Marked Decrease In Sensitivity Research Articles

Comparison of four test kits for feline leukemia virus antigen

Summary The sensitivity and specificity of 4 commercial FeLV elisa kits, using blood, were compared with results of virus isolation from blood and immunofluorescent antibody (ifa) testing on blood. Significant differences were not found among the 4 elisa kits. Marked decrease in sensitivity of the elisa kits was detected when virus isolation was used as the standard of positivity rather than the ifa test. Virus isolation was a more sensitive indicator of early infection, with marked discrepancy among results obtained by virus isolation, elisa, and the ifa test. Results became progressively more concordant as infection became fully established. Cats FeLV-positive by virus isolation alone were more likely to eliminate viremia. All cats FeLV-positive by ifa testing remained persistently viremic. Virus isolation, elisa, and ifa testing appear to differ in their prognostic value. The use of blood rather than serum for the elisa resulted in several discordant results. Six cats were FeLV-positive by elisa when blood was tested but were FeLV-negative when serum was tested. Positive elisa results were obtained for 4 of these cats when serum was tested, using extended incubation to increase sensitivity. It is possible that blood may actually be more sensitive than serum for use of the elisa method.

Hearing in a primitive ensiferan: the auditory system of Cyphoderris monstrosa (Orthoptera: Haglidae)

1. Insects of the family Haglidae are relicts of primitive Ensifera. Members of this group display acoustic behaviour in the typical ensiferan pattern, with males producing stereotyped acoustic signals by tegminal stridulation. They are closely related to the major groups of acoustic Ensifera, but their auditory system has not been previously studied. I present here a description of the morphology, and physiology of the peripheral auditory system of Cyphoderris monstrosa. 2. The tympana of C. monstrosa are similar to those of Tettigoniidae, but less well-differentiated from normal leg cuticle. The acoustic trachea is well-developed, but does not form a single, continuous tube in the leg proximal to the tympana. The organization of the auditory organ is similar to the Tettigoniidae, with the tibial organ comprising the subgenual organ, intermediate organ, and crista acustica. Projections of the tibial organ sensory cells to the prothoracic ganglion are also typical of acoustic Orthoptera. The meso- and metathoracic legs possess tibial organs similar to that of the prothoracic leg, although lacking tympana and well-developed acoustic tracheae. Central projections of the mesothoracic tibial organ are similar to those of the prothoracic. 3. Auditory whole nerve responses are not tuned to the frequency of the species calling song. Auditory best frequency (BF) is 2 kHz; calling song frequency is 12 kHz. Threshold intensity levels at BF are typical for insect hearing organs (35–45 dB SPL). The response of the auditory organ is not strongly directional at the calling song frequency. Occlusion of the acoustic trachea has no effect on the sensitivity, tuning, or directionality of the auditory system. Occlusion of either of the tympana alone also has no effect on auditory responses, but occlusion of both tympana leads to a marked decrease in sensitivity. Tuning is not affected. The tibial organ of the mesothoracic leg is sensitive to airborne sound at low frequencies (BF = 1 kHz) with thresholds comparable to the ear. 4. The auditory system of C. monstrosa is a pressure receiver, adapted to low frequency sensitivity. This low frequency tuning, in contrast to the calling song frequency, suggests an auditory system adapted to another function in addition to intraspecific communication.

Effects of Serotonin on Platelets and Blood Vessels

We advance the hypothesis that ketanserin, a 5-HT2 receptor antagonist, may provide vascular protection. This is due mainly to inhibition of the effect of serotonin, released by platelets activated at the site of arterial wall injury, on platelets and vascular smooth muscle cells which contribute to vascular smooth muscle cell proliferation and connective tissue synthesis, vasospasms in areas of defective endothelial cell-dependent relaxation and to platelet-dependent thrombus formation in various experimental scenarios. Clinical data obtained so far with ketanserin in patients, subjected to coronary angioplasty, with critical coronary stenosis and at risk for vascular accidents due to atherosclerosis, suggest that, within certain limitations, vascular protection by ketanserin might also occur in man.

