Psychological care over patients with lymphoma and lymphoma survivors.

Lymphomas are characterized by a relatively favorable prognosis and a good five-year survival rate, but they are associated with increased psychosocial distress. There is insufficient evidence on the efficacy of psychological interventions for lymphoma patients. This review aimed to present the research findings on currently used psychological interventions for (non-) Hodgkin lymphoma patients and survivors. A literature search on English language peer-reviewed original publications on psychological interventions for lymphoma patients published prior to December 2021 was performed in PubMed, Medline, Web of Science, Scopus and ResearchGate. Titles and abstracts were screened for the relevant terms including psychological intervention and psychological management along with (non-) Hodgkin lymphoma. The retrieved articles were evaluated by independent reviewers, the lists of eligible publications were compared, and disagreements were resolved by discussion. Of the 50 publications sought for retrieval, 8 articles were shortlisted based on their content. The papers were classified according to their content and the methodology employed. Research themes including "promoting resilience in lymphoma survivors", "web-based self-management interventions for patients with lymphoma", "addressing unmet needs whilst undergoing chemotherapy", and "mind-body interactive exercise" were identified and presented in this review. As the number of lymphoma survivors is increasing, future research on evidence-based interventions addressing patients' and survivors' unmet psychological needs is warranted.

Application of Eye-tracking in research on the theory of mind in ASD.

Autism spectrum disorder (ASD) is a broad diagnostic category describing a group of neurodevelopmental disorders which includes the autistic disorder. Failure to develop normal social relationships is a hallmark of autism. An inability to understand and cope with the social environment can occur regardless of IQ. One of the hypotheses of the appearance of ASD symptoms is associated with the theory of mind (TOM). ASD patients do not have the ability to attribute the full range of mental states (goal states and epistemic states) to themselves and to others. Eye-tracking allows for observation of early signs of TOM in ASD individuals, even before they are 1 year old, without the need of developed motor and language skills. This provides a window for looking at the very basics of mindreading - detecting intentionality and eyes in our environment. Studies show that ASD children fail to recognize biological motion, while being highly sensitive to physical contingency within the random movement. Their perception of faces seems disorganized and undirected, while object recognition is intact. Evidence suggests that this orientation of attention following gaze cues is diminished in ASD patients. Available data also show deficits in emotion recognition, that cannot be accounted for by impairments in face processing or visual modality alone. Such observations provide an insight into disturbances of information processing and offer an explanation for poor social functioning of ASD patients. When combined with other methods, Eye-tracking has the potential to reveal differences in processing information on a neural circuitry level. Thus, it may help in understanding the complexity of TOM mechanisms, and their role in social functioning.

What causes distress in males undergoing infertility work-up?

OBJECTIVE: This panel study aimed to identify predictors of the risk for depression in involuntarily childless males undergoing fertility work-up. MATERIALS AND METHODS: A sample of 255 married males aged 22-51 years seeking their first fertility work-up completed the General Health Questionnaire-28 (GHQ-28) at four time-points. They were tested at the baseline, before their initial fertility evaluation (T1), before their second andrological appointment, two-three months after the diagnostic disclosure (T2), and before subsequent treatment/follow-up appointments (T3 and T4). The timing of assessment was synchronized with respondent's andrological appointments and medical procedures. Binomial logistic regression was applied to develop prediction models for subgroups with the male, female, mixed, and unexplained factors of infertility. RESULTS: The risk for depression in involuntarily childless males was associated with a constellation of factors, whose importance might vary depending on the factor of infertility. However, the stage of the andrological procedure was found to be the most significant predictor of the risk for depression in the MFI, FFI and Mixed FI respondents with the greatest odds for T2 and/or T3. CONCLUSIONS: The results of the current study have practical implications. They should be considered in support programs for individuals and/or couples with unintentional childlessness. Infertility treatment specialists or other healthcare professionals should be provided education training programs to help them understand how age, permanent residence or education may influence male distress. They should integrate the knowledge into practice so that they can provide adequate emotional support to unintentionally childless males.

Phases and phase transitions of hexagonal cobalt oxide films on Ir(100)-(1 × 1).

