Bowhead whales overwinter in the Amundsen Gulf and Eastern Beaufort Sea.

The bowhead whale is the only baleen whale endemic to the Arctic and is well adapted to this environment. Bowheads live near the polar ice edge for much of the year and although sea ice dynamics are not the only driver of their annual migratory movements, it likely plays a key role. Given the intrinsic variability of open water and ice, one might expect bowhead migratory plasticity to be high and linked to this proximate environmental factor. Here, through a network of underwater passive acoustic recorders, we document the first known occurrence of bowheads overwintering in what is normally their summer foraging grounds in the Amundsen Gulf and eastern Beaufort Sea. The underlying question is whether this is the leading edge of a phenological shift in a species' migratory behaviour in an environment undergoing dramatic shifts due to climate change.

Validation of the finding of hypertrophy of the clava in infantile neuroaxonal dystrophy/PLA2G6 by biometric analysis.

INTRODUCTION: Infantile neuroaxonal dystrophy (INAD), an autosomal recessive neurodegenerative disorder due to PLA2G6 mutation, is classified both as a PLA2G6-associated neurodegeneration (PLAN) disorder and as one of the neurodegeneration with brain iron accumulation (NBIA) disorders. Age of onset and clinical presentation in INAD is variable. Typically described imaging features of cerebellar atrophy, cerebellar cortex bright FLAIR signal, and globus pallidus iron deposition are variable or late findings. We characterize clinical and neuroimaging phenotypes in nine children with confirmed PLA2G6 mutations and show a useful imaging feature, clava hypertrophy, which may aid in earlier identification of patients. Measurements of the clava confirm actual enlargement, rather than apparent enlargement due to volume loss of the other brain stem structures. METHODS: A retrospective clinical and MRI review was performed. Brain stem measurements were performed and compared with age-matched controls. RESULTS: We identified nine patients, all with novel PLA2G6 gene mutations. MRI, available in eight, showed clava hypertrophy, regardless of age or the absence of other more typically described neuroimaging findings. Brain autopsy in our cohort confirmed prominent spheroid bodies in the clava nuclei. CONCLUSION: Clava hypertrophy is an important early imaging feature which may aid in indentification of children who would benefit from specific testing for PLA2G6 mutations.

Dermatosparaxis in two white Dorper lambs.

CASE HISTORY AND CLINICAL FINDINGS: Two White Dorper lambs from the North Island of New Zealand, 2 and 4 weeks of age, were presented with large skin flaps hanging from the flanks, separation of skin from the subcutis over mobile joints, and de-gloving injuries of the limbs and tail. The lambs were subject to euthanasia on humane grounds. PATHOLOGICAL FINDINGS: Large skin tears with associated haemorrhage, periarticular S/C oedema and generalised skin fragility were observed in both lambs at post-mortem examination. Histology of the affected skin revealed diffuse hyalinisation of dermal collagen compared with control lambs, protein-filled peri-adnexal clefts and areas of deep dermal and S/C granulation tissue consistent with previous separation of skin from the subcutis. Analysis of hair follicles, collected from one of the lambs, using a commercially available genetic test in Australia was consistent with the lamb being homozygous for the mutation responsible for ovine dermatosparaxis. DIAGNOSIS: Likely dermatosparaxis. CLINICAL RELEVANCE: These findings strongly suggest that the mutation responsible for dermatosparaxis in White Dorper sheep is present in New Zealand. Dermatosparaxis should be considered when investigating skin fragility in lambs with White Dorper genetics. Confirmation of the disorder is possible through genetic analysis of hair follicles.

Ultrasound biomicroscopy in the management of retinoblastoma.

