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PubMed2001

Reversible polymerizations and aggregations.

The aggregation of monomers into polymers, whether by covalent or noncovalent interactions, is often reversible and frequently occurs with the entropy and enthalpy of the aggregation sharing the same sign. In such a case, the aggregation goes forward or reverses, depending on such variables as temperature and composition, rather like a phase transition. We explore the physical chemistry of three such systems: an organic monomer (alpha-methylstyrene), an inorganic monomer (sulfur), and a biopolymer (actin). We compare the available theories and experiments and list issues still open.

Actins↗

PubMed1982

Analysis of volume displacement and length changes of the diaphragm during breathing.

Diaphragmatic volume displacements cause equal displacements of abdominal contents. Since the rib cage forms a variable part of the abdominal container (the variable part being its area of apposition with the diaphragm) the rib cage and ventral abdominal wall share in abdominal displacements. The fraction of total rib cage volume displacement (delta Vrc) contributing to abdominal displacement is predicted from anatomic considerations and measurements. During quiet inspirations it is estimated that more than half of delta Vrc goes into abdominal expansion. This displacement plus the outward displacement of the anterolateral abdominal wall constitute the diaphragmatic displacement. In a typical inspiration in which delta Vrc accounts for 3/4 of the lung volume change, the diaphragm displaces nearly the same volume. Associated changes in diaphragm length are estimated with a model. Diaphragm shortening during an inspiration in which only the rib cage expands is estimated to be only 11% less than during a normal inspiration. We conclude that the direct rib cage contribution to lung volume change is much less, and that diaphragmatic contribution is much more than was previously thought.

Abdominal Muscles↗

PubMed2003

Adding further power to the Haseman and Elston method for detecting linkage in larger sibships: weighting sums and differences.

Haseman and Elston (H-E) proposed a robust test to detect linkage between a quantitative trait and a genetic marker. In their method the squared sib-pair trait difference is regressed on the estimated proportion of alleles at a locus shared identical by descent by sib pairs. This method has recently been improved by changing the dependent variable from the squared difference to the mean-corrected product of the sib-pair trait values, a significantly positive regression indicating linkage. Because situations arise in which the original test is more powerful, a further improvement of the H-E method occurs when the dependent variable is changed to a weighted average of the squared sib-pair trait difference and the squared sib-pair mean-corrected trait sum. Here we propose an optimal method of performing this weighting for larger sibships, allowing for the correlation between pairs within a sibship. The optimal weights are inversely proportional to the residual variances obtained from the two different regressions based on the squared sib-pair trait differences and the squared sib-pair mean-corrected trait sums, respectively, allowing for correlations among sib pairs. The proposed method is compared with the existing extension of the H-E approach for larger sibships. Control of the type I error probabilities for sibships of any size can be improved by using a generalized estimating equation approach and the robust sandwich estimate of the variance, or a Monte-Carlo permutation test.

Computer Simulation↗

PubMed1994

Molecular structure and regulation of vertebrate Na+/H+ exchangers.

Na+/H+ exchangers (NHE), also called antiporters, are vital transmembrane transporters involved in multiple cellular functions including the regulation of intracellular pH, the control of cell volume and transepithelial ion transport. These transporters are highly regulated by a remarkably wide variety of stimuli which can modulate their expression level and activity. Five isoforms of Na+/H+ exchangers have been cloned and characterized to date; they define a new gene family of vertebrate transporters. These isoforms share the same overall structure but exhibit differences with respect to amiloride-sensitivity, cellular localization, kinetic variables, regulation by various stimuli and plasma membrane targeting in polarized epithelial cells. Biochemical techniques and molecular genetics tools provide the means of analyzing these transporters at the molecular level. The purpose of this manuscript is to give an overview of the main features of the Na+/H+ exchangers with emphasis on recent advances in comprehension of the structure-function relationship and regulation mechanisms of the ubiquitous isoform: NHE-1.

