Spatial memory of children and adults assessed in the radial maze

To assess the development of accurate spatial memory and its relationship to organized search strategies, children (18-71 months old) and college students searched for rewards hidden at the ends of the arms of an eight-arm radial maze. Subjects made their first four choices in random order selected by the experimenter (forced choice) or in whatever order they wished (free choice). In some conditions, a retention interval was imposed between arm choices 4 and 5, followed by a resumption of the task. With free choice, accuracy of spatial memory increased linearly with age, and the proportion of tests on which the child entered four adjacent arms in sequence during the first four choices, a measure of organized searching, also increased linearly with age. Disrupting this sequential search strategy (forced choice) reduced accuracy for both children and college students, although the reduction with college students was small. Delays had minimal effects for children who met criterion at 0-delay and for college students. Although response patterns seem unimportant in accurate spatial memory in rats, systematic search strategies mature together with, and probably contribute to, the improvement of spatial memory with age in humans.     

Effects of dopamine agonists on hypothalamic defensive attack in cats

The effects of methamphetamine (MAT) and apomorphine (APO), dopamine agonists, were studied in 16 cats to evaluate their effects on threshold for defensive attack behavior elicited by electrical stimulation of the ventromedial hypothalamic nucleus (VMH). Directed attack and hissing were selected from elementary responses as constituting a defensive attack. Hissing threshold was measured in two situations, one with human provocation and the other without provocation. MAT administered systemically lowered the thresholds for all three types of responses in a dose-related manner (0.5, 1.0, and 3.0 mg/kg). The effects of 1.0 mg/kg of APO were almost identical to those observed with 0.5 or 1.0 mg/kg of MAT. These results suggest that MAT-induced aggressive behavior may be mediated by a dopamine-induced increase in the excitability of the VMH.     

Prostaglandin F(2alpha), cytokines and cyclic mechanical stretch augment matrix metalloproteinase-1 secretion from cultured human uterine cervical fibroblast cells

Human uterine cervical tissue is composed mainly of fibroblast cells and the extracellular matrix in which collagen types I and III predominate. It is hypothesized that these collagens are degraded by matrix metalloproteinases (MMPs) in the initial step of uterine cervical ripening during parturition. Among the MMPs, MMP-1, -8 and -13 have substrate selectivity for collagen types I and III. In the present study, we examined the regulation of MMP-1 secretion from the human uterine cervix. Immunohistochemistry detected strong staining of MMP-1, but not of MMP-8 or -13, in stromal cells of the pregnant uterine cervix. The MMP-1 expression in the pregnant uterine cervix was further confirmed by Western blot analysis and RT-PCR. To clarify the regulation of MMP-1 production, we subsequently investigated the effects of prostaglandins, inflammatory cytokines and cyclic mechanical stretch on the secretion of MMP-1 from cultured human uterine cervical fibroblast cells. Treatment with prostaglandin (PG)F(2alpha) (10(-7) to 10(-5) mol/l) or interleukin (IL)-1alpha (0.01-1.0 ng/ml) or stimulation with cyclic mechanical stretch increased MMP-1 secretion from cultured human uterine cervical fibroblast cells, with maximal increases of 3.4-, 4.5- and 1.9-fold respectively (24 h of treatment, P < 0.05 for all comparisons). These data suggest that MMP-1 may play a significant role in the degradation of extracellular collagen types I and III in the pregnant uterine cervix during the process of cervical ripening, in response to various stimulations such as PGF(2alpha), IL-1alpha and mechanical stretch.     

Single-equation models for the tear film in a blink cycle: realistic lid motion.

We consider model problems for the tear film over multiple blink cycles that utilize a single equation for the tear film; the single non-linear partial differential equation that governs the film thickness arises from lubrication theory. The two models that we consider arise from considering the absence of naturally occurring surfactant and the case when the surfactant is strongly affecting the surface tension. The film is considered on a time-varying domain length with specified film thickness and volume flux at each end; only one end of the domain is moving, which is analogous to the upper eyelid moving with each blink. Realistic lid motion from observed blinks is included in the model with end fluxes specified to more closely match the blink cycle than those previously reported. Numerical computations show quantitative agreement with in vivo tear film thickness measurements under partial blink conditions. A transition between periodic and non-periodic solutions has been estimated as a function of closure fraction and this may be a criterion for what is effectively a full blink according to fluid dynamics.     

