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PubMed1992

Prognostic value of CA 125 in advanced ovarian cancer.

CA 125 was measured during early chemotherapy in 121 patients with FIGO stage III or IV ovarian cancer to investigate if the antigen could be used as a prognostic parameter. CA 125 was determined before the start of chemotherapy and 1 month after the first, second, and third course. The antigen level before the start of chemotherapy held no prognostic information. CA 125 was a significant prognostic parameter in all three courses but its correlation with survival improved with the number of courses. Patients with high marker levels (greater than 100 U/ml) 1 month after the third course had a median survival of 7 months. This should be compared with a 50% 5-year survival in patients who had 10 U/ml or less and a median survival of 22 months among patients with intermediate CA 125 levels. Cox regression analysis of the covariation between survival, CA 125, and five variables (age, FIGO stage, histopathology, tumor grade, and bulk of residual tumor) showed that the CA 125 value was the most significant prognostic parameter. As a consequence of this study, chemotherapy of patients with high CA 125 levels 1 month after the third course may be discontinued and replaced by palliative therapy if other curative regimens are not available.

Adult↗
PubMed2004

Seasonal and temporal trends in polychlorinated biphenyls and organochlorine pesticides in East Greenland polar bears (Ursus maritimus), 1990-2001.

Persistent organochlorine (OC) contaminants (PCBs, DDTs, chlordanes (CHLs), dieldrin, hexachlorocyclohexanes (HCHs), chlorobenzenes (CBzs)) were determined in adipose tissue of 92 polar bears (Ursus maritimus) sampled between 1999 and 2001 in central East Greenland (69 degrees 00'N to 74 degrees 00'N). OC data were presented from subadults (S: females: x 5 years and males: x 6 years), adult females (F: x 5 years) and adult males (M: x 6 years). Summed chlorobiphenyl (SigmaCBs) concentrations (41 congeners including co-eluters), SigmaCHLs and SigmaDDTs were the dominant classes of OCs. SigmaCBs concentrations were found to be 6470, 8240 and 9100 ng/g lipid weight (lw) i subadults, adult females and adult males, respectively. The corresponding figures were: 2010 (S), 2220 (F) and 1710 (M) ng/g lw for SigmaCHLs and 462 (S), 462 (F) and 559 (M) ng/g lw for SigmaDDTs. The dominant CB congeners were CB153 (32.3%), CB180 (21.4%), CB170 (12.2%) and CB138 (11.0%). The metabolite p,p'-DDE (88.2%) dominated the SigmaDDTs, while oxychlordane was the dominant (57.1%) CHL-related compound. Concentrations of SigmaCBs, SigmaCBzs, SigmaDDTs, mirex and dieldrin were highest in adult males, whereas concentrations of SigmaHCHs were lower than in adult females but not than those in subadults. Adult females had the lowest concentrations of SigmaCBzs, mirex and dieldrin. Concentrations of SigmaCHLs were lowest in adult males, intermediate in subadults and highest in adult females. SigmaCB, SigmaHCH and SigmaCHL concentrations showed high seasonal variability in adult females but remained relatively constant in adult males and subadults. In general, the OC levels in females appeared to be highest in March and lowest in January or September. Concentrations of SigmaCBzs and dieldrin showed seasonal variability in all three groups, with a maximum in March in adult females. SigmaCBz concentrations in adult males and subadults of both sexes peaked in April-July, and dieldrin concentrations peaked in April-July in subadults, but not until August in adult males. SigmaDDT concentrations increased from January to a maximum in April-July for subadults and in August for adults. Temporal trends within the last decade were examined by comparing the present data to the concentrations reported in samples from 1990 from the same region. SigmaCB, p,p'-DDE and SigmaHCH concentrations in 1999-2001 were 22.1%, 66.3% and 39.3% lower than the 1990 concentrations, respectively. in contrast, SigmaCHL and dieldrin concentrations showed differences amongst sex and age groups in the temporal trends, where present concentrations are between 24.4% to 69.3% and 27.0% to 69.0% lower, respectively, relative to the 1990 levels. However, power analysis suggested that firm conclusions could not be drawn regarding the general time trend based on these two sampling periods. The range of half-lives of the various OC classes were estimated to lie between 4.5 and 20.6 years depending on the age and sex groups considered.

Adipose Tissue↗
PubMed1982

TRH receptor binding in retina and pituitary: major species variation.

