A double recombinant herpes virus of turkeys for the protection of chickens against Newcastle,infectious laryngotracheitis and Marek’s diseases

A double recombinant strain of herpes virus of turkeys (HVT) was constructed that contains the fusion (F) gene from Newcastle disease virus (NDV) and the gD plus gI genes from infectious laryngotracheitis virus (ILTV) inserted into a non-essential region of the HVT genome. Expression of the F protein was controlled by a human cytomegalovirus promoter, whereas expression of gD plus gI was driven by an ILTV promoter. The double recombinant vaccine virus (HVT-NDV-ILT) was fully stable genetically and phenotypically following extended passage in cell culture and infection of chickens. Safety of the vaccine virus was confirmed by overdose and backpassage studies in specific-pathogen-free chickens. Chickens vaccinated with a single dose of HVT-NDV-ILT administered by the in ovo route were highly protected from challenge with the velogenic NDV (GB Texas), ILTV (LT 96-3) and Marek’s disease virus (GA 5) strains (97%, 94% and 97%, respectively). Similarly, chickens vaccinated with a single dose by subcutaneous (SC) route at 1 day of age were highly protected from challenge with the same three viruses (100%, 100%, and 88%, respectively). The protection level of a single dose given by in ovo or SC route against challenge with a virulent Marek’s disease virus strain demonstrates that insertion of multiple genes from two different pathogens within the HVT genome had no adverse effect on the capacity of HVT to protect against Marek’s disease. These results demonstrate that HVT-NDV-ILT is a safe and efficacious vaccine for simultaneous control of NDV, ILTV and Marek’s diseases.     

Myoarchitectural disarray of hypertrophic cardiomyopathy begins pre‐birth

Myoarchitectural disarray – the multiscalar disorganisation of myocytes, is a recognised histopathological hallmark of adult human hypertrophic cardiomyopathy (HCM). It occurs before the establishment of left ventricular hypertrophy (LVH) but its early origins and evolution around the time of birth are unknown. Our aim is to investigate whether myoarchitectural abnormalities in HCM are present in the fetal heart. We used wild‐type, heterozygous and homozygous hearts (n = 56) from a Mybpc3‐targeted knock‐out HCM mouse model and imaged the 3D micro‐structure by high‐resolution episcopic microscopy. We developed a novel structure tensor approach to extract, display and quantify myocyte orientation and its local angular uniformity by helical angle, angle of intrusion and myoarchitectural disarray index, respectively, immediately before and after birth. In wild‐type, we demonstrate uniformity of orientation of cardiomyocytes with smooth transitions of helical angle transmurally both before and after birth but with traces of disarray at the septal insertion points of the right ventricle. In comparison, heterozygous mice free of LVH, and homozygous mice showed not only loss of the normal linear helical angulation transmural profiles observed in wild‐type but also fewer circumferentially arranged myocytes at birth. Heterozygous and homozygous showed more disarray with a wider distribution than in wild‐type before birth. In heterozygous mice, disarray was seen in the anterior, septal and inferior walls irrespective of stage, whereas in homozygous mice it extended to the whole LV circumference including the lateral wall. In conclusion, myoarchitectural disarray is detectable in the fetal heart of an HCM mouse model before the development of LVH.     

A live attenuated turkey rhinotracheitis virus vaccine. 1. Stability of the attenuated strain

Compared with the severe clinical disease caused by two virulent strains of turkey rhinotracheitis virus (TRTV), an attenuated strain has been shown to cause only slight respiratory infection in 7-day-old TRT-free turkey poults, yet still to be capable of stimulating TRT antibodies and of protecting the poults against challenge with virulent TRTV 21 days later. The stability of the attenuation during 12 turkey-turkey passages of the strain has been demonstrated; the poult passaged and prepassaged strains causing only mild respiratory signs even when bacteria, known to be associated with severe outbreaks of TRT in the field, were included in the inoculum.     