PURPOSE: To determine the role of ultrasound biomicroscopy (UBM) in the management of children affected with retinoblastoma. METHODS: A review of clinical records of children with the diagnosis of retinoblastoma at the Hospital for Sick Children from January 1995 to December 2007, for whom UBM was used to determine the extent of intraocular tumor. Clinical characteristics were compared with UBM. Pathological correlation was performed for enucleated eyes. RESULTS: In total, 101 eyes of 75 patients were included in the final analysis. Only 11 eyes were diagnosed on UBM to have extension of the tumor anterior to the ora serrata, and were enucleated. Histopathological examination confirmed the anterior extension in all the 11 eyes. In total, 50 eyes were enucleated because of various reasons, such as poor visual prognosis (12 eyes), unilateral group D or E (23 eyes), recurrences (8 eyes), and treatment failure (7 eyes). None of those patients were found to have anterior extension of the disease on histopathological examination. UBM did not yield any false negative (0/50) or any false positives (0/11). CONCLUSIONS: The UBM provided a sensitive and reproducible visualization of the anterior retina, ciliary region, and anterior segment allowing a better staging of the advanced disease process. Primary assessment of the true extent of retinoblastoma is critical for the selection of an optimal management approach.

Complex V TMEM70 deficiency results in mitochondrial nucleoid disorganization.

Mutations in the TMEM70 gene are responsible for a familial form of complex V deficiency presenting with 3-methylglutaconic aciduria, lactic acidosis, cardiomyopathy and mitochondrial myopathy. Here we present a case of TMEM70 deficiency due to compound heterozygous mutations, who displayed abnormal mitochondria with whorled cristae in muscle. Immunogold electron microscopy and tomography shows for the first time that nucleoid clusters of mtDNA are disrupted in the abnormal mitochondria, with both nucleoids and mitochondrial respiratory chain complexes confined to the outer rings of the whorls. This could explain the differential effects on the expression and assembly of complex V in different tissues.

Rhombencephalosynapsis: prenatal imaging and autopsy findings.

OBJECTIVES: Rhombencephalosynapsis is a rare, but increasingly recognized, brain malformation characterized by congenital fusion of the cerebellar hemispheres and absence of the vermis. Rhombencephalosynapsis is associated with significant developmental delay, seizures and involuntary head movements. We report four cases, with correlation of prenatal and postnatal imaging and autopsy findings. METHODS: Over a 2-year period, four cases of rhombencephalosynapsis were diagnosed in the perinatal period, three in one center and one in another center. The clinical cases were reviewed, and correlation was made between the prenatal and postnatal imaging and autopsy findings where available. RESULTS: All cases presented initially with ventriculomegaly on prenatal ultrasound examination. Subsequent magnetic resonance imaging (MRI) established the diagnosis in two cases and postnatal MRI established the diagnosis in a further two cases. Autopsy was available and confirmed the diagnosis in two cases. In one case the pregnancy was terminated, two infants died in the neonatal period and one died in infancy. CONCLUSIONS: The cases in this perinatal series of rhombencephalosynapsis showed a very poor prognosis. The presence of ventriculomegaly on prenatal ultrasound imaging should alert the physician to consider rhombencephalosynapsis in the differential diagnosis. MRI appears to be the imaging modality of choice in establishing the diagnosis.

Cerebroretinal microangiopathy with calcifications and cysts (CRMCC).

Extensive intracranial calcifications and leukoencephalopathy are seen in both Coats plus and leukoencephalopathy with calcifications and cysts (LCC; Labrune syndrome). Coats plus syndrome is additionally characterized by the presence of bilateral retinal telangiectasia and exudates while LCC shows the progressive formation of parenchymal brain cysts. Despite these apparently distinguishing features, recent evidence suggests that Coats plus and LCC represent the same clinical entity with a common primary pathogenesis involving a small vessel obliterative microangiopathy. Here, we describe eight previously unreported cases, and present an update on one of the original Coats plus patients to highlight the emerging core clinical features of the "cerebroretinal microangiopathy with calcification and cysts" (CRMCC) phenotype.

Rapid degradation of the Cry1F insecticidal crystal protein in soil.

