Asbestosis mortality in the USA: facts and predictions.

BACKGROUND: Mortality trends in the USA show that deaths from asbestosis are increasing, while deaths related to other pneumoconiosis are declining. OBJECTIVES: To analyse the association between asbestos consumption and asbestosis mortality trends. METHODS: In an epidemiological time series study, we used a modern computer-intensive local regression method to evaluate the relationship between asbestos consumption per capita (1900-2006) as the predictor variable and number of deaths from asbestosis (1968-2004). The predictor variable was progressively lagged by annual increments from 30 to 60 years and the goodness of fit assessed for each lag period. The model having the smallest Akaike's Information Criteria was used to derive extrapolated estimates of future mortality based on more recent asbestos consumption data. RESULTS: Asbestos consumption per capita reached a peak in 1951 and gradually declined until 1973, when it started to drop rapidly. In 2006, it was 0.0075 kg/person/year. There were 25 564 deaths from asbestosis over the period 1968-2004. The best-fitting model (adjusted coefficient of determination (R(2)) = 99.7%) for 1968-2004 deaths from asbestosis used asbestos consumption per capita 48 years prior (1920-1956) and the log value of asbestos consumption per capita 43 years prior (1925-1961). This model predicts a total of 29 667 deaths (95% CI 19 629 to 39 705) to occur during 2005-2027 (an average of 1290 deaths per year). CONCLUSIONS: This study demonstrates a clear association between asbestos consumption and deaths from asbestosis and indicates that asbestosis deaths are not expected to decrease sharply in the next 10-15 years.

Rapidly progressive coal workers' pneumoconiosis in the United States: geographic clustering and other factors.

BACKGROUND: Despite significant progress made in reducing dust exposures in underground coal miners in the United States, severe cases of coal workers' pneumoconiosis (CWP), including progressive massive fibrosis (PMF), continue to occur among coal miners. AIMS: To identify US miners with rapidly progressive CWP and to describe their geographic distribution and associated risk factors. METHODS: Radiographic evidence of disease progression was evaluated for underground coal miners examined through US federal chest radiograph surveillance programmes from 1996 to 2002. A case of rapidly progressive CWP was defined as the development of PMF and/or an increase in small opacity profusion greater than one subcategory over five years. County based prevalences were derived for both CWP and rapidly progressive cases. RESULTS: A total of 886 cases of CWP were identified among 29 521 miners examined from 1996 to 2002. Among the subset of 783 miners with CWP for whom progression could be evaluated, 277 (35.4%) were cases of rapidly progressive CWP, including 41 with PMF. Miners with rapidly progressive CWP were younger than miners without rapid progression, were more likely to have worked in smaller mines (<50 employees), and also reported longer mean tenure in jobs involving work at the face of the mine (in contrast to other underground mining jobs), but did not differ with respect to mean underground tenure. There was a clear tendency for the proportion of cases of rapidly progressive CWP to be higher in eastern Kentucky, and western Virginia. CONCLUSIONS: Cases of rapidly progressive CWP can be regarded as sentinel health events, indicating inadequate prevention measures in specific regions. Such events should prompt investigations to identify causal factors and initiate appropriate additional measures to prevent further disease.

Broncholithiasis and lithoptysis associated with silicosis.

A case of broncholithiasis associated with massive silicosis is reported, showing a rare aspect of parenchymal lesions generating broncholiths as well as the presence of recurrent lithoptysis, with subsequent regression of radiological lesions. Aetiological, clinical, physiopathological, and radiological aspects of the disease are discussed, demonstrating the importance of the use of computed tomography in diagnosis. The mineralogical analysis of expectorated fragments is also shown.

Enhanced inhibition of HIV-1 replication in macrophages by antisense oligonucleotides, ribozymes and acyclic nucleoside phosphonate analogs delivered in pH-sensitive liposomes.

An antisense oligodeoxynucleotide against the human immunodeficiency virus type 1 (HIV-1) Rev response element, a ribozyme complementary to the HIV-1 5'-LTR, and the reverse transcriptase inhibitors 9-(2-phosphonylmethoxyethyl) adenine (PMEA) and (R)-9-(2-phosphonylmethoxypropyl)-adenine (PMPA) inhibited virus replication in monocyte-derived macrophages more effectively when delivered in pH-sensitive liposomes compared to the free drugs.

Single-copy gene detection using branched DNA (bDNA) in situ hybridization.

