Molecular evidence for the early history of living amphibians

PURPOSE: To evaluate the feasibility of introducing exogenous genes and phosphorothioate oligonucleotides into the anterior chamber tissues of rats and monkeys using the authors' fusogenic liposomes. METHODS: Hemagglutinating virus of Japan liposomes containing LacZ DNA-high-mobility group 1 complexes or fluorescein isothiocyanate (FITC)-labeled phosphorothioate oligonucleotides were prepared and injected into the anterior chambers of rats (3 microliters) and rhesus monkeys (30 microliters). The expression of LacZ DNA was visualized histochemically by beta-Galactosidase assay and was followed for as long as 60 days in rats and 30 days in monkeys. FITC-labeled phosphorothioate oligonucleotides were observed by fluorescence microscopy for as long as 14 days in rats and 7 days in monkeys. RESULTS: Injection of LacZ DNA-high-mobility group 1 complexes encapsulated in hemagglutinating virus of Japan liposomes resulted in blue staining in the trabecular meshwork and iris-ciliary body of rats and selectively in the trabecular meshwork of monkeys at the concentrations used. This LacZ expression lasted for as long as 14 days after injection in both animals. Phosphorothioate oligonucleotides (3 microM) also were introduced into the rat trabecular meshwork and iris-ciliary body and into the primate trabecular meshwork when encapsulated in hemagglutinating virus of Japan liposomes, although the injection of naked FITC-labeled phosphorothioate oligonucleotides at the same concentration resulted in little fluorescence in any anterior chamber tissue. CONCLUSIONS: This study shows that the use of hemagglutinating virus of Japan liposomes can transfer LacZ DNA and phosphorothioate oligonucleotides to adult rat and primate trabecular meshwork. This system may enable progress in glaucoma research and in the development of nonviral somatic gene therapy of the trabecular meshwork to treat glaucoma.     

Natural history of early primary biliary cirrhosis

BACKGROUND: In 1986, we reported a group of 29 patients who were positive in serum for antimitochondrial antibody (AMA), the disease-specific marker for primary biliary cirrhosis (PBC), but who had normal liver function test results and no symptoms of liver disease. However, liver histology was diagnostic or compatible with PBC in 24 patients and normal in only two. The aims of this 10-year follow-up study were to establish whether patients with AMA have very early PBC, to assess the outlook for such patients, and to follow the progression of the disease. METHODS: All patients were assessed every year at our PBC clinic: records were reviewed, cause of death verified when applicable, and current clinical and biochemical data collected, including repeat liver histology as indicated. Serum samples from the original study were located. Original and follow-up serum samples were tested by ELISA for E2 components of pyruvate dehydrogenase complex and 2-oxoglutarate dehydrogenase complex. FINDINGS: Five patients died during follow-up; no deaths were attributable to liver disease. Median follow-up of patients who survived was 17.8 years (range 11.0-23.9) from first-detected AMA to the last follow-up review. Overall, 22 (76%) developed symptoms of PBC and 24 (83%) had liver function tests persistently showing cholestasis. Repeat liver biopsy samples were obtained from ten patients; among these patients PBC progressed from Scheuer grade 1 to grade 2 in two and from grade 1 to grade 3 in two. No patient developed clinically apparent cirrhosis. ELISA of baseline serum samples from 27 patients was positive in 21, all of whom had original liver histology compatible with or diagnostic of PBC. Of the six patients who tested negative, only one had an original liver biopsy sample that was compatible with PBC. INTERPRETATION: This study confirms that before the advent of any clinical or biomedical indications, individuals positive for AMA do have PBC. This finding extends the natural history of PBC back in some cases for many years. What determines the eventual progression to biochemically and clinically apparent disease is not yet understood. During our study no patient developed clinically apparent portal hypertension or cirrhosis. Thus, although the finding of a solitary persistently raised AMA is confirmation of a diagnosis of PBC, patients with AMA but no other signs or symptoms of PBC seem to have slow progression of the disease.     

