Larval nutritional-stress and tolerance to extreme temperatures in the peach fruit fly, Bactrocera zonata (Diptera: Tephritidae).

Within the factors affecting insect tolerance to extreme environmental conditions, insect nutrition, particularly of immature stages, has received insufficient attention. In the present study, we address this gap by investigating the effects of larval nutrition on heat and cold tolerance of adult Bactrocera zonata - an invasive, polyphagous fruit fly pest. We manipulated the nutritional content in the larval diet by varying the amount of added yeast (2-10% by weight), while maintaining a constant sucrose content. Adults derived from the different larval diets were tested for their tolerance to extreme heat and cold stress. Restricting the amount of yeast reduced the efficacy of the larval diet (i.e. number of pupae produced per g of diet) as well as pupal and adult fresh weight, both being significantly lower for yeast-poor diets. Additionally, yeast restriction during the larval stage (2% yeast diet) significantly reduced the amount of protein but not lipid reserves of newly emerged males and females. Adults maintained after emergence on granulated sugar and water for 10 days were significantly more tolerant to extreme heat (i.e. knock-down time at 42 oC) when reared as larvae on yeast-rich diets (8% and 10% yeast) compared to counterparts developing on a diet containing 2% yeast. Nevertheless, the composition of the larval diet did not significantly affect adult survival following acute cold stress (exposure to -3°C for 2 hrs.). These results are corroborated by previous findings on Drosophilid flies. Possible mechanisms leading to nutrition-based heat-tolerance in flies are discussed.

MRI evidence of impaired CSF homeostasis in obesity-associated idiopathic intracranial hypertension.

BACKGROUND AND PURPOSE: Impaired CSF homeostasis and altered venous hemodynamics are proposed mechanisms for elevated pressure in IIH. However, the lack of ventricular expansion steered the focus away from CSF homeostasis in IIH. This study aims to measure intracranial CSF volumes and cerebral venous drainage with MR imaging to determine whether increased CSF volume from impaired CSF homeostasis and venous hemodynamics occur in obesity-related IIH. MATERIALS AND METHODS: Two homogeneous cohorts of 11 newly diagnosed pretreatment overweight women with IIH and 11 overweight healthy women were prospectively studied. 3D volumetric MR imaging of the brain was used to quantify CSF and brain tissue volumes, and dynamic phase contrast was used to measure relative cerebral drainage through the internal jugular veins. RESULTS: Findings confirm normal ventricular volume in IIH. However, extraventricular CSF volume is significantly increased in IIH (290 ± 52 versus 220 ± 24 mL, P = .001). This is even more significant after normalization with intracranial volume (P = .0007). GM interstitial fluid volume is also increased in IIH (602 ± 57 versus 557 ± 31 mL, P = .037). Total arterial inflow is normal, but relative venous drainage through the IJV is significantly reduced in IIH (65 ± 7% versus 81 ± 10%, P = .001). CONCLUSIONS: Increased intracranial CSF volume that accumulates in the extraventricular subarachnoid space provides direct evidence for impaired CSF homeostasis in obesity-associated IIH. The finding of larger GM interstitial fluid volume is consistent with increased overall resistance to cerebral venous drainage, as evident from reduced relative cerebral drainage through the IJV. The present study confirms that both impaired CSF homeostasis and venous hemodynamics coexist in obesity-associated IIH.

Endoscopic management of a rare case of nasal glioma in Meckel's cave in an adult: case report.

BACKGROUND: Nasal glioma or glial heterotopia is a rare embryologic anomaly that heralds its presence shortly after birth or in childhood. Nasal glioma in an adult is very rare, often asymptomatic and the occurrence of nasal glioma in Meckel's cave in an adult has not been previously reported. CASE REPORT: The authors encountered a case of an incidentally diagnosed Meckel's cave nasal glioma in a 40-year-old male which was successfully excised by an endonasal endoscopic transmaxillary transpterygoid approach. CONCLUSION: The occurrence of a nasal glioma in Meckel's cave an adult is very rare. Considering the deep skull base location, endonasal endoscopic surgery provides a minimal access technique to reach this location with excellent results.

Endovascular treatment of isolated dissecting aneurysm of the posterior inferior cerebellar artery.

