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C Brenner

Publications and source records attributed to C Brenner.

137 records · Page 8Linked to original sources
PubMedDate not supplied

Crystal structure of the worm NitFhit Rosetta Stone protein reveals a Nit tetramer binding two Fhit dimers.

BACKGROUND: The nucleotide-binding protein Fhit, among the earliest and most frequently inactivated proteins in lung cancer, suppresses tumor formation by inducing apoptosis. In invertebrates, Fhit is encoded as a fusion protein with Nit, a member of the nitrilase superfamily. In mice, the Nit1 and Fhit genes have nearly identical expression profiles. According to the Rosetta Stone hypothesis, if the separate Nit and Fhit genes could be shown to occur in the same subset of genomes (that is, to share a phylogenetic profile), then the existence of a fusion protein in invertebrates and the coordinated expression of separate mRNAs in mouse suggest that Nit and Fhit function in the same pathway and that the structure of invertebrate NitFhit may reflect the nature of Nit-Fhit interactions. RESULTS: To satisfy the phylogenetic profile criterion for functional significance of protein fusion events, we cloned additional Nit homologs from organisms with Fhit homologs. We used fluorescent nucleotide analogs of ApppA to follow the purification and to characterize the nucleotide specificity of NitFhit from Caenorhabditis elegans, crystallized the 200 kDa tetrameric complex, and solved the structure of NitFhit from a single mercury derivative phased by two-wavelength anomalous diffraction. CONCLUSIONS: Nit monomers possess a new alpha-beta-beta-alpha sandwich fold with a presumptive Cys-Glu-Lys catalytic triad. Nit assembles into a tetrameric, 52-stranded beta box that binds Fhit dimers at opposite poles and displays Nit active sites around the middle of the complex. The most carboxy-terminal beta strand of each Nit monomer exits the core of the Nit tetramer and interacts with Fhit. Residence in the NitFhit complex does not alter the nucleotide specificity of Fhit dimers, which are oriented with ApppA-binding surfaces away from Nit.

Acid Anhydride Hydrolases↗
PubMedDate not supplied

Two hydrolase resistant analogues of diadenosine 5',5"'-P1,P3-triphosphate for studies with Fhit, the human fragile histidine triad protein.

The design and synthesis of analogues of diadenosine 5',5"'-P1,P3-triphosphate that are resistant to pyrophosphate hydrolysis is described in relation to their rôle in signalling and tumorigenesis involving the Fhit protein, the human fragile histidine triad protein, which is a novel Ap3A binding/cleaving protein.

Acid Anhydride Hydrolases↗
PubMedDate not supplied

Cytoplasmic transfer in assisted reproduction.

This report details the use of cytoplasmic transfer in human oocytes. The introduction of a small amount of ooplasm from a donor oocyte or zygote may alter the function of oocytes, with probable deficiencies. Cytoplasmic transfer from fertile donor oocytes or zygotes into compromised oocytes from patients with recurrent implantation failure after assisted reproduction has now led to the birth of nearly 30 healthy babies worldwide. Transfer of small amounts of cytoplasm probably involves mRNAs, proteins and mitochondria, as well as other factors and organelles. Even though the use of cytoplasmic transfer has been employed in several IVF clinics--and pregnancies have resulted--it is not known definitively whether the physiology of the early embryo is affected. This review outlines the experimental cytoplasmic transfer techniques and postulates the future impact in assisted reproduction.

Animals↗
PubMedDate not supplied

[Potentially treatable subacute forms of infection due to the HTLV-1].