Scanning of the dopamine D1 and D5 receptor genes by REF in neuropsychiatric patients reveals a novel missense change at a highly conserved amino acid

In previous analyses of schizophrenic patients, multiple missense changes and one nonsense change were identified in the D5 dopamine receptor (DRD5) gene, but no sequence changes of likely functional significance were identified in the D1 dopamine receptor (DRD1) gene. In the present study, we examined these genes in patients with certain other neuropsychiatric disorders that may be related to dopaminergic dysregulation. The coding regions of the DRD1 and DRD5 genes were examined in 25 and 25 autistic patients, 25 and 28 attention deficit hyperactivity disorder patients, and 51 and 43 alcoholic patients, respectively. In addition, the DRD5 gene was examined in 75 schizophrenic patients to search for additional variants affecting protein structure or expression (VAPSEs). These patients were analyzed with REF (restriction endonuclease fingerprinting), a hybrid between SSCP and restriction endonuclease digestion, which allows the entire coding sequence to be screened in one lane of a gel. Approximately 800 kb of genomic sequence were examined. No sequence changes were identified in the DRD1 gene among the 101 patient samples analyzed. Two sequence changes were identified in the DRD5 gene among the 171 patient samples. These included one previously identified silent polymorphism at base pair 978 (P326P). The change was identified in patients from all disease categories and from different ethnic backgrounds. One novel missense change, L88F, occurred in transmembrane domain II at a highly conserved amino acid in all dopamine receptors as well as in α1- and β-adrenergic receptors. The mutation was identified in a Caucasian male patient with autism. Further analysis is necessary to determine if this missense change is associated with a particular neuropsychiatric phenotype. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:172–178, 1998. © 1998 Wiley-Liss, Inc.     

A Pneumatic Device for Rapid Loading of DNA Sequencing Gels

This work describes the design and construction of a device that facilitates the loading of DNA samples onto polyacrylamide gels for detection in the Perkin Elmer/Applied Biosystems (PE/ABI) 373 and 377 DNA sequencing instruments. The device is mounted onto the existing gel cassettes and makes the process of loading high-density gels less cumbersome while the associated time and errors are reduced. The principle of operation includes the simultaneous transfer of the entire batch of samples, in which a spring-loaded air cylinder generates positive pressure and flexible silica capillaries transfer the samples. A retractable capillary array carrier allows the delivery ends of the capillaries to be held up clear of the gel during loader attachment on the gel plates, while enabling their insertion in the gel wells once the device is securely mounted. Gel-loading devices capable of simultaneously transferring 72 samples onto the PE/ABI 373 and 377 are currently being used in our production sequencing groups while a 96-sample transfer prototype undergoes testing.     

The nuclear/mitotic apparatus protein NuMA is a component of the somatodendritic microtubule arrays of the neuron

Neurons are terminally post-mitotic cells that utilize their microrubule arrays for the growth and maintenance of axons and dendrites rather than for the formation of mitotic spindles. Recent studies from our laboratory suggest that the mechanisms that organize the axonal and dendritic microtubule arrays may be variations on the same mechanisms that organize the mitotic spindle in dividing cells. In particular, we have identified molecular motor proteins that serve analogous functions in the establishment of these seemingly very different microtubule arrays. In the present study, we have sought to determine whether a non-motor protein termed NuMA is also a component of both systems. NuMA is a ~230 kDa structural protein that is present exclusively in the nucleus during interphase. During mitosis, NuMA forms aggregates that interact with microtubules and certain motor proteins. As a result of these interactions, NuMA is thought to draw together the minus-ends of microtubules, thereby helping to organize them into a bipolar spindle. In contrast to mitotic cells, post-mitotic neurons display NuMA both in the nucleus and in the cytoplasm. NuMA appears as multiple small particles within the somatodendritic compartment of the neuron, where its levels increase during early dendritic differentation. A partial but not complete colocalization with minus-ends of microtubules is suggested by the distribution of the particles during development and during drug treatments that alter the microtubule array. These observations provide an initial set of clues regarding a potentially important function of NuMA in the organization of microtubules within the somatodendritic compartment of the neuron.     