Retinas and anterior pituitary glands of nine readily available mammalian and one avian species have been examined for their TRH-sensitive binding of [3H]-[3-Me-His2]TRH. Among mammals, major species variations in TRH receptor binding have been detected in both tissues, amounting to about 100-fold in the retina and 20-fold in the pituitary. In the retina, TRH receptor binding was very high in the rat, quite high in sheep and guinea pig, intermediate in rabbit, pig, and mouse, and low but detectable in chicken, cat, calf and dog. In the pituitary gland, binding was very high in sheep, quite high in rabbit, rat, pig, calf and guinea pig, intermediate in chicken, and fairly low in mouse, cat, and dog. A number of possible interfering variables, including affinity differences, albino vs. non-albino strains, barbiturate anesthesia, time after death, sex and estrous cycle, age, and history of light exposure, were considered and/or tested directly, with generally negative results.

Animals↗
PubMed1987

Distribution and orthograde axonal transport of HRP in feline eyes following intravitreal injection: an ultrastructural study.

The retina and optic nerve in the cat were examined by electron microscopy at five different time periods (1-, 3-, 8-, 16- and 24 hr) following the injection of horseradish peroxidase (HRP) into the vitreous cavity. Intra- and intercellular HRP was found in ganglion cells, Müller cells and horizontal cells even at 1 hr. Intra-axonal HRP in the retina and the retrolaminar optic nerve was seen most frequently at 3- and 8 hr. At 16- and 24 hr, many phagocytes containing HRP were noted in the nerve-fibre layer; subsequently HRP activity decreased throughout the retina. On the other hand, HRP activity in the intracanalicular optic nerve was significantly increased at 16 hr. Intra-axonal HRP appeared to be morphologically distributed in two forms: (i) HRP granules bound by a single-unit membrane mostly 0.1-0.4 micron in diameter; (ii) granules less than 0.05 micron which were occasionally hard to distinguish from artefacts such as stain deposit. The rate of orthograde axonal transport of HRP granules larger than 0.05 micron was examined on the basis of the frequency of HRP granules appearing in the retrolaminar and intracanalicular parts of the optic nerves. Though the rate seemed to be widely variable, the major velocity was calculated to be 45 mm per day, which is equal to intermediate axonal flow rates.

Animals↗
PubMed1999

The relation between height, foot length, pelvic adequacy and mode of delivery.

OBJECTIVE: To investigate the value of maternal height and foot length as predictors of pelvic adequacy and to evaluate the influence of body components' proportions on the mode of delivery. METHODS: Retrospective study of the anthropometry of women having normal vertex deliveries (NVD), caesarean sections (CS) and vaginal birth after caesarean (VBAC). RESULTS: NVD patients were taller, had a longer vertebral column, longer lower limbs and longer feet than CS and than VBAC patients. The anthropometric measurements of VBAC patients yielded values intermediate between CS and NVD patients. The ratios of height to any of the other measured variables (vertebral column, lower limb and foot length) were similar in the three groups indicating that the body proportions were the same. CONCLUSION: Maternal height and foot length are of limited value as predictors of pelvic (in-)adequacy. The anthropometric features of women delivered by CS only are similar to those of women having a vaginal birth after Caesarean.

Anthropometry↗
PubMed2002

Cell cycle dependent morphology changes and associated mitochondrial DNA redistribution in mitochondria of human cell lines.

Mitochondria of osteosarcoma cells (143B) in culture have variable morphologies, classified according to the shape and size of the organelle as reticular, fragmented or intermediate. Synchronization and release from G0 has shown that the morphology of mitochondria oscillates between the reticular and fragmented state in a cell cycle dependent manner. Cells in G1 have reticular mitochondria while those in S phase have fragmented mitochondria. By using a novel method of fluorescence in situ hybridization, the morphology of mitochondria was correlated with mitochondrial DNA distribution. MtDNA molecules were seen in clusters of two to four along mitochondrial filaments. In the fully fragmented state, each mitochondrion contained at least one cluster. We discuss the importance of fission and fusion events in regulating the morphology of mitochondria, segregation of mtDNA and maintenance of the organelle's functional unity.

Journal Article↗
PubMed1993

Flexibility impaired by mutations revealed the multifunctional roles of the loop in glutathione synthetase.

