Sinusitis-induced enophthalmos: the silent sinus syndrome.

Enophthalmos caused by inadequate maxillary sinus function was first reported in 1964. Since this initial report, scattered case reports and, more recently, reviews have appeared in the literature detailing the pathophysiology, clinical findings, and management of this process. We present a classic case of the asymptomatic development of enophthalmos caused by maxillary sinus hypoventilation: the silent sinus syndrome. In addition, this case included findings in the ethmoid sinuses that suggested their contribution to this disorder, which by our review of the literature has not been well described.

Invasive fungal sinusitis in the acquired immunodeficiency syndrome.

Invasive fungal sinusitis can present as either an indolent or fulminant process that primarily affects immunocompromised individuals. In this article, the clinical characteristics of four cases of invasive fungal sinusitis in patients with AIDS are analyzed and 22 additional previously reported cases in the literature are reviewed. In addition to HIV infection, other variables common to these cases include facial pain or headache out of proportion to clinical or radiographic findings, CD4 lymphocyte count less than 50 cells/mm(3), absolute neutrophil count less than 1,000 cells/mm(3), subtle radiographic evidence suggesting invasion and an indolent clinical course of the invasive infection. The most common pathogen detected was Aspergillus fumigatus. Maintaining a high index of suspicion, critically assessing these clinical findings, and prudently reviewing CT scans may facilitate early diagnosis and prompt intervention in these patients.

Expression and hormonal regulation of the Sox4 gene in mouse female reproductive tissues.

The SOX genes define a family of transcriptional regulators whose diverse patterns and tightly controlled temporal profiles of expression suggest that they play key roles in determination of cell fate during development. One of the family members, Sox4, is expressed in the gonads of adult mice, but expression in the reproductive tissues has not been studied. As previous studies in this laboratory had shown that the SOX4 gene was regulated by ovarian hormones in breast cancer cells, murine Sox4 expression was analyzed in the reproductive tissues of mice by Northern blot analysis and ribonuclease protection assays. Sox4 mRNA expression was detected in the uterus and, at a lower level, in the mammary glands of pubertal and adult mice. Expression was modulated in the uterus of intact mice at various stages of the estrous cycle and was reduced by estradiol treatment of ovariectomized mice. Progesterone treatment partially reversed the estradiol effect. Although no modulation of Sox4 expression in the mammary glands was detected by Northern blot analysis, further evaluation of Sox4 protein expression at a cellular level is required. No modulation of Sox4 levels was observed in the thymus. The results presented here suggest that expression of the Sox4 gene is under ovarian hormone control in the uterus and implicate Sox4 in the complex effects controlled by ovarian hormones in the female reproductive system.

Regulation of the expression and activity by progestins of a member of the SOX gene family of transcriptional modulators.

The mammalian testis-determining gene Sry and the related Sox genes define a family of transcriptional regulators widely expressed during embryogenesis. Tightly controlled temporal profiles of expression are a feature of the Sox gene family and may be required for initiation of a cascade of gene expression, yet the molecular mechanisms that control Sox gene expression are unknown. We now show that human SOX4 is expressed in the normal breast and in breast cancer cells. In these cells SOX4 is a progesterone-regulated gene, the expression of which is increased by progestins, leading to a marked increase in SOX-mediated transcriptional activity. Treatment of T-47D breast cancer cells with the synthetic progestin ORG 2058 directly increased SOX4 transcription, resulting in a 4-fold increase in SOX4 mRNA levels within 4 h of treatment. No effect of ORG 2058 was noted on other SOX genes measured, nor were other hormone-regulated HMG box proteins detected in this system, suggesting that the observed ability of progestin to increase SOX mRNA expression was confined to SOX4. The increase in SOX4 transcription was reflected in increased SOX4 protein expression, as progestin treatment of T-47D cells transfected with a SOX-responsive reporter resulted in a marked increase in reporter gene expression. Progesterone is essential for normal development and differentiation of the female reproductive system, plays an essential role in regulating growth and differentiation of the mammary gland and is required for opposing the proliferative effects of estrogen in specific cell types. The detection of SOX4 expression in the normal and malignant breast and the demonstration that SOX4 expression is under progesterone control suggests that changes in SOX4 gene expression may play a role in commitment to the differentiated phenotype in the normal and malignant mammary gland.

Coexpression of alternatively spliced estrogen and progesterone receptor transcripts in human breast cancer.

