Acetylcholine receptor at neuromuscular junctions by EM autoradiography using mask analysis and linear sources

Several methods of analyzing EM autoradiograms are now available. Two such procedures, the grain density distribution (or histogram) method and the mask method use the resolution of the EM autoradiographic technique to generate grain distributions expected from postulated sources, and compare these with the observed grains in the autoradiograms. These two methods are here compared in the analysis of label on linear sources: the distribution of labeled acetylcholine receptor (AChR) down the postjunctional folds of lizard and frog neuromuscular junctions. The receptors were labeled with I-25-α-bungarotoxin and the autoradiograms coated with the high resolution Kodak emulsion 129–01. We found that both methods gave similar results in confirming that the bulk of the AChR is concentrated on the thickened region of the membrane at the top ∼2000 A of the junctional folds, and that there may be a gradient of receptor concentration down the folds. The grain density distribution method is simpler, but does not lend itself easily to quantifying the extent of deviation from simple models. Although computer graphics is not necessary for either method, its use allows the expected grains from linear sources to be generated quickly, making the mask analysis a feasible routine method for assigning the extent of label in different membrane regions.     

Fatigue cracks at notches

The failure of a component or specimen due to a fatigue crack growing from a notch is considered. Previous methods of analysis involving stress and strain concentration factors are shown to be inadequate. By defining equivalent cracks in notched and un-notched situations as cracks with equal growth rates, the concept of notch contribution to crack length is introduced. Theoretical notch contributions are obtained for a variety of central and edge elliptical notches via stress intensity factor solutions. These results when extended to a very wide range of general notch shapes can be reduced to a useful and simple design rule where e is the contribution to a crack of length l growing from a notch of depth D and root radius . This rule combines the size and shape effects long known to affect fatigue behaviour and defines the extent of the notch field as 0·13√(D).The fatigue crack propagation lives of a wide variety of notches were estimated by this rule and comparisons with experimental values revealed very small errors normally well within the scatter of fatigue lives.The design rule is extended to enable the conventional stress intensity factor method to be employed. A fatigue concentration factor is proposed which takes into account the presence of a fatigue crack which all previous methods have ignored.     

First-trimester growth and the risk of low birth weight

BACKGROUND: Previous studies have demonstrated a correlation between first-trimester size and birth weight. It is not known, however, whether low birth weight is related to first-trimester growth. We sought to determine whether the risk of low birth weight and birth weight that was low for gestational age is related to the size of the embryo or the fetus in the first trimester. METHODS: From a data base of ultrasound records of more than 30,000 pregnancies, we identified women who had no important medical problems, a normal menstrual history, and a first-trimester ultrasound scan in which the crown-rump length of the embryo or fetus had been measured. We examined the relation between the outcome of 4229 pregnancies and the difference between the measured and the expected crown-rump length in the first trimester, expressed as equivalent days of growth. RESULTS: A first-trimester crown-rump length that was two to six days smaller than expected was associated with an increased risk (as compared with a normal or slightly larger than expected crown-rump length) of a birth weight below 2500 g (relative risk, 1.8; 95 percent confidence interval, 1.3 to 2.4), a birth weight below 2500 g at term (relative risk, 2.3; 95 percent confidence interval, 1.4 to 3.8), a birth weight below the fifth percentile for gestational age (relative risk, 3.0; 95 percent confidence interval, 2.0 to 4.4), and delivery between 24 and 32 weeks of gestation (relative risk, 2.1; 95 percent confidence interval, 1.1 to 4.0), but not with delivery between 33 and 36 weeks (relative risk, 1.0; 95 percent confidence interval, 0.7 to 1.5). CONCLUSIONS: Suboptimal first-trimester growth may be associated with low birth weight, low birth-weight percentile, and premature delivery.     