The loop from Ile-226 to Arg-241 in the glutathione synthetase (GSHase) from Escherichia coli B is rich in glycine and alanine and too flexible to take a fixed conformation [Yamaguchi, H., Kato, H., Hata, Y., Nishioka, T., Kimura, A., Oda, J., & Katsube, Y. (1993) J. Mol. Biol. 229, 1083-1100; Tanaka, T., Kato, H., Nishioka, T., & Oda, J. (1992) Biochemistry 31, 2259-2265]. To restrict the flexibility, three residues in the loop, Pro-227, Gly-229, and Gly-240, were replaced with alanine and valine residues. Variability in conformations of the mutant loops and shifts in the distribution of conformers between the open and closed states were assessed by steady-state kinetics, X-ray crystallographic structure analysis, and proteolysis with arginyl endopeptidase. Mutant enzymes replaced with a valine residue at the basal positions of the loop (P227V, G240V, and P227V/G240V) were identical with the wild-type enzyme in their crystal structures, except the loop region. The mutant loops retained apparent conformational variability, so as to take the open and closed states and to protect the acyl phosphate intermediate from the decomposition uncoupled from glutathione synthesis, but lost the catalytic activity; Kmapp values for glycine and gamma-Glu-Cys were sensitive to the mutations and drastically increased, and the k0app value was fatally reduced in the P227V/G240V mutant enzyme. The present results suggest that adjustability of the loop to the closed state is required for the recognition of the substrates, gamma-Glu-Cys and glycine, and for the chemical interactions with the bound substrates.

Amino Acid Sequence↗
PubMed2003

First practical synthesis of formamidine ureas and derivatives.

Isonitriles and ureas undergo a condensation reaction in the presence of acid chlorides to give formamidine ureas, for which no general synthetic routes currently exist. A mechanism is proposed in which the key intermediate is an electrophilic adduct of isonitrile and acid chloride. The process is tolerant of moderate variability in the nature of the components, and access to formamidine ureas of varying substitution patterns is further enhanced by a facile exchange reaction with amines. [reaction: see text]

Amidines↗
PubMed1980

Effect of cyclic AMP-dependent phosphorylation on the reactivity of sulphydryl groups in cardiac sarcoplasmic reticulum.

Phosphorylation of cardiac sarcoplasmic reticulum by cyclic AMP-dependent protein kinase results in enhanced Ca2+ transport even though Ca2+-dependent ATPase is not a substrate for the kinase. The mechanisms involved in this enhancement are not clear. In the present study, we used the reactivity of sulphydryl groups in the Ca2+-dependent ATPase as an index of conformational change during the Ca2+ transport cycle and examined the effects of protein kinase-catalysed phosphorylation. N-Ethylmaleimide alkylation allowed the distinction of several thiol groups with variable functional significance for the ATPase. A sulphydryl group involved in the formation of the phosphorylated intermediate (EP) of the Ca2+-dependent ATPase was protected by adenosine 5'-[beta, gamma-imido]triphosphate. Reactivity of an additional thiol group was related to EP dephosphorylation and was dependent on Ca2+. The Ca2+ concentration for change in the reactivity of this sulphydryl group and ATPase inhibition occurred within the range for Ca2+ binding to the high-affinity sites. Phosphorylation of cardiac sarcoplasmic reticulum by cyclic AMP-dependent protein kinase resulted in decreased N-ethyl[1-14C]-maleimide binding and the ATPase inhibition; the thiol groups involved in EP dephosphorylation were selectively protected. The results indicate that protein kinase-catalysed phosphorylation results in conformational changes of the ATPase, which renders certain thiol groups inaccessible to N-ethylmaleimide. This conformational change may facilitate functional movements involved in Ca2+ transport.

Animals↗
PubMed2003

p57kip2 is useful in the classification and differential diagnosis of complete and partial hydatidiform moles.

AIMS: To determine the utility of p57kip2 in the diagnosis of hydatidiform mole. p57kip2 protein is a cyclin-dependent kinase inhibitor (CDKI) and is strongly paternally imprinted, being expressed from the maternal allele. It has been hypothesized that complete mole (CHM) with only the paternal genome would display reduced or nearly absent expression of p57kip2 compared to partial mole (PHM) having both paternal and maternal genomes. METHODS AND RESULTS: The immunohistochemical expression of p57kip2 protein was investigated using paraffin-embedded tissue sections in histologically unequivocal cases of CHM (n = 51), PHM (n = 7), invasive mole (n = 1), and hydropic miscarriage (n = 2), as well as in histologically undetermined cases (n = 9). In the histologically unequivocal complete and invasive moles, expression of p57kip2 was absent except for one case in which villous cytotrophoblast covering the villous stroma was positive (51/52) as well as villous stromal cells (51/52). In contrast, it was strongly and continuously expressed in both villous cytotrophoblast and stromal cells in all cases of PHM and hydropic miscarriage. Among the nine histologically undetermined cases, five cases showing p57kip2 immunopositivity and hyperploid DNA were classified as PHMs, two cases showing p57kip2 immunonegativity and hyperploidy as CHMs, and two cases with p57kip2 immunopositivity and diploid DNA as hydropic miscarriage and diploid PHM, respectively, upon review of the histopathological findings. Intermediate trophoblast forming trophoblastic columns or anchoring villi and extravillous trophoblast at the implantation site showed variable expression of p57kip2 in all gestational conditions. Maternal decidua showed diffuse and strong p57kip2 expression, whereas syncytiotrophoblast was completely negative in all cases regardless of the diagnosis. CONCLUSIONS: In summary, p57kip2 immunostaining results correlated well with morphological features of molar pregnancies and were helpful in determining histologically equivocal cases.

