained 4%-5% below baseline values after the 7th day of bedrest and during recovery (p less than 0.05). Pulmonary blood flow decreased by 16% during head-down bedrest and recovered partially within the following 5 days (p less than 0.05). We conclude that during and after simulated weightlessness marked alterations in cardiovascular function and marginal affections of gas exchange can be demonstrated already at rest. They may be considered as contributing factors to orthostatic and exercise intolerance observed after space flight.

Adult

Pulmonary responses to lower body negative pressure and fluid loading during head-down tilt bedrest.

Exposure to microgravity redistributes body fluids with important secondary effects on cardiovascular function. We tested the hypothesis that the fluid shifts also affect pulmonary gas exchange. Microgravity was simulated in six male volunteers by a 10-day period of bedrest at 6 degrees head-down tilt (HDT). Lower body negative pressure (LBNP) and intravenous saline loading superimposed acute changes in fluid distribution on the prolonged effects of HDT. HDT produced relative dehydration and hypovolemia with decreased pulmonary blood flow and diffusing capacity. Before bedrest, pulmonary blood flow decreased by 24% during LBNP and diffusing capacity by 7%, while functional residual capacity increased by 14% (p less than 0.05). Intravenous saline loading caused a 24% increase in pulmonary blood-flow (p less than 0.05). Functional residual capacity decreased by 10% and diffusing capacity by 6% (p less than 0.05). Lung tissue volume did not change significantly. Head-down tilt had only minor effects on the responses to LBNP and saline loading. We conclude that LBNP and intravenous saline loading produce major changes in pulmonary blood-flow and minor effects on pulmonary gas exchange, and that the response to acute changes in fluid distribution is not significantly altered during simulated microgravity.

Adult

Cardiovascular response to lower body negative pressure before, during, and after ten days head-down tilt bedrest.

The haemodynamic response to lower body negative pressure (LBNP) was studied in 6 test subjects before (baseline), during, and after (recovery) ten days of 6 degrees head-down bedrest. The LBNP protocol consisted of a 35 min control period, application of a staircase differential pressure profile (15 min at -15 mmHg; 5 min at -30 mmHg; 15 min at -40 mmHg), and a 10 min post-stress observation period. Cardiac output was measured by a foreign gas rebreathing technique. Finger plethysmographic arterial blood pressure (BP), ECG, and heart rate (HR), lower limb crossectional area, and the electrical impedance of three body segments were recorded continuously. As expected, HDT caused a decrease in plasma volume and total body fluid volume. Resting CO at the end of HDT was 16% below the baseline level and similar to CO in the upright position before HDT. Stroke volume (SV) was also reduced, but there were no significant changes in control HR or BP. Absolute changes in CO and SV during LBNP were similar at baseline and during HDT, but the relative changes were larger during HDT. HR and vasoconstriction responses were enhanced, but presyncope occurred in two subjects. Reduced cardiac filling with decreased stroke volume at rest is the apparent primary cause of the altered LBNP response during HDT.

Adult

Influence of posture and prolonged head-down tilt on cardiovascular reflexes.

We investigated the influence of ten days 6 degrees head-down tilt (HDT) on short-term cardiovascular control. To help differentiate between the effects of HDT-induced fluid redistribution and changed autonomic cardiovascular modulation under prolonged HDT, the effect of acute posture changes was investigated as well. Six healthy male volunteers were studied. Continuous finger blood pressure was measured non-invasively by means of Finapres. Heart rate (HR) was derived from the electrocardiogram. Responses to forced breathing (FRSA), Valsalva's manoeuvre (VM), Mental Stress (MS) and Sustained Handgrip (SHG) were measured. Changing posture from HDT to standing enhanced the BP and HR responses to VM, both during straining and after release. During prolonged HDT, responses to VM changed toward the pattern seen in the upright posture before HDT, suggesting a strong influence of fluid redistribution. Neither posture nor prolonged HDT influenced HR variation during FRSA and responses to MS and SHG. BP variation during FRSA was influenced by posture but not by prolonged HDT. Thus, cardiovascular reflex tests which reflect the parasympathetic (FRSA) or the sympathetic (MS and SHG) efferents to the heart were not influenced by posture or prolonged HDT. Only the responses to VM were affected by both posture and prolonged HDT. These results are probably due to a decrease in blood volume and stroke volume under prolonged HDT, an increase in venous distensibility and, to a lesser extent, to inadequate cardiovascular regulatory responses.

Adult

Progesterone effect on intracellular inorganic sulphate in uterine epithelial cells.

The effect of progesterone on the available intracellular sulphate pool in subcultured glandular epithelial cells from guinea-pig endometrium is reported. Progesterone in concert with 17 beta-estradiol was shown to cause an increase in the available intracellular sulphate pool. The maximum effect was obtained for 10(-8) M and 10(-7) M progesterone. This effect of progesterone on the available intracellular sulphate pool essentially concerned the intracellular inorganic sulphate and was inhibited by the antiprogesterone steroid RU 486 (5 x 10(-7) M). Sulphate incorporation into the endometrial epithelial cells was suppressed by the inhibitor of anion transport diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and the protein synthesis inhibitor, cycloheximide. These results would suggest that a sulphate transport system may be involved in the accumulation of the intracellular sulphate, stimulated by progesterone. This phenomenon could be an early process in the preparation of the endometrium for implantation.

Animals

Interleukin-4 induced IgE and IgG4 secretion by B cells from atopic dermatitis patients.

Peripheral blood mononuclear cells from 8 normals and 8 patients with atopic dermatitis (AD) were cultured with recombinant interleukin-4 (IL-4) and the IgE and IgG subclass levels in the culture supernatants measured by radioimmunoassays. IL-4 induced IgE and IgG4 secretion by B cells from both normals and AD patients whereas it has no consistent effect on IgG1, IgG2 and IgG3 secretion. The IL-4 dose response was similar for IgE and IgG4 secretion by cells from both normals and AD patients. On the average, the patients' cells secreted more IgE and less IgG4 than the cells from normals, but because of a large variation, the differences were not significant. However, the ratio of IgG4:IgE secretion was significantly greater for normals than AD patients (mean +/- SEM 7.1 +/- 1.6:1 vs. 1.5 +/- 0.4:1; p less than 0.01). The data demonstrate that IL-4 induces IgE and IgG4 secretion by B cells from both normals and AD patients and suggest that the IL-4 induced switch from IgM to IgG4 or IgE secretion may proceed preferentially to IgE in AD patients as compared to normals.

Adult

[Control with progesterone of intracellular sulfate available in glandular epithelial cells of endometrium in culture].

Sulfate incorporation was measured in subcultured glandular epithelial cells from guinea-pig endometrium, treated by estradiol alone or in concert with progesterone. Progesterone significantly increased sulfate incorporation in cellular and secreted macromolecules. However, the greatest effect of progesterone was on the size of the intracellular sulfate pool available for sulfation. This effect of progesterone was correlated with the percentage of cells exhibiting progesterone receptors in vitro.

Animals