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PubMed1978

Legalized abortion: effect on national trends of maternal and abortion-related mortality (1940 through 1976).

Both non-abortion-related maternal and abortion-related mortality declined prior to the Supreme Court decisions of 1973. In order to determine the effect of legalized abortion on maternal mortality, we have analyzed the secular trends in national abortion mortality ratios for 1940 through 1976, compared the trends to those maternal mortality ratios, and hypothesized reasons for differences between these trends. Between 1940 and 1950 and after 1965, deaths from abortion declined more rapidly than deaths from other causes associated with childbirth. However, between 1951 and 1965, maternal mortality related to pregnancy of childbirth declined more rapidly than abortion-related mortality. Five possible explanations exist for the more rapid decline in abortion deaths since 1965--selected underreporting, changes in coding practices, improved safety of illegal abortion, introduction of more effective contraception, and increased availability of legal abortion. We consider the last two explanations as the most likely reasons for the accelerated decline in abortion-related deaths.

Abortion, Legal↗
PubMed1986

Joint angle signaling by muscle spindle receptors.

Nerve impulses were recorded from sensory fibers supplying the tibialis anterior and soleus muscles of anesthetized cats as the ankle joint was moved from one end of the flexion-extension axis to the other and back again in steps of 6-7 degrees. The rate of movement from one position to the next was 40 deg/s and each position was held for 16-18 s. Plots were made of receptor discharge frequency as a function of ankle joint angle during joint movement (dynamic input-output (I-O) functions) as well as 2 and 15 s after movement terminated (2 and 15 s static I-O functions). Only receptors with a sustained (5s) static response within the physiological range were studied. A total of 229 tibialis anterior receptors met this criterion, of which 11 were identified as tendon organs. One hundred and five soleus receptors were studied, of which 6 were tendon organs. Thus tendon organ activity accounted for only a small part of the muscle afferent signal under passive conditions. The spindle receptors in soleus and tibialis anterior divided the ankle flexion-extension range about equally between them, those in soleus signaling over the flexion half of the range and those in tibialis anterior over the extension half. At angles where the receptors in a particular muscle did not signal joint angle, the tendon of the muscle was observed to be slack. Thus the total muscle afferent discharge in a relaxed animal is high at one end of the range, declines progressively as the ankle is displaced to an intermediate position, and then increases again as the joint moves toward the opposite end of the range. The spindle receptors within an individual muscle were recruited rather early as the muscle came under tension so that over most of a muscle's signaling range joint angle could have been coded by changes in receptor discharge frequency but not by which spindle receptors were active. To evaluate the information signaled by individual muscle spindle receptors, the following measurements were made from plots of impulse frequency vs joint angle: dynamic response, defined as the frequency difference between the dynamic and 2 s static I-O functions during muscle lengthening; adaptation, defined as the frequency difference between the 2 and 15 s static I-O functions during muscle lengthening.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗
PubMed1994

New material for low-cost intraocular lenses.

A UV-hardening lacquer material based on polyurethane, used in Philips compact disc lens systems, was tested as suitable material for low-cost intraocular lenses (IOLs). A slightly changed composition (code number I-0.5A) came out as the best and was subsequently tested, with reference to poly(methyl methacrylate) (PMMA), as a 'lobster-claw' lens in Hollander rabbit eyes for a period of 24 wk. No carcinogenic effects were found, while only minor vascularization of the cornea at the incision area occurred. The in vitro biocompatibility tests of the material were positive. Scanning electron microscopy images of the IOLs at 2, 6, 12 and 24 wk postoperative showed portions of an acellular membrane, multinuclear giant cells which hyalinize and stay as pigmented plaques, microphages and fibroblasts with fibrillar strands, long pseudopodia, and broad microplicea. The chosen UV lacquer showed a foreign body reaction and properties comparable with PMMA, and is suitable for manufacturing low-cost IOLs.

Animals↗
PubMed1983

Changes in the amino acid code.

The genetic code is characterized by a pattern arising from "wobble-pairing" between codons and anticodons, so that one nucleotide in the first anticodon position can pair with more than one nucleotide in the third position of a codon. Earlier codes may have existed in which there were fewer anticodons than at present, so that these earlier codes contained fewer amino acids. The universal code was formerly thought to be the only currently existing code used by terrestrial species. It is now known that differences exist from the universal code in mitochondrial coding systems, and also that mitochondrial systems differ from each other. These findings lend support to the proposal that archetypal codes preceded the present universal code. Such archetypal codes may have had some resemblances to mitochondrial codes.