Adolescent↗
PubMed2003

Halogenated inhalational anaesthetics.

The halogenated inhalational anaesthetics halothane, enflurane, isoflurane and desflurane can produce metabolic hepatocellular injury in humans to a variable extent. During metabolism of these anaesthetics, tissue acetylation occurs due to the formation of reactive intermediates. Proteins modified by acetylation may constitute neo-antigens with a potential for triggering an antibody-mediated immune response. The likelihood of suffering post-operative immune hepatitis depends on the amount of the anaesthetic metabolized and is thereby considerably less with enflurane, isoflurane or desflurane compared with halothane. Plasma inorganic fluoride concentrations are regularly increased after sevoflurane. Elevated inorganic fluoride concentrations have been associated with nephrotoxicity following methoxyflurane anaesthesia but not after sevoflurane. Another source of concern is the products of degradation from reactions with carbon dioxide absorbents. Most important is compound A, which has been shown to exhibit nephrotoxicity in rodents. However, no significant changes in renal function parameters have been reported in surgical patients.

Anesthetics, Inhalation↗
PubMed1984

Simulation of the metabolism of absorbed energy-yielding nutrients in young sheep.

A mathematical model is described, which simulates the metabolism of absorbed nutrients (amino acids, acetic acid, butyric acid, glucose, lipid and propionic acid) in growing sheep. The basic assumption of the model is that each nutrient is partitioned between synthetic, oxidative or intermediate reactions with rates of reaction which are described using enzyme kinetics. These rates depend on the relationship between maximum reaction rates, constants of affinity and inhibition and the concentrations of metabolites as determined by the model. Synthetic reactions calculate fat and protein deposition while intermediate reactions involve the production of ATP and NADPH. There is a total of twelve state variables and the model, programmed in CSMP and ACSL, is solved by integration of twelve differential equations. The model calculates the efficiency of utilization of metabolizable energy for different nutrient inputs and the results may be interpreted in terms of fluxes through the metabolite pools. Simulations using inputs representing forage- and concentrate-based diets indicated decreased efficiency for the forage at high levels of intake and possible reasons for this were further studied in simulations where the inputs of protein and glucose were varied.

Acetates↗
PubMed1995

Distribution of parvalbumin in specific fibre types of chicken skeletal muscles.

1. The distribution of parvalbumin (PA), which functions as a relaxing factor in the skeletal muscles, was examined in slow anterior latissimus dorsi (ALD), fast posterior latissimus dorsi (PLD), mixed sartorius (SA), pectoralis superficialis (PS) and pectoralis profundus (PP) muscles from chickens. 2. The biochemical characteristics of these muscles were confirmed by the assay of total lactate dehydrogenase (LDH) activity as well as the LDH isozymes for anaerobic metabolism, and by the photometrical analysis of myoglobin for anaerobic metabolism, and by the photometrical analysis of myoglobin for aerobic metabolism. 3. PA in individual muscles was determined by a sandwich ELISA and was demonstrated by 2-dimensional polyacrylamide-gel electrophoresis. 4. Because of poor myoglobin and higher LDH activity or M-type isozyme pattern, the PLD was confirmed as containing primarily fast-twitch glycolytic and oxidative-glycolytic (FG/FOG) fibres, while the SA was shown to be composed mostly of FOG fibres because of the highest myoglobin content and the intermediate LDH activity or H and M-type isozyme pattern. PA content was high and variable in both PLD and SA. 5. PA was undetectable in the ALD which appears to contain exclusively slow-tonic (ST) fibres, being verified by its myoglobin-rich nature and lowest LDH activity or predominant H-type isozyme characteristics. PA was absent from the PS ad PP, which probably contain predominantly FG fibres because of negligible amounts of myoglobin and the highest LDH activities or M-type isozyme pattern.

Animals↗
PubMed2001

Ki-1+ anaplastic large cell lymphoma in a child with unpredictable clinical course.