Rabies surveillance in the United States during 1997

In 1997, 49 states, the District of Columbia, and Puerto Rico reported 8,509 cases of rabies in nonhuman animals and 4 cases in human beings to the Centers for Disease Control and Prevention. Nearly 93% (7,899) were wild animals, whereas 7% (610) were domestic species. The total number of reported cases increased 19.4% from that of 1996 (7,128 cases). Increases were apparent in each of the major species groups, with the exception of cattle. The relative contributions of these groups to the total reported for 1997 were as follows: raccoons (50.5%; 4,300 cases), skunks (24.0%; 2,040), bats (11.3%; 958), foxes (5.3%; 448), cats (3.5%; 300), dogs (1.5%; 126), and cattle (1.4%; 122). The 958 cases of rabies reported in bats represented a 29.3% increase over the total reported for 1996 and the greatest number reported since 1984, with cases reported by 46 of the 48 contiguous states. The epizootic of rabies in raccoons expanded into Ohio in 1997 and now includes 19 states and the District of Columbia. Thirteen states, where rabies in raccoons is enzootic, reported increases over 1996 in total numbers of reported cases. New York (1,264 cases), North Carolina (879), Virginia (690), and Maryland (619) reported the greatest numbers of cases [corrected]. Five states reported increases that exceeded 50%, compared with cases reported in 1996: Ohio (673.3%; 15 cases in 1996 to 116 in 1997). Massachusetts (144.3%; 115 to 281), South Carolina (97.9%; 96 to 190), Connecticut (97.4%; 274 to 541), and Maine (86.3%; 131 to 244). Cases of rabies associated with foci of rabies in foxes in west central Texas and in dogs and coyotes in southern Texas continued to decline, with this state reporting 78.3% fewer rabid foxes (13 cases), 26.7% fewer rabid dogs (11), and 63.2% fewer rabid coyotes (7) during 1997, compared with 1996. Reported cases of rabies in cats (300) and dogs (126) increased 12.8% and 13.5%, respectively, whereas cases in cattle (122) decreased by 6.9%. Thirty states, the District of Columbia, and Puerto Rico reported increases in rabies in animals during 1997, compared with decreases reported by 31 states and the District of Columbia in 1996. One state (Mississippi; 5 cases) remained unchanged. Hawaii was the only state that did not report a case of rabies in 1997. Four indigenously acquired cases of rabies reported in human beings were the result of infection with rabies virus variants associated with bats.     

Minor histocompatibility antigens as targets for T-cell therapy after bone marrow transplantation

BACKGROUND: Topical antimicrobials have been considered for treatment of secondarily infected wounds because of the potential for reduced risk of adverse effects and greater patient convenience. We compared mupirocin cream with oral cephalexin in the treatment of wounds such as small lacerations, abrasions, or sutured wounds. METHODS: In 2 identical randomized double-blind studies, 706 patients with secondarily infected wounds (small lacerations, abrasions, or sutured wounds) received either mupirocin cream topically 3 times daily or cephalexin orally 4 times daily for 10 days. RESULTS: Clinical success at follow-up was equivalent in the two groups: 95.1% and 95.3% in the mupirocin cream and the cephalexin groups, respectively (95% confidence interval [CI], -4.0% to 3.6%; P = .89). The intention-to-treat success rate was 83% in both groups. Bacteriologic success at follow-up was also comparable: 96.9% in the mupirocin cream and 98.9% in the cephalexin groups (95% CI, -6.0% to 2.0%; P = .22). The occurrence of adverse experiences related to study treatment was similar for the 2 groups, with fewer patients in the mupirocin cream group reporting diarrhea (1.1% vs 2.3% for cephalexin). CONCLUSIONS: Mupirocin cream applied topically 3 times daily is as effective as oral cephalexin given 4 times daily for the treatment of secondarily infected wounds and was well tolerated.     

