bluuebunny/crossref_metadata_2025 huggingface dataset:
The mbk‐2 kinase is required for inactivation of MEI‐1/katanin in the one‐cell Caenorhabditis elegans embryo
Authors: Quintin Sophie , Mains Paul E , Zinke Andrea , Hyman Anthony A
Published: November 2003

The Caenorhabditis elegans early embryo is widely used to study the regulation of microtubule‐related processes. In a screen for mutants affecting the first cell division, we isolated a temperature‐sensitive mutation affecting pronuclear migration and spindle positioning, phenotypes typically linked to microtubule or centrosome defects. In the mutant, microtubules are shorter and chromosome segregation is impaired, while centrosome organization appears normal. The mutation corresponds to a strong loss of function in mbk‐2, a conserved serine/threonine kinase. The microtubule‐related defects are due to the postmeiotic persistence of MEI‐1, a homologue of the microtubule‐severing protein katanin. In addition, P‐granule distribution is abnormal in mbk‐2 mutants, consistent with genetic evidence that mbk‐2 has other functions and with the requirement of mbk‐2 activity at the one‐cell stage. We propose that mbk‐2 potentiates the degradation of MEI‐1 and other proteins, possibly via direct phosphorylation.
Drawing up boundaries: a technique
Authors: Wilkinson Simon
Published: November 2003

A technique is described for eliciting information about family structure in terms of boundaries and alliances through an individual session with a child using the medium of drawing. An advantage of this approach is that the child's perspective is elicited through a medium with which the child feels familiar and at ease, which can subsequently be taken further with the child in or out of the family.
Feminism and family therapy—a possible meeting point
Authors: Pilalis Jennie , Anderton Joy
Published: November 2003

This paper centres on the question ‘Is it possible to be a feminist and to practise family therapy?’ We explore the essence of feminism and family therapy and conclude that a style of feminist family therapy is possible. Feminist family therapy has a particular theoretical base and is characterized by a particular combination of practice principles. It also raises general issues for the training and practice of all family therapists.
My mind is alive and well and fouling up the system: existential‐phenomenological considerations in family therapy
Authors: Kaye John
Published: November 2003

It is customary amongst family therapists who work within a general systems framework to reject any consideration of individual phenomenology in their evaluation and treatment of family difficulties. One of the reasons often cited for this is the supposed incompatibility between the systems and intrapsychic perspectives. It is argued in this paper (a) that the two perspectives, while derived from two different levels of conceptualization, are not mutually exclusive or unconnected; (b) that an understanding of the experiential world of family members as this contributes to family interaction patterns can promote effective intervention. A framework is suggested drawing on existential (experiential) concepts and the thesis is illustrated by means of a case‐study.
Enhancement of health‐giving family support versus treatment of family pathology
Authors: Falloon Ian R. H. , Pederson Jean , Al‐Khayyal Manhal
Published: November 2003

Family assessment and therapy has emphasized the negative, pathogenic features of the family relationships of persons who have suffered episodes of schizophrenia. The role of the family as the major provider of supportive care for the disabled patient has received much less attention. A case is made for greater emphasis on the coping abilities of families and family therapy methods that specifically increase these functions through enhancing the problem‐solving skills of the family unit.
Preliminary psychometric evaluation of a standardized clinical family interview
Authors: Kinston Warren , Loader Peter
Published: November 2003

Though multiple task interviews are often preferable for family interaction research, clinical‐style interviews have a rôle to play. The ‘Standardized Clinical Family Interview’, whose development, structure and mode of administration have been described in an earlier paper, is designed to elicit family interaction in a clinically relevant fashion. A series of studies which evaluated the reliability, sensitivity, validity and acceptability of this instrument is now provided. The results suggest that the SCFI is useful and deserves further study; however, interviewer training is a major task.
A perspective on the brief hospitalization of whole families
Authors: Brendler John
Published: November 2003

This paper reviews our experiences as an interdisciplinary team treating entire families who live in our hospital apartments. Over 100 families have now been treated. The therapeutic effort is based on the expectation that families have the capacity to employ staff support and skills, to solve problems and move competently through transitions of increasing complexity. We have found that it is essential to capitalize on the crisis that hospitalization entails in order to help families take more effective charge of their own lives.
The Milan method—a preliminary critique*
Authors: Treacher Andy
Published: November 2003

