Range Of Normal Responses Research Articles

Possible hypothalamic impotencemale counterpart to hypothalamic amenorrhea?

Twenty-one men with erectile complaints who were found to have a low level of serum testosterone without a reciprocal elevation of the serum levels of luteinizing hormone were evaluated to identify whether the defect was of hypothalamic or of pituitary origin. Patients underwent a luteinizing hormone (LH)-follicle-stimulating hormone (FSH)-releasing hormone stimulation test that showed a normal but sluggish increase in LH and FSH levels, thus ruling out a pituitary defect and suggesting a suprapituitary abnormality. This was confirmed when, in response to clomiphene, patients had a normal increase in gonadotropin and testosterone levels. Although the basal as well as clomiphene and gonadotropin releasing hormone-stimulated levels of total testosterone and gonadotropins were identical in men less than and more than fifty years old, the elevation of free testosterone levels in response to clomiphene was higher in patients younger than fifty. This suggested that although the primary abnormality found in these patients is altered secretion of gonadotropin hormone-releasing hormone from the hypothalamus, an age-related decline in the responsivity of Leydig cells to LH may make it more manifest in older patients. Elevation of testosterone levels from a subnormal to a normal range in response to clomiphene administered for seven days suggests that the defect is functional and reversible and that the drug may be useful in treatment of sexual dysfunction in this group of patients.

New Technologies for Use in Toxicology Studies: Monitoring the Effects of Xenobiotics on Immune Function

New developments in flow cytometry are now being applied in toxicology studies. There are several reasons for using this technology. First, techniques are well characterized to measure functional parameters of single cells. Such measurements can be directly related to perturbations by xenobiotics, cell-mediated immune responses, or trauma. Second, there is a clear indication for movement toward in vitro systems as highly objective assessments of toxicologic interactions. By measuring specific cell functions at the single cell level, it is possible to define a range of normal responses. More importantly, a multiparametric analysis can be performed with flow cytometry and parameters can be directly related to one another. Furthermore, kinetic measurements can be made, providing vital clues to the mechanisms of actions of drugs or chemicals on functions of specific cell populations. Major advantages of this approach are that studies can be performed on very small volumes of blood, body fluid, or cell culture lines and it is not necessary to isolate pure populations of cells to perform these assays. We believe that this alternative approach in toxicology will provide valuable information unobtainable by traditional means.

Reticulospinal Control of Rapid Escape Turning Maneuvers in Fishes

SYNOPSIS. In teleost fishes, the C-start is a rapid avoidance maneuver that steers the animal away from the strike trajectory of a predator. We review how the axial motor pattern underlying this movement is organized by the reticulospinal system. This system includes the prominent Mauthner cells and other identifiable neurons. Typical of reticulospinal cells, the Mauthner neuron has inputs from auditory, vestibular, and visual areas and has outputs to the trunk motoneurons by means of mono- and disynaptic contacts. Because reticulospinal organization and function is conserved among the vertebrates, the Mauthner network is advantageous as a model for understanding control of movement. We develop three major points. First, despite its seeming anatomical simplicity, the escape network is not a simple hierarchial system with one cell that directs the entire movement. We present evidence that the escape response is mediated by an array of neurons which include the Mauthner cells. Second, though the firing of this cell is adequate to result in a major component of the movement, the Mauthner cell is not indispensible for its execution. The network producing this movement is capable of regulating its output so that the animal produces the normal range of responses despite the absence of one of its major contributors. These findings can be accounted for by one of two models, though the most likely one involves lateral interactions, or corollary discharges, within the array. Third, our recent work also shows that the movement pattern is generated by a ballistic command which does not rely on movement-induced sensory feedback. These system properties allow the animal to produce a highly reliable and orchestrated motor command in only 15 msec from sensory stimulus to EMG.

Parameters of normal grief: A delphi study

Abstract This study explored bereavement experts' perceptions of the parameters of normal grief. The purpose of the study was twofold: to identify the terms used by the experts to designate grief that falls outside normal parameters; and to identify the physical, emotional, and behavioral manifestations of grief that these experts used to differentiate between normal grief and grief that falls outside the normal response range (GONR). A modified Delphi technique was used. The 22 experts identified 34 different descriptors of GONR, and 31 items that indicated the parameters of normal grief. The experts agreed that, early in bereavement, numerous manifestations are within normal parameters. However, later in the bereavement period, many of these manifestations are perceived as possibly or definitely outside the normal response range. The majority of the experts perceived all of the 31 manifestations as outside normal parameters at five year post bereavement. Caution must be used in generalizing from this sm...

Properties of ion channels closed by light and opened by guanosine 3',5'‐cyclic monophosphate in toad retinal rods.