Amino Acids↗
PubMed1995

The nucleoside deaminases for cytidine and adenosine: structure, transition state stabilization, mechanism, and evolution.

Enzymatic deamination of cytidine and adenosine bases in RNA have recently been shown to be mechanisms for changing the coding specificity of messenger and transfer RNAs. The structures of the enzymes that carry out deamination of the corresponding nucleosides have been analyzed by X-ray crystallography. They are quite different from one another in most respects, including quaternary and tertiary structure, but they have similar chemical groups in their active sites. Both enzymes envelope their nucleoside substrates completely, perhaps accounting for the fact that they are inactive on RNA substrates. Much has been learned about catalytic mechanisms from the structures of the enzymes and their complexes with transition state analog inhibitors. Catalysis proceeds with the activation by zinc of a bound water molecule, presumably to hydroxide ion, which attacks the appropriate carbon to generate a tetrahedral intermediate. The detailed stereochemistry of the two resulting chiral centers is diastereoisomeric. Details of the ensuing proton transfer steps necessary to generate and release the products are also apparently different in the two enzymes. Thus, the active site similarities are probably the result of convergent evolution.

Adenosine Deaminase↗
PubMed1989

Characterization of a loss-of-function mutation in the isopenicillin N synthetase gene of Acremonium chrysogenum.

The N-2 strain of Acremonium chrysogenum accumulates the beta-lactam precursor tripeptide delta-(L-alpha-amino-adipoyl)-L-cysteinyl-D-valine and has no discernible activity for three of the cephalosporin C (Ce) biosynthetic enzymes. This phenotype is consistent with a mutation either within pcbC [the isopenicillin N synthetase (IPNS)-encoding gene] or in a pathway-regulator gene. To distinguish these possibilities we have cloned and sequenced pcbC from strain N-2. There is a single C----T mutation at nt 854 within the coding sequence, changing aa 285 from proline to leucine. An IPNS-specific monoclonal antibody recognises a catalytically inactive IPNS protein in extracts of N-2 cells. These findings suggest that strain N-2 carries a simple IPNS mutation and that IPNS or its biosynthetic product isopenicillin N is involved in regulation of the later stages of the Ce biosynthetic pathway.

Acremonium↗
PubMed1991

Integration of woodchuck hepatitis virus (WHV) DNA at two chromosomal sites (Vk and gag-like) in a hepatocellular carcinoma.

Integration of woodchuck hepatitis virus (WHV) DNA into the liver DNA of a woodchuck infected by the virus was investigated. Clonal viral integration was not detected three months before the appearance of four hepatocellular carcinomas (HCC). Integration of the viral DNA was detected in all four HCCs, of which one was chosen to determine the structure of the viral integration completely in a single tumor. The integration occurred in two sites. One part contains the viral DNA from the middle of the gene encoding surface antigen to two-thirds of the way through the gene encoding X protein (X) with no structural changes. The coding frame of the truncated X gene continues into the chromosomal sequence to make a possible fusion protein. The integration seems to have occurred by recombination within two direct repeats of the viral genome in one junction and by homologous recombination between viral DNA and chromosomal DNA in the other junction. The viral DNA is integrated into a spacer of the immunoglobulin L-chain Vk (IgVk) region without any chromosomal rearrangement accompanying the integration. The viral DNA at the second site has a complex structural rearrangement: part of the preS gene is duplicated and attached to the terminus of the gene encoding core antigen in a head-to-tail fashion, followed by three small fragments derived from other parts of the viral DNA. The integrated preS gene has its own 5' regulatory element and a coding frame consisting of the truncated preS gene, the other parts of viral DNA and the chromosomal sequence.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Transposon-induced rearrangements in the duplicated locus ph of Drosophila melanogaster can create new chimeric genes functionally identical to the wild type.

