Sequence variation and size ranges of CAG repeats in the Machado-Joseph disease, spinocerebellar ataxia type 1 and androgen receptor genes

A subgroup of trinucleotide repeat diseases result from abnormalexpansions of CAG repeats which are translated into polyglutaminestretches. As yet there is little understanding of how the polyglutaminesfunction either normally, or when expanded. We have investigatedthese sequences in the Machado-Joseph disease, androgen receptorand spinocerebellar ataxia type 1 genes in humans and otherprimates. None of the 748 normal chromosomes that were examinedhad more than 34 uninterrupted gluta-mine codons in the Machado-Josephdisease gene. Similarly, no normal alleles with more than 39uninterrupted glutamine codons have been reported for the otherdisease genes associated with polyglutamine expansions. Sequenceanalyses of the repeats in primates revealed shorter polyglutaminestretches in some of the non-human primates at all three lociand marked diversions from the expected polyglutamines in theorang-utan Machado-Joseph gene and in the marmoset spinocerebellarataxia type 1 gene. These data suggest that conservation ofthese polyglutamine stretches may not always be necessary fornormal gene function.     

Thyroid hormone promotes neurogenesis in the Xenopus spinal cord.

Three phases of neurogenesis can be recognized during Xenopus spinal cord development. An early peak during gastrulation/neurulation is followed by a phase of low level neurogenesis throughout the remaining embryonic stages and a later peak at early larval stages. We show here that several genes known to be essential for early neurogenesis (X-NGNR-1, XNeuroD, XMyT1, X-Delta-1) are also expressed during later phases of neurogenesis in the spinal cord, suggesting that they are involved in regulating spinal neurogenesis at later stages. However, additional neuronal determination genes may be important during larval stages, because X-NGNR-1 shows only scant expression in the spinal cord during larval stages. Thyroid hormone treatment of early larvae promotes neurogenesis in the spinal cord, where thyroid hormone receptor xTRalpha is expressed from early larval stages onward and results in precocious up-regulation of XNeuroD, XMyT1, and N-Tubulin expression. Similarly, thyroid hormone treatments of Xenopus embryos, which were coinjected with xTRalpha and the retinoid X receptor xRXRalpha, repeatedly resulted in increased numbers of neurons, whereas unliganded receptors repressed neurogenesis. Our findings show that thyroid hormones are sufficient to up-regulate neurogenesis in the Xenopus spinal cord.     

Disseminated infection with Nattrassia mangiferae in an immunosuppressed patient

Disseminated infection with the coelomycetous fungus Nattrassia mangiferae is a very rare disease affecting only the immunocompromised host. We report the first case of a disseminated infection with spondylodiscitis and granular skin lesions due to N. mangiferae in a renal transplant patient.     

Essential tremor, nystagmus and duodenal ulceration. A "new" dominantly inherited condition.

The familial occurrence of essential tremor combined with (congenital) nystagmus, duodenal ulceration and a narcolepsy-like sleep disturbance caused by an autosomal dominant gene with high penetrance and fairly uniform expressivity is reported in a family of Swedish-Finnish ancestry. Twelve of 17 affected family members had essential tremor which began between 30-40 years of age and which could be controlled temporarily by alcohol; this resulted in alcoholism in several affected individuals. The most severly affected persons showed cerebellar signs which may reflect a possible pathogenetic relationship of the syndrome to the genetic cerebellar atrophies. Nystagmus, observed in 12 of 17 affected family members (eight of whom were also affected with tremor) usually was congenital and accompanied by refractive errors. Duodenal ulcers occurred almost exclusively in individuals with the neurological syndrome, and preceded its onset in some cases. The ulcer disease therefore seems to be a component manifestation of the syndrome and is interpreted as a pleiotropic effect of the gene which also causes the nystagmus, tremor and sleep disturbance.     

Detection of methicillin-resistant Staphylococcus aureus and simultaneous confirmation by automated nucleic acid extraction and real-time PCR

A molecular assay for the simultaneous detection of a Staphylococcus aureus-specific gene and the mecA gene, responsible for the resistance to methicillin in staphylococci, was evaluated. The assay included an automated DNA extraction protocol conducted with a MagNA Pure instrument and real-time PCR conducted with a LightCycler instrument. The performance and robustness of the assay were evaluated for a suspension of methicillin-resistant S. aureus (MRSA) strain with a turbidity equivalent to a McFarland standard of 0.5, which was found to be the ideal working concentration. The specificity of the new molecular assay was tested with a panel of 30 gram-negative and gram-positive bacterial strains other than MRSA. No cross-reactivity was observed. In a clinical study, 109 isolates of MRSA were investigated. All clinical MRSA isolates gave positive results for the S. aureus-specific genomic target, and all but one were positive for the mecA gene. In conclusion, the new molecular assay was found to be quick, robust, and laborsaving, and it proved to be suitable for a routine molecular diagnostic laboratory.     

REACTIVITY OF LYMPHOCYTE SUBPOPULATIONS IN HUMAN MIXED LYMPHOCYTE CULTURE

Loss of antigenicity in the mixed lymphocyte culture (MLC) reaction of lymphocytes precultured at 22°C for 7–10 days was accompanied by a decrease in bone-marrow-derived lymphocytes (B cells) from 22 ± 1% to 13 ± 1%, and an increase in thymus-derived lymphocytes (T cells) from 65 ± 2% to 83 ± 1% (P < 0.001). Depletion of B cells from a fresh lymphocyte suspension by either antihuman immunoglobulin-coated column fractionation or by sheep red blood cell (SRBC) rosette formation resulted in a significant reduction of the cell's ability to stimulate in MLC (P < 0.001). Coating of lymphocytes with rabbit antihuman brain serum abrogated their ability to respond but not the ability to stimulate in MLC.     

Poly(2,5-dialkoxy-p-phenylene)s—synthesis and properties

The synthesis of poly(2,5-dialkoxy-p-phenylene)s (PPP) by palladium-catalyzed polycondensation of 2,5-dialkoxy-4-bromophenylboronic acids is described. Number-average degrees of polymerization of ca. 30 have been reached at best. The characterization of the polymers by NMR, IR, UV-VIS and fluorescence spectra, data on the bulk structure obtained by X-ray methods, melting behavior and thermal stability are reported. PPP's with long alkoxy side chains exhibit a layered phase structure, those with short or branched alkoxy side chains, cylindrical packing. Poly(2,5-dibutoxy-p-phenylene) was prepared with chain lengths 7 ≤ P_n ≤ 30. The polymer with P_n of 30 shows thermal transitions in the bulk phase at 182°C and 227°C. It forms an anisotropic melt above 227°C which only starts decomposing if heated above 300°C. The polymers of shorter chain length show isotropic melts, with the melting point strongly depending on chain length.