Animals↗

PubMed1995

Ca2+ versus Zn2+ transport in the gills of freshwater rainbow trout and the cost of adaptation to waterborne Zn2+

Previous work suggested that Ca2+ and Zn2+ share a common uptake pathway in rainbow trout gills. We here report on relationships between the kinetic variables for unidirectional Ca2+ influx and unidirectional Zn2+ influx during a 1 month exposure of freshwater rainbow trout to Zn2+ (150 µg l-1=2.3 µmol l-1 as total zinc, Zn). Initial exposure to Zn2+ caused a large competitive inhibition of Ca2+ influx, as indicated by a threefold increase in apparent Km for Ca2+ (measured in the presence of Zn2+). There was also a smaller non-competitive inhibition (50 % decrease in Jmax) of the Ca2+ transport system, which was abolished after 12 weeks of exposure. The Km, measured in the absence of Zn2+, decreased dramatically (i.e. elevated affinity) on days 14 but increased thereafter; both true and apparent Km finally stabilized significantly above control levels. However, the Km values for Ca2+ (<200 µmol l-1) were low relative to the Ca2+ level in the water (1000 µmol l-1), and therefore the changes did not influence the actual Ca2+ influx of the fish, which tracked Jmax. In contrast, water [Zn2+] (2.3 µmol l-1 as total Zn) was close to the reported apparent Km (3.7 µmol l-1) for Zn2+ influx in the presence of 1000 µmol l-1 Ca2+. Unidirectional Zn2+ influx increased during the first week of exposure to waterborne Zn2+, followed by a persistent reduction to about 50 % of control levels, effects that may be largely explained by the observed changes in true Km for Ca2+. We speculate that the initial response of the fish to elevated [Zn2+] is to compensate for a reduced availability of Ca2+ by markedly increasing the affinity of a dual Ca2+/Zn2+ transporter. Once the Ca2+ influx is 'corrected' by restoration of functional transport sites (Jmax), the system is tuned to limit the influx of Zn2+ by a persistent reduction in the affinities for both ions. The changes in influx characteristics for Ca2+ and Zn2+ were correlated with internal physiological alterations indicative of adaptation to Zn2+ and increased metabolic cost. Depressed plasma [Ca] was corrected within 1 week, and there were no effects on whole-body [Ca] or [Zn]. A slight accumulation of Zn in the gills was associated with increased branchial metallothionein levels. Rates of protein synthesis and degradation in the gills were initially increased and whole-body growth was transiently impaired, effects which were reversed after 18 days of exposure. Sublethal challenge with Zn2+ (at 450 µg l-1=6.9 µmol l-1 as total Zn) always depressed plasma [Ca] in control fish, but by 1 month of exposure to Zn2+ at 150 µg l-1 (as total Zn), experimental fish were resistant to challenge. However, the fish did not acquire increased survival tolerance (LT50) to a lethal concentration of Zn2+ (4 mg l-1=61 µmol l-1 as total Zn).

Journal Article↗

PubMed2005

Perinatal mental health in lesbian mothers: a review of potential risk and protective factors.

Postpartum depression and other perinatal mental illnesses are common complications of childbirth. The majority of research on these conditions has been conducted in heterosexual women; however, increasing numbers of women are choosing to parent in the context of lesbian relationships. Although many of the fundamental aspects of the transition to parenthood are shared between lesbian and heterosexual mothers, lesbian mothers may differ from heterosexual parents on a number of variables that have been previously associated with perinatal mental health. Lesbian mothers may be more likely than their heterosexual peers to lack social support, particularly from their families of origin, and may be exposed to additional stress due to homophobic discrimination. However, the likelihood that lesbian pregnancies will be planned, together with the relatively equal division of child-care labour observed in lesbian couples, may offer protection from perinatal depression. The study of perinatal mental health in lesbian mothers is warranted, both to ensure that the mental health needs of this largely invisible population are being met, and to further illuminate the role of psychosocial stress in perinatal mental health in all women.

Adult↗

PubMed2000

Genetic and environmental influences on a measure of infant attachment security.

A twin study of infant attachment security at age 24 months was conducted on archival data for a sample of 99 MZ pairs and 108 DZ pairs from the Louisville Twin Study. MZ concordance for attachment was 62.6%, which was significantly greater than the DZ concordance of 44.4%. Concordances were transformed into polychoric correlations, and LISREL was used to conduct a quantitative genetic analysis of the data. Results indicated that 25% of the variability in attachment was attributable to genetic factors, and the remaining 75% was attributable to non-shared environmental effects. No evidence was found for a contribution from shared environmental influences to attachment security. Possible concerns about the validity of twin methodology are addressed and various interpretations of the results are presented.

