The immune status indices of schoolchildren in the Donetsk region

With the purpose of studying the impact of ecological health hazard conditions on the juvenile organism, a total of 192 pupils of upper grades from schools in Donetsk, Makeyevka, Mariupol (conventionally a "dirty" zone) and 126 schoolchildren from Artemovsk and Krasny? Liman (conventionally a "clean" zone) were evaluated for the immunological status. Children from the polluted zone demonstrated decreased levels of lysozyme in saliva as well as of glycogen and acid phosphatase in leucocytes, there were also deviations from the norm in the peripheral blood picture. Young residents of Mariupol appeared to have the worst findings.     

Liver transplantation in Western Australia: improved services to an isolated population

OBJECTIVE: To assess performance of the Western Australian Liver Transplantation Service in the light of debate about whether small transplant centres can produce optimal outcomes. DESIGN: Review of patient data collected prospectively and confirmed by retrospective casenote review. SUBJECTS: All patients referred to the Western Australian Liver Transplantation Assessment Panel. Those who underwent transplantation at the Western Australian Liver Transplantation Service (to June 1996) were compared with those referred to other transplant centres before the elective service was established in July 1994. OUTCOME MEASURES: Numbers of referrals and transplants; characteristics of the transplantation procedure; and patient outcomes. RESULTS: Annual referrals for liver transplant in Western Australia (WA) increased from 12 (1985-1993) to 41 (July 1994-June 1996), with five deaths on the "activated" list before July 1994, but none after. To June 1996, 30 patients had received 31 transplants by the Western Australian Liver Transplantation Service (two emergency transplants in 1992 and 1993, respectively, and 28 elective transplants and one retransplant after June 1994), with median operation time of 5.5 hours (range, 3-10.5), median red cell transfusion of 4 units (range, 0-55) and median hospital stay of 24 days (range, 12-128). There was no severe primary graft dysfunction. Major complications included hepatic artery thrombosis or stenosis (5 patients, one requiring retransplant), biliary stricture not associated with hepatic artery pathology, bile leak and perihepatic abscess (4 each), and cytomegalovirus infection (3). Patient survival was 83% and graft survival 81% at a mean follow-up of 13 months, compared with 86% and 83%, respectively, at one year for WA patients who received transplants elsewhere before July 1994. CONCLUSIONS: Performance of the Western Australian Liver Transplantation Service compares favourably with national and international standards, and WA patients receiving liver transplants have increased dramatically since the service was established. This supports the viability of committed liver transplantation centres with only 10-15 patients a year and argues the need for nationally decentralised services.     

Ultrasound diagnosis of popliteal arterial aneurysms

"B" mode ultrasound scanning is useful in the diagnosis of popliteal arterial aneurysms. It offers advantages over physical examination and arteriography, since these aneurysms are sometimes difficult to palpate and may be partially filled with laminated clot. The technique is noninvasive and without known hazard in this location. "B" mode ultrasound scanning promises to be useful in the diagnosis of aneurysms of other extremity arteries. It has already been useful in confirming the presence of femoral false aneurysms. Greater familiarity with the technique and improvepd technology will result in even greater reliance on ultrasound diagnosis.     

Physiological memory in primary auditory cortex: characteristics and mechanisms

"Physiological memory" is enduring neuronal change sufficiently specific to represent learned information. It transcends both sensory traces that are detailed but transient and long-term physiological plasticities that are insufficiently specific to actually represent cardinal details of an experience. The specificity of most physiological plasticities has not been comprehensively studied. We adopted receptive field analysis from sensory physiology to seek physiological memory in the primary auditory cortex of adult guinea pigs. Receptive fields for acoustic frequency were determined before and at various retention intervals after a learning experience, typified by single-tone delay classical conditioning, e.g., 30 trials of tone-shock pairing. Subjects rapidly (5-10 trials) acquire behavioral fear conditioned responses, indexing acquisition of an association between the conditioned and the unconditioned stimuli. Such stimulus-stimulus association produces receptive field plasticity in which responses to the conditioned stimulus frequency are increased in contrast to responses to other frequencies which are decreased, resulting in a shift of tuning toward or to the frequency of the conditioned stimulus. This receptive field plasticity is associative, highly specific, acquired within a few trials, and retained indefinitely (tested to 8 weeks). It thus meets criteria for "physiological memory." The acquired importance of the conditioned stimulus is thought to be represented by the increase in tuning to this stimulus during learning, both within cells and across the primary auditory cortex. Further, receptive field plasticity develops in several tasks, one-tone and two-tone discriminative classical and instrumental conditioning (habituation produces a frequency-specific decrease in the receptive field), suggesting it as a general process for representing the acquired meaning of a signal stimulus. We have proposed a two-stage model involving convergence of the conditioned and unconditioned stimuli in the magnocellular medial geniculate of the thalamus followed by activation of the nucleus basalis, which in turn releases acetylcholine that engages muscarinic receptors in the auditory cortex. This model is supported by several recent findings. For example, tone paired with NB stimulation induces associative, specific receptive field plasticity of at least a 24-h duration. We propose that physiological memory in auditory cortex is not "procedural" memory, i.e., is not tied to any behavioral conditioned response, but can be used flexibly.     

