Hepatitis E virus infection in chimpanzees: a retrospective analysis

Summary.  Different patterns of disease were observed among 11 chimpanzees who were inoculated intravenously with hepatitis E virus (HEV) positive fecal specimens from four different outbreaks (Nepal 1981, Uzbekistan 1981, Pakistan 1985, and Mexico 1986). Five chimpanzees had marginal or no liver enzyme elevations within 70 days of inoculation. Two of the chimpanzees had limited viremia, but did not produce detectable antibody. The four remaining chimpanzees had liver enzyme elevations, viral shedding, viremia, seroconversion to anti-HEV, and detectable HEV antigen in liver biopsy specimens. These results may reflect the range of infection patterns that develop in humans after natural exposure to the HEV. Received December 29, 1999/Accepted February 21, 2000     

Geometric modeling of the human torso using cubic hermite elements

We discuss the advantages and problems associated with fitting geometric data of the human torso obtained from magnetic resonance imaging, with high-order (bicubic Hermite) surface elements. These elements preserve derivative (C ¹) continuity across element boundaries and permit smooth anatomically accurate surfaces to be obtained with relatively few elements. These elements are fitted to the data with a new nonlinear fitting procedure that minimizes the error in the fit while maintainingC ¹ continuity with nonlinear constraints. Nonlinear Sobelov smoothing is also incorporated into this fitting scheme. The structures fitted along with their corresponding root meansquared error, number of elements used, and number of degrees of freedom (df) per variable are: epicardium (0.91 mm, 40 elements, 142 df), left lung (1.66 mm, 80 elements, 309 df), right lung (1.69 mm, 80 elements, 309 df), skeletal muscle surface (1.67 mm, 264 elements, 1,010 df), fat layer (1.79 mm, 264 elements, 1,010 df), and the skin layer (1.43 mm, 264 elements, 1,010 df). The fitted surfaces are assembled into a combined finite element/boundary element model of the torso in which the exterior surfaces of the heart and lungs are modeled with two-dimensional boundary elements and the layers of the skeletal muscle, fat, and skin are modeled with finite elements. The skeletal muscle and fat layers are modeled with bicubic Hermite linear elements and are obtained by joining the adjacent surface elements for each layer. Applications for the torso model include the forward and inverse problems of electrocardiography, defibrillation studies, radiation dosage studies, and heat transfer studies.     

Inhibition of the development of immediate hypersensitivity by staphylococcal enterotoxin B

We investigated the ability of staphylococcal enterotoxin B (SEB) to modify the immediate hypersensitivity response induced in BALB/c mice following sensitization to ovalbumin (OVA), a response mediated by OVA-reactive Vβ8 T cells. Mice were sensitized by skin painting with OVA every second day over a period of 2 weeks. SEB, a potent activator of Vβ8⁺ T cells, was administered at the same site where OVA was applied (skin of the lower abdomen) following two different protocols. In protocol (A) SEB was injected intradermally 1 day before painting with OVA and on day 7; in protocol B, SEB was injected each time OVA was applied to the skin (eight times). SEB (but not SEA) altered the development of immediate hypersensitivity to OVA, as demonstrated by the reduction in allergen-specific IgE, decreased OVA-specific immediate skin test responsiveness, and prevented the development of increased airways responsiveness after bronchial challenge with OVA. Injections of SEB did not alter the proliferative responses of local draining lymph node cells or spleen mononuclear cells to OVA, indicating that administration of SEB did not inhibit the sensitization to OVA, but shifted the immune response away from an immediate type response (IgE/IgG₁) to IgG_2a, IgG_2b and IgG₃. Although both protocols of SEB treatment did not lead to a major deletion of the Vβ8 T cell population, they did reduce the proliferative response of Vβ8⁺ T cells to OVA. These data indicate that the bacterial toxin SEB is capable of modifying the immediate hypersensitivity response induced by OVA by altering the functional capacity of antigen-reactive Vβ8 T cells.     

Surgery for severe rhinosinusitis

Sinusitis is one of the most common reasons patients visit their primary care physician. The etiology of sinusitis is multifactorial in most cases. However, the final common pathway of disruption is usually made with a thorough history. The physical examination is often unremarkable. Complaints of nasal obstruction, mucopuluent nasal drainage, and facial pain/pressure are most diagnostic chronic sinusitis. Isolated headache is an uncommon presenting symptom. Computed tomography scans are the gold standard for diagnostic imaging. They can be used both for diagnosis and surgical treatment. All chronic sinusitis patients, being considered for endoscopic sinus surgery, should have failed a trial of maximal medical therapy. This includes a 4–6 wk course of oral antibiotics, nasal steroids, topical nasal decongestants, and oral prednisone if possible. Patients who fail maximal medical therapy have persistent symptoms that significantly effect their daily activities, have chronic abnormalities on computet tomography scan, and are candidates for endoscopic sinus surgery. Appropriate patient selection and preoperative counseling are key factors in patient satisfaction. Most patients with symptoms that significantly impact their daily activities will receive marked improvement in symptoms after sinus surgery. Endoscopic sinus surgery has undergone radical changes in the last 15 yr. Minimally invasive techniques, combined with advances in instrumentation and computers have reduced postoperative discomfort and improved patient satisfaction.     

Nucleic acid sequence of the VP1 region of attenuated MS-1 hepatitis A virus

The nucleotide sequence of the VP1 region of marmoset-attenuated hepatitis A virus (HAV), MS-1, was determined by incorporative dideoxynucleotide sequencing of the RNA obtained from purified, liver-derived virus. Comparison of this nucleotide sequence to those of four previously published isolates revealed that one of the isolates, HM-175, which was obtained from Australia and passed three times in marmosets, had a 8.5-11% nucleotide variability compared to the remaining four isolates which were isolated from North American sources. This nucleotide variability does not result in amino acid differences with the exception of two of the North American isolates, which were derived from tissue culture passage. These isolates have been shown to contain regions of variability generated by nucleotide insertions and/or deletions, while the remaining three isolates, including the Australian isolate, demonstrate limited amino acid differences within the VP1 molecule.     