Phorbol ester, vascular relaxation, and cyclic guanosine 3',5'-monophosphate.

The relaxation of phenylephrine-contracted blood vessels by acetylcholine, nitroprusside, or atrial natriuretic factor has been linked to elevations in cyclic guanosine 3',5'-monophosphate (cGMP). Also, 8-bromo-cGMP can induce vascular relaxation in isolated vascular smooth muscle contracted with phenylephrine. We determined whether these cGMP-dependent vasodilators could relax isolated rat aortas contracted with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. cGMP was measured by radioimmunoassay. Acetylcholine, nitroprusside, and atrial natriuretic factor induced relaxation in vascular smooth muscle contracted by 12-O-tetradecanoylphorbol-13-acetate. These relaxation responses were accompanied by elevations of cGMP. However, the sensitivity to these vasodilators was markedly decreased in phorbol ester-contracted vessels compared to phenylephrine-contracted vessels. Nifedipine and superoxide dismutase induced small but significant relaxations in phorbol ester-contracted vessels; however, blood vessels contracted with phenylephrine and phorbol ester relaxed completely with papaverine. There was a marked decrease in sensitivity to 8-bromo-cGMP in phorbol ester-treated vessels compared to phenylephrine-contracted vessels. Contractions induced by phorbol ester were not inhibited by amiloride or chlorpromazine. Also, following incubation in potassium-free salt solution, vessels incubated with phenylephrine or phenylephrine and phorbol ester underwent similar relaxations when exposed to potassium chloride. The contractile state induced by phorbol ester has decreased sensitivity to cGMP-dependent vasodilators. This may be due to nonspecific effects of the phorbol ester or to the mechanism by which protein kinase C activation maintains vascular tone.

Kinetics of Glucose Metabolism in Relation to Insulin Concentrations in Patients With Alcoholic Cirrhosis and in Healthy Persons

To characterize the insulin resistance in alcoholic cirrhosis we determined in vivo insulin-glucose disposal dose-response relationships in 6 patients with alcoholic cirrhosis of varying severity and in 6 control subjects, using the glucose-insulin clamp technique. Each subject was infused sequentially with insulin at rates of 0.5, 1.0, 2.0, and 10 mU/min X kg, each rate for 2 h. Euglycemia was maintained by a continuous servo-adjusted glucose infusion. The amount of glucose infused during the last 40 min of each 2-h period, corrected for accumulation in the glucose space, reflects overall net glucose metabolism. The dose-response curves demonstrated saturation kinetics. Lineweaver-Burk plots were consistently convex, rejecting a simple Michaelis-Menten relationship, but were linear when accommodated to allosterism with two active sites. The calculated affinity constant (i.e., the concentration of insulin leading to half-maximum glucose metabolism) of patients with cirrhosis was higher than that of normal controls (104 +/- 30 vs. 32 +/- 3 mU/L, mean +/- SD). In addition the maximum rate of glucose metabolism was significantly lower than that of normals (53 +/- 9 vs. 72 +/- 16 mumol/min X kg). We conclude that, in patients with alcoholic cirrhosis, insulin resistance is caused both by a marked decrease in sensitivity to insulin and a decreased maximum effect of insulin, indicating a combined receptor-postreceptor defect as the underlying cause.

How sensitizing is chlorocresol? Allergy tests in guinea pigs versus the clinical experience.

Chlorocresol is a biocide with widespread use in industry and pharmaceutical products. It is an occasional human contact sensitizer. The sensitizing potential of chlorocresol was judged strong using the guinea pig maximization test (GPMT) and doubtful in the less sensitive open epicutaneous test (OET). When different induction concentrations were used, the results indicated an optimal sensitizing concentration above which no further increase in the sensitization rate occurred. Rechallenge 2 weeks later showed a marked decrease in sensitivity. Consecutive human patch tests with chlorocresol 2% in pet. showed 11 reactions among 1462 patients tested, but none were explainable and reproducible during re-tests and provocative use tests, indicating that the GPMT overestimated the sensitization potential. The results from guinea pig allergy tests cannot stand alone but have to be validated by other sources of information.