Anxiety, Separation↗

PubMed2005

Disturbed population genetics: suspected introgressive hybridization between two Mnais damselfly species (Odonata).

Mnais costalis and M. pruinosa are damselflies (Odonata: Calopterygidae) with low dispersal abilities, both during their aquatic stream-living immature stage and their flying adult stage. A previous nuclear DNA (nDNA) sequencing and morphology study showed that these two species are very closely related, and cohabit widely in western Japan. The two species, however, segregate microhabitats along a stream: M. costalis lives in the lower reaches, and M. pruinosa in the upper reaches. In this study, our analyses were based on mitochondrial DNA (mtDNA), which usually mutates faster and is more variable among individuals than nDNA, and which is inherited maternally. We found that most COI haplotypes were shared between the two species, and that for most study sites interspecific riverine genetic structures were not clarified by mtDNA analysis. Incongruent population genetic structures based on nDNA and mtDNA suggested hybridization and introgression of mtDNA between the two species.

Animals↗

PubMedDate not supplied

The mechanism of peptidergic miosis. I. The structural basis of miotic potency among biologically active polypeptides.

The miotic potency of eleven naturally occurring polypeptides and poly-DL-alanine was tested on the isolated anterior segment of hooded rat and golden hamster eyes in order to gain information on the chemical nature of the peptides or classes of peptides which may be regarded as possible mediators of the miotic response of the mammalian eye to chemical irritants or mechanical or surgical trauma. Substance P, P-octapeptide, physalaemin and eledoisin, and eledoisin related peptide were found to be potent miotics on these preparations, yielding ED50 values in the range of 8 to 95 nM and complete pupillary constriction in the range of 100 to 1000 nM. This is comparable to the miotic potency of carbachol or serotonin. All of these peptides share a C-terminal sequence Phe-X-Gly-Leu-Met-NH2 (where "X" is a variable amino acid) which is characteristic of all tachykinins. Six other biologically active peptides or the synthetic poly-DL-alanine had no measureable miotic effect on these preparations up to a final concentration of 1000 to 10,000 nM. The miotic effect of SP on the rat iris was effectively, but not completely antagonized by the presence of 10(-7)M atropine sulfate in the incubation medium. Preliminary results indicate that the miotic effect of physalaemin, eledoisin and eledoisin related peptide on the anterior segment of rat eyes is similarly antagonized by atropine.

Animals↗

PubMed2000

Relationship of activity in the subthalamic nucleus-globus pallidus network to cortical electroencephalogram.

One of the functions of the excitatory subthalamic nucleus (STN) is to relay cortical activity to other basal ganglia structures. The response of the STN to cortical input is shaped by inhibition from the reciprocally connected globus pallidus (GP). To examine the activity in the STN-GP network in relation to cortical activity, we recorded single and multiple unit activity in STN and/or GP together with cortical electroencephalogram in anesthetized rats during various states of cortical activation. During cortical slow-wave activity (SWA), STN and GP neurons fired bursts of action potentials at frequencies that were similar to those of coincident slow ( approximately 1 Hz) and spindle (7-14 Hz) cortical oscillations. Spontaneous or sensory-driven global activation was associated with a reduction of SWA and a shift in STN-GP activity from burst- to tonic- or irregular-firing. Rhythmic activity in STN and GP neurons was lost when the cortex was inactivated by spreading depression and did not resume until SWA had recovered. Although rhythmic STN-GP activity was correlated with SWA, the phase relationships of activities of neurons within the STN and GP and between the nuclei were variable. Even when neurons displayed synchronous bursting activity, correlations on the millisecond time scale, which might indicate shared synaptic input, were not observed. These data indicate that (1) STN and GP activity is intimately related to cortical activity and hence the sleep-wake cycle; (2) rhythmic oscillatory activity in the STN-GP network in disease states may be driven by the cortex; and (3) activity of the STN-GP network is regulated in space in a complex manner.

Action Potentials↗

PubMed2001

Genetic influences on language impairment and literacy problems in children: same or different?