BACKGROUND AND PURPOSE: Isolated dissecting aneurysms of the posterior inferior cerebellar artery (PICA) carry a high risk of rebleeding with an associated increased mortality rate. Although rare, they present a therapeutic challenge. Surgical treatment carries a significant risk of neurologic complications, predominantly lower cranial nerve deficits because of the close relationship of the aneurysm with the brain stem and cranial nerves. The purpose of this article is to show that endovascular treatment of dissecting aneurysms of the PICA can be effective and can allow the patient to avoid the complications associated with surgery. METHODS: Six patients (age range, 28-70 years) with dissecting aneurysms of the PICA were treated at our center by endovascular occlusion with Guglielmi detachable coils or glue and followed for up to 30 months. Inclusion of patients in the study was based on careful angiographic assessment of the vascular anatomy and collateral supply of the posterior fossa. When on the basis of the anatomy, potential lack of sufficient collaterals was suggested, a test occlusion was performed to determine the feasibility of an endovascular approach. Four additional cases, which have been described in the literature, were included in the analysis of results. RESULTS: In all patients, the aneurysm was successfully occluded with no apparent procedure-related complications. Follow-up studies showed stable and complete occlusion of the aneurysm in all patients with no long-term neurologic deficits. CONCLUSIONS: Endovascular treatment by aneurysm and parent artery occlusion is a relatively safe and reliable alternative to surgery for isolated dissecting aneurysms of the PICA.

Neither B cells nor T cells are required for CNS demyelination in mice persistently infected with MHV-A59.

Murine hepatitis virus A59 infection of the central nervous system (CNS) results in CNS demyelination in susceptible strains of mice. In infected B-cell-deficient mice, demyelination not only occurred but was also more severe than in parental C57BL/6 animals. This increase may be due to the persistence of virus in the CNS in the absence of B cells. In mice lacking antibody receptors or complement pathway activity, virus did not persist yet demyelination was similar to parental mice. In infected RAG1(-/-) mice, moderately sized, typical demyelinating lesions were identified. Therefore, demyelination can occur in the absence of B and T cells.

Sequence analysis of the S gene of recombinant MHV-2/A59 coronaviruses reveals three candidate mutations associated with demyelination and hepatitis.

Coronaviruses, mouse hepatitis virus (MHV) strains, exhibit various degrees of neurotropism and hepatotropism following intracerebral (IC) infection of 4-week-old C57Bl/6 mice. Whereas MHV-A59 produces acute meningitis, encephalitis, hepatitis, and chronic demyelination, a closely related strain, MHV-2, produces only acute meningitis and hepatitis. We previously reported that the spike glycoprotein gene of MHV contains determinants of demyelination and hepatitis. To further investigate the site of demyelination and hepatitis determinants within the S gene, we sequenced the S gene of several nondemyelinating recombinant viruses. We found that three encephalitis-positive, demyelination-negative, hepatitis-negative recombinant viruses have an MHV-A59-derived S gene, which contains three identical point mutations (I375M, L652I, and T1087N). One or more of the sites of these mutations in the MHV-A59 genome are likely to contribute to demyelination and hepatitis.

Detection of lipoprotein(a) in intraparenchymal cerebral vessels: correlation with vascular pathology and clinical history.

Serum levels of lipoprotein(a), Lp(a), have been shown to be associated with increased risk of atherosclerosis (AS) and AS-related diseases such as myocardial and ischemic cerebral infarcts (ICI). Lp(a) has been detected in the vascular wall of the aorta and coronary vessels, and we documented the presence of apo(a) in cerebral vessels of the Circle of Willis, associated with AS changes. In this study we further investigated and characterized the biochemical nature of Lp(a) detected in both large and small cerebral parenchymal vessels. Autopsy specimens of cerebral vessels of 51 patients were examined by immunohistochemistry with monoclonal antibodies against apo(a), apoB, and plasminogen. Lp(a) was detected in cerebral capillaries and arterioles. All of the 8 patients with ICI expressed Lp(a) in parenchymal vessels, generally (6/8) in both capillaries and arterioles. Of 43 patients without ICI only 25 had Lp(a) detected. Among the patients without ICI, there was a slightly increased incidence of parenchymal Lp(a) in those patients who had severe hypoxic brain damage (12/20) compared to those patients without severe hypoxic damage (9/23). Thus, the presence of Lp(a) in small cerebral parenchymal vessels may reflect the role of Lp(a) in ICI.

Gene expression of apolipoprotein(a) within the wall of human aorta and carotid arteries.