Telekid Care: bringing health care into schools.

BACKGROUND: Telekid Care is a project that attempts to overcome the health and educational barriers faced by children in urban Kansas City, Kansas. Telemedicine units were placed in school nurses' offices and linked to physicians at the University of Kansas Medical Center (KUMC). This paper describes the development of this project, presents utilization data, and discuss the lessons learned from the application of telemedicine in a school setting. RESULTS: Project developers spent 11 months designing the protocol and procedures for a pilot test. Four elementary schools participated, and 187 consultations were conducted. The most common reason for consultation was ear, nose, and throat (ENT) problems, making up 28% of all consults. Mandatory school physical examinations and dermatology problems combined to make up an additional 40% of the consults. The average time that elapsed between the request for a consult and confirmation of an appointment was 23 minutes. When immediate service was requested, 85% of the consults occurred the day of the request. These results strongly demonstrate telemedicine's ability to offer immediate service to children in need. CONCLUSION: Telemedicine enabled underserved inner-city children to gain access to health services. This service was most effective when it was integrated into the delivery system. Furthermore, community groups strongly favored the project, positively influencing its acceptance as an innovative health care delivery system.     

Subsidized housing and children's nutritional status: data from a multisite surveillance study

BACKGROUND: A critical shortage of affordable housing for low-income families continues in the United States. Children in households that are food insecure are at high risk for adverse nutritional and health outcomes and thus may be more vulnerable to the economic pressures exerted by high housing costs. Only about one fourth of eligible families receive a federally financed housing subsidy. Few studies have examined the effects of such housing subsidies on the health and nutritional status of low-income children. OBJECTIVE: To examine the relationship between receiving housing subsidies and nutritional and health status among young children in low-income families, especially those that are food insecure. DESIGN: Cross-sectional observational study.Setting and PARTICIPANTS: From August 1998 to June 2003, the Children's Sentinel Nutrition Assessment Program interviewed caregivers of children younger than 3 years in pediatric clinics and emergency departments in 6 sites (Arkansas, California, Maryland, Massachusetts, Minnesota, and Washington, DC). Interviews included demographics, perceived child health, the US Household Food Security Scale, and public assistance program participation. Children's weight at the time of the visit was documented. The study sample consisted of all renter households identified as low income by their participation in at least 1 means-tested program. MAIN OUTCOME MEASURES: Weight for age, self-reported child health status, and history of hospitalization. RESULTS: Data were available for 11 723 low-income renter families; 27% were receiving a public housing subsidy, and 24% were food insecure. In multivariable analyses, stratified by household food security status and adjusted for potential confounding variables, children of food-insecure families not receiving housing subsidies had lower weight for age (adjusted mean z score, -0.025 vs 0.205; P<.001) compared with children of food-insecure families receiving housing subsidies. Compared with children in food-insecure, subsidized families, the adjusted odds ratio (95% confidence interval) for weight-for-age z score more than 2 SDs below the mean was 2.11 (1.34-3.32) for children in food-insecure, nonsubsidized families. CONCLUSIONS: In a large convenience sentinel sample, the children of low-income renter families who receive public housing subsidies are less likely to have anthropometric indications of undernutrition than those of comparable families not receiving housing subsidies, especially if the family is not only low income but also food insecure.     

Latent herpetic infections following experimental viraemia.

The spectrum of tissues harbouring latent herpes simplex virus following intravenous inoculation of mice was defined by in vitro co-cultivation techniques. The virus could be detected in central and peripheral nervous systems (including adrenal medulla), but could not be found in any non-neural tissues. Spinal ganglia were the organs most commonly involved. The relationship of these findings to the natural history of herpetic infections is discussed.