Primary transcripts of the human estrogen receptor (ER) and progesterone receptor (PR) are subject to a number of alternative splicing events resulting in a range of variant messenger ribonucleic acid species in receptor-positive tissues. Despite in vitro demonstrations of a possible role for some of these variants in hormonal sensitivity, the clinical significance of this process is uncertain. In this study the coexpression of variant ER and PR transcripts has been documented by RT-PCR and Southern blot analysis in a series of receptor-positive breast tumors. In 35 ER-positive tumors, a common profile of variant ER transcripts was present, with all tumors containing the delta2ER and delta7ER, 94% containing the delta4ER, and 83% containing the delta5ER. In 25 of these cases, which were also PR positive, the most highly expressed PR variants, the delta4PR, delta6PR, and delta(4/2)PR, a transcript from which a 126-bp portion of PR exon 4 was deleted, were detected in over 90% of the cases. The alternatively spliced ER variants were expressed at higher relative levels than the PR species, which had mean levels of expression less than 10% that of wild-type PR. The most abundant species was the delta7ER, which was present at levels ranging from 29-83% of the wild type. There was no relationship between the level of delta7ER in individual tumors and the pattern of expression of the estrogen-responsive proteins PR and pS2. The common profile of alternatively spliced ER and PR transcripts in breast tumors means that this feature cannot be used as a discriminator of hormone responsiveness or other clinical end points. Further, the low level of expression of the majority of variant species calls into question their potential for impacting significantly on receptor function.

Characterization of a truncated progesterone receptor protein in breast tumors.

The progesterone receptor (PR) mediates the actions of progesterone in the normal and malignant breast. PR is expressed as two proteins, PR B and PR A, which are expressed in normal progesterone target tissues and in breast cancers. A significant proportion of breast cancers contain, in addition, a smaller PR protein of molecular mass 78 kDa (PR78 kDa). The significance of PR78 kDa expression is unknown, and in particular, there are no data on whether PR78 kDa is able to bind ligand and therefore potentially exhibit transcriptional activity. If this smaller PR species exhibits similar differences in function as have been evidenced in vitro for PR A relative to PR B, it is possible that this PR species may be an important component in determination of progesterone response in breast cancer. The purpose of this study was to determine whether the PR78 kDa protein in breast tumors is able to bind ligand and to determine whether posttranscriptional mechanisms contribute to its formation in breast cancers. There was no evidence that PR78 kDa was derived from proteolytic activity of either PR B or PR A. Similarly, although exon-deleted PR transcripts were detected (which could, if translated, give rise to a PR protein similar in size to PR78 kDa), neither the abundance of such transcripts nor their relationship to levels of expressed PR78 kDa protein supported a role for exon deletion in formation of this truncated PR protein. PR78 kDa was not recognized by an antibody specific for PR B, indicating that, like PR A, it lacks the N-terminal portion of PR. PR78 kDa was able to bind the progestin ligand, indicating that it may have transcriptional activity. In summary, this study has shown that a truncated PR protein, found in breast cancers, is ligand-binding and seems to be derived from PR A, indicating that it may have a role in progesterone signaling, although a deeper understanding of its role, if any, in breast cancer remains to be established.

Probing the effects of cone potential in the electrospray ion source: consequences for the determination of molecular weight distributions of synthetic polymers.

Shifts in the relative intensities of oligomer ions are found to accompany changes in the cone potential in the electrospray ion source, which introduce uncertainties into average molecular weight determinations for polymer distributions. Similar shifts with changes in cone potential have long been recognized in the multiple-charge distributions of proteins and other biomolecules. In the case of multiple-charge distributions of a single, or small number of, species there are no major consequences for calculation of molecular weight; however, mass distributions and the averages thereof, are of major concern with synthetic polymers and understanding the shifts in relative intensities becomes critically important. We report here an evaluation of the effects of cone potentials on the molecular weight distributions of synthetic polymers, which we compare with the effects on charge-state distributions of peptides. The effects of cone potential have been modeled mathematically, from which we conclude that cone potentials exert a focusing effect dependent on the mass-to-charge ratios of ions. It is largely this focusing effect that determines the dependence of oligomer ion intensities upon cone potential in the ESI mass spectra of polymers. The influence of cone potential on molecular weight determinations of polymers of varying polydispersities (P(o)) is compared and discussed. For polymers with low polydispersities (e.g., narrow molecular weight poly(ethyleneglycol) standards with P(o) < 1.5), the variation in molecular weight determinations tends to be small (typically <5%), whereas with synthetic polymers with polydispersities greater than 2, variations in cone potential can influence molecular weight determinations significantly (by 100% or even more).

Quality of life claims in trials of anti-hypertensive therapy.