Cobalt oxides on the unreconstructed Ir(100) surface were prepared by reactive deposition of Co established by simultaneous oxygen flux at about 50 °C and subsequent annealing. The films were investigated by low-energy electron diffraction (LEED), scanning tunnelling microscopy (STM) and thermal desorption spectroscopy (TDS). We show that in spite of the quadratic unit mesh of the substrate, oxide films of (111) orientation develop. As long as oxygen-rich conditions are maintained they are of spinel-type Co(3)O(4)(111). They are non-pseudomorphic and transform to rocksalt-type CoO(111) when oxygen loss is induced by annealing at elevated temperatures. Thin films of CoO(111) are commensurate, and so, in order to realize that, they exhibit a slightly distorted unit cell when below a thickness equivalent to about seven cobalt monolayers. With increasing film thickness the uniaxial strain accompanied by the commensurability is gradually relieved by the insertion of dislocations so that eventually the film assumes ideal hexagonality. All CoO(111)-type surfaces are reconstructed at low sample temperatures equivalent to a [Formula: see text] superstructure. They reversibly transform into a (1 × 1) phase at about 50 °C.

Surface structure of polar Co(3)O(4)(111) films grown epitaxially on Ir(100)-(1 × 1).

Cobalt oxide films were prepared by oxidation of different amounts of cobalt deposited on Ir(100)-(1 × 1), where oxygen rich conditions were applied during deposition. The resulting oxide films with thicknesses of up to about 40 Å were investigated as regards their crystallographic structure and morphology, applying quantitative low energy electron diffraction (LEED) and scanning tunnelling microscopy (STM). It can be unequivocally shown that the spinel-type Co(3)O(4) phase develops, for which an excellent fit between measured and calculated LEED intensity spectra is achieved (Pendry R-factor R = 0.124). In spite of the quadratic unit cell of the substrate the oxide films are in the polar (111) orientation. Also, the native lattice parameter of the material is assumed, i.e. there is no pseudomorphic relation to the substrate. However, by means of orientational epitaxy, one of the unit-mesh vectors of the oxide and one of those of the substrate layer are aligned, leading to two mutually orthogonal domains in the oxide. The oxide is terminated by a sublayer of cobalt ions which in the bulk were tetrahedrally coordinated Co(2+) ions. There are drastic relaxations of layer spacings at and near the surface. As a consequence, the bond length between the surface terminating cobalt ions and oxygen ions below is considerably reduced, indicative of a substantial change of the ionicity of the cobalt and/or oxygen ions. This is interpreted as accounting for polarity compensation of the film, as surface reconstruction, oxygen vacancies and species adsorbed can be ruled out.

Induction of anchorage independence in human diploid foreskin fibroblasts by carcinogenic metal salts.

We studied whether arsenic, nickel, and chromium compounds that are human carcinogens could induce transformation of cultured primary human diploid foreskin cells (HFC). All nickel compounds tested, PbCrO4, K2Cr2O7, CrO3, Na2HAsO4, NaAsO2, and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) caused significant (p = 0.001) dose-dependent inductions of anchorage-independent colonies in HFC. KH2AsO4, CaCl2, MnCl2, and Hg(CH3CO2)2 did not induce anchorage independence. Optimal expression times for induction of anchorage independence in HFC were observed as early as 11 days following treatment with MNNG, Ni3S2, Ni(C2H3O2), or NiSO4. Cell strains derived from anchorage-independent colonies showed 33 to 429-fold higher plating efficiencies in soft agar than parental populations, and the anchorage-independent phenotype was stable for eight passages, at which time cells senesced. Anchorage-independent cell strains derived from metal salt-treated cells were not resistant to the cytotoxicity of metal salts, indicating metal salts induced rather than selected for anchorage independence. Nine of 10 cell strains derived from metal compound- or MNNG-induced anchorage-independent colonies displayed the same or lower saturation densities than untreated human fibroblasts. None of these cell strains escaped senescence or showed definitive morphological transformation. MNNG (1 micrograms/ml) induced anchorage independence and mutation to ouabain resistance and 6-thioguanine resistance in HFC, but concentrations of Ni2S3 that induced anchorage independence did not induce mutation at either locus in HFC. These results demonstrate that carcinogenic metal salts induce stable anchorage independence early in human diploid foreskin fibroblasts, and this anchorage independence is independent of other in vitro markers of fibroblast transformation, such as focus formation or immortality. Metal salt induction of anchorage independence can now be used as an assay to study mechanisms of genotoxicity exerted by carcinogenic metal compounds in human cells.