Long-acting blockade of biogenic amine transporters in rat brain by administration of the potent novel tropane 2beta-propanoyl-3beta-(2-Naphthyl)-tropane

2beta-Propanoyl-3beta-(2-naphthyl)-tropane (WF-23) is a potent cocaine analog with activity at dopamine and serotonin transporters. The purpose of these experiments was to characterize the time course of effects of acute administration of WF-23 on spontaneous locomotion and biogenic amine transporters. Rats received injections i.p. with WF-23 (1 mg/kg), cocaine (30 mg/kg) or vehicle and locomotor activity was measured at various times postinjection. Animals were killed immediately after behavioral activity. Locomotor activity was significantly increased by WF-23 administration, reaching maximum at 4 hr and persisting for 24 hr. Cocaine-elicited elevations in locomotor activity occurred only at the earliest times. WF-23 decreased DA transporter binding in striatal membranes ([125I]RTI-55 binding), with >50% loss in binding for up to 49 hr postinjection. WF-23 increased the Kd of the high affinity site, with no effect on Bmax. Cocaine depressed binding (20%) only at the earliest times. WF-23 decreased levels of [3H]WIN 35,428 binding sites up to 95% of control in both dorsal and ventral striatum with a similar time-course when assessed autoradiographically. WF-23 also reduced [3H]citalopram binding to serotonin transporter sites throughout the brain. The slow onset and very long duration of action of WF-23, taken together with its actions at dopamine and serotonin transporters, suggest a potential role for treatment of disorders characterized by their involvement of these neural systems.     

The functional anatomy of sound intensity discrimination

The human neuroanatomical substrate of sound intensity discrimination was investigated by combining psychoacoustics and functional neuroimaging. Seven normal subjects were trained to detect deviant sounds presented with a slightly higher intensity than a standard harmonic sound, using a Go/No Go paradigm. Individual psychometric curves were carefully assessed using a three-step psychoacoustic procedure. Subjects were scanned while passively listening to the standard sound and while discriminating changes in sound intensity at four different performance levels (d' = 1.5, 2.5, 3.5, and 4.5). Analysis of regional cerebral blood flow data outlined activation, during the discrimination conditions, of a right hemispheric frontoparietal network already reported in other studies of selective or sustained attention to sensory input, and in which activity appeared inversely proportional to intensity discriminability. Conversely, a right posterior temporal region included in secondary auditory cortex was activated during discrimination of sound intensity independently of performance level. These findings suggest that discrimination of sound intensity involves two different cortical networks: a supramodal right frontoparietal network responsible for allocation of sensory attentional resources, and a region of secondary auditory cortex specifically involved in sensory computation of sound intensity differences.     

Effective peer responses to impaired nursing practice

Subplate neurons, the first neurons of the cerebral cortex to differentiate and mature, are thought to be essential for the formation of connections between thalamus and cortex, such as the system of ocular dominance columns within layer 4 of visual cortex. To learn more about the requirement for subplate neurons in the formation of thalamocortical connections, we have sought to identify the neurotransmitters and peptides expressed by the specific class of subplate neurons that sends axonal projections into the overlying visual cortex. To label retrogradely subplate neurons, fluorescent latex microspheres were injected into primary visual cortex of postnatal day 28 ferrets, just prior to the onset of ocular dominance column formation. Subsequently, neurons were immunostained with antibodies against glutamate, glutamic acid decarboxylase (GAD-67), parvalbumin, neuropeptide Y (NPY), somatostatin (SRIF), or nitric oxide synthase (NOS). Retrograde labeling results indicate that the majority of subplate neurons projecting into the cortical plate reside in the upper half of the subplate. Combined immunostaining and microsphere labeling reveal that about half of cortically projecting subplate neurons are glutamatergic; most microsphere-labeled subplate neurons do not stain for GAD-67, parvalbumin, NPY, SRIF, or NOS. These observations suggest that subplate neurons can provide a significant glutamatergic synaptic input to the cortical plate, including the neurons of layer 4. If so, excitation from the axons of subplate neurons may be required in addition to that from lateral geniculate nucleus neurons for the activity-dependent synaptic interactions that lead to the formation of ocular dominance columns during development.