INTRODUCTION: Tropical spastic paraparesis due to HTLV-I virus is diagnosed at very advanced stages, when there is spinal atrophy present and so only symptomatic treatment can be given. Early diagnosis of HTLV-I infection in unusual syndromes and the use of corticosteroids may help to slow the development of the disease. CLINICAL CASES: We describe two Brazilian patients who developed symptoms due to HTLV-I present for less than one year: subacute myelopathy with a sensory level and an ataxic pyramidal syndrome associated with axonal neuropathy, which partly improved after treatment with corticosteroids. RESULTS: A 50 year old woman presented with progressive paraparesis following pain, cramps, feeling that her legs had 'gone to sleep' and sphincter dysfunction over the previous eleven months. Spinal MR showed a diffuse spinal hypersignal at D2. The 60 year old man had developed an ataxic syndrome and axonal polyneuropathy over the previous ten months. In both patients the anti-HTLV antibodies in blood and CSF were positive on ELISA as later confirmed by Western-blot. Thorough biochemical study ruled out other infectious etiologies. Both patients were treated with corticosteroids (i.v. methylprednisolone and oral prednisone respectively) and their symptoms improved, particularly the joint pains, ataxia and the 'gone to sleep' sensation of the legs. CONCLUSIONS: The ataxic syndrome and myelopathy due to HTLV-I, when these have been diagnosed early, may benefit from corticosteroid treatment and progression of the disorder be prevented. The myelitic phase of HTLV-I infection is associated with diffuse myelopathy, which was unusually seen in our first patient on spinal MR.

Anti-Inflammatory Agents↗
PubMedDate not supplied

[Type I neurofibromatosis presenting as a progressive cervical myelopathy. The first case reported in Kaxinawa Indians].

INTRODUCTION: Type I neurofibromatosis is an autosomal dominant disorder with an estimated prevalence of 1/3,000. Half of the new cases are due to mutations; their penetration is complete in adults and may affect any ethnic group. We describe the first reported case of type I neurofibromatosis in a Kaxinawa Indian from the state of Acre, Brazil, in whom the presenting symptoms were of progressive tetraparesis due to multiple paraspinal neurofibromata. CLINICAL CASE: A 16 year old indigenous Kaxinawa boy presented with progressive myelopathy for the past six months. On neurological examination he had hyperreflexive spastic tetraparesia, predominantly on the right side, with the sensory level at C3/C4, multiple medullary automatisms and respiratory difficulty. He also had diffuse café-au-lait stains, including one particularly prominent one measuring 15 cm on his right buttock. MR of the spine showed many hypo-intense lesions at T1 and hyperintense lesions at T2, which took up contrast and were present at all the conjugation foramens bilaterally. These lesions originated at the roots and were suggestive of neurofibromata. On mediastinal tomography there were several neurofibromata in the mediastinum. The patient had a surgical operation for spinal decompression, with a laminectomy at C1/C2 and removal of the neurofibromata on the spinal cord at C1 and C2. The patient has a sister with multiple café-au-lait stains. CONCLUSIONS: Because of the traditional isolation of the Kaxinawa Indians, with whom contact was made at the beginning of the twentieth century, this first case reported of type I neurofibromatosis may be due to a new mutation which presented as a florid form of the disease with multiple spinal neurofibromata.

Adolescent↗
PubMedDate not supplied

[Devic's neuromyelitis optica. Presentation of 2 new cases and review of the bibliography].

Devic's neuromyelitis optica is a clinical entity characterized by severe transverse myelitis, acute unilateral or bilateral optic neuropathy, no clinical involvement beyond the spinal cord or optic nerves and a monophasic or recurrent evolution. We report two cases, both female, affected by spinal cord and visual symptoms suggesting Devic's neuromyelitis. First patient, a 30 y.o. woman, was admitted due to acute flaccid tetraparesis preceded by left optic neuropathy five months before. CSF showed normal IgG level and no synthesis of oligoclonal bands. Brain and spinal cord MRI showed left optic neuropathy, signal hyperintensities at cervical and thoracic levels on the T2 weighted sequence, and diffuse enhancement after e.v. gadolinium DPTA. Second patient presented optical neuropathy at 19 years of age, transverse myelitis at 47 years of age, and a new cervical myelopathy two years later, at 49 y.o. Brain and spinal cord MRI showed bilateral optic atrophy and multiple hyperintensities among C1/C2 and C6/C7 levels, some of them cavitated. Pleocytosis, protein count of 511 mg/dl, presence of IgGs but negative oligoclonal bands was observed on CSF. In general, Devic's optic neuromyelitis has poor functional prognoses, recurrences may follow onset affecting spinal cord and optic nerves. In our two cases, we did not identify a specific cause despite all the diagnostic work-up.

Adult↗