Role of valence state and solubility of chromium compounds on induction of cytotoxicity, mutagenesis, and anchorage independence in diploid human fibroblasts.

We previously showed that carcinogenic nickel, arsenic, and chromium(VI) compounds induced anchorage independence (AI) in diploid human fibroblastic cells (HFC) derived from foreskins (K. A. Biedermann and J. R. Landolph, Cancer Res., 47: 3815-3823, 1987). To elucidate the role of the valence state of chromium and solubility of chromium compounds in inducing AI, we studied the ability of soluble and insoluble hexavalent [chromium(VI)] and trivalent [chromium(III)] chromium compounds to induce mutation and AI in HFC. Chromium(VI) compounds (PbCrO4, CaCrO4, Na2CrO4, and CrO3) were 1000-fold more cytotoxic to HFC (average 50% lethal dose 0.5 microM) than chromium(III) compounds (CrCl3, Cr2O3, Cr2S3; average 50% lethal dose 500 microM). However, equal concentrations (0.1-10.0 microM) of soluble or insoluble chromium compounds in either +6 or +3 valence states induced similar increases in frequencies of AI in HFC (100-200/10(5]. Chromium(VI)- and chromium(III)-induced AI was a stable phenotype. All soluble chromium(VI) and insoluble chromium(III) compounds studied induced mutation to 6-thioguanine resistance at cytotoxic concentrations in HFC. Insoluble PbCr(VI)O4 and a soluble form of Cr(III)Cl3 were inactive in this assay. Mutation induction by chromium(III) compounds only occurred at cytotoxic concentrations (100-1000 microM) 1000-fold greater than those concentrations of chromium(VI) compounds (0.25-1 microM) which were cytotoxic, mutagenic, and induced AI. Soluble hexavalent Na2(51)CrO4 was taken up facilely by cells at concentrations that induced cytotoxicity, mutation, and AI. At concentrations of 0.25-1.0 microM, which induced AI but were not cytotoxic or mutagenic, or concentrations of 1-1000 microM, which were cytotoxic and mutagenic, soluble trivalent 51CrCl3 was not taken up by cells. An insoluble form of CrCl3 was not taken up intracellularly but did avidly associate with cells over the concentration range 1 to 100 microM which induced AI, cytotoxicity, and mutagenicity. Therefore, both chromium(VI) and chromium(III) compounds induced genotoxic effects in human fibroblasts. Cellular uptake, cytotoxicity, mutagenicity, and AI induced by soluble chromium(VI) compounds all occurred at the low concentrations of 0.2 to 1.0 microM; hence mutagenicity and induction of AI may be coupled for soluble chromium(VI) compounds but not for insoluble PbCrO4, which induced AI but was not mutagenic. Cytotoxicity and mutagenicity of insoluble chromium(III) occurred at concentrations of 10-100 microM, but induction of AI occurred at concentrations of 0.1-10 microM, indicating that inductions of mutagenicity and AI were not coupled for chromium(III) compounds.(ABSTRACT TRUNCATED AT 400 WORDS)

Repair of DNA and chromosome breaks in cells exposed to SR 4233 under hypoxia or to ionizing radiation.