Variation in the number of gene copies can play a major role in changing the coding capacities of eukaryotic genomes. Different mechanisms, such as unequal recombination or transposon-induced chromosome rearrangements, are believed to be responsible for these events. We have used the direct tandem duplication at the complex locus polyhomeotic (ph) of Drosophila melanogaster as a model system to study functional redundancy associated with chromosomal rearrangements, such as duplications or deletions. The locus covers 28.6 kb and comprises two independent units, ph proximal and ph distal, which are not only similar on the molecular level, but appear to be functionally redundant [Dura et al., Cell 51 (1987) 829-839; Deatrick et al., Gene 105 (1991) 185-195]. We present a molecular and phenotypic analysis of two hypomorphic ph mutants, ph2 and ph4, induced during hybrid dysgenesis. Each corresponds to an internal deletion in the ph locus that overlaps both transcription units. We show that the deletions are likely due to a P/M hybrid dysgenesis-induced rearrangement between proximal and distal ph, that created a single new chimerical ph gene. At least one of the breakpoints must be located in a 1247-bp region that is rich in single sequence, and 100% identical between proximal and distal ph. Junction points between units are in the protein-coding regions, but could not be exactly localized on the genomic sequence of either mutant, because of the precise molecular mechanism that caused the deletions. Protein products of the hybrid genes contain the same functional domains as either wild-type (wt) product.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Maturational aspects of periodicity coding in cat primary auditory cortex.

The click-following responses for single units in the primary auditory cortex of the cat were explored as a function of age. Recordings were obtained in kittens from 9-53 days of age and assembled in four age groups; 10-15 days, 16-21 days, 22-27 days and 30-60 days. Age group means were compared to results obtained in adult cats. The stimulus consisted of one second long click trains presented every three seconds with click rates ranging from 1-32 clicks per second. The response was characterized by entrainment, rate Modulation Transfer Function (rMTF), vector strength (VS) and temporal Modulation Transfer Function (tMTF). Maturational effects on periodicity coding comprised changes in overall responsiveness as well as click-rate dependent changes. The number of spikes elicited by single stimuli increased on average 3-fold between the second post-natal week and adulthood, probably as a result of more efficient synapses in the central auditory pathway and some improvement in thresholds. Adaptation became less pronounced with age; neurons started to respond to the later clicks in the 8/s and 16/s click trains from the third post natal week on. By the end of the first post-natal month the click following responses resembled the adult ones qualitatively, however, increased firing rates and spontaneous rates together with rebound responses continued to produce quantitative differences between the 30-60 days olds and the adults. Limiting rates for the tMTF (50% of the response at 1/s) increased from 6 Hz in the 10-15 day old to 12 Hz in adults. The decrease in the duration of the post-activation suppression coupled with the increased response with age to trains with higher click rates suggested that the maturation of inhibitory processes in the cortex play a major role in this rate dependence.

Acoustic Stimulation↗
PubMed2004

Defining unrecognized myocardial infarction: a call for standardized electrocardiographic diagnostic criteria.

BACKGROUND: Unrecognized myocardial infarctions (UMI) are detected by surveillance electrocardiograms (ECGs). In epidemiologic studies, different sets of ECG criteria have been used to define myocardial infarction, possibly contributing to significant differences in prevalence estimates and risk factor associations. We sought to summarize the rationale behind the various UMI-ECG definitions and to suggest an approach to develop uniform criteria. METHODS: A comprehensive review of relevant publications from 1966 to 2002 was conducted. RESULTS: Out of 14 major studies, the occurrence of UMI as a proportion of all infarctions varied from 4% to 44%, with markedly varying ECG criteria. No study directly addressed the rationale behind selection of ECG criteria. Computerized ECG analysis appears superior to visual reading due to better reliability, speed and cost while maintaining a similar predictive validity. Criteria requiring only major Q waves have the highest specificity for ECG-MI and for prediction validity for future coronary heart disease in middle-aged white men. The addition of minor Q waves and ST-T abnormalities improves predictive validity in middle-aged women and elderly men. Minor Q waves can have their diagnostic accuracy improved by several strategies, including use of ST-T wave changes, Washington Code, vector cardiogram, chronic obstructive pulmonary disease-ECG criteria, and serial ECG analysis. CONCLUSION: Currently the most cost-effective and valid method for detecting UMI in epidemiologic studies appears to be computerized ECG analysis using major Q waves in middle-aged white men. Issues needing further research include morphologic validation of ECG-UMI criteria and the influence of age, sex, and race on ECG-MI criteria.

Adult↗
PubMed2004

Anterior basement membrane corneal dystrophy and pseudo-unilateral lattice corneal dystrophy in a patient with recurrent corneal erosions.