Atherosclerosis is associated with arterial deposition of low density lipoprotein (LDL) and lipoprotein(a), Lp(a). Both lipoproteins have been detected in atherosclerotic vessels; however, while LDL has been shown to be only blood-derived, it is not clear whether Lp(a) is also produced within the vessel wall. In the present investigation we studied gene expression of apo(a) and apoB in human blood vessels. Aorta, carotid arteries and liver specimens from 29 adult and pediatric autopsy cases were studied by RT-PCR and Southern blot analysis with primers and probes specific for apo(a), apoB and GAPDH (a control housekeeping gene). The mRNA of apo(a), but not apoB, was found within the vessel wall in both adult atherosclerotic arterial vessels and in pediatric non atherosclerotic vessels. Neither apo(a) nor apoB mRNA was detected in femoral veins. To verify the nature of the detected transcripts, we cloned the 162 base pair (bp) RT-PCR product derived from the arterial wall total RNA. Nucleotide sequencing revealed 100% homology with the apo(a) gene. Thus, while LDL in atherosclerotic arteries is exclusively blood-derived, the accumulation of Lp(a) within the artery may be due in part to in situ production of apo(a) within the vessel wall.

Mouse hepatitis virus type-2 infection in mice: an experimental model system of acute meningitis and hepatitis.

Infection with mouse hepatitis virus (MHV) strain A59 produces acute hepatitis, encephalitis, and chronic demyelination in mice. However, little is known about a closely related strain, MHV-2, which is only weakly neurotropic. To better understand the molecular basis of neurotropism of MHVs, we compared the pathogenesis and genomic sequence of MHV-2 with that of MHV-A59. Intracerebral injection of MHV-2 into 4-week-old C57B1/6 mice produces acute meningitis and hepatitis without encephalitis or chronic inflammatory demyelination. Sequence comparison between MHV-2 and MHV-A59 reveals 94-98% sequence identity of the replicase gene, 83-95% sequence identity of genes 2a, 3, 5b, 6, and 7, and marked difference in the sequence of genes, 2b, 4, and 5a. This information provides the basis for further studies exploring the mechanism of viral neurotropism and virus-induced demyelination.

Enhancement of the eighth cranial nerve and labyrinth on MR imaging in sudden sensorineural hearing loss associated with human herpesvirus 1 infection: case report.

The case of a 61-year-old woman who presented with herpes labialis, subclinical meningitis, and sudden onset of bilateral sensorineural hearing loss is presented. Contrast-enhanced MR imaging showed marked bilateral enhancement of the intracanalicular portion of the eighth cranial nerve, right cochlea, and left vestibule. Polymerase chain reaction was positive for human herpesvirus 1 obtained from the cerebral spinal fluid, which suggested the diagnosis of viral neuritis.

CXCR3 expression in human central nervous system diseases.

The CXCR3 chemokine receptor, expressed on activated T lymphocytes, is seen within the central nervous system (CNS) in inflammatory conditions where a T-cell response is prominent. However, the distribution of CXCR3 in parenchymal CNS cells is unknown. Using a monoclonal antibody against CXCR3 and post-mortem tissue of patients with and without CNS pathology, we have determined its expression pattern. CXCR3 was found in subpopulations of cells morphologically consistent with astrocytes, particularly reactive astrocytes, and in cerebellar Purkinje cells. It was also detected in arterial endothelial and smooth muscle cells, particularly in areas associated with atherosclerotic plaques. CXCR3-positive astrocytes were particularly prominent in the CNS of HIV-positive patients, in patients with Multiple Sclerosis (MS), in ischaemic infarcts and in astrocytic neoplasms. Immunofluorescence studies of mixed adult primary glial cultures and fetal glial cultures also showed expression of CXCR3 in astrocytes. CXCR3 mRNA was detected in Purkinje cells by in situ hybridization with a CXCR3-specific probe. Thus, the predominant expression of CXCR3 in reactive astrocytes may indicate that it plays a role in the development of reactive gliosis in a variety of infectious, inflammatory, vascular and neoplastic processes in the CNS. The relationship between CXCR3 expression in astrocytes to its expression in Purkinje cells, endothelial cells and smooth muscle cells is yet to be determined.

Murine coronavirus spike protein determines the ability of the virus to replicate in the liver and cause hepatitis.