Phosphoenolpyruvate carboxylase from pennywort (Umbilicus rupestris). Changes in properties after exposure to water stress

Umbilicus rupestris (pennywort) switches from C3 photosynthesis to an incomplete form of crassulacean acid metabolism (referred to as 'CAM-idling') when exposed to water stress (drought). This switch is accompanied by an increase in the activity of phosphoenolpyruvate carboxylase. This enzyme also shows several changes in properties, including a marked decrease in sensitivity to acid pH, a lower Km for phosphoenolpyruvate, very much decreased sensitivity to the allosteric inhibitor malate, and increased responsiveness to the allosteric effector glucose 6-phosphate. The Mr of the enzyme remains unchanged, at approx. 185 000. These changes in properties of phosphoenolpyruvate carboxylase are discussed in relation to the roles of the enzyme in C3 and in CAM plants.

The use of histolyn CYL in an enzyme immunoassay to detectHistoplasma capsulatumantibodies

Histolyn CYL, the yeast phase reagent, has been employed as the antigen in an enzyme immunoassay (ELISA) to detect antibody to Histoplasma capsulatum in sera from experimentally sensitized rabbits and from humans with histoplasmosis. Three different lots of Histolyn CYL were initially evaluated with respect to antibody detection in individual and pooled rabbit serum specimens. Optimal reactivity was obtained with 4.5 micrograms (total dry weight) per ml of lots 2 and 3 of the reagent. The optimally diluted pooled reagent detected antibody titers ranging from 1:16 to 1:8192 in 36 rabbit sera. In contrast, a marked decrease in sensitivity was evidenced when the same sera were assayed by complement fixation and immunodiffusion tests with commercially available reference reagents. Complement fixation titers ranged from 0 to 1:128 and immunodiffusion tests on undiluted sera were positive with only 5 specimens. Twenty-five sera from patients with acute, chronic and disseminated histoplasmosis were also assayed by the ELISA with the reagent described above. Titers ranged from less than 1:16 to 1:20,480 or greater. Complement fixation titers ranged from 0 to 1:1024 (mycelial antigen) and from 0 to 1:256 (whole yeast cell antigen). No antibody was detected in 7 specimens with mycelial antigen or in 3 specimens with the yeast cell antigen. Immunodiffusion tests on undiluted sera were positive with 9 of 11 specimens. Minimal cross reactivity was evidenced when Histolyn CYL was used in the ELISA to detect anti-Coccidioides immitis antibody in sera from infected animals and humans. These data encourage the continued development of this method for the serodiagnosis of human histoplasmal infection.

Bronchial response to histamine after inhaled propranolol and atropine in monkeys

To investigate the nature of the variable response to inhaled histamine in monkeys, we performed dose-response curves in a group of 10 anesthetized Macaca mulatta monkeys before and after administration of propranolol and atropine in inhaled doses sufficient to produce significant beta-adrenergic and cholinergic blockade of airway smooth muscle. Animals were studied in a volume-displacement body plethysmograph and changes in pulmonary resistance (R L), dynamic compliance (Cdyn), frequency (f), and tidal volume (V T) were plotted against inhaled histamine concentration (0.016 to 64 mg/ml). Sensitivity to histamine was assessed by the concentrations producing a 50% increase in R L and a 50% decrease in Cdyn. A wide range of sensitivity (0.44 to 3.3 mg/ml for R L, 0.47 to 11.3 mg/ml for Cdyn) was found in this small group of animals, and this was not influenced by prior inhalation of propranolol. Atropine inhalation resulted in a marked decrease in sensitivity in all animals but did not reduce the variability of response.

The resistance of crosslinked insulin derivatives to pepsin and trypsin.

The introduction of a crosslink between the amino groups of A1-glycine and B29-lysine of the insulin molecule leads to a marked decrease in sensitivity towards pepsin. Under conditions where insulin is completely degraded over 70% of N alpha A1, N epsilon B29-(carbonyl-bis-methionyl) insulin [OC(Met)2] remain intact. The resistance increases with the length of the crosslink, i.e. oxalyl less than OC(Met)2 less than dodecanedioyl insulin. The carbonyl-bis-methionyl derivative is also stabilized against tryptic attack, but to a smaller degree.