The elegance of the techniques developed by the Milan group has tended to blind family therapists to the many problems inherent in their approach. A close reading of their work uncovers many ethical and political issues which need to be addressed. This paper is a preliminary attempt to develop a critique of the group's method which recapitulates some of the most alienating aspects of the traditional medical model. It will concentrate solely on a critical reading of Paradox and Counterparadox and will not seek to come to terms with the more recent evolution of the Milan school.
‘Psychosomatic families’: Henry B. Richardson remembered*
Authors: Roy Ranjan
Published: November 2003

Henry B. Richardson's work is reassessed. It is argued that he demonstrated an understanding of the role of family factors in the etiology and perpetuation of psychosomatic disorders which was well ahead of his time. On the other hand, his contribution has largely been ignored by contemporary family theorists. This paper is an attempt to rectify that oversight.
A reframe by any other name: on the process of refraining in strategic, Milan and analytic therapy
Authors: Flaskas Carmel
Published: November 2003

This paper explores the process of reframing within strategic, Milan and analytic therapy. There are two purposes in exploring the different frameworks – the first is to clarify the differences in each framework; the second is to examine reframing as a generic process in therapy. In the course of the discussion, some common themes emerge. These include the question of the client's experience of therapy, the tendency to depersonalize the process of reframing, and the issue of truth in relation to reframing. Throughout the paper, there is an attempt to avoid the tendency in family therapy to treat difference competitively.
Risk factors for hypertension during pregnancy in South Australia
Authors: Jacobs Daniëlle J. , Vreeburg Sophie A. , Dekker Gus A. , Heard Adrian R. , Priest Kevin R. , Chan Annabelle
Published: November 2003

Objective: To identify risk factors for hypertension in pregnancy among South Australian women.

Design: A population‐based retrospective analysis using the South Australian perinatal data collection for 1998–2001.

Methods: Three groups of women with hypertension (pre‐existing hypertension, pregnancy hypertension, and superimposed pre‐eclampsia) were compared with normotensive women using unconditional logistic regression analysis on 70 386 singleton births to identify sociodemographic and clinical risk factors for hypertension in pregnancy.

Results:  Nulliparity, Aboriginal race and Caucasian race (compared with Asian) and pre‐existing and gestational diabetes were demonstrated to be risk factors for all hypertensive disorders, as was increasing maternal age for pre‐existing hypertension and superimposed pre‐eclampsia. Risk was increased for pregnancy hypertension and superimposed pre‐eclampsia among women who gave their occupation as ‘home duties’ and also for superimposed pre‐eclampsia among unemployed women. Women with hypertension were more likely to give birth in teaching hospitals. Urinary tract infections were not found to be a risk factor for any type of hypertension. Smoking during pregnancy was protective for all types of hypertension.

Conclusions: The present study used a statewide population perinatal database and has confirmed that Aboriginal race, Caucasians, nulliparity, and pre‐existing and gestational diabetes are independent risk factors for all types of hypertension in pregnancy. Increasing maternal age increased the risk for pre‐existing hypertension and superimposed pre‐eclampsia. There appeared to be appropriate referral of women with hypertensive disorders to teaching hospitals. A new finding is the increased risk among unemployed women and women engaged in home duties.
Simulating evolution of glyphosate resistance in Lolium rigidum II: past, present and future glyphosate use in Australian cropping
Authors: Neve P , Diggle A J , Smith F P , Powles S B
Published: November 2003

Glyphosate is a key component of weed control strategies in Australia and worldwide. Despite widespread and frequent use, evolved resistance to glyphosate is rare. A herbicide resistance model, parameterized for Lolium rigidum has been used to perform a number of simulations to compare predicted rates of evolution of glyphosate resistance under past, present and projected future use strategies. In a 30‐year wheat, lupin, wheat, oilseed rape crop rotation with minimum tillage (100% shallow depth soil disturbance at sowing) and annual use of glyphosate pre‐sowing, L. rigidum control was sustainable with no predicted glyphosate resistance. When the crop establishment system was changed to annual no‐tillage (15% soil disturbance at sowing), glyphosate resistance was predicted in 90% of populations, with resistance becoming apparent after between 10 and 18 years when sowing was delayed. Resistance was predicted in 20% of populations after 25–30 years with early sowing. Risks of glyphosate resistance could be reduced by rotating between no‐tillage and minimum‐tillage establishment systems, or by rotating between glyphosate and paraquat for pre‐sowing weed control. The double knockdown strategy (sequential full rate applications of glyphosate and paraquat) reduced risks of glyphosate and paraquat resistance to <2%. Introduction of glyphosate‐resistant oilseed rape significantly increased predicted risks of glyphosate resistance in no‐tillage systems even when the double knockdown was practised. These increased risks could be offset by high crop sowing rates and weed seed collection at harvest. When no selective herbicides were available in wheat crops, the introduction of glyphosate‐resistant oilseed rape necessitated a return to a minimum‐tillage crop establishment system.
Simulating evolution of glyphosate resistance in Lolium rigidum I: population biology of a rare resistance trait
Authors: Neve P , Diggle A J , Smith F P , Powles S B
Published: November 2003