We have developed a branched DNA in situ hybridization (bDNA ISH) method for detection of human papillomavirus (HPV) DNA in whole cells. Using human cervical cancer cell lines with known copies of HPV DNA, we show that the bDNA ISH method is highly sensitive, detecting as few as one or two copies of HPV DNA per cell. By modifying sample pretreatment, viral mRNA or DNA sequences can be detected using the same set of oligonucleotide probes. In experiments performed on mixed populations of cells, the bDNA ISH method is highly specific and can distinguish cells with HPV-16 from cells with HPV-18 DNA. Furthermore, we demonstrate that the bDNA ISH method provides precise localization, yielding positive signals retained within the subcellular compartments in which the target nucleic acid sequences are localized. As an effective and convenient means for nucleic acid detection, the bDNA ISH method is applicable to the detection of cancers and infectious agents. (J Histochem Cytochem 49:603-611, 2001)

Detecting child sexual abuse in general practice: a retrospective case-control study from Wales.

OBJECTIVE: To investigate if routine medical contacts provide indicators that would assist general practitioners in detecting male child abuse. DESIGN: A case-control study of the general practice records of male victims of a major episode of school-based child abuse and matched controls. SETTING: General practices serving cases and controls from two South Wales schools. SUBJECTS: 107 abused boys and 107 aged-matched controls. RESULTS: No boys had disclosed sexual abuse to general practitioners. Somatic and behavioural symptoms were reported by small numbers in both groups (18 cases/25 controls). Odds ratios showed no significant positive association between abuse and numbers of boys presenting with symptoms (odds ratio 0.66; 95% confidence interval 0.32-1.37), and no difference could be found in the nature of the symptoms complained of by boys from the two groups. However, abused boys were more likely than controls to present with symptoms that persisted for more than a year (eight cases compared with one control). The two-tailed p-value calculated using the Fisher exact test was 0.035, suggesting a statistically significant association between abuse and persistent symptoms. CONCLUSIONS: Sexually-abused boys are unlikely to visit general practitioners with open requests for help, and do not appear to present with behavioural or somatic symptoms different from those presented by non-abused boys. However, where boys complain of persistent, inexplicable, somatic or behaviour problems over a period of time, the possibility of abuse should be considered.

A case-control study of somatic and behavioural symptoms in sexually abused boys.

OBJECTIVES: To ascertain how often sexually abused boys present with somatic and behavioural symptoms. DESIGN: A case-control study. SETTING: A primary school in South Wales where a male teacher had been convicted of sexually abusing boys since 1981. The police investigation started in 1993 and he was convicted in 1994. A similar large primary school where abuse had not taken place. SUBJECTS: All 107 boys who had been identified by a police inquiry to have been subject to sexual abuse by a single teacher in a single primary school; 107 age matched controls. MAIN OUTCOME MEASURES: Symptoms that might have had a somatic or behavioural basis reported in general practice, hospital, and school health records. RESULTS: Somatic and behavioural complaints were uncommon in both cases and controls. There was no significant difference between the numbers of cases and controls who had presented with somatic and behavioural complaints (18 cases v 25 controls). However the difference between the cases and controls with symptoms lasting over a year was significant (p < 0.05). There were no differences in the nature of reported symptoms between the control and abused groups. CONCLUSIONS: This suggests that extensive investigation for possible abuse is not indicated where are short lived somatic symptoms but it should be considered as a possible diagnosis where symptoms are long standing.

Regulation of polyunsaturated fat induced postprandial hypercholesterolemia by a novel gene Phc-2.