3-Amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233) is a bioreductive anticancer drug which has a high selective toxicity to hypoxic cells. We have characterized the DNA and chromosome damage in wild-type Chinese hamster ovary (CHO) cells and mutant XR-1 cells after exposure to SR 4233 under hypoxia and compared it to the damage produced by ionizing radiation (gamma-rays). Using the technique of pulsed field gel electrophoresis, we found that the kinetics of rejoining of DNA double-strand breaks in CHO cells after treatment with SR 4233 was concentration dependent, varying from 95% (less than 50 microM) to 10% (200 microM) by 24 h. This contrasted with the dose-independent kinetics exhibited in cells after gamma-ray exposure. XR-1 cells were deficient in rejoining double-strand breaks produced by either SR 4233 or gamma-rays. XR-1 cells were 2-fold more sensitive than wild-type CHO cells to SR 4233 but were 10-fold more sensitive than CHO to gamma-rays. These results suggested that DNA double-strand breaks are involved in hypoxic cell killing by SR 4233, but the specific type of lesion produced is not identical with that causing cell killing by gamma-rays. To further investigate this, we measured chromosome breaks in CHO cells by premature chromosome condensation after equitoxic doses of SR 4233 under hypoxia and gamma-rays. SR 4233 produced lower initial but similar final (after 6 h of repair) numbers of chromosome breaks compared to gamma-rays at equitoxic doses. These results suggest that, at low doses, chromosome breaks can entirely account for hypoxic cell killing by SR 4233 and that chromosome breaks produced by SR 4233 are more damaging and/or more difficult to repair than those produced by gamma-rays.

Characterization of the DNA double strand break repair defect in scid mice.

The scid mutation in CB-17 mice confers a profound immunodeficiency, resulting from an inability to rearrange immunoglobulin and T-cell receptor genes during lymphocyte development. Moreover, we and others have recently demonstrated in these scid mice a hypersensitivity to the lethal effects of ionizing radiation and a defect in DNA double strand break rejoining. In this report, we further characterize the radiosensitivity and repair defect in cells from scid mice. In order to determine whether scid cells were specifically sensitive to agents that produce double strand breaks, restriction enzymes RsaI and Sau3AI were introduced into scid and parental C.B-17 cells by electroporation. scid cells were 2-fold more sensitive than C.B-17 cells to both the blunt and the staggered end cuts produced by these restriction enzymes. However, the scid cells proficiently ligated both staggered and blunt ends of transfected plasmids. To determine whether the extent of DNA rejoining in scid cells was dependent on the initial dose of gamma-rays, final levels of DNA double strand break rejoining in scid and C.B-17 cells were quantitated by asymmetric field inversion gel electrophoresis. The results indicate an apparent difference in repair levels dependent on the dose of gamma-rays, ranging from 75% rejoining at 10 Gy to 40% rejoining at 50 Gy. In contrast, > 90% rejoining was observed in control C.B-17 cells at all doses. Delineating the links between these aberrant recombinational events, abnormal V(D)J recombination, and double strand break repair defects, will aid in the understanding of the basic mechanisms involved in these processes.

Complementation of the radiosensitive phenotype in severe combined immunodeficient mice by human chromosome 8.

Severe combined immunodeficient (scid) C.B-17 mice are deficient in variable (diversity) joining region recombination, the process of assembling the immunoglobulin and T-cell receptor genes from gene segments, thereby creating much of the enormous diversity of antigen-binding capacity, scid mice are also sensitive to ionizing radiation, as a result of their deficiency in double-strand break repair. Here we report the complementation of the radiation-sensitive scid phenotype by transferring human chromosome 8 into scid cells. Somatic cell hybrids were generated by fusing scid cells with human HT-1080 cells, resulting in radioresistant hybrids with several human chromosomes. One of the identified human chromosomes in the radioresistant scid cell line 4.61, which retains only two human chromosomes, is a rearranged 8/21 translocation. Proof that chromosome 8 confers the complementation was achieved by transferring only human chromosome 8 into scid cells by microcell-mediated chromosome transfer (scid/hu8 cell line). The presence of chromosome 8 in our scid/hu8 cell line was monitored by fluorescence in situ hybridization and polymerase chain reaction. We demonstrated the radioresistance of this hybrid not only to high dose rate but also to low dose rate radiation. We also showed that transference of human chromosome 8 to scid cells fully complements the DNA double-strand break repair deficiency and the high sensitivity of scid cells to radiation-induced chromosome aberrations. Mapping the scid gene to human chromosome 8 is an important first step in cloning the scid gene, which will enhance our understanding of double-strand break repair pathways in humans.