1. In patch-clamp recordings from outer segments of dark-adapted rod photoreceptors, single-channel recordings were obtained from the light-sensitive conductance when divalent cations were omitted from the pipette solution bathing the extracellular face of the recorded patch of membrane. 2. Activity of the light-sensitive channel was suppressed by light within the normal response range of the dark-adapted rod. During dim, steady illumination, the rate of opening of the channel fluctuated dramatically, as expected qualitatively from statistical fluctuations in the number of photoisomerizations occurring within the effective collecting area of the recorded patch. 3. The light-sensitive channel flickered rapidly in the open state, so that individual events appeared as a burst of openings and closings. The average duration of a burst was 0.78 +/- 0.03 ms (mean +/- S.E.). The average duration of an individual opening was 0.18 +/- 0.008 ms. The average closed duration within a burst was 0.37 +/- 0.02 ms. 4. Hyperpolarization of the recorded patch had no effect on average burst or open duration, although opening frequency increased slightly (+18.6 +/- 4.9%; n = 13; mean +/- S.E.). Average single-channel current increased linearly with hyperpolarization, giving an estimated single-channel conductance of 20.5 +/- 1.1 pS. By extrapolation of the relation between channel current and hyperpolarization, the dark driving force was estimated to be about 48 mV. 5. In addition to reducing the rate of channel events, dim non-saturating light also reduced the average duration of a burst of openings and the average duration of openings within a burst. 6. About 50% of cell-attached patches showed no channel activity in darkness. Light-suppressable channel activity could be induced in these silent patches by perfusing the outer segment with low-Ca2+ Ringer solution. Similarly, activity could be increased dramatically by low-Ca2+ Ringer solution in patches that did show channel activity in the dark. From the maximal channel activity observed during low-Ca2+ perfusion, the lower limit for the number of channels per patch was 20-70, corresponding to an estimated channel density of 100-350 channels micron-2. 7. After recording light-sensitive channel activity in the intact rod, the patch of membrane was excised, exposing the intracellular membrane face. Application of guanosine 3',5'-cyclic monophosphate (cyclic GMP) to the intracellular face activated channels (Haynes, Kay & Yau, 1986; Zimmerman & Baylor, 1986; Matthews, 1986d, 1987) whose properties could then be compared directly with the light-sensitive channels recorded earlier in the same patch of membrane.(ABSTRACT TRUNCATED AT 400 WORDS)

Single-channel recordings demonstrate that cGMP opens the light-sensitive ion channel of the rod photoreceptor.

Patch-clamp recordings were made from outer segments of single dark-adapted rod photoreceptors from toad retina. When patch pipettes were filled with a solution free of divalent cations, inward current through individual light-sensitive ion channels was sufficiently large to allow single-channel recording. Channel activity was suppressed by illumination within the normal response range of the dark-adapted rod. When illumination was restricted to a portion of the outer segment, the effect of light on channel activity was spatially localized to the illuminated region. Hyperpolarization of the recorded patch did not reduce the frequency of channel opening, indicating that the suppression of channel activity by light was due to illumination itself and not to light-induced hyperpolarization of the rod. After recording single light-sensitive channel activity in the intact cell, the patch of membrane was detached to form an excised, inside-out patch. Cyclic GMP applied to the intracellular face of the excised patch then opened a channel that appeared to be the same as the light-sensitive channel recorded earlier from the same membrane in the intact, functioning rod. This provides direct evidence that cyclic GMP acts as an internal transmitter that opens the light-sensitive channel of the vertebrate photoreceptor.

Interleukin 1 production by peripheral blood mononuclear cells from leprosy patients.

Quantitation of interleukin 1 production by adherent mononuclear cells from peripheral blood was performed in patients with tuberculoid and lepromatous forms of leprosy. Cells from patients with tuberculoid leprosy either secreted interleukin 1 spontaneously or produced amounts within the normal range in response to lipopolysaccharide stimulation. Conversely, stimulated cells from lepromatous patients failed to produce interleukin 1 in 5 of 13 (38.5%) cases.

Reduced alternative complement pathway control protein levels in anorexia nervosa: response to parenteral alimentation

Serum levels of 16 proteins, including 11 component and control proteins of the complement system were determined before and after nutritional repletion in five female patients with severe malnutrition secondary to anorexia nervosa. Before parenteral alimentation significantly decreased serum levels were found for IgG, IgM, transferrin, Clq, C2, C3, factor B, beta lH, C3b inactivator, properdin, and C4 binding protein. A significant increase in posttreatment serum levels compared with pretreatment levels were found for transferrin, C3, factor B, beta lH, and C3b inactivator. Of the proteins measured, the C3b amplification loop control and component proteins, beta lH, C3b inactivator, C3, and factor B rose to the normal range in response to therapy most rapidly. In the absence of an acute phase reaction, these proteins appear to be particularly good indices of malnutrition and its response to therapy.