Brain lipid composition of the rat with experimental morphine dependence

OBJECTIVE: To develop and validate a prediction rule screening instrument, easily incorporated into the routine hospital admission assessment, that could facilitate discharge planning by identifying patients at the time of admission who are most likely to need postdischarge medical services. DESIGN: Prospective cohort study with separate phases for prediction rule development and validation. SETTING: Urban teaching hospital. PATIENTS/PARTICIPANTS: General medical service patients, 381 in the derivation phase and 323 in the validation phase, who provided self-reported medical history, health status, and demographic data as a part of their admission nursing assessment, and were subsequently discharged alive. MEASUREMENTS AND MAIN RESULTS: Use of postdischarge medical services such as visiting nurse or physical therapy, medical equipment, or placement in a rehabilitation or long-term care facility was determined. A prediction rule based on a patient's age and Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) physical function and social function scores stratified patients with regard to their risk of using postdischarge medical services. In the validation set, the rate of actual postdischarge medical service use was 15% (15 of 97), 36% (39 of 107), and 58% (57 of 98) among patients characterized by the prediction rule as being at "low", "intermediate," and "high" risk of using postdischarge medical services, respectively. CONCLUSIONS: This prediction rule stratified general medical patients with regard to their likelihood of needing discharge planning to arrange for postdischarge medical services. Further research is necessary to determine whether prospective identification of patients likely to need discharge planning will make the hospital discharge planning process more efficient.     

Correction of single-breath helium lung volumes in patients with airflow obstruction

STUDY OBJECTIVE: To determine whether alveolar volume (V(A)) measured during the single-breath diffusing capacity for carbon monoxide (DCO) can be used as a substitute measure for the multiple-breath total lung capacity (TLC) in subjects with and without airways obstruction. DESIGN: Retrospective review of pulmonary function test (PFT) results. SETTING: Pulmonary function laboratories at the Johns Hopkins Hospital (JHH) and the Johns Hopkins Asthma and Allergy Center (HAAC). PARTICIPANTS: Patients referred for spirometry, helium lung volumes, and Dco during a single visit between November 1993 and November 1996. RESULTS: JHAAC patients (n=2,477) were used to assess the relationship between V(A) and TLC. In patients with an FEV1/FVC > or = 0.70, there was good agreement between V(A) and TLC (V(A)/TLC=0.97 to 0.99). However, in patients with an FEV1/FVC <0.70, V(A) systematically underestimated TLC (V(A)/TLC=0.67 to 0.94). The degree of underestimation was related to the severity of airflow obstruction. To predict TLC using V(A) a regression equation was used to "correct" V(A) for the severity of obstruction. This equation was used to predict the multiple-breath TLC for JHH patients (n=2,892). Patients with an FEV1/FVC > or = 0.70 showed a high degree of correlation between V(A) and TLC (Pearson's correlation coefficient [r]=0.96 to 0.99; p<0.05). After adjusting for the severity of airflow obstruction, patients with an FEV1/FVC in the range of 0.40 to 0.70 also had a strong correlation between the corrected V(A) and the multiple-breath TLC (r=0.83 to 0.94; p<0.05). CONCLUSIONS: V(A) accurately predicts TLC in patients with mild or no airflow obstruction. For patients with moderate to severe obstruction, correcting V(A) for the severity of obstruction improves the accuracy of this relatively simple and rapid technique for measuring TLC.     