Identification and functional analysis of mutations in the hypocretin (orexin) genes of narcoleptic canines

Narcolepsy is a sleep disorder affecting animals and humans. Exon skipping mutations of the Hypocretin/Orexin-receptor-2 (Hcrtr2) gene were identified as the cause of narcolepsy in Dobermans and Labradors. Preprohypocretin (Hcrt) knockout mice have symptoms similar to human and canine narcolepsy. In this study, 11 sporadic cases of canine narcolepsy and two additional multiplex families were investigated for possible Hcrt and Hcrtr2 mutations. Sporadic cases have been shown to have more variable disease onset, increased disease severity, and undetectable Hypocretin-1 levels in cerebrospinal fluid. The canine Hcrt locus was isolated and characterized for this project. Only one novel mutation was identified in these two loci. This alteration results in a single amino acid substitution (E54K) in the N-terminal region of the Hcrtr2 receptor and autosomal recessive transmission in a Dachshund family. Functional analysis of previously-described exon-skipping mutations and of the E54K substitution were also performed using HEK-293 cell lines transfected with wild-type and mutated constructs. Results indicate a truncated Hcrtr2 protein, an absence of proper membrane localization, and undetectable binding and signal transduction for exon-skipping mutated constructs. In contrast, the E54K abnormality was associated with proper membrane localization, loss of ligand binding, and dramatically diminished calcium mobilization on activation of the receptor. These results are consistent with a loss of function for all three mutations. The absence of mutation in sporadic cases also indicates genetic heterogeneity in canine narcolepsy, as reported previously in humans.     

Adhesion activity of fetal gonadal cells to EGF and discoidin domains of milk fat globule-EGF factor 8 (MFG-E8), a secreted integrin-binding protein which is transiently expressed in mouse early gonadogenesis

MFG-E8, a secreted integrin-binding protein, consists of two EGF domains containing a RGD motif and two discoidin domains. In mouse embryogenesis, MFG-E8 is highly expressed in gonadal stromal cells near mesonephros at 11.5–12.5 dpc, but its function in gonadogenesis has not been characterized. To clarify a possible role of MFG-E8 in developing gonads, we analyzed the adhesion activity of 10.5–15.5 dpc gonadal cells to recombinant proteins of EGF or discoidin domains of MFG-E8. In EGF-coated wells, the gonadal cells at 11.5–12.5 dpc revealed a significantly higher adhesion activity as compared to those at 10.5 and 15.5 dpc, while discoidin domains showed a constant number of the adhered cells throughout these stages. To identify the adhesive cells of 11.5-dpc gonads, immunohistochemistry with anti-SF1/Ad4Bp antibody (a specific marker for supporting, steroidogenic, and coelomic epithelial cells) and staining for alkaline phosphatase (a germ cell marker) were carried out. As a result, EGF domains, as well as discoidin domains, were capable of binding to all three groups of SF1/Ad4Bp-positive and negative somatic cells, and germ cells of 11.5-dpc gonads. These findings therefore suggest that MFG-E8 mediates the cell-to-cell interaction among several somatic cell types and germ cells in mouse early gonadogenesis.     

Momentary changes in the cardiovascular autonomic system during mental loading in patients with panic disorder: a new physiological index "rho(max)"

BACKGROUND: Although panic disorder (PD) is suggestive of autonomic nervous system dysfunction, especially in the cardiovascular autonomic system (CAS), the results in many previous studies are still controversial. Using a new physiological index which could well reflect emotional reaction to visual stimuli (Yoshizawa, M., Sugita, N., Tanaka, A., Abe, K., Yambe, T., Nitta, S., 2001. Quantiatative Physioligical Evaluation of Three Dimensional Images. The Seventh International Conference on Virtual Systems and Multumedia, 25-27.), we studied momentary changes in the CAS in patients with PD during audiovisual stimulation (AS) as mental loading. METHODS: During AS, exposed to a video of imaginary experiences such as driving a motor vehicle or diving into the sea, blood pressure (BP) and heart rate (HR) were measured in 12 remitted patients with PD and 19 age- and sex-matched normal controls (NC). We used the maximum cross-correlation coefficient (rho(max)) from the BP to the HR, whose frequency components were limited to around 0.1 Hz. RESULTS: The rho(max) was an available index which could detect the momentary changes in the CAS during AS in both groups. The two-way ANOVA disclosed significant group and time effects on the rho(max). The momentary response to emotional stimuli in the PD patients was slower than that in the NC subjects. LIMITATIONS: Antidepressants have a potential impact on the autonomic variables in this study. CONCLUSIONS: These findings suggest that there may be a dysfunction of the CAS in remitted PD patients and that the dysfunction may be one of the trait markers of PD. To confirm these findings, however, further studies with a large sample size are required.     