Characterization of Serratia marcescens nuclease isoforms by plasma desorption mass spectrometry.

Isoforms of Serratia marcescens nuclease found in the natural nuclease produced by S. marcescens and in recombinant nuclease produced by Escherichia coli were structurally characterized by peptide mapping using plasma desorption mass spectrometry. The nuclease isoforms produced and secreted from S. marcescens B10M1, which are present in much greater amounts than in S. marcescens W225 nuclease produced by E. coli, were characterized completely and the information used to facilitate characterization of the recombinant nuclease isoforms. After purification of the nuclease the isoforms were separated on a DEAE-cellulose anion-exchange column and then digested with endoproteinase Lys-C. The peptides generated were isolated by reverse-phase HPLC and their molecular masses determined by plasma desorption mass spectrometry. Comparison of the peptides from the native nuclease, Sm2, and the two isoforms, Sm1 and Sm3, revealed that they differed only in the N-terminus, the latter being found to lack three amino acids in Sm1 and one amino acid in Sm3. No interior post-translational changes were found in either of the three isoforms. Using this information we were able to confirm that Sm1, the isoform lacking three amino acids, was also present in very small amounts in recombinant S. marcescens W225 nuclease produced and excreted by E. coli.

Do urban and rural residents living in Poland differ in their ways of coping with chronic diseases?

OBJECTIVE: Chronic disease is a critical life event which demands significant psychological adjustment. Coping strategies and resources such as sense of coherence, self-efficacy, etc. remain factors affecting stress response. PATIENTS AND METHODS: The examined group included patients with ischemic heart disease (n = 134), type 1 diabetes mellitus (n = 109) or rheumatoid arthritis (n = 92). 159 patients came from urban area whereas 176 came from rural setting. All patients filled up inventories of life satisfaction, severity of depression, coping strategies, self-efficacy, social support and sense of coherence. RESULTS: The analysis showed that patients from rural areas had higher levels of well-being, i.e., were characterized by lower severity of depression. The predictors of satisfaction with life included two types of resources i.e. self-efficacy, social support and two coping strategies i.e. turning to religion and self-distraction (R2 = 0.39; F = 26.87**). Life satisfaction was determined by social support, sense of coherence and positive reappraisal (R2 = 0.36; F = 29.11**). CONCLUSIONS: Rural/urban differences in the use of coping strategies may be associated with environmental or lifestyle differences. Patients with IHD, T1D or RA in Polish rural areas are high risk for depression so they may need help in finding systematic contact with specialists of healthcare.

Prevention of vertical HIV transmission: additive protective effect of elective Cesarean section and zidovudine prophylaxis. Swiss Neonatal HIV Study Group.

OBJECTIVE: To study the effect of elective Cesarean section and zidovudine prophylaxis on vertical HIV transmission. DESIGN: Prospective study. SETTING: Obstetric and paediatric clinics in Switzerland. PARTICIPANTS: Children of mothers with HIV infection identified before or at delivery. INTERVENTIONS: Routine use of elective Cesarean section for HIV-infected parturients by some Swiss centres since 1985. National recommendation for zidovudine prophylaxis in mid-1994. MAIN OUTCOME MEASURE: HIV infection status of children. RESULTS: In a cohort of 494 children born at least 6 months before the analysis date, 67 out of 414 children with known infection status were found to be infected, giving an overall transmission rate of 16.2% [95% confidence interval (CI), 13.0-18.51. Elective Cesarean section with intact membranes and without previous labour was associated with a lower transmission rate of 6% [odds ratio (OR), 0.29; 95% CI, 0.12-0.70; P = 0.006 versus other delivery modes]. Transmission rate was intermediate after spontaneous delivery or non-elective Cesarean section (18%), and higher after obstetric interventions (27%; test for trend, P < 0.001). Since mid-1994, 78% of all women with registered pregnancies have received some form of zidovudine prophylaxis. Transmission rate was reduced from 17 to 7% after any zidovudine exposure (OR, 0.4; 95% CI, 0.11-1.41). Combined use of elective Cesarean section and zidovudine resulted in a 0% transmission rate (none out of 31), compared with 8% (seven out of 86) after elective Cesarean section without zidovudine, 17% (four out of 24) after zidovudine alone, and 20% (55 out of 271) after no intervention. CONCLUSIONS: Elective Cesarean section and zidovudine prophylaxis appear to have an additive effect in the prevention of vertical HIV transmission.