Recombinant mouse hepatitis viruses (MHV) differing only in the spike gene, containing A59, MHV-4, and MHV-2 spike genes in the background of the A59 genome, were compared for their ability to replicate in the liver and induce hepatitis in weanling C57BL/6 mice infected with 500 PFU of each virus by intrahepatic injection. Penn98-1, expressing the MHV-2 spike gene, replicated to high titer in the liver, similar to MHV-2, and induced severe hepatitis with extensive hepatocellular necrosis. S(A59)R13, expressing the A59 spike gene, replicated to a somewhat lower titer and induced moderate to severe hepatitis with zonal necrosis, similar to MHV-A59. S4R21, expressing the MHV-4 spike gene, replicated to a minimal extent and induced few if any pathological changes, similar to MHV-4. Thus, the extent of replication and the degree of hepatitis in the liver induced by these recombinant viruses were determined largely by the spike protein.

Expression pattern of CXCR3, CXCR4, and CCR3 chemokine receptors in the developing human brain.

Chemokine receptors are essential components of the immune and central nervous systems, but little is known about their distribution during development. We evaluated the distribution of 3 chemokine receptors: CXCR3, CXCR4, and CCR3 in the human developing brain. Of these, CXCR3 was the only receptor expressed in fetal brain at 26 wk of gestation and its expression was restricted to glial cells, endothelial cells, and the choroid plexus. Neuronal staining was only seen at term in the Purkinje cells of the cerebellum. CCR3 appeared only at term in both neurons and glial cells. The expression pattern of these 2 receptors in the late gestation and term resembled that of adults. CXCR4 could not be detected in the fetal brain on neurons nor on glial cells. By examining pediatric cases, we determined that CXCR4 expression commences sometimes between 3.5 and 4.5 yr. Two of the chemokine receptors examined, CCR3 and CXCR4, can be used as co-receptor together with CD4 for HIV entry, but neither was expressed during the second trimester of pregnancy. Our findings suggest that it is unlikely that CCR3 or CXCR4 play a major role in HIV-1 transmission in the fetal brain before 37 wk of gestation.

Modulation of susceptibility and resistance to an autoimmune model of multiple sclerosis in prototypically susceptible and resistant strains by neutralization of interleukin-12 and interleukin-4, respectively.

Experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, is mediated by Th1 cells. The major Th1 inducer, IL-12, enhances EAE, while its blockade suppresses it. IL-4 suppresses EAE. Here, we determined IFN-gamma and IL-4 production by myelin basic protein-stimulated lymphocytes from prototypically EAE-susceptible SJL/J and EAE-resistant BALB/c mice, 9 days after immunization with spinal cord homogenate. While lymphocytes from SJL/J mice produce IFN-gamma and no IL-4, lymphocytes from BALB/c mice produce IL-4 and no IFN-gamma. Since early endogenous production of IL-12/IFN-gamma or IL-4 is linked to Th1 or Th2 responses, respectively, we determined whether neutralization of IL-12 or IL-4 at immunization modifies susceptibility or resistance to EAE. SJL/J mice given neutralizing anti-IL-12 mAb are protected from EAE. BALB/c mice given neutralizing anti-IL-4 mAb develop EAE, while those treated with control antibody remain resistant. These studies confirm the pivotal role of IL-12 in EAE development and show that endogenous IL-4 is important for determining the genetic resistance to EAE.

July 2000: A 70 year old with rigidity, decreased ocular movements, and dementia.

The July Case of the Month (COM): A 70 year old male presented with a four year history of cognitive decline, difficulty expressing himself, and an increasingly unsteady gait with numerous falls. At presentation he was wheel-chair bound. Examination showed some slowing of speech, mild memory impairment, but normal cranial nerves. Spastic weakness and brisk reflexes were also noted, with bilateral ankle clonus. MRI scans were normal. Four years later he was admitted with a urinary tract infection and was mute with severely impaired ocular motility. He died 18 months later and autopsy showed the classic neuropathological findings of typical Progressive supranuclear palsy, including tau-positive glial inclusions.

Cutting edge: C3, a key component of complement activation, is not required for the development of myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis in mice.

Experimental autoimmune encephalomyelitis (EAE), an inflammatory demyelinating disease of the CNS, is regarded as an experimental model for multiple sclerosis. The complement has been implicated in the pathogenesis of multiple sclerosis. To clarify the role of C in mouse EAE, we immunized mice deficient in C3 (C3(-/-)) and their wild-type (C3(+/+)) littermates with myelin oligodendrocyte glycoprotein peptide 35-55. C3(-/-) mice were susceptible to EAE as much as the C3(+/+) mice were. No differences were found for the production of IL-2, IL-4, IL-12, TNF-alpha, and IFN-gamma between C3(+/+) and C3(-/-) mice. This finding shows that C3, a key component in C activation, is not essential in myelin oligodendrocyte glycoprotein peptide-induced EAE in mice.