The natural history of syphilis. Implications for the transmission dynamics and control of infection

BACKGROUND: Syphilis remains a significant cause of morbidity in many developing countries and in some areas within North America and Europe. Mathematical models of the transmission dynamics of sexually transmitted infections have provided insights of relevance both to the interpretation of observed epidemiological patterns and to the design of control programs. Their use for the study of syphilis has been limited to date. GOALS AND STUDY DESIGN: The authors investigated the transmission dynamics of syphilis against a template based on the natural history of infection in individual patients with the aim of (1) identifying gaps in our understanding of the biology of infection, and (2) providing insights of relevance to the design of control policies. RESULTS: Analyses reveal that Treponema pallidum has a moderate to high probability of transmission during contact between susceptible and infectious sexual partners. This, combined with questions over the existence of any immunity to reinfection, helps to ensure the long-term persistence of syphilis within "core" activity groups. Patterns of treatment in North America are shown to have significantly altered the relative frequency of individuals in the different stages of disease. CONCLUSIONS: The analyses emphasize the benefits to be gained from treating infected people early in the primary stage of infection to reduce the effective period during which infected people can transmit to others. This form of treatment is beneficial for both the individual and the community. Treatment has greatly altered the incidence of different disease stages, but the full implications of treatment depend on whether immunity is present.     

The early history of boundary violations in psychoanalysis

The notion of professional boundaries is a relatively recent addition to psychoanalytic practice. Freud and his early disciples indulged in a good deal of trial and error as they evolved psychoanalytic technique. The study of these early boundary violations illuminates the study of the evolution of the concepts of transference and countertransference. The recent publication of the correspondence between Freud and Jung, between Freud and Ferenczi, and between Freud and Jones has provided us with extraordinary insights into the boundary transgressions that occurred in the early days of psychoanalysis. The boundary violations of the analytic pioneers have contributed to the legacy inherited by future generations of analysts. Institutional resistance to addressing these difficulties in contemporary psychoanalytic practice may relate in part to the ambiguities surrounding boundaries in the training analysis itself.     

Cytological study of the puncture biopsy specimens of the Douglas' pouch for early diagnosis of ovarian tumors

The conducted studies indicated the diagnostic opportunities of a cytologic analysis of exudates and smears from the Douglas space in patients with a suspicion to ovarian tumor. Tumor cells may be present in the peritoneal cavity not only in different stages of malignant ovarian tumors, but also in secernent and proliferating cystadenomas. A correlation between the peritoneal cell content in patients with different forms of ovarian neoplasms and press-smears from the dissected surface of the removed tumors and histological sections indicated the morphological identitiy of tumor elements and enabled the determination of the cytological criteria for the differential diagnosis of ovarian tumors prior to surgical intervention.     

The language environment of the young infant: Implications for early perceptual development.

Reviews recent research on young infants' use of auditory information during early language processing. Evidence indicates that infants actively process sounds, particularly those with acoustic attributes of their native language. Infants' prenatal experience with maternal speech may determine the early postnatal perceptual salience of a specific mother's speech, motherese speech, and native speech. Infants' sensitivity to suprasegmental aspects of speech may dictate much of what they attend to, while features of infant-directed speech seem to draw their attention to the speaker and elicit positive affective responses. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Predictability of early atopy by cord blood-IgE and parental history