Organization of retinal axons within the optic nerve, optic chiasm, and the innervation of multiple central nervous system targets Rana pipiens

Light microscopic analysis of the optic nerve, chiasm, and optic tracts of Rana pipiens after the anterograde and retrograde transport of horseradish peroxidase has shown that retinal ganglion-cell axons reach the optic nerve head in chronotopically organized fascicles that form bands across the intraocular optic nerve. These bands of fascicles are divided along the midline in a "zone of reorganization" to create two full maps of the retinal surface; however, this map is discontinuous in that nasal and temporal quadrants are adjacent to one another. In the intracranial portion of the optic nerve, axons undergo another reorganization such that peripheral retinal axons shift position and become localized laterally and ventrally, whereas centrally placed axons become localized dorsally. Within this reorganization, the nerve is reconfigured into laminae of axons, and each lamina consists of age-related axons organized into two retinal maps. In the ipsilateral chiasm, axons diverge to form three central, optic tracts: the medial optic tract, the projection to the corpus geniculatum, and the basal optic root. Ipsilateral axons leave the chiasm at the same level of the chiasm as do their contralateral counterparts. The remaining axons converge in the lateral diencephalon to form a fourth fascicle, the marginal optic tract. Thus, within the optic chiasm, a sequence of positional transformations occur that result in the formation of multiple optic pathways. The various changes in axonal trajectory always coincide with changes in the orientation of cell groups that lie within the nerve and optic chiasm.     

Molecular determinants of L-type Ca2+ channel inactivation. Segment exchange analysis of the carboxyl-terminal cytoplasmic motif encoded by exons 40-42 of the human alpha1C subunit gene

Recently we have described a splice variant of the L-type Ca2+ channel (alpha1C,86) in which 80 amino acids (1572-1651) of the conventional alpha1C,77 were substituted by another 81 amino acids due to alternative splicing of exons 40-42. Ba2+ current (IBa) through alpha1C,86 exhibited faster inactivation kinetics, was strongly voltage-dependent, and had no Ca2+-dependent inactivation. An oligonucleotide-directed segment substitution and expression of the mutated channels in Xenopus oocytes were used to study the molecular determinants for gating of the channel within the 80-amino acid domain. Replacement of segments 1572-1598 or 1595-1652 of the "slow" alpha1C,77 channel with the respective segments of the "fast" alpha1C,86 gave rise to rapidly inactivating alpha1C,86-like channel isoforms. We found that replacement of either motifs 1572IKTEG1576 or 1600LLDQV1604 of alpha1C,77 with the respective sequences of alpha1C,86 caused strong but partial acceleration of IBa inactivation. Replacement of both sequences produced an alpha1C, 86-like fast channel which had no Ca2+-dependent inactivation. These results support the hypothesis that motifs 1572-1576 and 1600-1604 of alpha1C,77 contribute cooperatively to inactivation kinetics of alpha1C and are critical for Ca2+-dependent inactivation of the channel.     

The rate of internalization of the mannose 6-phosphate/insulin-like growth factor II receptor is enhanced by multivalent ligand binding

The cation-independent mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF-II receptor) undergoes constitutive endocytosis, mediating the internalization of two unrelated classes of ligands, mannose 6-phosphate (Man-6-P)-containing acid hydrolases and insulin-like growth factor II (IGF-II). To determine the role of ligand valency in M6P/IGF-II receptor-mediated endocytosis, we measured the internalization rates of two ligands, beta-glucuronidase (a homotetramer bearing multiple Man-6-P moieties) and IGF-II. We found that beta-glucuronidase entered the cell approximately 3-4-fold faster than IGF-II. Unlabeled beta-glucuronidase stimulated the rate of internalization of 125I-IGF-II to equal that of 125I-beta-glucuronidase, but a bivalent synthetic tripeptide capable of occupying both Man-6-P-binding sites on the M6P/IGF-II receptor simultaneously did not. A mutant receptor with one of the two Man-6-P-binding sites inactivated retained the ability to internalize beta-glucuronidase faster than IGF-II. Thus, the increased rate of internalization required a multivalent ligand and a single Man-6-P-binding site on the receptor. M6P/IGF-II receptor solubilized and purified in Triton X-100 was present as a monomer, but association with beta-glucuronidase generated a complex composed of two receptors and one beta-glucuronidase. Neither IGF-II nor the synthetic peptide induced receptor dimerization. These results indicate that intermolecular cross-linking of the M6P/IGF-II receptor occurs upon binding of a multivalent ligand, resulting in an increased rate of internalization.