PURPOSE: To report the utility of genetic testing in the diagnosis and management of patients with suspected corneal dystrophies. DESIGN: Case report. METHODS: A 58-year-old man with a history of recurrent corneal erosions was diagnosed with bilateral anterior basement membrane dystrophy and unilateral lattice corneal dystrophy. All 17 exons of the TGFBI gene were screened for mutations previously associated with lattice corneal dystrophy as well as novel coding region changes. RESULTS: No mutations were found in the 17 exons of the TGFBI gene. A nucleotide change in exon 6 (651C>G) did not result in a change in the encoded amino acid (Leu217Leu). CONCLUSIONS: In cases of suspected TGFBI corneal dystrophies, genetic testing is a useful tool to confirm the clinical diagnosis. In this case of suspected unilateral lattice corneal dystrophy, screening of the TGFBI gene ruled out the diagnosis, raising the possibility that the corneal changes were related to the coexistent anterior basement membrane dystrophy.

Basement Membrane↗
PubMed2005

Evolution: natural selection in the evolution of humans and chimps.

We now have more or less full sequences of both human and chimp genomes, allowing comparison that sheds light on their evolution. A few hundred genes show significant evidence for adaptive evolution in the two lineages, but the actual number might be much higher. Natural selection has eliminated about 75% of amino acid changes in coding sequence since the split of the human and chimpanzee genomes.

Adaptation, Biological↗
PubMed2004

Oncomodulatory signals by regulatory proteins encoded by human cytomegalovirus: a novel role for viral infection in tumor progression.

A high frequency of human cytomegalovirus (HCMV) genome and antigens in tumor samples of patients with different malignancies is now well documented, although the causative role for HCMV in the development of the neoplasias remains to be established. HCMV infection can modulate multiple cellular regulatory and signalling pathways in a manner similar to that of oncoproteins of small DNA tumor viruses such as human papilloma virus or adenoviruses. However, in contrast to these DNA tumor viruses, HCMV infection fails to transform susceptible normal human cells. There is now growing evidence that tumor cells with disrupted regulatory and signalling pathways enable HCMV to modulate their properties including stimulation of cell proliferation, survival, invasion, production of angiogenic factors, and immunogenic properties. In contrast to previously suggested "hit and run" transformation we suggest that persistence in tumor cells is essential for HCMV to fully express its oncomodulatory effects. These effects are observed particularly in persistent HCMV infection and are mediated mainly by activity of HCMV regulatory proteins. In persistently HCMV-infected tumor cell lines - a selection of novel, slowly growing virus variants with changes in coding sequences for virus regulatory proteins takes place. As a result, oncomodulatory effects of HCMV infection may lead to a shift to more malignant phenotype of tumor cells contributing to tumor progression.

Cell Cycle↗
PubMed2004

Postmortem molecular screening in unexplained sudden death.

OBJECTIVES: We examined the prevalence of defects in arrhythmia-related candidate genes among patients with unexplained sudden cardiac death (SCD). BACKGROUND: Patients with unexplained sudden death may constitute up to 5% of overall SCD cases. For such patients, systematic postmortem genetic analysis of archived tissue, using a candidate gene approach, may identify etiologies of SCD. METHODS: We performed analysis of KCNQ1 (KVLQT1), KCNH2 (HERG), SCN5A, KCNE1, and KCNE2 defects in a subgroup of 12 adult subjects with unexplained sudden death, derived from a 13-year, 270-patient autopsy series of SCD. Archived, paraffin-embedded myocardial tissue blocks obtained at the original postmortem examination were the source of deoxyribonucleic acid for genetic analysis. RESULTS: Two patients were found to have the same HERG defect, a missense mutation in exon 7 (nucleotide change G1681A, coding effect A561T). The mutation was heterozygous in Patient 1, but Patient 2 appeared to be homozygous for the defect. Patch-clamp recordings showed that the A561T mutant channel expressed in human embryonic kidney cells failed to generate HERG current. Western blot analysis implicated a trafficking defect in the protein, resulting in loss of post-translational processing from the immature to the mature form of HERG. No mutations were detected among the remaining four candidate genes. CONCLUSIONS: In this autopsy series, only 2 of 12 patients with unexplained sudden death were observed to have a defect in HERG among five candidate genes tested. It is likely that elucidation of SCD mechanisms in such patients will await the discovery of multiple, novel arrhythmia-causing gene defects.

Adult↗
PubMed2006

Extension of corticocortical afferents into the anterior bank of the intraparietal sulcus by tool-use training in adult monkeys.

