A nonsense mutation of the human luteinizing hormone receptor gene in Leydig cell hypoplasia

Leydig cell hypoplasia (LCH) is a form of male pseudohermaphroditismin which Leydig cell differentiation and testosterone productionare impaired. This report describes the first case of a nonsensemutation (A1635C) in exon 11 of the human luteinizing hormonereceptor (hLHR) gene in two sisters with LCH. This mutationcauses loss of function of the receptor by introducing a stopcodon at residue 545 in transmembrane helix 5 of the hLHR. Surfaceexpression of the truncated hLHR (hLHR-t545) in human embryonickidney cells stably transfected with cDNA encoding hLHR-t545was diminished compared to the wild-type hLHR and hCG-inducedcAMP accumulation was impaired. These results establish thatsingle base mutations in exon 11 of the hLHR gene can produceinactivation as well as activation of the hLHR. Furthermore,they demonstrate that functional domains between transmembranehelix 5 and the C-terminal cytoplasmic tail of the hLHR arerequired for normal cell surface expression of the receptorand signal transduction.     

Integration of local inputs in visual cortex

In mammalian visual cortex, local connections are ubiquitous, extensively linking adjacent neurons of all types. In this study, optical maps of intrinsic signals and responses from single neurons were obtained from the same region of cat visual cortex while the effectiveness of the local cortical circuitry was altered by focally disinhibiting neurons within a column of known orientation preference. Maps of intrinsic signals indicated that local connections provide strong and functional subthreshold inputs to neighboring columns of other orientation preferences, altering the observed orientation preference to that of the disinhibited column. However, measuring the suprathreshold response using single-cell recordings revealed only mild changes of preferred orientation over the affected region. Because strongly tuned subthreshold inputs from cortex only marginally affect the tuning of a cortical cell's output, it is concluded that local cortical inputs are integrated weakly compared to geniculate inputs. Such circuitry potentially allows for the normalization of responses across a wide range of input activity through local averaging.      

Devine exclusion for unresectable carcinoma of the stomach.

Between July 1986 and July 1988, Devine exclusion was performed in 20 patients with unresectable carcinoma of the gastric antrum. All 20 patients presented with repeated vomiting. On endoscopy, 16 patients had complete gastric outlet obstruction while the remainder manifested significant gastric outlet stenosis. There was no hospital mortality. All except two patients could take an oral diet after surgery until their demise. Devine exclusion is safe and effective in relieving gastric outlet obstruction and is not associated with prolonged delay in return of gastric emptying.     

Visibility of gallstone fragments at US and fluoroscopy: implications for monitoring gallstone lithotripsy

To assess the value of ultrasound (US), fluoroscopy, and spot radiography in the detection, counting, and measurement of gallstone fragments during lithotripsy, in vitro visibility studies were conducted on fragments from 20 stones. Fluoroscopic visibility was evaluated during and after lithotripsy on 185 fragments placed in an anthropomorphic phantom. Three US experiments were performed on the fragments to study the visibility of fragments as a function of size, the accuracy of the count with large numbers of fragments, and the ability of observers to detect and count fragments larger than both 4 mm and 5 mm. With fluoroscopy, fragment detection rates ranged from 20% (fragments larger than 2.5 mm) to 80% (fragments larger than 4.5 mm). With US, all fragments larger than 1.5 mm were detected, and US was significantly better than fluoroscopy and spot radiography for detection of fragments 2.5 mm or smaller. US was also more accurate than fluoroscopy (11% vs 59% error) in the assessment of the number of fragments. When fragments larger than 4 mm or 5 mm were being counted with US, 92% of the fragments were visualized. The results suggest that US is more accurate for monitoring gallstone lithotripsy than fluoroscopy or spot radiography.     

The cold stability of microtubules increases during axonal maturation

The development of cold-stable microtubules (MTs) was studied in maturing rat sciatic nerves. From 4 to 10 weeks of age, there was a large increase in the proportion of tubulin associated with stable MTs. A greater fraction of axonal tubulin than nonaxonal tubulin was associated with stable MTs. The labeled tubulin remaining behind the peak of slow axonal transport was more highly associated with stable MTs than tubulin in the peak itself. Immunoassay confirmed that the sciatic nerve contains a pool of stable MTs not identical to the peak of tubulin transport. The developmental increase in MT stability is not associated with any increase in the acetylation of tubulin or with alterations in the major MT-associated proteins. One aspect of maturation of the axonal cytoskeleton may involve deposition of tubulin into stable MTs that are either stationary or moving slowly with regard to the peak of transported tubulin.     

Sulfur mustard as a carcinogen: application of relative potency analysis to the chemical warfare agents H, HD, and HT

A relative potency method for assessing potential human health effects from exposures to relatively untested chemicals is presented and documented. The need for such a method in evaluating the carcinogenic potential of the chemical warfare agent sulfur mustard (agent HD) from a limited data base is specifically addressed. The best-estimate potency factor for sulfur mustard relative to benzo[a]pyrene is 1.3, with an interquartile range of 0.6 to 2.9. The method is applied to (1) the estimated fence-boundary air concentrations of mustard during operation of a proposed agent incinerator at Aberdeen Proving Ground (APG), Maryland, and (2) the current approved general population exposure level of 1 X 10(-4) mg HD/m3 and the occupational exposure level of 3 X 10(-3) mg HD/m3. Maximum estimates of excess lifetime cancer risk for individuals at sites along the APG boundary range between 3 X 10(-8) and 1 X 10(-7). Lifetime cancer risk estimates less than or equal to 10(-6) are not now regulated by the U.S. Environmental Protection Agency or the Food and Drug Administration. Maximum estimates of excess lifetime cancer risk assuming daily exposure to the approved standards during the proposed 5 years of incinerator operation are on the order of 10(-5) for the general public and 10(-4) for the worker population. These values are considered upper limit estimates.     

A study of experimental endocarditis in pigs

In a proposed study of fibrinolytic therapy in experimental streptococcal endocarditis, this disease was induced in pigs by preinoculation damage to the aortic valve; the technique of this is described. If untreated, the disease runs a protracted course, similar to that in man. Fibrinolytic activity, normally low in the pig, can be increased by stress, by urokinase, by plasmin and briefly by streptokinase if supplemented by human plasminogen. The proposed experiments were abandoned in pigs, chiefly because of technical difficulties in obtaining frequent samples of blood and maintaining infusions. In experiments on the response of ADP-induced aggregation of pig platelets to prostacyclin, they were found to be about 10 times more resistant than human platelets. It is suggested that this resistance to prostacyclin, together with their usually low state of systemic fibrinolytic activity, may explain the susceptibility of pigs to bacterial endocarditis.