Data from two twin studies are examined to assess genetic and environmental influences on literacy, and the etiological relationship between language and literacy. Study 1 used children from 86 families previously recruited for a study of the genetics of specific language impairment (see Bishop, North, & Donlan, 1995), who completed tests of single-word reading and spelling. Literacy problems in this sample were common, were strongly heritable, and showed a close genetic relationship with poor nonword repetition. Study 2 included two subsets of children: 37 twin pairs who had taken part in study 1, 3 to 4 years earlier, and 100 twin pairs recruited from the general population by Bishop et al. (1999). All children were given a standardised test of nonword reading. There was no genetic influence on nonword reading ability, either across the normal range, or at the lower extreme, though there were significant associations with some social variables. However, bivariate DeFries Fulker analysis suggested that in this study, as in study 1, there was shared genetic variance between poor nonword repetition and literacy deficits. It is concluded that poor nonword repetition, which is known to be highly heritable, puts the child at risk for literacy problems. However, in a general population sample, such as that included in study 2, poor nonword repetition is a relatively rare correlate of literacy problems, which are more likely to have an environmental origin. Thus the different pattern of results in the two studies can be explained if one assumes that genetic influences are substantial only when literacy problems are severe and/or accompanied by oral language difficulties.

Child↗

PubMedDate not supplied

Expression of c-erbB-2 gene in human head and neck carcinoma.

The c-erbB-2 oncoprotein is a transmembrane protein the presence of which has been associated with poor prognosis in several human neoplasms. However, there has been no comprehensive assessment of its value as a potential prognostic marker in head and neck squamous cell carcinoma. Archival specimens from 93 patients, treated surgically for squamous cell carcinoma of the head and neck between 1981 and 1989, were analyzed by immunohistochemistry using an anti-c-erbB-2 monoclonal antibody; of these, 43 (46%) were positive for c-erbB-2 staining. The majority of stained specimens (41%) displayed staining predominantly at the cell surface, while mixed membrane and cytoplasmic staining was less common (9%). Only 4% shared exclusively cytoplasmic staining. Since the specimens were archival, the cytoplasmic staining is probably a consequence of variable handling and/or fixation at the time of tissue removal. Therefore, only cases exhibiting distinct cell surface membrane staining in more than 10% of tumor cells were regarded as positive. There is a definite association between immunohistochemical detection of c-erbB-2 and head and neck squamous cell carcinoma, since almost half of the tumor specimens manifested detectable c-erbB-2 protein. However, this association could not be extended to a predicted disease progression or outcome, since there was no significant correlation between c-erbB-2 staining and tumor size, stage of disease, histologic differentiation, lymph node status or patient survival.

Antibodies, Monoclonal↗

PubMedDate not supplied

[Genetic basis in chronic interstitial familial pneumopathy. Familial study of SFTPC].

Mutations in the gene encoding surfactant protein C (SP-C) SFTPC have been found to be associated with chronic interstitial lung disease. A 5-year-old girl oxygen dependent from birth and affected by interstitial lung disease (ILD) is heterozygous for a T to C change in exon 3 resulting in the substitution of threonine for isoleucine at codon 73 (173T), already described in association with ILD. We studied 25 members of her family where the 173T mutation in the SP-C gene is associated to chronic pulmonary diseases. Five members in the mother's family showed respiratory diseases with great diversity in clinical features: her mother was affected by restrictive pneumopathy and emphysema, her grand-mother by asthma and recurrent pneumonia, 2 uncles underwent lung transplantation in the adult age, an aunt was clinically diagnosed having pulmonary fibrosis. All the family members affected by pulmonary diseases and one with no clinical symptoms showed the presence of the mutation 173T. Among the other family members the mutation was found in six subjects for whom no clinical data were available, yet. Our results confirm that heterozygosity for the mutation 173T may cause chronic inflammation of the lung or progressive pulmonary fibrosis. In addition, the possibility to study a large pedigree allowed us to perform a genotype-phenotype correlation indicating a marked phenotypic variability. The diversity in symptoms, age at onset, clinical course, duration of lung disease in the relatives sharing this mutation indicates an incomplete penetrance of the mutation. This might be due to the influence of other genetic factors thus indicating that the phenotype may be complicated by additional components.

Child, Preschool↗

PubMed1989

[Phenotypic analysis of human T-cell lymphoma with reference to cell differentiation and morphological classification].

