ANO5-muscular dystrophy: clinical, pathological and molecular findings.

BACKGROUND AND PURPOSE: Anoctamin 5 (ANO5) is a putative intracellular calcium-activated chloride channel. Recessive mutations in ANO5 cause primary skeletal muscle disorders (limb-girdle muscular dystrophy 2L and distal muscular dystrophy), which are phenotypically similar to dysferlinopathy, a muscular dystrophy due to dysferlin-encoding gene (DYSF) mutations. METHODS: This study reports the phenotype and genotype of seven unrelated patients with ANO5-muscular dystrophy. RESULTS: Three patients had amyloid deposition in muscle and two had cardiac involvement. An additional patient without skeletal muscle amyloidosis had cardiac involvement with septal hypokinesis and supraventricular tachycardia requiring ablation. Amyloid subtyping using laser capture microdissection and mass spectrometry-based proteomic analysis did not identify ANO5 or any fragment of ANO5 in the amyloid deposits, but detected other known amyloidogenic proteins. Three patients had myotonic discharges without clinical myotonia. Four ANO5 mutations are novel, including a heterozygous 0.4 Mb deletion involving the entire ANO5 gene. CONCLUSIONS: The results of the present study suggest that ANO5 mutations can be associated with amyloid deposition in muscle, but the nature of the amyloid deposits remains indeterminate, as does their relationship with cardiac involvement. ANO5 analysis should be considered in cases of muscle amyloid deposition of indeterminate etiology. Electrical myotonia can accompany ANO5-muscular dystrophy.

Varied electrophysiologic patterns in spinocerebellar ataxia type 2.

The autosomal dominant ataxias are a heterogenous group of disorders. Almost 30 different genetic loci have been identified. Spinocerebellar ataxia type 2 (SCA2) is one of many autosomal dominant cerebellar ataxias. Electrophysiologic studies in SCA2 have shown mainly a sensory neuropathy or neuronopathy. To determine if electrophysiologic testing reveals concomitant or isolated involvement of motor nerves in SCA2 we reviewed historic and electrophysiologic data on all cases of genetically confirmed SCA2 who underwent nerve conduction studies and needle electromyographic during initial evaluation at our institution. We performed electrophysiologic studies in six genetically confirmed, unrelated, cases of SCA2 and discovered that in three patients, there were findings consistent with motor neuronopathy or neuropathy without sensory involvement. One patient had normal results and only one had a pure sensory neuropathy or neuronopathy. The sixth patients had mixed sensorimotor neuropathy. This is the first study that demonstrates isolated involvement of motor neurons and/or axons occur in SCA2. Therefore, electrophysiologic findings in SCA2 are not limited to mainly a sensory neuropathy but are varied and can even mimic slowly progressive motor neuron disease.

Yolk protein endocytosis by oocytes in Drosophila melanogaster: immunofluorescent localization of clathrin, adaptin and the yolk protein receptor.

The process of yolk protein (YP) uptake by developing oocytes in Drosophila melanogaster has been investigated by immunofluorescent localization of the endocytosis proteins, clathrin, alpha-adaptin and the putative yolk protein receptor (YP receptor). Data suggests that YPs from the follicle cells are trafficked into the oocyte during early stages of vitellogenesis, and that hemolymph YPs are sequestered by nurse cells adjacent to the developing oocyte during late stages of vitellogenesis. Yolk proteins were immunolocalized to both follicle cells and nurse cells during these processes. Diapausing female Drosophila melanogaster undergo a pre-vitellogenic arrest of ovarian development associated with the absence of ovarian alpha-adaptin, clathrin and putative YP receptor. Diapause termination by transfer of whole animals from 11 degrees C to 25 degrees C, or by 20-hydroxyecdysone injection, results in the appearance of immunopositive material in the nurse cells for all three proteins between 12 h and 16 h post upshift and within four days of injection. Immunopositive material was not noted in the follicle cells during diapause termination. In vitro warming of diapausing ovaries, or incubation in the presence of 1 &mgr;M 20-hydroxyecdysone failed to initiate early vitellogenic development suggesting that diapause termination requires factor(s) external to the ovary. Western blotting analysis of extracts of 24 h post-eclosion wild type and ap(56f) females identified putative yolk protein receptor with a molecular weight of 208 kDa and clathrin with a molecular weight of 178 kDa.

Thalamic hematoma from a ruptured posterior cerebral artery aneurysm.

BACKGROUND: The location of parenchymal hemorrhage often indicates the site of the aneurysm in subarachnoid hemorrhage. CASE REPORT: We present the first case of a thalamus hematoma associated with a small ruptured (P1) posterior cerebral artery aneurysm with rapid washout of subarachnoid blood mimicking a ganglionic hemorrhage. CONCLUSION: Thalamus hematoma with subarachnoid hemorrhage points at a ruptured proximal posterior circulation aneurysm.

Spinal manifestations of vertebral artery dissection.

Among 111 patients with vertebral artery dissection (VAD), two presented with spinal manifestations: one with a C5-C6 radiculopathy and the other with a cervical myelopathy. Of 13 previously reported cases of spinal manifestations of VAD (mean age 37 years), ischemic cervical myelopathy was noted in seven; cervical radiculopathy, often at C5-C6 and primarily motor, in five; and hemorrhagic complications in one, with chest pain being part of the presentation.

Fulminant case of hereditary neuropathy with liability to pressure palsy.