EFFECTS OF THE PROSTAGLANDINS ON THE UTERUS

The effect of intravenous and intrauterine administration of PGE1 or PGE2 and PGF2 alpha as well as oral administration of PGE2 on the sensitivity and reactivity of the nonpregnant human uterus was studied. With the use of the flaccid microballoon technique or a micro transducer catheter, uterine recordings were made at frequent intervals throughout the menstrual cycle. Independently of the route of administration and of the phase of the cycle, treatment with PGF2 alpha invariably resulted in stimulation of uterine motility. A high sensitivity to PGF2 alpha was noted during the late secretory phase both in normal and dysmenorrheic women. A marked decrease in sensitivity to both PGE2 and PGF2 alpha administered by the intrauterine route was observed in the periovulatory phase. Inhibition of uterine contractility by PGE2 following both intrauterine and oral administration was noted during active menstrual bleeding in normal as well as in dysmenorrheic women. These findings suggest that endogenous prostaglandins may play a role in the regulation of the normal uterine motility during the menstrual cycle and that the main reason for the abnormal contractility pattern seen in dysmenorrheic women during menstrual bleeding is an increased PGF2 alpha/PGE2 ratio.

The influence of locally administered prostaglandin E2 and F2alpha on uterine motility in the intact non-pregnant human uterus.

Clinical studies on the effect of locally administered prostaglandin E2 and F2alpha on the sensitivity and reactivity of the non-pregnant human uterus were performed in 16 volunteers. With the use of the flaccid microballoon technique, uterine recordings were made at frequent intervals throughout the menstrual cycle. As little as 0.25 microgram PGF2 or 1.0 microgram PGF2alpha effected an increase in uterine motility during most of the proliferative and secretory phases of the menstrual cycle. However, a marked decrease in sensitivity and suppression of reactivity to either prostaglandin compound was observed around ovulation. Moreover, an inhibition of uterine contractility in response to PGE2 but not to PGF2alpha was noted during active menstrual bleeding. Circulating levels of estrogen could be correlated generally with these uterine responses. Endogenous prostaglandins normally occur in the secretory endometrium in levels compatible with the amount of exogenously administered prostaglandins which elicited increased, decreased, or unchanged uterine activity in this study. These findings suggest that local prostaglandin E2 and F2alpha in concert with variable levels of circulating estrogen, may play important roles in the cyclic regulation of uterine motility during the menstrual cycle.

Trimethoprim-Sulfamethoxazole Compared to Ampicillin in the Treatment of Shigellosis

Twenty hospitalized children between 1 and 11 years of age were enrolled in a comparative randomized evaluation of trimethoprim-sulfamethoxazole (TM-SM) and ampicillin for the treatment of shigellosis. Each drug was provided for five days. The group treated with ampicillin had significantly more stools per day (mean 21.25) compared to the TM-SM group (8.64). Treatment with TM-SM appeared to be associated with a more rapid reversion of stool cultures to normal, but these differences compared to ampicillin were not statistically significant. Review of all isolates of Shigella from our hospital revealed a marked decrease in sensitivity to ampicillin over the last six years. This pattern has been observed in other centers. TM-SM may be the best drug for the treatment of shigellosis in areas where multiple antibiotic-resistant organisms are common.

The effect of locally administered PGE 2 on the contractility of the nonpregnant human uterus [formula omitted

The effect of locally administered prostaglandin E 2 on the sensitivity and reactivity of the nonpregnant human uterus during the menstrual cycle was studied in seven women. An increase in uterine contractility in response to as little as 0.25 μg PGE 2 could be observed during both the mid-proliferative and mid-secretory phases of the menstrual cycle, but around ovulation a marked decrease in sensitivity to PGE 2 was noted. An inhibition of uterine motility was observed during menstruation in response to 30–40 μg PGE 2. Endogenous E prostaglandin normally occurs in the secretory endometrium in levels comparable to the amount of exogenous PGE 2 which elicited increased or decreased uterine activity in this study. These findings suggest that PGE 2 may play an important role in the cyclical regulation of uterine motility during the menstrual cycle.