When humans use a tool, it becomes an extension of the hand physically and perceptually. Common introspection might occur in monkeys trained in tool-use, which should depend on brain operations that constantly update and automatically integrate information about the current intrinsic (somatosensory) and the extrinsic (visual) status of the body parts and the tools. The parietal cortex plays an important role in using tools. Intraparietal neurones of naïve monkeys mostly respond unimodally to somatosensory stimuli; however, after training these neurones become bimodally active and respond to visual stimuli. The response properties of these neurones change to code the body images modified by assimilation of the tool to the hand holding it. In this study, we compared the projection patterns between visually related areas and the intraparietal cortex in trained and naïve monkeys using tracer techniques. Light microscopy analyses revealed the emergence of novel projections from the higher visual centres in the vicinity of the temporo-parietal junction and the ventrolateral prefrontal areas to the intraparietal area in monkeys trained in tool-use, but not in naïve monkeys. Functionally active synapses of intracortical afferents arising from higher visual centres to the intraparietal cortex of the trained monkeys were confirmed by electron microscopy. These results provide the first concrete evidence for the induction of novel neural connections in the adult monkey cerebral cortex, which accompanies a process of demanding behaviour in these animals.

Afferent Pathways↗
PubMed2005

A unique corneal dystrophy of Bowman's layer and stroma associated with the Gly623Asp mutation in the transforming growth factor beta-induced (TGFBI) gene.

PURPOSE: To report a unique corneal dystrophy characterized by deposits at Bowman's layer and stromal lattice lines associated with the Gly623Asp missense mutation in the transforming growth factor beta-induced (TGFBI) gene. DESIGN: Experimental study. PARTICIPANTS AND CONTROLS: The proband, 3 affected siblings, 4 unaffected relatives, and 100 control individuals. METHODS: Slit-lamp examination, photographic documentation, and isolation of genomic DNA from buccal mucosal swabs obtained from each family member examined. Exons 4 and 11 to 14 of the TGFBI gene were amplified and sequenced in these family members and in control individuals. MAIN OUTCOME MEASURES: Clinical characteristics of corneal opacification in affected patients and presence of coding region changes in the TGFBI gene. RESULTS: Significant phenotypic variability, including polymorphic Bowman's layer opacities and stromal lattice lines, was noted in the 4 affected siblings who were examined. Screening of TGFBI exon 14 in the proband, 3 affected siblings, and a 19-year-old unaffected relative revealed a missense change, Gly623Asp, that was absent in the other 3 unaffected relatives screened and in 200 control chromosomes. CONCLUSIONS: We report a novel corneal dystrophy phenotype secondary to the Gly623Asp mutation in the TGFBI gene that is associated with clinical features of both lattice corneal dystrophy and a Bowman's layer dystrophy. The presence of clinical features considered atypical for a TGFBI-associated dystrophy in this pedigree, as well as the wide range of phenotypic expressions of the Gly623Asp mutation in affected members, underscore the clinical utility of molecular genetic analysis in the diagnosis of suspected corneal dystrophies.

Adult↗
PubMed1985

Intraoperative myocardial protection: a comparison of blood and asanguineous cardioplegia.

Cardiac arrest was achieved in 84 patients using asanguineous cardioplegia and in 97 patients using cold blood potassium cardioplegia. The patient groups were similar in age, sex ratio, and preoperative risk factors. Other than the cardioplegic solution used, the conduct of each operation was identical. There were no differences in mean total pump time (118 minutes for the asanguineous cardioplegia group versus 117 minutes for the cold blood cardioplegia group) or cross-clamp time (73.5 versus 70 minutes, respectively). However, the blood cardioplegia group had a greater number of distal anastomoses per patient (3.9 versus 3.7; p less than 0.05). Myocardial protection was assessed clinically and by serial electrocardiograms. Cellular integrity was determined by release of the myocardial isoenzyme of serum creatine kinase (CK-MB). Cellular morphology was studied in 6 randomly selected patients in each group by electron microscopic examination of left ventricular myocardial samples obtained before and after bypass. Three patients given blood cardioplegia and 5 given asanguineous cardioplegia required intraaortic balloon counterpulsation at termination of bypass. There were no ultrastructural changes in either group. Electrocardiographic changes (Minnesota code) occurred in 12 of 84 patients receiving asanguineous cardioplegia versus 12 of 97 patients receiving cold blood potassium cardioplegia. To maintain a satisfactory cardiac index (greater than 2.0 L/min/m2), 38 of 84 patients given asanguineous cardioplegia versus 25 of 97 patients given blood cardioplegia required inotropic support up to 24 hours postoperatively (p less than 0.05). Infarct size determined from CK-MB release was significantly greater (p less than 0.05) in patients given asanguineous cardioplegia (36.27 gm-equivalents) than in those given blood cardioplegia (26.7 gm-equivalents).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Transfusion↗