BACKGROUND: Atopic family history and cord blood IgE have been used as predictors of atopic disease in newborns for about 20 years, but at least for cord blood IgE the sensitivity has been shown to be very low. The objective of this paper was to evaluate whether parental history and cord blood-IgE were more accurate predictors for the appropriate atopic phenotypes in the infants rather than for any atopy. METHODS: A total of 1314 newborn infants was recruited in six German obstetric departments in 1990 and followed-up for 2 years. Four hundred and ninety-nine (38%) were at high risk for atopy with at least two first degree atopic family members and/or elevated cord-blood IgE concentrations. RESULTS: The cumulative incidence of atopic dermatitis over the first 2 years of life (AD24) amounted to 20.1%, and there was a significant association with AD history of the mother (OR 2.5, 95%CI 1.46-4.26) and of the father (OR 3.53, 95%CI 1.90-6.54). The cumulative incidence of recurrent wheezing in the first 2 years of life (RW24) amounted to 16.1%, and was positively associated with asthma history (OR 2.11, 95%CI 1.33-3.60) and sensitization history (OR 1.64, 95%CI 1.34-2.36) of the mother, but with neither for the father. RW24 was less prevalent in girls than in boys (OR 0.64, 95%CI 0.47-0.89). Thirty-one per cent of infants were sensitized (CAP test value > 0.35 kU/L) against at least one of nine food or inhalative allergens (S24) and this was significantly associated with cord blood-IgE value (OR 2.43, 95%CI 1.69-3.49), and sensitization history of the mother (OR 1.64, 95%CI 1.18-2.41). Using multiple logistic regression analysis, the prediction of AD24 by AD of parents, of RW24 by asthma of parents, and of sensitization by cord blood IgE was of low accuracy. CONCLUSION: The predictive capacity of parental history and cord blood IgE is not high enough to recommend them as screening instruments for primary prevention. The majority of atopic manifestations and of sensitization occur in infants with no demonstrable risk at birth.     

A semi-automated method for the determination of oestrogens in early morning urine specimens from normal and infertile women

The effects of caffeine (3.125, 6.25, 12.5, 25, 50, and 100 mg/kg) on lever pressing, schedule induced licking and water consumption induced by a fixed interval 1 min schedule were studied. Changes in these dependent variables were assessed when animals were reduced to 80% of their initial body weight by partial food deprivation and when body weights recovered after the animals were returned to conditions of ad lib feeding. Results indicate differential effects of the drug between animals at 80% body weight and when they are permitted to recover. Tolerance was examined for a single large dose only for the same dependent variables in animals at 80% body weight.     

Predominance of a maternal history of diabetes for patients with non-insulin-dependent diabetes mellitus. Implications for the intrauterine transmission of diabetes

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder characterized by multiple congenital anomalies and mental retardation. SLOS has an associated defect in cholesterol biosynthesis, but the molecular genetic basis of this condition has not yet been elucidated. Previously our group reported a patient with a de novo balanced translocation [t(7;20)(q32.1;q13.2)] fitting the clinical and biochemical profile of SLOS. Employing fluorescence in situ hybridization (FISH), a 1.8 Mb chromosome 7-specific yeast artificial chromosome (YAC) was identified which spanned the translocation breakpoint in the reported patient. The following is an update of the on-going pursuit to physically and genetically map the region further, as well as the establishment of candidate genes in the 7q32.1 breakpoint region.     

Evidence for an early appearance of modern post-switch isotypes in mammalian evolution; cloning of IgE, IgG and IgA from the marsupial Monodelphis domestica

In birds, reptiles and amphibians the IgY isotype exhibits the functional characteristics of both of IgG and IgE. Hence, the gene for IgY most likely duplicated some time during early mammalian evolution and formed the ancestor of present day IgG and IgE. To address the question of when IgY duplicated and formed two functionally distinct isotypes, and to study when IgG and IgA lost their second constant domains, we have examined the Ig expression in a non-placental mammal, the marsupial Monodelphis domestica (grey short-tailed opossum). Screening of an opossum spleen cDNA library revealed the presence of all three isotypes in marsupials. cDNA clones encoding the entire constant regions of opossum IgE (epsilon chain), IgG (gamma chain) and IgA (alpha chain) were isolated, and their nucleotide sequences were determined. A comparative analysis of the amino acid sequences for IgY, IgA, IgE and IgG from various animal species showed that opossum IgE, IgG and IgA on the phylogenetic tree form branches clearly separated from their eutherian counterparts. However, they still conform to the general structure found in eutherian IgE, IgG and IgA. Our findings indicate that all the major evolutionary changes in the Ig isotype repertoire, and in basic Ig structure that have occurred since the evolutionary separation of mammals from the early reptile lineages, occurred prior to the evolutionary separation of marsupials and placental mammals.     