The recognition of the dichotomy of the immune system was a first step in differentiating between a humoral and cellular immune response. This distinction was to be of fundamental importance in the subsequent demonstration of distinct compartments in the lymphatic cell system. Animal studies and investigations on humans with congenital immune defects soon made it possible to differentiate between functionally different cell compartments in lymphatic tissue even on morphological grounds. This formed the basis for the subdivision of lymphatic tissue into B- and T-cell areas. A multiplicity of morphologically highly varied lymphatic neoplasias confronted this clear division. In principle, there are two possible explanations for the morphological and immunological heterogeneity of neoplasias: 1. The variety of lymphatic neoplasias is an expression of a dedifferentiation of cells in which neither the morphological picture nor the immunological properties of the stem cells are expressed. 2. Lymphatic neoplasias represent stages of "arrested" differentiation in the normal cell development. The present study attempts to demonstrate the distribution and development of normal T lymphocytes by analysis of their morphology and antigen constellation. The knowledge thus gained should then make it possible to define the neoplasias of the T-cell system. Thirty-six monoclonal antibodies were employed in addition to standard enzyme-histochemical methods for demonstration of cell antigens; some of the monoclonal antibodies were developed especially for this purpose. The study included normal tissue and samples from 148 lymphomas and leukemias of the T-cell system. Subdivision of the various entities was based on morphology, which enabled us to make a direct distinction between the morphologically defined entity and its corresponding phenotype. These phenotypic analyses of malignant T-cell lymphomas were conducted in pursuit of 3 basic goals: 1. To catch T-cell neoplasias in the full variety of their phenotypical spectrum by using assorted T-cell properties. 2. To bring these varied entities into a sequence corresponding to normal cell differentiation by correlating the neoplasias to normal cell compartments. 3. To determine the extent to which neoplastic equivalents exist for normal T cells with varied phenotypes and/or functional properties. A clear morphological subdivision of the T-cell neoplasias is already possible: 1. lymphoblastic lymphomas and leukemias; 2. peripheral or mature cell T-cell lymphomas. The lymphoblastic lymphomas and leukemias have until now been characterized primarily according to their positivity for the enzyme TdT. The T-lymphoblastic lymphomas and leukemias we analysed phenotypically shared the constant features of CD7 antigen expression, whereas other T-cell features showed a clear variability.

Adolescent↗

PubMed1986

Anaerobic contribution to distance running performance of trained cross-country athletes.

Recent reports have suggested that running economy (RE) defined as oxygen consumption at standardized treadmill speeds may be an important determinant for successful distance running performance. The purpose of this study was to examine the additional role, if any, played by anaerobic factors in distance running performance. Highly trained male cross-country runners (N = 12) were administered a battery of standardized aerobic and anaerobic laboratory evaluations. Maximal oxygen uptake (VO2max) and RE (ml X kg-1) were measured using open circuit spirometry during treadmill exercise. RE was measured at 241 and 295 m X min-1, and ventilatory threshold (Tvent) was determined and verified using a number of non-invasive ventilatory measures (VE, VE/VO2, VE/VCO2, VCO2, FECO2). Anaerobic measures included the Margaria power test and the Monod critical power test to determine anaerobic work capacity (AWC). The data were subjected to a SAS-STEPWISE analysis which combines stepwise addition and backward elimination and were used to predict performance time in a 8.05-km (5-mile) cross-country race in which all the runners participated. The subjects averaged 26.21 min for the 8.05 km run, with 72.1 ml X kg-1 X min-1 for the VO2max with a Tvent at 60.4 ml X kg-1 X min-1 (84% VO2max). AWC (Monod) was 17400 Joules with a range of 8,000-28,400 Joules. The STEPWISE procedure reveals that AWC contributes significantly (P less than 0.003) to a 3 variable model predicting race performance (R2 = 0.76, P less than 0.01). AWC accounts for 58% of total shared variance with VO2max and an indirect measure of Tvent accounting for the remaining 17%.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise Test↗

PubMedDate not supplied

Treatment of early rheumatoid arthritis: a review of current and future concepts and therapy.