Inbred mouse strains vary in susceptibility or resistance to dietary induced atherosclerosis. To investigate the effect of polyunsaturated fat feeding on postprandial serum cholesterol levels, in C57BL/67 (B6) and BALB/cJ inbred mice, we fed by stomach gavage previously fasted mice, a mixture containing 30% sunflower oil, 5% cholesterol, 2% sodium cholate and 0.5% choline chloride. The most significant difference in serum cholesterol levels between B6 and BALB/cJ mouse strains was observed at 2 h postfeeding. Susceptible B6 strain mice had a 41% postprandial increment in serum cholesterol. The resistant BALB/cJ strain had an insignificant 16% rise in serum cholesterol, at 2 h. We next examined eight other inbred mouse strains, to identify the gene(s) that regulate the observed 2 h postprandial hypercholesterolemia response, in the susceptible B6 mouse strain. Only the C57BR/cdJ and C57L/J strains developed postprandial hypercholesterolemia, at 2 h. The C57BR/cdJ strain had a 20% increase and the C57L/J strain a 62% increase in postprandial serum cholesterol levels. From this result, we found that the postprandial hypercholesterolemic response to an acute polyunsaturated fat-cholesterol feed, cosegregated with the a allele at the Gpd-1 and Ahd-1 loci, on mouse chromosome 4. In this study, non-responsiveness cosegregated with the b allele at the Gpd-1 and Ahd-1 loci. Thus polyunsaturated fat-cholesterol induced postprandial hypercholesterolemia appeared to be genetically determined by a gene located between the Gpd-1 and Ahd-1 loci, in mice. The putative gene regulating polyunsaturated fat-cholesterol induced post-absorptive hypercholesterolemia was designated Phc-2.(ABSTRACT TRUNCATED AT 250 WORDS)

CD spectral comparisons of the acid-induced structures of poly[d(A)], poly[r(A)], poly[d(C)], and poly[r(C)].

CD spectra were used to compare the acid-induced structural transitions of poly[d(A)] and poly[d(C)] with those of poly[r(A)] and poly[r(C)], respectively. The types of base pairing were probably the same in the acid self-complexes of both A-containing polymers and in the acid self-complexes of both C-containing polymers. Similar base pairings were indicated by similarities in the difference CD spectra showing the changes during the first major acid-induced transitions of the polymers. Information from the CD spectra and pKa values of the transitions suggested that the transitions for the RNA polymers involved similar structural changes. The two DNA polymers were markedly different. Single-stranded poly[d(A)] was in the most stacked structure and had the lowest pKa for forming an acid self-complex. Single-stranded poly[d(C)] was in the least stacked structure and had the highest pKa for forming a protonated duplex.

Isolation and molecular characterization of the human CD34 gene.

The human CD34 surface antigen is selectively expressed on hematopoietic stem/progenitor cells, suggesting that it plays an essential role in early hematopoiesis. Using a 1.5-kb partial human CD34 cDNA sequence, RNA-polymerase chain reaction (PCR), and rapid amplification of cDNA ends (RACE) methods, we cloned and sequenced the full-length (2.65 kb) cDNA. The cDNA encodes a type I transmembrane protein with no obvious homology to other known proteins. The entire CD34 gene of 28 kb was cloned, and the coding sequences mapped to eight exons. Mapping of the 5' termini of mRNAs by 5'-RACE and RNAase protection analyses has indicated that the human CD34 gene uses multiple transcription initiation sites. Analysis of the upstream regulatory sequences revealed the absence of TATA and CAAT box sequences, and the presence of myb, myc, and ets-like DNA binding motifs. We have identified significant homology between human and mouse CD34 genes in 5' and 3' untranslated regions, amino acid coding sequences, and 5' flanking sequences. This investigation of the CD34 gene should facilitate study of the function and regulation of this stem cell antigen.

Thermodynamic parameters for loop formation in RNA and DNA hairpin tetraloops.

We determined the melting temperatures (Tm) and thermodynamic parameters of 15 RNA and 19 DNA hairpins at 1 M NaCl, 0.01 M sodium phosphate, 0.1 mM EDTA, at pH 7. All these hairpins have loops of four bases, the most common loop size in 16S and 23S ribosomal RNAs. The RNA hairpins varied in loop sequence, loop-closing base pair (A.U, C.G, or G.C), base sequence of the stem, and stem size (four or five base pairs). The DNA hairpins varied in loop sequence, loop-closing base pair (C.G, or G.C), and base sequence of the four base-pair stem. Thermodynamic properties of a hairpin may be represented by nearest-neighbor interactions of the stem plus contributions from the loop. Thus, we obtained thermodynamic parameters for the formation of RNA and DNA tetraloops. For the tetraloops we studied, a free energy of loop formation (at 37 degrees C) of about +3 kcal/mol is most common for either RNA or DNA. There are extra stable loops with delta G degrees 37 near +1 kcal/mol, but the sequences are not necessarily the same for RNA and DNA. The closing base pair is also important; changing from C.G to G.C lowered the stability of several tetraloops in both RNA and DNA. These values will be useful in predicting RNA and DNA secondary structures.

A thermodynamic study of unusually stable RNA and DNA hairpins.