Desmoplastic response in biopsy specimens of early colorectal carcinoma is predictive of deep submucosal invasion

PURPOSE: The aim of this study was to evaluate the role of histopathology of biopsy specimens in predicting depth of infiltration in early colorectal carcinomas before treatment. METHODS: Early colorectal carcinomas that had been resected surgically or endoscopically between 1984 and 1995 were analyzed. Histopathologic findings, including differentiation of adenocarcinoma and a desmoplastic response were investigated. RESULTS: One hundred nine early colorectal carcinomas consisted of 73 lesions of carcinoma in situ, 13 submucosal carcinomas with minimum invasion, 8 lesions with moderate invasion, and 15 lesions with deep invasion. Of 73 carcinoma in situ lesions, 72 (approximately 99 percent) showed well-differentiated adenocarcinomas and no desmoplastic response. Twelve (92 percent) of 13 submucosal carcinomas with minimum invasion also revealed well-differentiated adenocarcinoma without a desmoplastic response. Sixty-three percent (5/8) of lesions with moderate invasion revealed well-differentiated adenocarcinoma. None of the lesions had a desmoplastic response. Among lesions with deep invasion, 73 percent (11/15) demonstrated moderately differentiated adenocarcinoma, and 11 lesions had a prominent desmoplastic response (73 percent; P < 0.01). CONCLUSIONS: These results suggest that if histopathologic findings of biopsy specimens taken from them before treatment demonstrated adenocarcinoma associated with a desmoplastic response, the lesions had at least deep invasion carcinomas. These lesions should be resected surgically. Submucosal carcinomas with minimum invasion, which have no desmoplastic response, could be treated endoscopically.     

The origin of the Australasian marsupial fauna and the phylogenetic affinities of the enigmatic monito del monte and marsupial mole

Alternative hypotheses in higher-level marsupial systematics have different implications for marsupial origins, character evolution, and biogeography. Resolving the position of the South American monito del monte (Order Microbiotheria) is of particular importance in that alternate hypotheses posit sister-group relationships between microbiotheres and taxa with disparate temporal and geographic distributions: pediomyids; didelphids; dasyuromorphians; diprotodontians; all other australidelphians; and all other marsupials. Among Australasian marsupials, the placement of bandicoots is critical; competing views associate bandicoots with particular Australasian taxa (diprotodontians, dasyuromorphians) or outside of a clade that includes all other Australasian forms and microbiotheres. Affinities of the marsupial mole are also unclear. The mole is placed in its own order (Notoryctemorphia) and sister-group relationships have been postulated between it and each of the other Australasian orders. We investigated relationships among marsupial orders by using a data set that included mitochondrial and nuclear genes. Phylogenetic analyses provide support for the association of microbiotheres with Australasian marsupials and an association of the marsupial mole with dasyuromorphs. Statistical tests reject the association of diprotodontians and bandicoots together as well as the monophyly of Australasian marsupials. The origin of the paraphyletic Australasian marsupial fauna may be accounted for by (i) multiple entries of australidelphians into Australia or (ii) bidirectional dispersal of australidelphians between Antarctica and Australia.     

Meteorites as specimens for microgravity research

The microstructural features of nickel-iron and stony-iron (pallasite) meteorites contain structures both similar to and different from natural and engineered terrestrial materials. The similarities can be accounted for by nonequilibrium solidification. The differences are attributable to the role of micro-gravity forces in effect during solidification. The fundamental assumptions and the historical roots of currently accepted meteorite formation theory as they are interwoven with the development of physical metallurgy theories are evaluated. A theoretical background necessary for the reinterpretation of the meteoritic Widmanstätten structure as a product of microgravity solidification is presented. Meteorites may be used as prototypes of materials solidified under microgravity conditions.     