Nationwide epidemic of septicemia caused by contaminated intravenous products: mechanisms of intrinsic contamination.

Between 1 July 1970 and April 1971, in many hospitals in this country, there were outbreaks of nosocomial septicemia caused by Enterobacter cloacae of E. agglomerans (formerly Erwinia, herbicola-lathyri). All of these hospitals used infusion products manufactured by one company, Abbott Laboratories, and all affected patients had onset of septicemia while receiving the company's infusion products. Septicemia was epidemiologically and microbiologically traced to intrinsic contamination of the company's screw-cap closure for infusion bottles which was sealed with a newly introduced elastomer liner. Epidemic organisms were isolated from these closures. Investigations both in the laboratory and in the manufacturing plant into the mechanism of contamination of these products revealed the following. (i) Epidemic strains were present in numerous areas throughout the manufacturing plants. (ii) Viable microorganisms gained access to the interior of screw-cap closures after the autoclave step of production. (iii) Cooling closures actively drew moisture through the thread interstices into the inner-most depths of the closure. (iv) Transfer of contaminants from closures to fluid was easily effected by simple manipulations duplicating normal in-hospital use. (v) The red-rubber liner used in the company's screw-cap closures before the introduction of elastomer contained a broad-spectrum antimicrobial inhibitor. The findings from this epidemic and the associated studies show that the screw-cap closure as it is now designed cannot be considered secure for products that must remain sterile.     

Molecular characterization and heterogeneity of feline immunodeficiency virus isolates

Summary We have molecularly cloned the complete genomic DNA of TM2 strain of feline immunodeficiency virus (FIV) isolated in Japan and compared its nucleotide and the deduced amino acid sequence with those of previously described U.S. isolates, FIV Petaluma and FIV PPR. The infectious molecular clone of FIV TM2 is different from FIV Petaluma in host cell range; the clone can not infect Crandell feline kidney cells which were permissive for FIV Petaluma. The amino acid sequence homologies, ingag, pol, andenv genes between FIV TM2 and Petaluma were 90%, 87%, and 81%, respectively. On the other hand, comparative analysis of each gene between FIV Petaluma and PPR showed 96, 95, and 85%, respectively. These results suggested that the genomic diversity was present among FIV strains isolated from geographically distant areas. Interestingly,tat- andrev-like short open reading frames contained in-frame stop codons in the FIV Petaluma but not in the FIV TM2.     

Comparison of culture screening methods for detection of nasal carriage of methicillin-resistant Staphylococcus aureus: a prospective study comparing 32 methods

Screening for carriage of methicillin-resistant Staphylococcus aureus (MRSA) is fundamental to modern-day nosocomial infection control, both for epidemiologic investigation and day-to-day decisions on barrier isolation. Numerous microbiologic techniques have been advocated for screening for nasal carriage of MRSA, including the use of charcoal rather than rayon swabs, preincubation of swabs in Stuart's medium, preincubation of swabs in salt-containing trypticase soy broth (TSB), use of mannitol-salt agar (MSA), use of MSA containing oxacillin (MSA(Ox)), use of Mueller-Hinton agar containing oxacillin (MHA(Ox)), and the use of MSA containing lipovitellin with an oxacillin disk (MSAL(Ox)). We report a prospective clinical trial undertaken to test all of these methods concurrently. Patients at high risk for MRSA carriage were screened with eight consecutive nasal swabs (four standard rayon, four charcoal-coated rayon), which were processed by primary plating on MSA, MSA(Ox), MHA(Ox), and MSAL(Ox); Stuart's preincubation for 72 h followed by plating on the solid media; overnight enrichment in salt-containing TSB followed by plating; and Stuart's preincubation for 72 h followed by overnight enrichment in TSB and plating. All of the above methods were repeated with charcoal swabs. Each patient was screened by 32 culture methods. Forty-three (42%) of 102 patients studied were positive for MRSA by one or more methods. Among the four media evaluated with direct plating, MSAL(Ox) was 11 to 25% more sensitive for detecting MRSA (MSAL(Ox) versus MSA(Ox) or MHA(Ox) or MSA, each P < 0.01). Preincubation in Stuart's medium for 72 h did not enhance recovery of MRSA. Enrichment in salt-containing TSB further increased yield 9%. MSAL(Ox) also showed the best specificity, 93%. Charcoal swabs showed no advantage over standard rayon swabs. Our results suggest that the highest yield will be achieved by using standard rayon swabs that are enriched overnight in TSB with inoculation onto MSAL(Ox) medium. Direct inoculation of swabs onto MSAL(Ox) allows detection of 90% of MRSA carriers.