The increasing use of so-called quality of life assessments in clinical trials can be seen as a laudable attempt to gather information about the impact of treatment on patients which goes beyond the purely clinical. However, there is a growing tendency for pharmaceutical companies to use quality of life claims in marketing strategies. The varying protocols and study populations, together with multicentre and multicountry trials and the variety of implied definitions of quality of life raise serious issues concerning the scientific credibility of conclusions about quality of life as an endpoint. This paper reviews reports of randomized controlled trials of anti-hypertensive therapy which used 'quality of life', assessed by patient-completed questionnaires, as one of the outcome variables. Criteria referring to definitions of quality of life, the validity and reliability of the measures used, administration procedures, treatment of data, adequacy of discussion of alternative explanations of the findings and the legitimacy of the findings are spelled out. It is concluded that none of the studies reviewed were justified in the claims made concerning differential effects of therapies on 'quality of life'.

Chinese hamster ovary cells produce sufficient recombinant insulin-like growth factor I to support growth in serum-free medium. Serum-free growth of IGF-I-producing CHO cells.

Insulin-like growth factor I has similar mitogenic effects to insulin, a growth factor required by most cells in culture, and it can replace insulin in serum-free formulations for some cells. Chinese Hamster Ovary cells grow well in serum-free medium with insulin and transferrin as the only exogenous growth factors. An alternative approach to addition of exogenous growth factors to serum-free medium is transfection of host cells with growth factor-encoding genes, permitting autocrine growth. Taking this approach, we constructed an IGF-I heterologous gene driven by the cytomegalovirus promoter, introduced it into Chinese Hamster Ovary cells and examined the growth characteristics of Insulin-like growth factor I-expressing clonal cells in the absence of the exogenous factor. The transfected cells secreted up to 500 ng/10(6) cells/day of mature Insulin-like growth factor I into the conditioned medium and as a result they grew autonomously in serum-free medium containing transferrin as the only added growth factor. This growth-stimulating effect, observed under both small and large scale culture conditions, was maximal since no further improvement was observed in the presence of exogenous insulin.

Housing conditions and mental health in a disadvantaged area in Scotland.

OBJECTIVE: To examine the mental health impact of different aspects of poor housing. DESIGN: This was a post hoc analysis of data from a household interview survey. SETTING: A public sector housing estate on the outskirts of Glasgow. SUBJECTS: These comprised 114 men and 333 women aged between 17 and 65 from 451 households. MEASURES: Dependent variable: scoring > or = 5 on the 30 item general health questionnaire (GHQ30). INDEPENDENT VARIABLES: self reported data on household composition, whether ill health was a factor in the move to the current dwelling, length of time at address, household income, whether the respondent was employed, chronic illness, and 6 problems with the dwelling. RESULTS: Reporting a problem with dampness was significantly and independently associated with scores of > or = 5 on the GHQ30 after controlling for possible confounding variables. CONCLUSION: Initiatives to tackle housing dampness may be important in developing a strategy to improve mental health for the study area. More research on the mental health impact of different aspects of poor housing is required.

Processing of mutated human proinsulin to mature insulin in the non-endocrine cell line, CHO.

Heterologous genes encoding proproteins, including proinsulin, generally produce mature protein when expressed in endocrine cells while unprocessed or partially processed protein is produced in non-endocrine cells. Proproteins, which are normally processed in the regulated pathway restricted to endocrine cells, do not always contain the recognition sequence for cleavage by furin, the endoprotease specific to the constitutive pathway, the principal protein processing pathway in non-endocrine cells. Human proinsulin consists of B-Chain-C-peptide-A-Chain and cleavage at the B/C and C/A junctions is required for processing. The B/C, but not the C/A junction, is recognised and cleaved in the constitute pathway. We expressed a human proinsulin and a mutated proinsulin gene with an engineered furin recognition sequence at the C/A junction and compared the processing efficiency of the mutant and native proinsulin in Chinese Hamster Ovary cells. The processing efficiency of the mutant proinsulin was 56% relative to 0.7% for native proinsulin. However, despite similar levels of mRNA being expressed in both cell lines, the absolute levels of immunoreactive insulin, normalized against mRNA levels, were 18-fold lower in the mutant proinsulin-expressing cells. As a result, there was only a marginal increase in absolute levels of insulin produced by these cells. This unexpected finding may result from preferential degradation of insulin in non-endocrine cells which lack the protection offered by the secretory granules found in endocrine cells.

Super-CHO-A cell line capable of autocrine growth under fully defined protein-free conditions.