This review contrasts the difficulty of differentiating early rheumatoid arthritis (RA) from the many other causes of inflammatory polyarthritis and emphasizes the need for early treatment of RA with drugs that are present considered inappropriate for a mild, self-limiting disease. Pointers to help establish a definitive diagnosis of RA include the use of the American College of Rheumatology (ACR; formerly the American Rheumatism Association) diagnostic criteria, the presence of rheumatoid factor (RF), a raised erythrocyte sedimentation rate (ESR), raised serum levels of C-reactive protein (CRP) and low concentrations of serum sulphydryl (SH) groups. More sophisticated tests that are helpful and indicative of erosive-type disease are genetic markers such as the human leukocyte antigen HLA DR4 (especially the third allelic variable of DR beta 1) as well as an impaired sulphoxidation status. Similarly, the presence of the shared epitope alleles 0401 and 0404 quantitatively increases disease susceptibility and severity as their penetration increases. Experience with treatment indicates that control of the inflammatory process of RA reduces the progression of radiological damage. It is concluded that antimalarials are effective in mild disease, as is auranofin, whilst sulphasalazine is more effective than hydroxychloroquine in patients with disease diagnosed as definitive or classical RA. Intramuscular gold also lessens the development of erosions. The role of corticosteroids has not been defined. A number of combinations of drugs have been used, although they are probably not indicated as the first choice treatment for very early disease. Attitudes towards early treatment are changing; these are briefly reviewed and the authors' opinions on the management of early disease are outlined. Finally some new ideas, both theoretical and practical, on future development are summarized.

Anti-Inflammatory Agents↗

PubMed1993

Doppler-derived aortic valve gradients: imaging versus non-imaging techniques.

BACKGROUND: Quantitative Doppler echocardiography has become an established method for estimating aortic valve area in aortic stenosis, replacing cardiac catheterization as the confirmatory study. The technique is time consuming, especially when measuring the transaortic velocity, which is performed by convention. This is accomplished by interrogating multiple windows with a non-imaging probe to record the maximal velocity. To determine how the examination could be expedited, we prospectively compared aortic valve gradients measured by Pedof and duplex transducers. METHODS: One hundred eighty-two consecutive patients with native aortic valve disease, mechanical or bioprosthetic aortic valves were studied. Two technicians measured maximal transaortic valve velocities from apical, subcostal, right parasternal and suprasternal notch windows with a 2 MHz Pedof probe and from the apical window with a 3-3.5 MHz duplex probe using color flow to orient the continuous wave beam. Angle-corrected and non-angle-corrected signals were recorded. There were 109 comparisons read by two observers; intra- and inter-reader variations were 0.4% and 2.0%, respectively. RESULTS: Duplex imaging velocity gradients were consistently smaller than Pedof non-imaging measurements with a mean +/- 1 standard deviation difference between peak velocities of 0.40 +/- 0.71 meters per second (m/s) for angle-corrected, and 0.76 +/- 0.68 for non-angle-corrected signals (both p < 0.001). Technician variability accounted for some of the difference (p < 0.02). CONCLUSION: Although non-imaging and imaging methods share the apical window, the Pedof probe scans unlimited planes to locate the maximal aortic valve gradient, whereas the duplex probe is confined to the plane providing the optimal two-dimensional image. Therefore, Doppler echocardiographic estimations of aortic valve areas still require careful, time-intensive non-imaging recordings of transaortic velocities.

Aortic Valve↗

PubMed1996

Third molar surgical procedures: practices by maxillofacial and oral surgeons in South Africa.

An audit of the treatment procedures routinely adopted by maxillofacial and oral surgeons for the removal of impacted third molars under general anaesthesia was undertaken in South Africa. Most maxillofacial and oral surgeons agree on the method of bone removal, the prescribing of antibiotics, analgesic agents and mouthwashes, the suturing of the incision wound and the post-operative review of patients. The results were compared to a similar study undertaken by Falcon and Roberts (1992) in the UK. With the exception of the method of bone removal, maxillofacial and oral surgeons in both groups share a similar approach to the treatment procedures adopted in the removal of impacted third molars. Some variability, however, existed in both studies with regard to the use of intra-operative local anaesthetic agents, the administration of peri-operative steroids and the use of non-steroidal anti-inflammatory agents.

Adolescent↗