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M Chau

Publications and source records attributed to M Chau.

6 recordsLinked to original sources
PubMed2000

Structural and functional differences between 3-repeat and 4-repeat tau isoforms. Implications for normal tau function and the onset of neurodegenetative disease.

Tau, MAP2, and MAP4 are members of a microtubule-associated protein (MAP) family that are each expressed as "3-repeat" and "4-repeat" isoforms. These isoforms arise from tightly controlled tissue-specific and/or developmentally regulated alternative splicing of a 31-amino acid long "inter-repeat:repeat module," raising the possibility that different MAP isoforms may possess some distinct functional capabilities. Consistent with this hypothesis, regulatory mutations in the human tau gene that disrupt the normal balance between 3-repeat and 4-repeat tau isoform expression lead to a collection of neurodegenerative diseases known as FTDP-17 (fronto-temporal dementias and Parkinsonism linked to chromosome 17), which are characterized by the formation of pathological tau filaments and neuronal cell death. Unfortunately, very little is known regarding structural and functional differences between the isoforms. In our previous analyses, we focused on 4-repeat tau structure and function. Here, we investigate 3-repeat tau, generating a series of truncations, amino acid substitutions, and internal deletions and examining the functional consequences. 3-Repeat tau possesses a "core microtubule binding domain" composed of its first two repeats and the intervening inter-repeat. This observation is in marked contrast to the widely held notion that tau possesses multiple independent tubulin-binding sites aligned in sequence along the length of the protein. In addition, we observed that the carboxyl-terminal sequences downstream of the repeat region make a strong but indirect contribution to microtubule binding activity in 3-repeat tau, which is in contrast to the negligible effect of these same sequences in 4-repeat tau. Taken together with previous work, these data suggest that 3-repeat and 4-repeat tau assume complex and distinct structures that are regulated differentially, which in turn suggests that they may possess isoform-specific functional capabilities. The relevance of isoform-specific structure and function to normal tau action and the onset of neurodegenerative disease are discussed.

Alternative Splicing↗
PubMed2000

A sparse matrix approach to the solubilization of overexpressed proteins.

Many biophysical experiments depend on large amounts of pure, soluble protein. Indeed, the revolution in structural biology has depended on molecular biology's potential to make experiments possible by allowing the overexpression of normally rare proteins in a heterologous host. All too often, however, overexpressed proteins are poorly soluble in buffers that attempt to mimic physiological conditions. Often in such cases the overexpressed protein is assumed to be present in inclusion bodies and hopes of obtaining the desired sample from the overexpression vector are abandoned. We have developed a sparse matrix approach to the solubilization of such proteins that is often successful. This approach relies on well accepted theories of protein solubility and folding to build a sparse matrix that samples 'solubility space' effectively. The buffers of the sparse matrix are used to make crude extracts that are rapidly assayed for soluble protein using gel electrophoresis. We describe our approach and give examples of its application.

Buffers↗
PubMed1997

Mortality from pancreatic and lymphopoietic cancer among workers in ethylene and propylene chlorohydrin production.

OBJECTIVES: A previous study reported a fivefold increase in mortality from pancreatic cancer and a threefold increase in lymphopoietic and haematopoietic cancer among 278 men who were assigned to a now dismantled Union Carbide chlorohydrin unit in the Kanawha Valley of West Virginia. There were also significant trends with duration of employment. The purpose of this study was to determine whether a comparable increased risk in mortality from pancreatic cancer and lymphopoietic and haematopoietic cancer occurred among male employees assigned to the Dow Chemical Company's ethylene and propylene chlorohydrin production processes. METHODS: The cohort consisted of 1361 male employees who worked at the company's Freeport, Texas, Plaquemine, Louisiana or Midland, Michigan plants. Subjects were considered to have had a minimum of 30 days of workplace experience in 1940-92, in the ethylene chlorohydrin and propylene chlorohydrin process areas. These process areas were located within the ethylene oxide and propylene oxide production plants. A total of 300 deaths was observed to 31 December 1992. RESULTS: The standardised mortality ratio (SMR) for all malignant neoplasms was 94 (95% CI 74 to 118). There was one pancreatic cancer death compared with 4.0 expected (SMR 25, 95% CI 1 to 140). There were 10 lymphopoietic and haematopoietic cancer deaths compared with 7.7 expected (SMR 129, 95% CI 62 to 238). Additional analyses, which examined location, production process, duration of employment, and a 25 year induction latency period, were not significant. CONCLUSIONS: The results provide some assurance that the Dow Chemical cohort, to date, has not experienced increased risks of pancreatic cancer and lymphopoietic and haematopoietic cancer as previously reported in a different cohort of chlorohydrin workers. Possible reasons are discussed for the inconsistent findings between the two cohorts.

Chlorohydrins↗
PubMed1993

Cervical spine abnormalities in institutionalized adults with Down's syndrome.

The prevalence of increased anterior atlanto-odontoid distance (AAOD), a risk factor for spinal cord compression, and degenerative disease of the cervical spine (DDCS) in a population of institutionalized adults with Down's syndrome (DS) was determined and compared with age- and sex-matched 'normals' presenting to a hospital emergency department. Radiographs of the cervical spines of 99 adults with DS and 198 'normals' were compared using a standardized rating scale. The prevalence of an AAOD of 3 mm or greater, the threshold of risk from the literature, was 8% for DS cases and 2% for controls (P < 0.01). The mean AAOD for DS cases was 2.0 +/- 1 mm and for controls 1.5 +/- 0.5 mm (P < 0.01). There was a negative correlation between AAOD and age of DS cases. The prevalence of any degree of DDCS among the DS cases was 64%, the controls 39% (P < 0.001); for moderate or severe DDCS the prevalence among DS cases was 45%, controls 12% (P < 0.001). The prevalence of DDCS increased with age in both groups, but the severity of DDCS was significantly increased with age in both groups, but the severity of DDCS was significantly greater for DS individuals in all age groups. The levels of the cervical spine affected ranged from C2 to C6; the most commonly affected level was C5-C6. While DS adults are at increased theoretical risk for spinal cord compression due to increased AAOD, its clinical significance would appear to be small and to decline with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

A comparison of paracetamol and diflunisal for pain control following 3rd molar surgery.

A double-blind randomised cross-over study to compare 2 regimes of paracetamol and diflunisal for postoperative pain relief following 3rd molar surgery was designed. 35 patients received one of the regimes at one visit and the alternative at the other visit. Both drugs, namely a single dose of 500 mg of diflunisal given preoperatively or 2 doses of 1000 mg of paracetamol, given preoperatively and 4 h postoperatively, produced adequate pain relief, without the need for supplementary analgesics during the 10-h test period. The differences in the mean overall pain scores in the 2 regimes were not statistically significant.

Acetaminophen↗