About 70% of the RNA tetra-loop sequences identified in ribosomal RNAs from different organisms fall into either (UNCG) or (GNRA) families (where N = A, C, G, or U; and R = A or G). RNA hairpins with these loop sequences form unusually stable tetra-loop structures. We have studied the RNA hairpin GGAC(UUCG)GUCC and several sequence variants to determine the effect of changing the loop sequence and the loop-closing base pair on the thermodynamic stability of (UNCG) tetra-loops. The hairpin GGAG(CUUG)CUCC with the conserved loop G(CUUG)C was also unusually stable. We have determined melting temperatures (Tm), and obtained thermodynamic parameters for DNA hairpins with sequences analogous to stable RNA hairpins with (UNCG), C(GNRA)G, C(GAUA)G, and G(CUUG)C loops. DNA hairpins with (TTCG), (dUdUCG), and related sequences in the loop, unlike their RNA counterparts, did not form unusually stable hairpins. However, DNA hairpins with the consensus loop sequence C(GNRA)G were very stable compared to hairpins with C(TTTT)G or C(AAAA)G loops. The C(GATA)G and G(CTTG)C loops were also extra stable. The relative stabilities of the unusually stable DNA hairpins are similar to those observed for their RNA analogs.

CD evidence that the alternating purine-pyrimidine sequence poly[d(A-C).d(G-T)], but not poly[d(A-T).d(A-T)], undergoes an acid-induced transition to a modified secondary conformation.

Circular dichroism and UV absorption data showed that poly[d(A-C).d(G-T)] (at 0.01M Na+ (phosphate), 20 degrees C) underwent two reversible conformational transitions upon lowering of the pH. The first transition was complete at about pH 3.9 and resulted in an acid form of the polymer that was most likely a modified, protonated duplex. The second transition occurred between pH 3.9 and 3.4 and consisted of the denaturation of this protonated duplex to the single strands. UV absorption and CD data also showed that the separated poly[d(A-C)] strand formed two acid-induced self-complexes with pKa values of 6.1 and 4.7 (at 0.01M Na+). However, neither one of these poly[d(A-C)] self-complexes was part of the acid-induced rearrangements of the duplex poly[d(A-C).d(G-T)]. Acid titration of the separated poly[d(G-T)] strand, under similar conditions, did not show the formation of any protonated poly[d(G-T)] self-complexes. In contrast to poly[d(A-C).d(G-T)], poly[d(A-T).d(A-T)] underwent only one acid-induced transition, which consisted of the denaturation of the duplex to the single strands, as the pH was lowered from 7 to 3.

CD of six different conformational rearrangements of poly[d(A-G).d(C-T)] induced by low pH.

On the basis of circular dichroism (CD) data, we have now identified six different conformational states (other than the duplex) of poly[d(A-G).d(C-T)] at pH values between 8 and 2.5 (at 0.01M Na+; 20 degrees C). Three of these structural rearrangements were observed as the pH was lowered from 8 to 2.5, and three additional rearrangements were observed as the pH was raised from 2.5 back to neutral pH. The major components of the six conformational states were defined using appropriate combinations of the CD spectra of the duplex, triplex, and denatured forms of this polymer, as well as the CD spectra of the individual single strands and their respective acid-induced self-complexes. Our results show that the acid-induced rearrangements of poly[d(A-G).d(C-T)] include not only the poly[d(C+-T).d(A-G).d(C-T)] triplex, but also include the poly[d(C-T)] loop-out structure and a self-complexed form of the poly[d(A-G)] strand that is pH-dependent.

Circular dichroism of two conformations of poly[d(G-C)] induced by low pH.

Circular dichroism (CD) and UV absorption data showed that poly[d(G-C)] (at 0.09M NaCl, 0.01M Na+ (phosphate), 20 degrees C) underwent two conformational transitions upon lowering of the pH by the addition of HCl. The first transition was complete at about pH 3.0. The second transition was complete upon lowering the pH to 2.6 or upon raising the temperature, at pH 3.0, to about 40 degrees C. There was no indication of denaturation during either transition. The CD spectrum for the second acid conformation had large CD bands including a positive one at 288nm, a characteristic associated with C X C+ base-pairs. Electron microscopy showed no significant formation of condensed supramolecular aggregates corresponding to the first or second acid forms of poly[d(G-C)]. On the basis of spectral data, electron microscopy, and proton-uptake measurements, we propose models for the secondary structures that poly[d(G-C)] adopts in its two acid conformations.