Lysozyme binds to elastin and protects elastin from elastase-mediated degradation.

Lysozyme has been shown to be associated with damaged elastic fibers in many tissues and organs. To better characterize this interaction, binding of lysozyme to elastin was studied using solution-based binding assays. Under physiologic conditions, radio-labeled lysozyme bound specifically to elastin in a time- and concentration-dependent manner. Binding was reversible and was inhibited by unlabeled human and hen lysozyme but not by other proteins. Lysozyme had no elastolytic activity as assessed by a standard tritium-release assay, but, importantly, prevented the proteolytic degradation of elastin by human leukocyte elastase, pancreatic elastase, thermolysin, and Pseudomonas elastase. A striking feature of lysozyme's anti-elastase activity was that it did not function in the classical sense of inhibiting directly the enzymatic activity of the protease. Instead, by binding to elastin, lysozyme prevented the protease from interacting with the elastin substrate in ways that normally favor proteolysis. These results show that lysozyme binds to the elastin component of elastic fibers and that this interaction has important biological consequences for elastic fiber degradation. By preventing degradation of elastin, lysozyme can function as an important natural inhibitor that exerts a protective effect on elastic fibers at sites of tissue injury.

Sleep and the sleep electroencephalogram across the menstrual cycle in young healthy women.

Cyclic changes in hormones, body temperature, and metabolic rate characterize the menstrual cycle. To investigate whether these changes are associated with changes in sleep and the sleep electroencephalogram (EEG), a total of 138 sleep episodes from 9 women with no premenstrual syndrome symptoms were recorded every second night throughout one ovulatory menstrual cycle and analyzed in relation to menstrual phase. Ovulation and menstrual cycle stage were confirmed by measurements of temperature, urinary LH, and midluteal plasma levels of estrogen and progesterone. No significant variation across the menstrual cycle was observed for subjective ratings of sleep quality and mood as well as for objective measures of total sleep time, sleep efficiency, sleep latency, rapid eye movement sleep latency, and slow wave sleep. In nonrapid eye movement sleep, EEG power density in the 14.25-15.0 hertz band, which corresponds to the upper frequency range of the sleep spindles, exhibited a large variation across the menstrual cycle, with a maximum in the luteal phase. The data show that in healthy young women, sleep spindle frequency activity varies in parallel with core body temperature, whereas homeostatic sleep regulatory mechanisms, as indexed by the time course of EEG slow wave activity are not substantially affected by the menstrual cycle.

Quantitative anti-p24 determinations can predict the risk of vertical transmission. Swiss HIV and Pregnancy Collaborative Study Group.

Quantitative serum antibody to p24 was evaluated as a predictor of risk of vertical transmission of human immunodeficiency virus type 1 (HIV-1) infection. HIV-positive mothers, 13 with HIV-infected children and 24 with noninfected children were investigated during pregnancy and at the time of delivery. A statistically significant difference in anti-p24 titers was found between the mothers with infected and those with noninfected children independent of whether antibodies were measured during pregnancy or at the time of delivery. High anti-p24 levels correlated with a low risk of vertical transmission, whereas low anti-p24 titers were associated with an increased risk of vertical transmission. Although the number of CD4+ T-cells was lower and neopterin and beta-2 microglobulin values were higher in the group of mothers with infected children than in the noninfected group, no statistical significance was achieved due to the small sample size.

Characterization of a CHO cell line resistant to killing by the hypoxic cell cytotoxin SR 4233.

