Age and seasonal distribution of menarche in Korean girls.

PIP: This paper examines the menarchal age of Korean girls and its monthly distribution to define the possible relationship between menarche and season. Menarchal age is influenced by diverse factors such as hereditary, geography, climate, psychological factors, socioeconomic status, body weight and height, nutritional state, body fat and exercise as well as the presence of chronic illness. In Korea, there is evidence of secular change toward earlier menarchal age, where the average menarchal age was 14.8 in 1952, 14.4 years in 1979, 13.4 years in 1986, and 12.5 years in 1988. A cross-sectional study was conducted from July 1993 to July 1995 among 4237 female middle and high school students, aged 14-20 years, in Ansan, Korea, to obtain data on demographic characteristics, menarchal age, month of menarche, and the menarchal age of the participant's mother. Findings revealed that average menarchal age is 12.5 years for the girls and 15.4 +or- 2.3 years for their mothers. Menarche is most common in August and January (summer), January and December (winter) in decreasing order. Seasonal pattern of menarche may also be related to the psychological factors during school vacation such as relaxation, decrease stress from studies, and/or physical rest.^ieng

The heat-shock protein HslVU from Escherichia coli is a protein-activated ATPase as well as an ATP-dependent proteinase.

HslVU in Escherichia coli a new two-component ATP-dependent protease composed of two heat-shock proteins, the HslU ATPase and the HslV peptidase which is related to proteasome beta-type subunits. Here we show that the reconstituted HslVU enzyme degrades not only certain hydrophobic peptides but also various polypeptides, including insulin B-chain, casein, and carboxymethylated lactalbumin. Maximal proteolytic activity was obtained with a 1:2 molar ratio of HslV (a 250-kDa complex) to HslU (a 450-kDa complex). By itself, HslV could slowly hydrolyze these polypeptides, but its activity was stimulated 20-fold by HslU in the presence of ATP. The ATPase activity of HslU was stimulated up to 50% by the protein substrates, but not by nonhydrolyzed proteins, and this stimulation further increased 2-3-fold in the presence of HslV. Concentrations of insulin B-chain that maximally stimulated the ATPase allowed maximal rates of the B-chain hydrolysis. Furthermore, addition of increasing amounts of ADP or N-ethylmaleimide reduced ATP and protein or peptide hydrolysis in parallel. Thus, HslVU is a protein-activated ATPase as well as an ATP-dependent proteinase, and these processes appear linked. Surprisingly, the protein and peptide substrates do not compete with each other for hydrolysis. Lactacystin strongly inhibits protein degradation, but has little effect on peptide hydrolysis, while the peptide aldehydes are potent inhibitors of hydrolysis of small peptides, but have little effect on proteins. Thus, the functional requirements for ATP-dependent hydrolysis of peptides and proteins appear different.

Mutagenesis of two N-terminal Thr and five Ser residues in HslV, the proteolytic component of the ATP-dependent HslVU protease.

HslVU in E. coli is a new type of ATP-dependent protease consisting of two heat shock proteins: the HslU ATPase and the HslV peptidase that has two repeated Thr residues at its N terminus, like certain beta-type subunit of the 20S proteasomes. To gain an insight into the catalytic mechanism of HslV, site-directed mutagenesis was performed to replace each of the Thr residues with Ser or Val and to delete the first or both Thr. Also each of the five internal Ser residues in HslV were replaced with Ala. The results obtained by the mutational analysis revealed that the N-terminal Thr acts as the active site nucleophile and that certain Ser residues, particularly Ser124 and Ser172, also contribute to the peptide hydrolysis by the HslVU protease. The mutational studies also revealed that both Thr, Ser103, and Ser172, but not Ser124, are involved in the interaction of HslV with HslU and hence in the activation of HslU ATPase as well as in the HslVU complex formation.

Mutational analysis of the ATP-binding site in HslU, the ATPase component of HslVU protease in Escherichia coli.

HslU is the ATPase component of the ATP-dependent HslVU protease in Escherichia coli. To gain an insight into the structure and function of HslU, site-directed mutagenesis was performed to generate a mutation in the ATP-binding site of the ATPase (i.e., to replace the Lys63 with Thr). Unlike the wild-type HslU, the mutant form (referred to as HslU/K63T) could not hydrolyze ATP or support the ATP-dependent hydrolysis of N-carbobenzoxy-Gly-Gly-Leu-7-amido-4-methyl coumarin by HslV. The wild-type HslU (a mixture of monomer and dimer) formed a multimer containing 6-8 subunits in the presence of either ATP or ADP, indicating that ATP-binding, but not its hydrolysis, is required for oligomerization of HslU. However, HslU/K63T remained as a monomer whether or not the adenine nucleotides were present. Furthermore, ATP or ADP could protect HslU, but not HslU/K63T, from degradation by trypsin. These results suggest that the mutation in the ATP-binding site results in prevention of the binding of the adenine nucleotides to HslU and hence in impairment of both oligomerization and ATPase function of HslU.

Factors associated with the decline in cirrhosis death rates among young adults in Allegheny County, Pennsylvania, 1973-1985.

From 1973 to 1985, the age-adjusted death rate from liver cirrhosis (International Classification of Diseases, Ninth Revision, code 571) dropped by 62.7% among adults aged 25-54 years in Allegheny County, Pennsylvania. The authors investigated factors associated with this decline by verifying causes of death on death certificates from medical records, coroner's reports, and autopsy reports. Although death rates from cirrhosis were slightly underestimated from death certificates, the underestimation did not alter the declining mortality trend. This decline in rates was significant after adjustment of the age, sex, and race effect using statistical modeling. No significant variability in the time trends was noted between sexes, races, and age groups. Neither did the trends in alcohol-related and "unspecified" cirrhosis differ. However, the trends varied significantly between the cirrhosis deaths certified by the coroner and by noncoroner physicians. From 1973-1975 to 1976-1978, the rate initially dropped by 51% among the coroner cases, whereas it dropped by only 9% among the noncoroner cases. By the period 1982-1985, the death rates of both coroner and noncoroner cases declined to approximately 50% of their 1973-1975 rates. These results suggest that the decline during the years 1973-1985 was real and that the trend was initiated by the pronounced decline during the early years in the coroner-certified cirrhosis deaths.

