Factors contributing to variation in lipoprotein (a) in Melbourne Anglo-Celtic population.

AIM: The purpose of this report is to survey the factors contributing to variation in lipoprotein(a) (Lp(a)) in a population-based sample of Anglo-Celtic Melburnians. RESULTS: The plasma Lp(a) levels were highly skewed towards low levels in this population, with a median of 156 mg/l and a mean of 262 mg/l. Approximately 33% had plasma Lp(a) above the threshold value of 300 mg/l, while 35% had Lp(a) levels below 100 mg/l. The most commonly occurring phenotype was apo(a) S3. In this phenotype, Lp(a) concentrations ranged from 10 to 596 mg/l. Lp(a) was consistently associated with diastolic blood pressure, systolic blood pressure, total protein, albumin and nitrogen excretion in the 40-60 y age group. Multiple stepwise regression analyses, in non-dietary factors, were used to explain about 13% of the variance in Lp(a) (19% in men and 23% in women). Remarkably, in the <40 y age group, non-dietary factors may account for 86% of the variance in Lp(a) and dietary factors, analysed separately, 46%. Thus, although Lp(a) is mainly genetically determined, there are clearly other factors which contribute to variations in Lp(a) concentrations.

Plasma lipoprotein (a) concentrations and apolipoprotein (a) phenotypes in an Aboriginal population from Western Australia.

Factors contributing to the variation in plasma lipoprotein (a) (Lp(a)) concentration were surveyed in an Aboriginal population (175 men and 219 women), aged 24-86 years, from Western Australia. The plasma Lp(a) levels were highly skewed towards low levels in this population, with a median of 84 mg/L and a mean of 166 mg/L. Approximately 20% had plasma Lp(a) above the threshold value of 300 mg/L, while 52% had Lp(a) levels below 100 mg/L. The most commonly occurring phenotype was apolipoprotien(a) S4. In this phenotype, Lp(a) concentrations ranged from not detectable to 468 mg/L. There was a positive relationship between cigarette smoking and plasma Lp(a) concentration in men. Apolipoprotein A1 and bilirubin were positively associated with Lp(a) in the 40-60 age group and a positive relationship between weight and Lp(a) concentrations was observed in those aged 60 years or over. Thus, although Lp(a) is mainly genetically determined, there are clearly other factors which contribute to variations in Lp(a) concentrations.

Cross-cultural comparison of Lp(a) profiles.

Lipoprotein(a) (Lp(a)) and apolipoprotein(a) (apo(a)) phenotypes as genetic markers for coronary heart disease (CHD) have been the focus of great interest in recent times. Included in this study were four Australian populations comprising 348 Anglo-Celtic Melburnians (157 men and 191 women), 339 Chinese Melburnians (169 men and 170 women), 402 South Asian Melburnians (216 men and 186 women) and 394 Aboriginal Australians from Western Australia (175 men and 219 women). Plasma Lp(a) concentrations were more highly skewed towards the lower range in the Chinese and Aboriginal groups than in the Anglo-Celtics and South Asians. Approximately 33% of Anglo-Celtics, 20% Aboriginals, 13% Chinese and 44% South Asians had plasma Lp(a) levels above the generally accepted risk threshold values of 300 mg/L. In Aboriginals and Chinese, the S4 apo(a) phenotype predominated while in Anglo-Celtics and South Asians, the highest frequency occurred in the S3 phenotype. In the S4 phenotype, Lp(a) values varied between the four populations but there was no significant difference in concentration between gender.

Induction of physiological acrosome reactions in caput epididymal spermatozoa of mice.

Mouse caput spermatozoa are considered immature and thus unable to fertilize oocytes. In this study, we determined whether washing mouse caput spermatozoa increased their ability to acrosome react in response to a physiological stimulus. The results obtained showed that mouse caput spermatozoa incubated in Earles' modified medium containing calcium chloride and supplemented with BSA and pyruvate for 1 h at 37 degrees C and then washed acrosome reacted in response to both solubilized zonae and immunoaggregation of a zona binding site. In addition, the material removed from caput spermatozoa by washing blocked induced acrosome reactions of cauda spermatozoa. The data indicate that mouse caput epididymal spermatozoa, if incubated and washed, can undergo physiological acrosome reactions.