Chinese Hamster Ovary (CHO) cells are widely used for the large scale production of recombinant biopharmaceuticals. Growth of the CHO-K1 cell line has been demonstrated in serum-free medium containing insulin, transferrin and selenium. In an attempt to get autocrine growth in protein-free medium, DNA coding for insulin and transferrin production was transfected into CHO-K1 cells. Transferrin was expressed well, with clones secreting approximately 1000 ng/10(6) cells/24h. Insulin was poorly expressed, with rates peaking at 5 ng/10(6) cells/24h. Characterisation of the secreted insulin indicated that the CHO cells were incompletely processing the insulin molecule. Site-directed mutagenesis was used to introduce a furin (prohormone converting enzyme) recognition sequence into the insulin molecule, allowing the production of active insulin. However, the levels were still too low to support autocrine growth. Further investigations revealed insulin degrading activity (presumably due to the presence of insulin degrading enzymes) in the cytoplasm of CHO cells. To overcome these problems insulin-like growth factor I (instead of insulin) was transfected into the cells. IGF-1 was completely processed and expressed at rates greater than 500 ng/10(6)cells/24h. In this paper we report autonomous growth of the transfected CHO-K1 cell line expressing transferrin and IGF-1 in protein-free medium without the addition of exogenous growth factors. Growth rates and final cell densities of these cells were identical to that of the parent cell line CHO-K1 growing in insulin, transferrin, and selenium supplemented serum-free media.

Measuring psychological well-being. The adapted General Well-Being Index in a primary care setting: a test of validity.

The measurement of health outcomes is central to the development of health services. Many acute and chronic illnesses and health interventions have implications for mental health. This study tests the validity of a 22 item measure of psychological well-being, the adapted general well-being index (AGWBI). A postal health survey, including the AGWBI, was sent to a 10% random sample of patients aged 16 or over drawn from the computerized list of one general practice. Two hundred and sixty-six respondents returned questionnaires (a response rate of 76%). The AGWBI was fully completed by 94% (249) of the respondents who returned their questionnaires. Only respondents who fully completed the AGWBI are included in the analysis. The AGWBI significantly discriminated people with a limiting long term illness, those reporting suffering from anxiety, depression or bad nerves, users of general practitioner services over the previous two weeks and respondents reporting taking anti-depressants, tranquillizers or sleeping tablets. It was also able to discriminate respondents with psychosocial difficulties in a small sub-sample who reported that they were in excellent health and did not have a limiting long term health problem or psychological illness. The results are broadly supportive of the validity of the AGWBI and suggest it may be appropriate for use in the evaluation of several developing areas of primary care. Further research is needed to test concurrent validity, responsiveness and to establish population norms.

A measure of family disruption for use in chickenpox and other childhood illnesses.

A search of the literature showed the lack of a suitable measure for assessing the impact of minor illness on children and their families. Such illness can lead to considerable disruption within the family and particularly to the parent primarily responsible for the care of the ill child. Discussion groups were run with parents who had a child who had had chickenpox within the previous 6 months. Analysis of the transcripts from the groups produced items indicating three types of disruption; parents' distress, changes in the behaviour of the ill child and general disruption to family arrangements. Items from the transcripts were formed into a questionnaire which was then used in a study of 61 families in which a child had become ill with chickenpox within the previous 7 days. The principal carer completed the measure every evening for a fortnight. The results of the study showed considerable disruption over the first few days of the child's illness, followed by a steady reduction over the whole 2-week period.(ABSTRACT TRUNCATED AT 250 WORDS)

Preliminary report on the development of a disease-specific instrument for assessing quality of life of adults with growth hormone deficiency.

It is notable that many of the feelings described by the people in the sample are similar to those experienced at times by people who do not suffer from GHD, that is, lapses of memory, feeling drained of energy, loss of temper, loss of motivation, difficulty in concentrating, forgetfulness and having a tendency to gain weight. Adults with GHD, however, appear to suffer these problems more frequently and to a more extreme degree than other people. It is clear that the range of problems that afflict people with GHD is great, and that the repercussions affect virtually all aspects of their lives. The results from these interviews will form the basis of a measure designed specifically to assess the quality of life of patients with GHD, and to determine the changes in quality of life after treatment with GH.

Childhood chickenpox: its impact on child and family.

Sixty-nine parents took part in nine discussion groups designed to explore the effect of childhood chickenpox on the behaviour of the affected child, on family routines and on the parents themselves. Although most parents thought of chickenpox as a relatively trivial illness, it was found that there was considerable disruption to family organization and plans and, often, great strain was imposed on a parent, usually the mother. Some families incurred extra financial burdens in terms of time taken from work, the purchase of over the counter preparations, childminders and special treats for the sick child. It was apparent that parents needed more information and reassurance about the nature and course of the illness.