Identification of a novel cysteine string protein variant and expression of cysteine string proteins in non-neuronal cells

Cysteine string proteins (Csps) are synaptic vesicle proteins thought to be involved in calcium-dependent neurotransmitter release at nerve endings. Here, we report the cloning of two Csp variants, termed Csp1 and Csp2, from bovine adrenal medullary chromaffin cells. The bovine Csp1 appears to be the homologue of rat brain Csp, sharing 95% identity at the amino acid level. The nucleotide sequence of csp2 is identical with that of csp1 except for a 72-base insert which introduces a stop codon into the coding sequence, which would be predicted to result in a truncated protein 3.3 kDa smaller than Csp1. Furthermore, polymerase chain reaction analysis detected homologues of Csp1 and Csp2 in rat kidney, liver, pancreas, spleen, lung, and adrenal gland. Expression of Csps in non-neuronal tissues was confirmed by Northern blotting and by immunoblotting with anti-Csp1 antiserum which also demonstrated expression of both full-length and truncated Csps in spleen. The widespread tissue distribution is inconsistent with a role of Csps as specific regulators of presynaptic calcium channels as previously proposed. We suggest that Csps may have a more general role in membrane traffic in non-neuronal as well as neuronal cells.     

The association of non-insulin-dependent diabetes mellitus and cognitive function in an older cohort

This is the first demonstration of the use of accelerator mass spectrometry (AMS) as a tool for the measurement of 3H with attomole (10(-18) mol) sensitivity in a biological study. AMS is an analytical technique for quantifying rare isotopes with high sensitivity and precision and has been most commonly used to measure 14C in both the geosciences and more recently in biomedical research. AMS measurement of serially diluted samples containing a 3H-labeled tracer showed a strong correlation with liquid scintillation counting. The mean coefficient of variation of 3H AMS based upon the analysis of separately prepared aliquots of these samples was 12%. The sensitivity for 3H detection in tissue, protein, and DNA was approximately 2-4 amol/mg of sample. This high sensitivity is comparable to detection limits for 14C-labeled carcinogens using 14C AMS and demonstrates the feasibility of 3H AMS for biomedical studies. One application of this technique is in low-dose, dual-isotope studies in conjunction with 14C AMS. We measured the levels of 3H-labeled 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 14C-labeled 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in rat liver tissue and bound to liver DNA and protein 4.5 h following acute administration of individual or coadministered doses in the range of 4-5100 pmol/kg of body weight. Levels of PhIP and MeIQx in whole tissue and bound to liver protein were dose-dependent. MeIQx-protein and -DNA adduct levels were higher than PhIP adduct levels, which is consistent with their respective carcinogenicity in this organ. Coadministration of PhIP and MeIQx did not demonstrate any measurable synergistic effects compared to administration of these compounds individually. These studies demonstrate the application of AMS for the low-level detection of 3H in small biological samples and for its use in conjunction with 14C AMS for dual-labeling studies.     

Association analysis in an evolutionary context: cladistic analysis of the DRD2 locus to test for association with alcoholism

Recent clinical trials of adjuvant therapy for early stage breast cancer support two general observations. First, overall survival is not impacted by the extent of surgery. Low rates of axillary relapse in patients treated with total mastectomy alone combined with the availability of systemic therapy as a substitute for surgical control of the axilla mean that patients can often be spared the morbidity of axillary node dissection. In problematic cases, newer diagnostic approaches, such as sentinel node biopsy, can help in making appropriate treatment decisions. Second, systemic therapy can reduce the clinical manifestations of disease. The incorporation of more sophisticated approaches to predicting outcomes, to varying timing and dose of treatment, and to developing new modalities of treatment, including immunotherapy, will contribute to a general strategy aimed at reducing the tumor to a harmless parasite. These observations support a paradigm shift in our definition of 'adjuvant'. Rather than referring to the use of systemic therapy after the patient's known disease has been surgically removed, adjuvant therapy would be re-defined to refer to local therapy used to eradicate any residual tumor remaining after systemic therapy has been completed.     

Hyers-ulam stability of functional equations with a square-symmetric operation

The stability of the functional equation f(x composite function y) = H(f(x), f(y)) (x, y in S) is investigated, where H is a homogeneous function and composite function is a square-symmetric operation on the set S. The results presented include and generalize the classical theorem of Hyers obtained in 1941 on the stability of the Cauchy functional equation.     

Reoperations on the spine--outcome studies

Rheumatoid arthritis is described by Swanson (1995) as 'the greatest crippler from the standpoint of severity and prolonged disability' (p. 1307). One key factor in keeping persons with rheumatoid arthritis independent in their activities of daily living is maintaining functional use of their hands. In rural areas, where a move to assisted accommodation may require a person to leave the locality, this splint may help older citizens to remain functional and at home. The deformity and instability caused in rheumatoid arthritic hands by radial deviation of the wrist and subsequent ulnar deviation of the metacarpophalangeal (MCP) joints can greatly affect functional use of the hands. In this article, design and fabrication instructions for a lycra working splint which is suitable for the rheumatoid arthritic hand with MCP ulnar deviation are presented. Health professionals working in rural areas will find this splint inexpensive and easy to design, either alone or, ideally, with the assistance of regional occupational therapists.     

Unattached intracranial extra-axial schwannoma

We describe an intracranial extra-axial petroclival schwannoma which did not arise from any cranial nerve, nor was it attached to brain parenchyma or dura. The possible pathogenesis is discussed.