Hereditary neuropathy with liability to pressure palsy (HNPP) is typified as isolated nerve palsies caused by trivial compression or trauma. It rarely presents in two extremities and even more infrequently affects all four limbs simultaneously. We present a patient who concurrently experienced right shoulder, left hand, and bilateral foot weakness mimicking several multifocal conditions. Electromyography suggested HNPP and subsequent nerve biopsy and genetic testing were confirmatory. The case demonstrates that HNPP can present in a fulminant manner and should be included in the differential diagnosis of acute multiple mononeuropathies. The possible causes for such a rapid clinical course in our patient are discussed.

Moyamoya-like vasculopathy from cocaine dependency.

We herein describe two cases of moyamoya vasculopathy occurring in two men who used alkaloidal cocaine for years. One patient presented with aneurysmal subarachnoid hemorrhage and one with infarction in both lobes. Particularly impressive was a significant degree of collateral development with lenticulostriate networks.

The myeloid zinc finger gene (MZF-1) delays retinoic acid-induced apoptosis and differentiation in myeloid leukemia cells.

The myeloid zinc finger gene, MZF-1, is a hematopoietic transcription factor expressed in developing myeloid cells. To characterize further the role of MZF-1 in myelopoiesis, we used retroviral gene transduction to overexpress MZF-1 in HL-60 cells to produce HL-60-MZF-1 cells. HL-60 cells respond to retinoic acid (RA) with growth inhibition, granulocytic differentiation and apoptosis. However, HL-60-MZF-1 cells exposed to RA continue to proliferate in response to RA as evidenced by a higher percentage of cells in S phase, higher peak cell counts, and later peak cell counts. Morphologic differentiation of the RA-induced HL-60-MZF-1 cells is delayed with half as many of the HL-60-MZF-1 cells compared to the wild-type HL-60 cells that are differentiated after 3 days of RA, although both cells types responded with 80-95% mature granulocytes after 6 days of RA. Apoptosis was delayed in the MZF-1 transduced cells as measured by internucleosomal DNA fragmentation patterns, the terminal transferase end labeling reaction (TUNEL), and quantitation of fragmented DNA by the diphenylamine reaction. Several markers of differentiation were identical in both HL-60 and HL-60-MZF-1 cells including CD11b, CD33, CD34, CD13, CD16 and CD14. However, following 6 days of RA, only half as many HL-60-MZF-1 cells expressed CD18 compared to the wild-type HL-60 cells. Expression of the bcl-2 proto-oncogene transcript and protein was higher in the HL-60-MZF-1 cells compared to wild-type HL-60s and expression persisted for 5 days following RA in the HL-60-MZF-1 cells compared to only 3 days in the parental HL-60 cells suggesting that bcl-2 may contribute to the inhibition of apoptosis. Overexpression of MZF-1 had no effect on PMA-induced monocyte/macrophage differentiation of HL-60 cells. Together these findings indicate that MZF-1 can stimulate cell proliferation and delay RA-induced differentiation and apoptosis in HL-60 cells. MZF-1 may function in a similar role in myelopoiesis allowing myeloid precursors to expand their numbers before going on to terminally differentiate.

An unusual complication of nasolacrimal duct probing.

A 4-mm segment of the tip of a 0000 probe broke off inside the nasolacrimal duct of an 11-month-old girl during probing for congenital nasolacrimal duct obstruction. Despite numerous attempts, the tip could not be extracted. Examination of the 000 end of the double-ended probe showed a narrow neck approximately 4 mm from the bulbous tip. Choosing an appropriate probe design, inspecting the probe before use, and selecting the appropriate probe size will help prevent this unusual complication.

Can tritiated water-dilution space accurately predict total body water in chukar partridges?

Total body water (TBW) volumes determined from the dilution space of injected tritiated water have consistently overestimated actual water volumes (determined by desiccation to constant mass) in reptiles and mammals, but results for birds are controversial. We investigated potential errors in both the dilution method and the desiccation method in an attempt to resolve this controversy. Tritiated water dilution yielded an accurate measurement of water mass in vitro. However, in vivo, this method yielded a 4.6% overestimate of the amount of water (3.1% of live body mass) in chukar partridges, apparently largely because of loss of tritium from body water to sites of dissociable hydrogens on body solids. An additional source of overestimation (approximately 2% of body mass) was loss of tritium to the solids in blood samples during distillation of blood to obtain pure water for tritium analysis. Measuring tritium activity in plasma samples avoided this problem but required measurement of, and correction for, the dry matter content in plasma. Desiccation to constant mass by lyophilization or oven-drying also overestimated the amount of water actually in the bodies of chukar partridges by 1.4% of body mass, because these values included water adsorbed onto the outside of feathers. When desiccating defeathered carcasses, oven-drying at 70 degrees C yielded TBW values identical to those obtained from lyophilization, but TBW was overestimated (0.5% of body mass) by drying at 100 degrees C due to loss of organic substances as well as water.(ABSTRACT TRUNCATED AT 250 WORDS)

Temperature and manganese as determining factors in the presence of diatom or blue-green algal floras in streams.

Diatoms are usually the major component of the algal flora in many streams, although green and blue-green algae may be present. These experiments were designed to determine if high temperature or a shift in the chemical composition of the water might bring about a dominance of blue-green algae and/or green algae rather than a dominance of diatoms in the algal flora.The results of these experiments indicate that an average temperature of 34 degrees to 38 degrees C results in a shift of dominance in the algal flora from diatoms to blue-green algae. Furthermore, a blue-green and green algal flora of species typically found in organically polluted water in favored if the manganese content is a few parts per billion. If the manganese content averaged 0.02-0.043 mg/liter in the natural stream to 0.04-0.28 mg/liter in the recycled water experiment, a diatom flora remained dominant.