Role of TGF-beta in RA-induced cleft palate in CD-1 mice

Retinoic acid (RA) plays an important role in embryogenesis, by regulating morphogenesis, cell proliferation, differentiation, and extracellular matrix production. RA exposure on gestational day (GD) 12 in CD-1 mice results in delayed palatal shelf elevation and subsequent clefts in the secondary palate. Given the dynamic and complex nature of palate development, it is not surprising that this system is susceptible to changes in retinoid levels. There is evidence that experimental manipulation of retinoid status during development alters normal transforming growth factor-beta (TGF-beta) status. To study the role of perturbation in TGF-beta levels in RA-induced cleft palate, gravid CD-1 mice were treated with 70 mg/kg RA on GD 12. We examined changes in TGF-beta proteins and the steady-state level of TGF-beta mRNA within the first 24 hr after exposure. The interactions between RA and TGF-beta s were very complex. RA differentially regulated the mRNA and protein levels of TGF-beta 1. Changes in mRNA steady-state levels were rapid and transient in nature, indicating a direct mediation by RA. Differential regulation was evident, because RA treatment resulted in an increase in TGF-beta 1 mRNA steady levels followed by a decrease in the intracellular and extracellular forms of TGF-beta 1 protein. Moreover, the patterns of localization and levels of TGF-beta 2 and TGF-beta 3 proteins were not dramatically affected, although there was an increase in TGF-beta 3 mRNA steady-state levels. The increases in mRNA steady-state levels for TGF-beta 2 and TGF-beta 3, as for TGF-beta 1, were rapid and transient in nature, again arguing for direct mediation by RA. These data provide evidence for interactions between RA and TGF-beta s, and indicate that RA is capable of differentially regulating TGF-beta isoforms through processes involving different stages of TGF-beta synthesis and secretion. Further, changes in TGF-beta isoforms were observed prior to changes in mesenchyme morphology and must be considered as mediators of RA's effects on mesenchyme development.     

Diagnostic features of clinical neurologic feline infectious peritonitis

Feline infectious peritonitis (FIP) is a fatal Arthus-type immune response of cats to infection with FIP virus, a mutant of the ubiquitous feline enteric coronavirus (FECV). The disease may occur systemically or in any single organ system, and primary neurologic disease is a common subset of such manifestations. We examined 16 domestic cats with clinical neurologic FIP and 8 control cats with nonneurologic FIP, with the intention of identifying the ante- and postmortem diagnostic tests that most contribute to accurate diagnosis. Of the 16 cats with neurologic FIP, 15 were less than 2 years of age and all 16 originated from large multiple-cat households. The most useful antemortem indicators of disease were positive anti-coronavirus IgG titer in cerebrospinal fluid, high serum total protein concentration, and findings on magnetic resonance imaging suggesting periventricular contrast enhancement, ventricular dilatation, and hydrocephalus. Postmortem diagnosis was facilitated by FIP monoclonal antibody staining of affected tissue and coronavirus-specific polymerase chain reaction. Most cats with neurologic and ocular forms of FIP had patchy, focal lesions, suggesting that recently developed technologies described in this report may be useful for evaluation of cats with suspected FIP.     

Evolution and systematics of Anopheles: insights from a molecular phylogeny of Australasian mosquitoes

Relationships among the genus Anopheles and its many sibling species-groups are obscure despite the importance of anophelines as the vectors of human malaria. For the first time, the interrelationships and the origin of Australasian members of the subgenus Cellia are investigated by a cladistic analysis of sequence variation within the mitochondrial cytochrome oxidase subunit II gene. Estimated divergence times between many Australasian and Oriental taxa predate the mid Miocene collision of Australasia and Southeast Asia. Phylogenetic analysis suggests that two-way exchanges with Oriental mosquitoes rather than only immigration may have been a characteristic of anopheline paleobiogeography in Australasia. The Australasian fauna is mostly included in a large clade. The medically important Punctulatus Group is monophyletic and appears derived from Oriental stock. Populations within this group from as far apart as Australia and Vanuatu were in contact in the recent past (i.e., 0.35-2.44 mya), supporting dispersal rather than vicariance explanations. Some support for the monophyly of the Myzomyia, Neomyzomyia, and Pyretophorus Series was found. However, the subgenera Anopheles and Cellia and the Neocellia Series are paraphyletic, but branch support at these taxonomic levels was poor. The COII gene shows promise for questions concerning alpha taxonomy but appears to be of limited use for resolving deeper relationships within the Anopheles.     

Unilateral asymptomatic carotid disease does not require surgery

If a stimulus (e.g. tone or light) is repeatedly pre-exposed without consequences, it subsequently shows retarded conditioning when paired with a reinforcer (e.g. footshock) compared with a non-pre-exposed stimulus. This is latent inhibition (LI). Haloperidol-treated animals show potentiated LI, and it has been suggested that this is due to retarded switching to respond according to the stimulus-reinforcer contingency. Recently, it has been argued that the slowed control of behaviour by the stimulus-reinforcement contingency is due to a haloperidol-induced decrease in the impact, or salience, of the reinforcer, and thus should be antagonized by increasing the impact of reinforcement. Two experiments tested this prediction. In both, LI was assessed using an off-baseline conditioned emotional response procedure in rats licking for water. In Experiment 1, rats were given 10 light pre-exposures and conditioned with two footshocks of either a low (0.5 mA) or a high (1 mA) intensity. In Experiment 2, rats were given 30 pre-exposures and conditioned with either two or five footshocks of 1 mA. In Experiment 1, no-drug controls did not show LI at both shock intensities. Haloperidol (0.1 mg/kg) was ineffective in potentiating LI at low-intensity shock, but produced LI when shock level was increased. In Experiment 2, no-drug controls showed LI with two but not five conditioning trials. Haloperidol was ineffective in potentiating LI with two conditioning trials, but produced LI with five conditioning trials. Although the effect of haloperidol on LI could thus be modified by manipulating shock intensity or the number of conditioning trials, the direction of such modification indicates that the potentiating effect of haloperidol on LI is not in general antagonized by increasing the impact of reinforcement.     