Vehicular crashes and alcohol involvement in drivers at fault, and related fatalities.

This descriptive, population-based retrospective review of coroner's and related law enforcement agency's records, and hospital emergency-room records, evaluates the characteristics of fatal traffic crashes in Allegheny County, Pennsylvania, according to whether the driver at fault had been drinking alcohol or not, and examines the relationship between alcohol consumption of drivers at fault, and their respective victims. Our data suggest that passengers of alcohol-positive drivers are as much at risk for fatal crash injuries as are the drivers themselves. Nondrinking drivers should be designated to avoid such risks. The data also show a substantial proportion of crashes involving BAC-negative victims and alcohol-uninvolved drivers at fault. These non-alcohol-related crashes need further evaluation to enable better methods of prevention.

[Proteinase activity in the isolates of Trichomonas vaginalis according to their pathogenicity].

Ten axenic isolates of Trichomonas vaginalis were subcutaneously injected to the BALB/c mice in order to assess their pathogenicity by means of so-called "mouse assay" method. All the isolates revealed neutral and acid proteinase activities both in their lysates and in culture media, but the specific activities of both proteinases in the severely pathogenic group were significantly higher than the mildly pathogenic group (p < 0.05). In the SDS-PAGE system in which the electrophoretic gels contained 0.4% gelatin as the substrate, five different banding patterns of trichomonal proteinases were detected, and the patterns were closely related with the pathogenicity of the isolates of T. vaginalis. All five bands might be regarded as cysteine proteinases group in the inhibitor assays. The cytotoxicity of the lysates of T. vaginalis to the target Chinese hamster ovarian (CHO) cell line was also significantly different according to the pathogenicity of the isolates, and generally lower in the lysates treated with cysteine proteinase inhibitors than in the control lysates. In summarizing the results, it might be considered that the proteinases of T. vaginalis showing five electrophoretic banding patterns are closely related with the pathogenicity and cytotoxicity of the isolates of T. vaginalis.

Detection of fatal therapeutic misadventures by an urban medico-legal system.

Very few population-based studies have evaluated fatal therapeutic misadventures, in particular the adequacy of their detection. We therefore assessed the adequacy of the reporting and detection of fatal therapeutic misadventures in an urban setting medico-legal system. The coroner's files and the related hospital records were reviewed as to the circumstances of the incidents and the adequacy of notification by the care providers in Allegheny County, Pennsylvania, for the period of January 1, 1982 through December 31, 1991. The annual average rate of fatal misadventures was 2.2 per 100,000 hospital admissions or 4.7 per million inhabitants (total 63 cases). The survival time from the occurrence of the misadventure was within 24 h in 60% of the cases. University-related hospitals had double the rate of misadventure fatalities (118.2 per 100,000 beds per year), compared to that in community-based hospitals (53.9 per 100,000 bed per year). In more than half of the cases, the hospitals reported the incidents within an hour from the pronouncement of death, 28.6% within 5 h, and 19% after more than 5 h. In 10 cases (15.9%), the notification by the hospitals was clearly deficient in determining the manner of death. In a few cases, the incident was initially reported by the relatives, by the hospital pathologists, or by the media. A high likelihood of under-reporting of fatal misadventures to the medico-legal system is substantiated by comparing with the results reported by others. The possible measures to increase the monitoring and reporting, and to reduce the related mortality are further discussed.

Quantitative computer tomography in Alzheimer's disease: a re-evaluation.

This investigation addresses the question of usefulness of computer-tomographic (CT) scanning in discriminating patients with Alzheimer's disease (AD) from healthy, aged controls. Quantitative measures of brain volume loss found to be significant by other investigators as well as additional unique variables are used to discriminate 58 longitudinally studied patients meeting NINCDS-ADRDA criteria for the clinical diagnosis of probable AD from 59 controls. The sensitivity and specificity of both single CT scan parameters and multivariate models comprised of such CT parameters are explored. Reasons for diagnostic misclassification are also illuminated.

The biosynthesis of the chromophore of phycocyanin. Pathway of reduction of biliverdin to phycocyanobilin.

The later stages in the pathway of biosynthesis of phycocyanobilin, the chromophore of phycocyanin, were studied by using radiolabelled intermediates. Three possible pathways from biliverdin IX-alpha to phycocyanobilin were considered. 14C-labelled samples of key intermediates in two of the pathways, 3-vinyl-18-ethyl biliverdin IX-alpha and 3-ethyl-18-vinyl biliverdin IX-alpha, were synthesized chemically and were administered to cultures of Cyanidium caldarium that were actively synthesizing photosynthetic pigments in the light. Neither of these two compounds was apparently incorporated into the phycobiliprotein chromophore, suggesting that two of the three pathways were not operative. By elimination, the results imply that the third possible pathway, which involves phytochromobilin, the chromophore of phytochrome, represents the route for biosynthesis of phycocyanobilin. Unfortunately, since 14C-labelled phytochromobilin is not available, no direct proof of this pathway could be obtained. However, if correct, the present interpretation represents a unified pathway for biosynthesis of all plant bilins, via the intermediacy of phytochromobilin.