Binding of a murine proteinase inhibitor to the acrosome region of the human sperm head.

Proteinase inhibitors are present in the various glands, tissues, and secretions of the male reproductive tract. Some of these inhibitors bind to the acrosomal region of the sperm, and their release during in vitro or in utero incubation suggests that they may play a role in capacitation. In the mouse, the binding site for a trypsin-acrosin inhibitor, the acceptor, has been implicated in capacitation, zona binding, and the acrosome reaction. This presentation demonstrates that a component, molecular weight approximately 20,000, on the human sperm head may recognize the murine inhibitor. Furthermore, the acrosome reaction can be induced in capacitated human sperm by immunoaggregation of bound murine inhibitor. The data indicate that the proteinase inhibitor binding site on the human sperm head may, as with a similar site on murine sperm, play a role in the early events of fertilization.

Competition between zonae pellucidae and a proteinase inhibitor for sperm binding.

Murine sperm bind a proteinase inhibitor of seminal vesicle origin at ejaculation. The inhibitor binds in the acrosomal region of the sperm head and is removed during in utero or in vitro incubation. Adding inhibitor to sperm reduces their ability to bind zonae, while adding the purified inhibitor binding site to cumulus-free, zona-intact oocytes reduces the ability of the oocytes to bind sperm. Immuno-aggregation of the inhibitor binding site results in exocytosis of the acrosome. These observations suggest that the inhibitor binding site may participate in zona binding and the acrosome reaction. If the inhibitor binding site binds both the zona and the seminal inhibitor, then these components should compete with each other for that site on the sperm. We show that purified seminal inhibitor, as well as other proteinase inhibitors, block zona-induced acrosome reactions. Likewise, zona glycopeptides block inhibitor/anti-inhibitor-induced acrosome reactions in a concentration-dependent fashion. The inhibitor/anti-inhibitor-induced acrosome reaction is sensitive to pertussis toxin and proteinase inhibitor and thus is similar to zona-induced reactions. These findings support the suggestion that the trypsin inhibitor binding site on the head of the sperm functions to insure sperm-zona binding and induction of the acrosome reaction.

Value of visual evoked response and oligoclonal bands in cerebrospinal fluid in diagnosis of spinal multiple sclerosis.

To assess the predictive value of prolongation of visual evoked response (VER) plus the presence of oligoclonal bands in the cerebrospinal fluid (CSF) in the diagnosis of multiple sclerosis (MS) in patients with isolated cord lesions, the false-positive rate for the two tests combined was determined by a prospective analysis of 42 patients with a structural spinal cord lesion. The false-positive rate for the combination of VER and CSF abnormalities was zero, but the individual false-positive rates were 10% for VER and 12% for CSF protein oligoclonal bands. According to Bayes' theorem, and taking into account the false-positive rates of the tests in the population studied and the prevalence of MS and the true-positive rates for the tests as derived from published reports, abnormalities of VER and CSF protein together gave a probability of MS of 100%. However, if only either the VER or the CSF were abnormal, the probability of MS was 44% or 49%, respectively. An abnormal result for both tests thus indicates a sufficiently high probability of MS to exclude myelography, but a positive result in only one test warrants the procedure.

Improved measurement of monoclonal paraproteins in serum using agarose gel electrophoresis.

Serum paraproteins can be accurately and precisely measured by means of agarose gel electrophoresis and densitometry at 520 nm after staining with Coomassie Brilliant Blue G. The results obtained for this method agree closely with the quantity of paraprotein recoverable from preparative agarose gel electrophoresis. The method is preferable to cellulose acetate electrophoresis stained with Ponceau S.

A comparative study of commercial human and bovine albumin preparations.

A number of commercial human and bovine albumin preparations were compared using seven assay procedures, to assess their suitability as reference materials for albumin and total protein assays. The results indicate that before a particular commercial albumin preparation can be used for standardisation purposes, its suitability should be checked in several assay systems which measure a different functional aspect of the protein molecule. The measurement of extinction coefficient in the range 278-280 nm does not appear to be a valid measure of protein content if the albumin preparation is to be used for standardisation of immunochemical or dye-binding assays.