Asian mothers' risk factors for perinatal death--the same or different? A 10 year review of Leicestershire perinatal deaths.

A case-control study of all perinatal deaths in Leicestershire was established in 1976. By 1985 some 1342 singleton perinatal deaths had occurred. Perinatal mortality among patients of Asian origin was consistently higher than that among European women.

The analysis of event history data: a review of progress and outstanding problems.

This paper reviews methods for the analysis of event history data by both parametric (exponential/Poisson) and semi-parametric methods. It identifies a need for software for handling the data structures of complex event histories and shows that, with such software, most Markov and semi-Markov models of event history data may be dealt with in the framework of generalized linear models. Finally, the emergent 'frailty' models for associated risks are discussed together with their implications for statistical software.

Purification and characterization of human mitochondrial transcription factor 1.

We purified to near homogeneity a transcription factor from human KB cell mitochondria. This factor, designated mitochondrial transcription factor 1 (mtTF1), is required for the in vitro recognition of both major promoters of human mitochondrial DNA by the homologous mitochondrial RNA polymerase. Furthermore, it has been shown to bind upstream regulatory elements of the two major promoters.

Inaccuracies in manometric central venous pressure measurement.

Manometric measurement of CVP was compared to electronic measurement in ten patients. Manometric measurement was found to give readings of up to 5 cmH2O greater than electronic, with a mean difference of 2.4 cmH2O.

Probes for rare mRNAs reveal distributed cell subsets in canary brain.

cDNA clones of 7 low-abundance canary brain RNAs hybridize in situ to different subsets of brain cells. Although these cell sets are distinct, they are dispersed in a variety of brain regions with overlapping anatomical distributions. These cDNA clones were initially selected by their relative hybridization to forebrain and rest-of-brain RNAs and represent a sampling of a much larger population of differentially expressed RNAs present at individual concentrations of 10(-7) to 10(-4) as a fraction of polyadenylated RNA mass.

Nuclear gene products that function in mitochondrial DNA replication.

Mammalian mitochondrial DNAs replicate unidirectionally from two distinct strand-specific origins. A round of replication begins at the heavy-strand origin (the D-loop) where transcripts from an upstream promoter serve as the primers for DNA synthesis. The transition from RNA to DNA synthesis occurs within short, conserved nucleotide sequence blocks and is mediated by specific endonucleolytic cleavage of the primary transcript.

Yeast mitochondrial RNA polymerase is homologous to those encoded by bacteriophages T3 and T7.

Analysis of the nucleotide sequence of the genetic locus for yeast mitochondrial RNA polymerase (RPO41) reveals a continuous open reading frame with the coding potential for a polypeptide of 1351 amino acids, a size consistent with the electrophoretic mobility of this enzymatic activity. The transcription product from this gene spans the singular reading frame. In vivo transcript abundance reflects codon usage and growth under stringent conditions for mitochondrial biogenesis and function results in a several fold higher level of gene expression than growth under glucose repression.

Empirical Bayes estimates of age-standardized relative risks for use in disease mapping.

There have been many attempts in recent years to map incidence and mortality from diseases such as cancer. Such maps usually display either relative rates in each district, as measured by a standardized mortality ratio (SMR) or some similar index, or the statistical significance level for a test of the difference between the rates in that district and elsewhere. Neither of these approaches is fully satisfactory and we propose a new approach using empirical Bayes estimation.

Affinity chromatographic purification of nucleosomes containing transcriptionally active DNA sequences.

The unfolding of nucleosome cores in transcriptionally active chromatin uncovers the sulfhydryl groups of histone H3, making them accessible to SH-reagents. This has suggested that nucleosomes from active genes could be retained selectively on organomercurial/agarose columns. When nucleosomes released from rat liver nuclei by limited digestion with micrococcal nuclease were passed through an Hg affinity column, a run-off fraction of compact, beaded nucleosomes was separated from a retained nucleosome fraction.

Promoter selection in human mitochondria involves binding of a transcription factor to orientation-independent upstream regulatory elements.

Selective transcription of human mitochondrial DNA requires a transcription factor (mtTF) in addition to an essentially nonselective RNA polymerase. Partially purified mtTF is able to sequester promoter-containing DNA in preinitiation complexes in the absence of mitochondrial RNA polymerase, suggesting a DNA-binding mechanism for factor activity. Functional domains, required for positive transcriptional regulation by mtTF, are identified within both major promoters of human mtDNA through transcription of mutant promoter templates in a reconstituted in vitro system.

Models for temporal variation in cancer rates. II: Age-period-cohort models.

Our first paper reviewed methods for modelling variation in cancer incidence and mortality rates in terms of either period effects or cohort effects in the general multiplicative risk model. There we drew attention to the difficulty of attributing regular trends to either period or cohort influences. In this paper we turn to the more realistic problem in which neither period nor cohort effects alone lead to an adequate description of the data.

Models for temporal variation in cancer rates. I: Age-period and age-cohort models.