Physician-assisted suicide: reflections on Oregon's first case

The authors analyze Oregon's first reported assisted suicide of Mrs. A as a real life application of the Oregon Death with Dignity Act. They critique the effectiveness of the Act's safeguards as illustrated by the case of Mrs. A. They point out that the Act does not require that physicians be adequately trained in palliative care in order to participate in assisted suicide. Most physicians do not have such training. Without it, they are not able to effectively present alternatives to patients requesting assisted suicide. Most physicians also lack the expertise to assess patients' decision-making capacity. Nor does the Act ensure that physicians will be in a position to assess coercion of patients' decisions. The Act requires physicians to report only minimal information about their cases, and there are no enforcement provisions to see that even this is done. Under the Act, a good faith standard rather than the more usual negligence standard immunizes physicians from civil or criminal liability even when they act negligently. The authors demonstrate that the Act protects physicians more than patients, and encourages secrecy. The authors conclude that secrecy will need to be replaced by openness to permit the kind of examination the practice of assisted suicide warrants.     

Molecular, clinical, and pathologic comparison of two distinct strains of Haemobartonella felis in domestic cats

PURPOSE: To evaluate the long-term effect of photoastigmatic refractive keratectomy (PARK) on mild keratoconus. SETTING: Laser Unit, Ein Tal Eye Center, Tel Aviv, Israel. METHODS: Eight eyes of 6 patients with stable compound myopic astigmatism and topography features of keratoconus were treated with a VISX Twenty-Twenty excimer laser. The laser beam slit width ranged between 4.8 and 5.0 mm according to the degree of cylinder. Preoperative slitlamp examination did not reveal significant thinning, ectasia, or scarring. Astigmatism ranged between -2.00 and -7.50 diopters and follow-up, between 36 and 48 months. RESULTS: In 7 of 8 eyes, uncorrected visual acuity (UCVA) before PARK ranged between 6/30 and finger counting. After PARK, it ranged between 6/9(-) and 6/15, and patients could manage in most of their daily activities without using spectacles. In 2 eyes, the final UCVA was 6/15(-) and 6/15. In 1 eye, treatment failed to improve UCVA and corneal topography revealed progression of the keratoconus. CONCLUSIONS: Photoastigmatic keratectomy was partially effective in eyes with mild stable keratoconus. However, the long-term results may be altered by progression of corneal thinning and ecstatic disease. In addition to the mild nature of the keratoconus, this is a small series and further studies are needed to confirm these results.     

Collaborative video searching on a tabletop

Almost all system and application design for multimedia systems is based around a single user working in isolation to perform some task yet much of the work for which we use computers to help us, is based on working collaboratively with colleagues. Groupware systems do support user collaboration but typically this is supported through software and users still physically work independently. Tabletop systems, such as the DiamondTouch from MERL, are interface devices which support direct user collaboration on a tabletop. When a tabletop is used as the interface for a multimedia system, such as a video search system, then this kind of direct collaboration raises many questions for system design. In this paper we present a tabletop system for supporting a pair of users in a video search task and we evaluate the system not only in terms of search performance but also in terms of user–user interaction and how different user personalities within each pair of searchers impacts search performance and user interaction. Incorporating the user into the system evaluation as we have done here reveals several interesting results and has important ramifications for the design of a multimedia search system.     

An analogue and propositional hybrid model for the perception of computer generated graphical images

This research investigated two alternative models, analogue and propositional, which describe how three-dimensional (3-D) graphical images are represented and stored in human memory. In order to differentiate between the two models, three separate experiments were performed using a variation of the Shepard-Metzler mental rotation paradigm (Shepard and Metzler 1971). For each experiment, the effects of three independent variables on the performance of a 'mental rotation' task were examined: (a) three levels of figure complexity, ( b) three axes of rotation and (c) four angles of rotation. The subjects' task was to compare specific angle, axis or depth versus picture plane rotations for pairs (rotated and non-rotated versions) of 3-D graphic figures displayed on a CRT. The results indicated that response times varied depending on level of figure complexity, axis or angle of rotation. A new hybrid model integrating components of both the analogue and propositional positions is proposed to explain the reaction time data. In this model, analogue processes occur when processing requirements for cognitive tasks are low, whereas propositional processes occur when processing requirements are high. Implications of the results for the internal representation of 3-D images in human memory and for the design of graphic work stations are discussed.     

Effects of Low-dose Gamma Irradiation on the Shelf Life and Quality Characteristics of Cut Romaine Lettuce Packaged under Modified Atmosphere

Cut romaine lettuce, packaged under modified atmosphere, was subjected to 0.15 and 0.35 kGy gamma irradiation. Irradiation at 0.35 kGy decreased aerobic plate counts by 1.5 logs and yeast and mold counts by 1 log; these differences were maintained through the 22-d storage. Irradiation at 0.15 kGy caused smaller reductions in microbial counts. A decrease in headspace CO₂ was observed in the 0.35-kGy-treated lettuce, although CO₂ concentrations increased in all samples with storage. O₂ concentration was not affected by irradiation. Ten percent loss in firmness was observed at 0.35 kGy, while other sensory attributes such as color, generation of off-flavor, and appearance of visual defects were not affected.