A history of the T-group and its early applications in management development.

The growth of the field of group dynamics was synonymous with the rise of the T-group in leadership education. This article documents the tumultuous history of the T-group movement in the United States, particularly as it has been applied in management development. Although the T-group is commonly dismissed as a management fad, the author suggests that it represented an important phenomenon in the history of applied behavioral science and was the first serious attempt at large-scale management and leadership development. The notion of providing managers with feedback on how their behavior impacts others is as popular today as it was 50 years ago. What has changed is the mechanisms by which such feedback is provided. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of crystalloid solutions on circulating lactate concentrations: Part 1. Implications for the proper handling of blood specimens obtained from critically ill patients

OBJECTIVES: a) To test the hypothesis that circulating lactate concentrations are the same in simultaneously collected arterial and central venous blood specimens; b) to test the hypothesis that even small amounts of crystalloid solutions, which are inadequately "cleared" from these indwelling arterial and venous catheters, can lead to clinically important and misleading changes in the measured lactate values. DESIGN: A prospective, multiexperiment study. SETTING: A critical care research laboratory and a 20-bed intensive care unit (ICU). PATIENTS: Three hundred fifty-five patients. INTERVENTIONS: Blood samples were collected. MEASUREMENTS AND MAIN RESULTS: Experiment 1: Simultaneously collected arterial and central venous blood specimens were obtained on 148 occasions from 48 medical ICU patients receiving no lactated Ringer's solution (RL). Arterial and central venous lactate values were nearly identical in these patients. The correlation between the arterial and central venous lactate concentrations was excellent (r2 = .85; p < .0001) and the agreement between the arterial and central venous lactate concentrations was also excellent (bias and precision = 0.04 mmol/L and +/- 0.38 mmol/L, respectively). Experiment 2: Arterial and mixed venous blood samples were obtained from 100 percutaneous transluminal coronary angioplasty (PTCA) and 75 cardiac surgical patients immediately before the performance of these cardiac procedures. We found the central venous lactate concentrations to be higher than arterial lactate values in the cardiac surgical group, and there was a very poor correlation (r2 = .07) between arterial and central venous lactate values in the cardiac surgical group. The correlation between central venous and arterial lactate concentrations in the PTCA patients was excellent (r2 = .84) and similar to the findings of experiment 1. Since the cardiac surgical patients received RL and the PTCA patients received no RL, we speculated that the intravenous infusion of RL in the cardiac surgical group accounted for these discordant findings. To test this speculation, we performed experiments 3 and 4. Experiment 3: In a large bench study, blood specimens were divided into multiple 1-mL aliquot portions, to which 0.01, 0.05, 0.10, 0.50, or 1.0 mL of various crystalloid solutions, containing or not containing RL, were added. In a volume-dependent and linear manner, solutions containing RL increased the circulating lactate concentration from 10% to > 400% of the baseline lactate value. In a volume-dependent and linear fashion, the non-RL crystalloid solutions decreased the lactate concentration by 0 to 66% of the baseline nondiluted lactate concentration. Experiment 4: In 30 different cardiac surgical patients, we simultaneously obtained central venous and arterial blood specimens. Patients this time received no RL, and catheter lines were adequately cleared (removal > 5 mL) of crystalloid solutions. We found a correlation (r2 = .82; p < .0001) that was virtually identical to the findings of experiment 1 and to the findings in the PTCA group of experiment 2. CONCLUSIONS: a) Arterial and central venous lactate concentrations are similar in hemodynamically stable critically ill patients, b) Even small amounts of RL-containing solutions in catheters used for blood sampling may cause false increases in the circulating lactate concentration. c) Even small amounts of non-RL crystalloid solutions in catheters used for blood sampling may falsely decrease circulating lactate values. d) When blood specimens are drawn from indwelling catheters, all crystalloid solutions must be cleared from the line.