A main concern of descriptive epidemiologists is the presentation and interpretation of temporal variations in cancer rates. In its simplest form, this problem is that of the analysis of a set of rates arranged in a two-way table by age group and calendar period. We review the modern approach to the analysis of such data which justifies traditional methods of age standardization in terms of the multiplicative risk model.

A mammalian mitochondrial RNA processing activity contains nucleus-encoded RNA.

Ribonuclease mitochondrial RNA processing, a site-specific endoribonuclease involved in primer RNA metabolism in mammalian mitochondria, requires an RNA component for its activity. On the basis of copurification and selective inactivation with complementary oligonucleotides, a 135-nucleotide RNA species, not encoded in the mitochondrial genome, is identified as the RNA moiety of the endoribonuclease. This finding implies transport of a nucleus-encoded RNA, essential for organelle DNA replication, to the mitochondrial matrix.

Features of a seminal proteinase inhibitor- zona pellucida-binding component on murine spermatozoa.

Murine cauda epididymal sperm contain sites on the plasma membrane over the apical portion of the acrosome that recognize proteinase inhibitors and the homologous zona pellucida. Ten times more of the component can be extracted from cauda and ductus sperm than from equal numbers of caput and corpus sperm. Likewise, few sperm from the upper epididymal regions are able to bind seminal inhibitor, while the majority of sperm from the cauda and ductus do bind.

A novel endoribonuclease cleaves at a priming site of mouse mitochondrial DNA replication.

Priming at the mouse mitochondrial origin of heavy-strand DNA replication is effected by transcripts from the light-strand promoter. The transition from RNA synthesis to DNA synthesis occurs at specific locations between 75 and 165 nucleotides downstream from the transcriptional initiation site. We have identified and partially purified an endonucleolytic activity that cleaves RNA accurately near one of these transition sites; this finding implies a role of specific RNA processing in DNA replication.

Diagnostic plots for departures from proportional hazards in cohort study data.

The assumption of proportional hazards is routinely made in the analysis of cohort studies, whether a simple SMR calculation or a full survival analysis is used. In this paper, we introduce simple plots for checking the validity of the assumption. The plots are of two kinds.

Cellular promoters incorporated into the adenovirus genome: cell specificity of albumin and immunoglobulin expression.

Recombinant adenoviruses were constructed in which the viral E1A gene was deleted and the E1B promoter was replaced by the rat albumin, mouse beta-major globin, or mouse immunoglobulin heavy-chain promoter. After infection of human or rat hepatoma cells, E1B-containing mRNAs could be detected only from the virus containing the albumin promoter. Conversely, only the immunoglobulin promoter was active in virus-infected myeloma cells.

Precise assignment of the heavy-strand promoter of mouse mitochondrial DNA: cognate start sites are not required for transcriptional initiation.

Transcription of the heavy strand of mouse mitochondrial DNA starts from two closely spaced, distinct sites located in the displacement loop region of the genome. We report here an analysis of regulatory sequences required for faithful transcription from these two sites. Data obtained from in vitro assays demonstrated that a 51-base-pair region, encompassing nucleotides -40 to +11 of the downstream start site, contains sufficient information for accurate transcription from both start sites.

Precise assignment of the light-strand promoter of mouse mitochondrial DNA: a functional promoter consists of multiple upstream domains.

Using deletion mutagenesis we localized the promoter for the light strand of mouse mitochondrial DNA to a 97-base-pair region, from -88 to +9 nucleotides of the transcriptional initiation site. Within this region the light-strand promoter could be dissected into at least three different functional domains. The specificity region, a maximum of 19 base pairs between -10 and +9 of the transcriptional initiation site, was essential and sufficient for accurate transcriptional initiation.

In vitro transcription of human mitochondrial DNA: accurate termination requires a region of DNA sequence that can function bidirectionally.

Mammalian mitochondrial genomes have a presumptive transcription termination site at the 16S rRNA-tRNALeu gene boundary. We have developed an in vitro system from human KB cells that terminates transcription at this gene boundary. By S1 nuclease protection, the 3' ends of terminated transcripts were mapped 3 and 4 base pairs upstream of the 16S rRNA-tRNALeu gene boundary, in agreement with in vivo data.

DNA primase of human mitochondria is associated with structural RNA that is essential for enzymatic activity.

DNA primase isolated from human mitochondria sediments in glycerol density gradients at 30S and 70S. These unusually high sedimentation coefficients are a result of association of the primase activity with RNA. Treatment of primase with nuclease not only affects its sedimentation behavior, but also inactivates the primase activity.

Tumour basement membrane laminin in adenocarcinoma of rectum: an immunohistochemical study of biological and clinical significance.

Well-defined basement membrane laminin was seen in 98/158 (62%) rectal adenocarcinomas stained by an immunoperoxidase method. Only 27 (28%) patients with laminin-positive tumours developed distant metastases, compared with 39 (65%) patients with laminin-negative carcinomas. The corrected 5-year survival rates for patients with laminin-positive and laminin-negative tumours were 65% and 23%, respectively.