Ki-1+ anaplastic large cell lymphoma (Ki-1+ ALCL) is a subtype of non-Hodgkin lymphoma (NHL) with defined histopathological characteristics but with highly variable clinical presentation and outcome. Although in most of the patients the disease behaves as an intermediate- or high-grade lymphoma, some patients present with an indolent clinical course. Factors that determine the clinical behavior of this lymphoma have not yet been identified. A case is reported of a 13-year-old girl who initially presented with Ki-1+ ALCL but later developed recurrent localized cutaneous disease and followed a clinical course similar to that of a low-grade lymphoma.

Adolescent↗
PubMed1996

Osseous manifestations of SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome.

The SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome includes a complex group of disorders characterized by peculiar bone lesions, most commonly involving the anterior chest wall, and sometimes accompanied by dermatologic manifestations. The clinical and radiographic features of this syndrome are well described, but few studies have examined the histologic features of the bone lesions. We describe the clinical, radiographic, and histologic features of the osseous lesions encountered in eight patients with a clinical diagnosis of SAPHO syndrome. The patients included five female and three male patients ranging in age from 5 to 63 years (mean, 35.3 years). The most common clinical presentation was pain related to the sites of osseous involvement. Two patients also had some form of pustular dermatosis. The radiographic features of the osseous lesions varied but often suggested the possibility of a neoplasm. Nine pathologic specimens were available for review, five from the clavicle, two from the first rib, one from the calcaneus/cuboid, and one from the tibia. The histologic features varied but seemed related to the duration of the patients' musculoskeletal symptoms. Early lesions contained acute inflammation, edema, and prominent periosteal bone formation, histologically indistinguishable from ordinary bacterial osteomyelitis, whereas late lesions demonstrated markedly sclerotic bone trabeculae with prominent marrow fibrosis and only mild chronic inflammation; one of these biopsies appeared virtually identical to Paget's disease. One biopsy was performed after an intermediate duration of symptoms and contained prominent chronic inflammation only. The histologic findings in SAPHO are variable and nonspecific and may depend on the duration of disease, but it is important to recognize the spectrum of histologic changes possible in the syndrome and to realize that clinicopathologic correlation is necessary to avoid misdiagnosis and unnecessary long-term antibiotic therapy.

Acne Vulgaris↗
PubMed1982

Use of blood gas values to estimate the source of blood withdrawn from a wedged flow-directed catheter in critically ill patients.

A technique for sampling blood from the damaged pulmonary microvasculature in patients with acute respiratory failure is described. Blood was aspirated through the distal lumen of wedged pulmonary arterial catheters in 28 critically ill patients. Successful aspiration was achieved in 88% of the attempts and 20 ml of blood drawn before sampling was optimal for clearing mixed venous precapillary blood. The blood gas values obtained were classified as "capillary" when the wedge (w) PO2 greater than PaO2 and PwCO2 less than PaCO2 (17 patients, 61%); "mixed venous" when PwO2 and PwCO2 were equal to values obtained from the main pulmonary artery (5 patients, 18%); and "mixed source" when intermediate PwO2 and PwCO2 were noted, i.e., PaO2 greater than PwO2 greater than PVO2 and PwCO2 variably greater than or less than PaCO2 (6 patients, 21%). When mixed venous samples are eliminated, microvascular sampling can be assumed in 82% of the successful aspirations.

Adult↗
PubMed1994

An examination of the diagnostic criteria for antisocial personality disorder in substance abusers.

In this article, we compare problem severity and adult antisocial behavior among three groups of cocaine- or alcohol-dependent patients: those with antisocial personality disorder (APD), those who met adult but not childhood APD criteria (A-APD), and those who met neither (non-APD) in order to determine the clinical utility of the A-APD category. Subjects were 269 male veterans admitted for substance abuse treatment. The Addiction Severity Index was used to determine problem severity and the NIMH Diagnostic Interview Schedule was used to obtain positive DSM-III APD criteria and APD diagnoses. More APD subjects reported arrests, illegal behavior, and chronic lying than A-APD and non-APD subjects. On several variables (recent family/social problems, trouble controlling violent behavior, and time incarcerated), A-APD subjects were intermediate in severity. Overall, the non-APD subjects had the least severe problem status. When the APD and A-APD groups were equated on number of positive adult APD criteria, the only differences that consistently remained were difficulty controlling violent behavior and commission of criminal acts, which were endorsed more frequently in the APD group. It appears that the unique contribution of the early onset criteria for the APD diagnosis is that it identifies individuals more likely to engage in criminal and violent behavior. The more general irresponsibility and disregard for the rights of others characteristic of APD is equally evident in both antisocial groups. This work indicates that the APD versus non-APD distinction may not be fine grained enough for clinical or research purposes.

Adult↗