One approach to understanding the mechanism of selective hypoxic cell killing by the benzotriazine-di-N-oxide, SR 4233, is to characterize cell lines that exhibit increased resistance to killing by this drug. The Chinese Hamster Ovary cell line BL-10 was originally isolated on the basis of its hypersensitivity to killing by bleomycin. It is 2.7-fold more resistant to hypoxic cell killing by SR 4233 than wild-type CHO on comparison of D0's. However, both BL-10 and CHO possess the same sensitivity to killing by SR 4233 under aerobic conditions. We have excluded the explanation that differential metabolism of SR 4233 is responsible for its increased survival as both BL-10 and CHO produce the two-electron product SR 4317 at the same rate (3 nmoles/hr/10(6) cells). Analysis of free radical production, DNA double-strand break induction, and glutathione (GSH) levels suggested that the resistance of BL-10 to killing by SR 4233 might result from increased intracellular radical scavenger pathways. Using buthionine sulfoximine (BSO) to decrease cellular GSH levels, we found a marked increase in the sensitivity of BL-10 cells to SR 4233 killing under hypoxia, but a much smaller increase in the sensitivity of CHO cells. Taken together, these data imply that the high GSH levels in BL-10 cells is responsible for its resistance to SR 4233 cytotoxicity.

Changes in sleep and sleep electroencephalogram during pregnancy.

The impairment of sleep quality is a common complaint during pregnancy. To investigate the changes in sleep in the course of pregnancy, the sleep electroencephalogram (EEG) was recorded and analyzed in nine healthy women on 2 consecutive nights during each trimester of pregnancy. Waking after sleep onset increased from the second (TR2) to the third (TR3) trimester, whereas rapid eye movement (REM) sleep decreased from the first trimester (TR1) to TR2. Spectral analysis of the EEG in nonrapid eye movement (NREM) sleep revealed a progressive reduction of power density in the course of pregnancy. In comparison to TR1, the values in TR2 were significantly lower in the 10.25-11.0-Hz and 14.25-17.0-Hz bands. In TR3, the significant reduction extended over the ranges of 1.25-12.0 Hz and 13.25-16.0 Hz. The largest decrease (30%) occurred in the 14.25-15.0-Hz band. In REM sleep, the spindle frequency range was not affected, and a minor reduction of power density in some frequency bins below 12 Hz was present only in TR3. The study documents major alterations of the sleep EEG that are not evident from the sleep scores and that may be associated with the characteristic hormonal changes occurring during pregnancy.

Mathematical modeling of proteinase A overproduction by Saccharomyces cerevisiae.

A simple, structured model was developed to describe the growth and product formation behavior of two recombinant strains of Saccharomyces cerevisiae (JG176 and JG180), both overproducing extracellular proteinase A. The model parameters were estimated to data from continuous fermentations obtained at steady-state conditions. Model predictions show good agreement with experimental data obtained by batch fermentations. The two concerned organisms are distinguished from each other by the type of promoter on the plasmids controlling the proteinase A expression. The proteinase A transcription is controlled by the natural proteinase A promoter in JG176 and by a tpi promoter in JG180. By means of experiments and simulations, the extracellular product formation from the two strains with different promoter systems was compared in batch and continuous fermentations. The results showed that the proteinase A formation kinetic from JG176 was a combination of growth and nongrowth associated (production in the stationary growth phase), whereas the proteinase A formation from JG180 was truly growth associated (production in the exponential growth phase). In both batch and continuous cultivations JG176 gave the highest product concentrations and volumetric productivities.

The use of antibodies for characterization and quantification of a recombinant protein.

In this study, we characterized proteinase A secreted by recombinant Saccharomyces cerevisiae bearing a multicopy plasmid containing the encoding gene (PEP4). Polyclonal and monoclonal antibodies were raised to study the product heterogeneity. Characterization of proteinase A was performed by immunoelectrophoresis and immunoblotting techniques. None of the monoclonal antibodies raised against proteinase A was found to react with the glycosyl side chains; thus cross-reaction with other glycosylated proteins (e.g. carboxypeptidase Y) was very low. This study allowed us to develop an ELISA method for the quantification of proteinase A in culture supernatants as well as the evaluation of monoclonal antibodies for their use in immunoaffinity chromatography.