Regulation of Leishmania populations within the host. II. genetic control of acute susceptibility of mice to Leishmania donovani infection.

The acute growth rates of Leishmania donovani populations in twenty-five inbred mouse strains fall into two distinct groups: the susceptible (S) and the resistant (R). Hybrids within either category resemble their parents in susceptibility. Hybrids between categories are moderately resistant. Back-crossing of F1 hybrids to R and S parents, and interbreeding the F1 generation, give susceptibility ratios consistent with single gene control of acute susceptibility to visceral leishmaniasis. The distribution of this character among inbred mouse strains does not correspond to any well-studied gene nor does it appear to be linked to the H2 histocompatibility locus.     

Distinctive neurophysiological properties of embryonic trigeminal and geniculate neurons in culture

Neurons in trigeminal and geniculate ganglia extend neurites that share contiguous target tissue fields in the fungiform papillae and taste buds of the mammalian tongue and thereby have principal roles in lingual somatosensation and gustation. Although functional differentiation of these neurons is central to formation of lingual sensory circuits, there is little known about electrophysiological properties of developing trigeminal and geniculate ganglia or the extrinsic factors that might regulate neural development. We used whole cell recordings from embryonic day 16 rat ganglia, maintained in culture as explants for 3-10 days with neurotrophin support to characterize basic properties of trigeminal and geniculate neurons over time in vitro and in comparison to each other. Each ganglion was cultured with the neurotrophin that supports maximal neuron survival and that would be encountered by growing neurites at highest concentration in target fields. Resting membrane potential and time constant did not alter over days in culture, whereas membrane resistance decreased and capacitance increased in association with small increases in trigeminal and geniculate soma size. Small gradual differences in action potential properties were observed for both ganglion types, including an increase in threshold current to elicit an action potential and a decrease in duration and increase in rise and fall slopes so that action potentials became shorter and sharper with time in culture. Using a period of 5-8 days in culture when neural properties are generally stable, we compared trigeminal and geniculate ganglia and revealed major differences between these embryonic ganglia in passive membrane and action potential characteristics. Geniculate neurons had lower resting membrane potential and higher input resistance and smaller, shorter, and sharper action potentials with lower thresholds than trigeminal neurons. Whereas all trigeminal neurons produced a single action potential at threshold depolarization, 35% of geniculate neurons fired repetitively. Furthermore, all trigeminal neurons produced TTX-resistant action potentials, but geniculate action potentials were abolished in the presence of low concentrations of TTX. Both trigeminal and geniculate neurons had inflections on the falling phase of the action potential that were reduced in the presence of various pharmacological blockers of calcium channel activation. Use of nifedipine, omega-conotoxin-MVIIA and GVIA, and omega-agatoxin-TK indicated that currents through L-, N-, and P/Q- type calcium channels participate in the action potential inflection in embryonic trigeminal and geniculate neurons. The data on passive membrane, action potential, and ion channel characteristics demonstrate clear differences between trigeminal and geniculate ganglion neurons at an embryonic stage when target tissues are innervated but receptor organs have not developed or are still immature. Therefore these electrophysiological distinctions between embryonic ganglia are present before neural activity from differentiated receptive fields can influence functional phenotype.     

Lack of functional estrogen receptor beta influences anxiety behavior and serotonin content in female mice

Estrogen has been linked to the modulation of anxiety in females. Here we report results of anxiety tests conducted in female estrogen receptor beta (ERbeta) knockout (ERbetaKO) and wild-type (WT) mice. Ovariectomized (OVX) mice treated with chronic estradiol (E2) replacement did not behave differently on the elevated plus-maze when compared with OVX mice that did not experience hormone replacement. However, a genotype difference was noted; WT females were more likely to explore the distal portion of the open arm of the maze than ERbetaKO littermates. In addition, ERbetaKO female mice had significantly lower serotonin (5-HT) content than WT littermates in several brain regions including: the bed nucleus of the stria terminalis, preoptic area, and hippocampus. A similar trend was noted in the dorsal raphe nucleus. Dopamine content was reduced within the caudate putamen in ERbetaKO mice as compared to brains from WT animals. Thus, in the absence of functional ERbeta, regardless of the presence or absence of circulating E2 in plasma, female mice exhibited enhanced anxiety and decreased concentrations of 5-HT or dopamine in several brain regions. We hypothesize that ERbeta is required during development to modulate the effects of estrogen on anxiety and catecholamine concentrations in female mouse brains.     

Serodiagnosis of viral hepatitis A by a modified competitive binding radioimmunoassay for immunoglobulin M anti-hepatitis A virus.

A competitive binding radioimmunoassay (CBA) for antibody to hepatitis A virus (HAV) was evaluated and compared with a standard solid-phase radioimmunoassay for anti-HAV, CBA was found to be sensitive and specific for the detection of anti-HAV, as demonstrated by the 98% concordance of CBA and solid-phase radioimmunoassay test results. The standard CBA test was modified for the differential detection of acute (immunoglobulin M) and convalescent (immunoglobulin G) anti-HAV by incorporation of a step in which immunoglobulin G anti-HAV was preferentially absorbed with S. aureus cells (protein A). The modified CBA test was shown to be capable of differentiating between acute- and convalescent-phase sera. The modified CBAM test was able to detect immunoglobulin M anti-HAV up to approximately 4 weeks after the onset of illness.