The gene for the core Cry1F insecticidal crystal protein (ICP) from Bacillus thuringiensis Berliner (Bt) has been incorporated into the genome of maize plants, Zea mays L. Plants expressing this ICP are protected from attack by various Lepidopteran pests including the European corn borer, Ostrinia nubilalis (Hübner). The stability of the Cry1F ICP in soil was assessed in a laboratory study designed to determine the persistence of the active protein residue in soil over time, using insect bioassay as the analytical quantification method. The GI(50) (concentration estimated to inhibit growth by 50%) rose at each consecutive incubation interval, indicating a consistent decline in Cry1F activity over time. The residue data were poorly described by a first-order model when fit to either the full data or a truncated data set where the last interval (28 days) was excluded. Data were well described by a shift-log model, and this model predicted DT(50) (time until 50% decay) and DT(90) (time until 90% decay) values of 0.6 and 6.9 days, respectively. This rapid degradation rate was consistent with other Bt proteins evaluated in our laboratory.

Toxicities of emamectin benzoate homologues and photodegradates to Lepidoptera.

The toxicity of a number of emamectin benzoate homologues and photodegradates to five species of Lepidoptera was investigated using diet and foliar bioassays. The emamectin benzoate homologues B1a and B1b were equally toxic in the diet and foliar assays to Spodoptera exigua (Hübner), Heliothis virescens (F.), Tricoplusia ni (Hübner), and Spodoptera frugiperda (J. E. Smith), within each of these species. Plutella xylostella (L.) was the most sensitive species to emamectin benzoate. The AB1a photodegradate of emamectin benzoate was as toxic as the parent compound in the diet assay. However, in the foliage assay AB1a was 4.4-fold less toxic to S. exigua than the parent compound. The MFB1a photodegradate of emamectin benzoate was as toxic as the parent compound to P. xylostella, and 3.1 to 6.2 times as toxic as the parent compound to the other species in the diet assay. The order of toxicity of the photodegradates were AB1a > MFB1a > FAB1a > 8,9-Z-MAB1a > PAB1a.

Establishment of Cry9C susceptibility baselines for European corn borer and southwestern corn borer (Lepidoptera: Crambidae).

In 1997 and 1998, Cry9C susceptibility baselines were established for field-collected populations of European corn borer, Osrinia nubilalis (Hubner), and southwestern corn borer, Diatraea grandiosella Dyar. Bioassay of neonate European corn borer larvae of 16 colonies collected from the midwestern United States indicated LC50 values ranging from 13.2 to 65.1 ng of Cry9C protein per square centimeter. Neonate European corn borer LC50 values ranged from 46.5 to 214 ng/cm2. Neonate larvae of three colonies of southwestern corn borer collected from the southern and southwestern United States exhibited LC50 values from 16.9 to 39.9 ng of Cry9C protein per square centimeter. Southwestern corn borer neonate LC90 confidence limit values ranged from 40.3 to 157 ng of Cry9C protein per centimeter. The most sensitive southwestern corn borer colony was collected from the Mississippi delta exhibiting an LC50 value of 22.6 ng of Cry9C per cm2 and also displayed the widest LC0 confidence limits of 40.3-94.8 ng of Cry9C per cm2. Geographic baseline susceptibility data establishes the natural genetic variation and provides the foundation for future testing of insect populations exposed to increased use of Bacillus thuringiensis-based crops. Insect resistance management and stewardship of Cry9C will rely upon baseline data for the validation of discriminating dose assays for European corn borer and southwestern corn borer.

Synapse loss associated with abnormal PrP precedes neuronal degeneration in the scrapie-infected murine hippocampus.