Studies of mitogen-induced lymphocyte transformation by a semi-microtechnic.

The authors have demonstrated that mitogen-induced lymphocyte transformation can be effectively studied in a semi-microsystem allowing multiple studies from a reasonably small volume of blood, which makes the technic more feasible for clinical studies of cellular immune mechanisms. The variability among individuals, and from day to day in the same individual, makes repeated, careful kinetic studies necessary for valid data. Moreover, the very wide range of normal responses in man makes the interpretation of cellular hyporesponsiveness difficult in pathologic states and necessitates the use of several mitogen concentrations and sequential kinetic studies to establish the validity of results.

Responses of serum luteinizing hormone and follicle-stimulating hormone levels to synthetic luteinizing hormone-releasing hormone (LH-RH) in various forms of testicular disorders.

ABSTRACT Synthetic luteinizing hormonereleasing hormone (LH-RH) was administered to normal men and to patients with oligospermia, azoospermia and hypergonadotropic and hypogonadotropic eunuchoidism. Intramuscular injection of 100 μg of LH-RH provoked significant increases in both serum LH and FSH levels in 30 min. The magnitude of responses in serum LH and FSH levels was largely dependent on basal levels, i.e., larger increments were observed in cases with higher basal levels. Responses of serum LH levels in cases with hypogonadotropic eunuchoidism were below the normal range, while those of serum FSH levels showed a considerable overlap into the normal range of responses. There were no responses of LH or FSH levels to LH-RH in cases of hypogonadotropic eunuchoidism under the treatment with testosterone or in cases of prostatic cancer under estrogen treatment.

Evaluation of a Semi-micro Method for Measuring Platelet Aggregation in Whole Blood Samples

SummaryPlatelet aggregation has been measured rapidly and simply in 0.5 ml samples of citrated whole blood, by counting the unaggregated platelets remaining after the samples were mixed with aggregating agents, and the erythrocytes rapidly sedimented by adding physiological saline. Concentration-dependent aggregation responses were obtained with adenosine diphosphate, glass beads, serotonin and connective tissue. Aggregation induced by mixing alone was also measured.The aggregation responses were altered by minor changes in citrate concentration, and increased during the first hour after venepuncture. In heparinised blood samples, platelet counts were reduced and all aggregation responses substantially increased. Extending the time interval between aggregating stimulus and platelet counting had no significant effect on the aggregation responses. The main source of technical error was sampling for platelet counts, and the variablility was inversely related to the size of micropipette used. Results of tests in volunteers established the normal range of responses to aggregating agents, and showed that blood samples taken weeks apart from the same subject gave more variable responses than did samples taken an hour apart.

Some effects of cold exposure, nutrition and experimental handling on serum free fatty-acid levels in sheep

Blood serum free fatty acid (FFA) levels have been measured in sheep subjected to: (a) short periods (20–24 hours) of fasting, (b) physical and emotional disturbances associated with experimental handling, and (c) exposure to cold temperatures when either pregnant or unmated.The first two factors acted additively, each causing a small elevation of about 100–200 μ-equiv/litre above the pre-existing FFA level. The effect of short-fasting gradually disappeared during the first 6 hours after feeding; the effect of experimental disturbance lasted less than 2 hours.The effect of severe cold treatment (exposure to approximately 60°C subcriticai ambient temperatures for 2–10 hours) was very marked, producing mean FFA elevations of about 2000 μ-equiv/litre.Mild cold exposure (3−8°C below the critical temperature), even when maintained for several days, produced little change in the FFA levels already typical of either well-fed or short-fasted sheep. Exposures of moderate intensity (25°C below the critical temperature) apparently produced small elevations in short-fasted sheep only.It was concluded that a large increase in FFA level was the normal response to acute cold exposure. Elevations due to other factors were, in the context of these experiments, very small. Within the normal range of response to cold exposure there was considerable individual variation in the degree of FFA elevation, but this variation was not generally related to cold resistance expressed as the ability to maintain rectal temperature. However, a few sheep which failed to raise FFA values to the normal extent did show poor cold resistance.

Plasma cortisol and corticosterone response to infused corticotrophin in normal subjects

Infusion of 25 i.u. corticotrophin over 8 h has been performed in 16 normal subjects. Plasma cortisol and corticosterone have been assayed specifically by a fmorimetric method for samples obtained before, and at stated times during these infusions. The normal range of response was found to be confined within fairly narrow limits. Attention is drawn to the possible application of this test of adrenal cortical reserve, which is of especial value in cases showing a mild degree of adrenocortical hypofunction.