The effect of locally administered PGF 2α on the contractility of the nonpregnant human uterus in vivo

The effect of locally administered prostaglandin F 2α on the sensitivity and reactivity of the nonpregnant human uterus during the menstrual cycle was studied. An increase in uterine contractility in response to as little as 1.0 μg PGF 2α could be observed in all patients during both the early and late portions of the menstrual cycle, but at the time of ovulation a marked decrease in sensitivity was noted. Endogenous prostaglandin normally occurs in the secretory endometrium in levels compatible with the amount of exogenous prostaglandin which elicited increased uterine activity. These findings support the hypothesis that PGF 2α plays an important physiological role in the cyclical regulation of uterine motility during the human menstrual cycle.

The effect of locally administered PGE 2 on the contractility of the nonpregnant human uterus in vivo

The effect of locally administered prostaglandin E 2 on the sensitivity and reactivity of the nonpregnant human uterus during the menstrual cycle was studied in seven women. An increase in uterine contractility in response to as little as 0.25 μg PGE 2 could be observed during both the mid-proliferative and mid-secretory phases of the menstrual cycle, but around ovulation a marked decrease in sensitivity to PGE 2 was noted. An inhibition of uterine motility was observed during menstruation in response to 30–40 μg PGE 2. Endogenous E prostaglandin normally occurs in the secretory endometrium in levels comparable to the amount of exogenous PGE 2 which elicited increased or decreased uterine activity in this study. These findings suggest that PGE 2 may play an important role in the cyclical regulation of uterine motility during the menstrual cycle.

Cyclic AMP in isolated corpora lutea of the rat: influence of gonadotrophins and prostaglandins.

ABSTRACT Corpora lutea were isolated from 34–39 day-old rats injected with 10 IU PMSG when 30 days old leading to ovulation early in the morning of day 33. Three day-old corpora lutea were incubated in Krebs bicarbonate buffer containing 5.5 mmol/l glucose. Addition of LH to the incubation medium increased accumulation of cyclic 3′, 5′-AMP (cAMP) in a dose-dependent way in the isolated tissue and caused a release of cAMP to the incubation medium. cAMP was determined by the protein binding technique of Gilman (1970). There was a continuous rise in the levels of cAMP in both tissue and medium with increasing incubation time in presence of LH. Neither prolactin nor FSH could influence the cAMP levels in the corpus luteum tissue in vitro. Prostaglandin E2 (PGE2) caused a stimulation with respect to cAMP formation. The time-course of the PGE2 effect was quite different from that of LH: PGE2 gave maximal tissue cAMP content within 5–15 min with decreasing levels thereafter, compared to the continuous rise with LH stimulation for at least 1 h. In experiments performed on corpora lutea of different ages (1–7 day-old), tissue levels of cAMP were determined after incubations with LH or PGE2. There was a dramatic increase of tissue cAMP in the very young corpus luteum and a marked decrease in sensitivity to LH with increasing age of the corpus luteum with a very small but still significant effect on the old corpora lutea. The stimulatory effect of PGE2 on cAMP levels on the other hand showed only a minimal change. A few experiments on the first generation of corpora lutea from mature cycling rats are also reported for comparison.

Experimental Deafness

CONTINUED investigation similar to that described elsewhere1 has provided evidence for the view that the phenomenon designated auditory fatigue by Ewing and Littler2 and Bawdon-Smith1 is in reality the result of the intervention of certain cortical factors. The marked decrease in sensitivity of the human ear following upon stimulation by loud pure tones for several minutes is, it has been found, not confined to the ear stimulated. The nominally unstimulated ear suffers a loss of sensitivity sometimes as great as that in the stimulated ear. Further, the loss of sensitivity in either may be temporarily removed or lessened in many cases by subjecting the observer to an unexpected stimulus (such as momentary darkness). This will be clear from Fig. 1.