Numbers of neurones, synapses and axon terminals were quantified in a murine scrapie model with severe hippocampal pyramidal cell loss, in which definite clinical scrapie is evident from 226 days post-infection (dpi) and death occurs around 250 dpi. Disease-specific PrP accumulations were first seen at 70 dpi (28% of the incubation period (IP)) in thalamus and as sparse foci within the stratum pyramidale of CA1. By 98 dpi (39% IP), PrP was seen in the stratum radiatum and was found at later stages throughout all levels of the hippocampus. At the ultrastructural level in the stratum radiatum of CA1, a decrease in the numbers of simple synapses from 84 dpi (34% IP) and in perforated synapses from 98 dpi (42% IP) was found using an unbiased stereological method, the disector analysis. Degeneration of axon terminals was found from 98 dpi (39% IP) onwards. Neuronal loss was detected in CA1 from 180 dpi (72% IP). The results suggest that the fundamental lesion in the hippocampus of ME7-infected mice is associated with PrP release from CA1 pyramidal neurones, which perturbs synaptic function and leads to degeneration of preterminal axons, and that subsequent pathological changes including neurone loss are sequelae to this initial insult.

AIDS- and non-AIDS-related PML association with distinct p53 polymorphism.

A population-based analysis of progressive multifocal leukoencephalopathy (PML) showed PML frequencies of 5.1% among patients with AIDS and 0.07% among patients with hematologic malignancies, but similar clinical features of PML in both groups. Sequencing of the p53 gene, exon 4, showed heterozygosity (Arg-Pro) at codon 72 in five of six PML patients. These findings indicate that frequencies of non-AIDS- and AIDS-related PML differ markedly but p53 polymorphisms may influence the occurrence of PML in both groups.

Cell-mediated allergy to a cerebral aneurysm clip: case report.

BACKGROUND AND IMPORTANCE: Titanium aneurysm clips have superior imaging characteristics and have been supplanting their stainless steel counterparts. We report the case of a 36-year-old woman with a histologically demonstrated cell-mediated reaction to a cobalt alloy aneurysm clip. CLINICAL PRESENTATION: The patient underwent a craniotomy and clip placement for a ruptured cerebral aneurysm. Both the aneurysm clip and the wires used to fix the craniotomy were made of stainless steel (cobalt and nickel) alloys. Postoperatively, the patient was plagued by intense pruritus. INTERVENTION: Skin patch testing revealed a severe reaction to nickel and cobalt. Surgical removal of the aneurysm clip and wires resulted in the disappearance of the patient's symptoms. A histological analysis of the tissue adjacent to the clip and wires was consistent with Type IV delayed type hypersensitivity. CONCLUSION: Stainless steel surgical implants in the head can cause diffuse, severe pruritus in susceptible individuals. Although the role of the aneurysm clip, as opposed to the more superficial wires, in the genesis of the patient's symptoms is not certain, this case demonstrates that a cobalt alloy aneurysm clip can activate T cells and cause an immunological reaction in the central nervous system.

Metastatic meningioma detected in pleural fluid.

Meningiomas with both malignant cytologic features and clinical behavior are rare. A 39-yr-old man with recurrent meningioma developed a pleural effusion which, on cytologic examination, contained metastatic meningioma. The diagnosis was subsequently confirmed histologically and ultrastructurally. In conclusion, metastatic meningiomas can retain meningotheliomatous cytologic features which may allow a diagnosis to be made of clinically unanticipated tumor spread.

Induction of monocyte chemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS dementia.

Activated monocytes release a number of substances, including inflammatory cytokines and eicosanoids, that are highly toxic to cells of the central nervous system. Because monocytic infiltration of the central nervous system closely correlates with HIV-1-associated dementia, it has been suggested that monocyte-derived toxins mediate nervous system damage. In the present study, we show that the HIV-1 transactivator protein Tat significantly increases astrocytic expression and release of monocyte chemoattractant protein-1 (MCP-1). Astrocytic release of beta-chemokines, which are relatively less selective for monocytes, including RANTES, macrophage inflammatory protein-1alpha, and macrophage inflammatory protein-1beta, was not observed. We also show that MCP-1 is expressed in the brains of patients with HIV-1-associated dementia and that, of the beta-chemokines tested, only MCP-1 could be detected in the cerebrospinal fluid of patients with this condition. Together, these data provide a potential link between the presence of HIV-1 in the brain and the monocytic infiltration that may substantially contribute to dementia.

Immunoreactivity of human MAb BT32/A6 with neuroepithelial tumors.

The present study was undertaken to determine the pattern of immunoreactivity of BT32/A6, a human IgM monoclonal antibody (MAb), with the following histological panels: 1) 30 human and non-human cell lines, 2) 32 normal human tissues, and 3) 28 tumors of central neuroepithelial origin (16 astrocytic; 11 non-astrocytic). Antibody BT32/A6 recognizes a surface and cytoplasmic antigen present on a variety of human tumor cell lines including gliomas, melanomas, neuroblastomas, and a few sarcomas. The antigen is present (at least focally) on 15/16 astrocytic tumor tissue sections (94%), and in some cases, on close to 100% of cells. All malignant cell types, including small anaplastic cells, giant cells, gemistocytic cells, and cells forming pseudopalisades were labeled by MAb BT32/A6. Non-astrocytic neuroepithelial tumors did not stain appreciably with MAb BT32/A6. There was weak immunoreactivity in a small subset of normal human tissues of epithelial and lymphoid origin, with the exception of adrenal cortex, which exhibited weak to moderate staining. All normal tissues of neuroectodermal and mesenchymal origin were unreactive. In conclusion, MAb BT32/A6 appears to be unique in that it recognizes a highly-expressed astrocytic tumor-associated antigen that is present on both low and high grade tumors. This makes it a strong candidate for further studies aimed at establishing its usefulness in the treatment of human astrocytic tumors.

Limb girdle muscular dystrophy in Manitoba Hutterites does not map to any of the known LGMD loci.

Limb girdle muscular dystrophy (LGMD) is a heterogeneous group of disorders affecting primarily the shoulder and pelvic girdles. Autosomal dominant and recessive forms have been identified; 8 have been mapped and 1 more has been postulated on the basis of exclusion of linkage. An autosomal recessive muscular dystrophy was first described in 1976 in the Hutterite Brethren, a North American genetic and religious isolate [Shokeir and Kobrinsky, 1976; Clin Genet 9:197-202]. In this report, we discuss the results of linkage analysis in 4 related Manitoba Hutterite sibships with 21 patients affected with a mild autosomal recessive form of LGMD. Because of the difficulties in assigning a phenotype in some asymptomatic individuals, stringent criteria for the affected phenotype were employed. As a result, 7 asymptomatic relatives with only mildly elevated CK levels were assigned an unknown phenotype to prevent their possible misclassification. Two-point linkage analysis of the disease locus against markers linked to 7 of the known LGMD loci and 3 other candidate genes yielded lod scores of < or = -2 at theta = 0.01 in all cases and in most cases at theta = 0.05. This suggests that there is at least 1 additional locus for LGMD.

AIDS dementia complex with generalized myoclonus.

Focal and segmental, but not generalized, myoclonus have been described with human immunodeficiency virus (HIV) infection. We describe three patients with generalized myoclonus and acquired immunodeficiency syndrome (AIDS) dementia complex. In each, myoclonus persisted until death, invariably after a course of a few months. In two patients, myoclonus was elicited by sudden auditory stimuli and resembled a startle response. This form of myoclonus may be subcortical in origin. We suggest that the AIDS dementia complex be included among the causes of myoclonic dementia.

Primary cerebellar T-cell lymphoma with acquired immunodeficiency syndrome.

We report a 33-year-old man with the acquired immunodeficiency syndrome (AIDS) and a solitary T-cell lymphoma. Systemic sites of lymphomatous involvement could not be identified. Subtotal resection of the lesion with cranial irradiation resulted in a marked neurologic improvement. Our case suggests that T-cell lymphomas should be considered in the differential diagnosis of a solitary mass of the cerebellum in patients with AIDS and that aggressive therapy may be warranted.