Despite frequent use for the past 25 years, resistance to glyphosate has evolved in few weed biotypes. The propensity for evolution of resistance is not the same for all herbicides, and glyphosate has a relatively low resistance risk. The reasons for these differences are not entirely understood. A previously published two‐herbicide resistance model has been modified to explore biological and management factors that account for observed rates of evolution of glyphosate resistance. Resistance to a post‐emergence herbicide was predicted to evolve more rapidly than it did to glyphosate, even when both were applied every year and had the same control efficacy. Glyphosate is applied earlier in the growing season when fewer weeds have emerged and hence exerts less selection pressure on populations. The evolution of glyphosate resistance was predicted to arise more rapidly when glyphosate applications were later in the growing season. In simulations that assumed resistance to the post‐emergence herbicide did not evolve, the evolution of glyphosate resistance was less rapid, because post‐emergence herbicides were effectively controlling rare glyphosate‐resistant individuals. On their own, these management‐related factors could not entirely account for rates of evolution of resistance to glyphosate observed in the field. In subsequent analyses, population genetic parameter values (initial allele frequency, dominance and fitness) were selected on the basis of empirical data from a glyphosate‐resistant Lolium rigidum population. Predicted rates of evolution of resistance were similar to those observed in the field. Together, the timing of glyphosate applications, the rarity of glyphosate‐resistant mutants, the incomplete dominance of glyphosate‐resistant alleles and pleiotropic fitness costs associated with glyphosate resistance, all contribute to its relatively slow evolution in the field.
The Death of the Collective Subject in Uwe Johnson's Mutmassungen über Jakob
Authors: Kenosian David
Published: November 2003

In previous interpretations of Uwe Johnson's Mutmassungen über Jakob, critics have focused primarily on Johnson's relationship to socialism on the complex narrative structure of the novel. In this essay, I explore a topic that has received comparatively little attention: Johnson's notion of subjectivity. I show that Johnson's attempt to challenge Marxist concepts of the collective subject is inseparably linked to his views on representing history. Johnson's first move is to eliminate the omniscient Socialist Realist narrator who is supposed to have a greater understanding of societal forces than do the characters in the fictional world. But in Mutmassungen über Jakob, it is the protagonist (Jakob) who has a greater understanding of politics than the former Socialist Realist narrator (Rohlfs). Their relationship undermines the political hierarchy constituted by workers and party. In addition, history in the novel is not narrated from a privileged epistemological position. Rather, it is reconstructed in a negotiation among various subjects (characters) at the porous border between history and memory. This self‐reflexive model of historiography is, as implied by Uwe Johnson, democratic, in contradistinction to Socialist Realism. Finally, I point out that this model of writing history in Mutmassungen über Jakob anticipates the polyphonic representation of the past in Johnson's Jahrestage (1970–83). In Johnson's final work, German history is consequently written in dialogues with Germans, immigrants from Eastern Europe, Holocaust survivors, and textual sources from various countries.
Progression of destructive periodontal diseases in three urban minority populations: role of clinical and demographic factors
Authors: Craig Ronald G. , Yip Julie K. , Mijares Dindo Q. , LeGeros Racquel Z. , Socransky Sigmund S. , Haffajee Anne D.
Published: November 2003

Background, aims: Differences in prevalence, severity and risk factors for destructive periodontal diseases have been reported for ethnic/racial groups. However, it is not certain whether this disparity is due to ethnicity/race or factors associated with ethnicity/race. Therefore, the present study addressed whether the rates of disease progression and clinical and demographic factors associated with disease progression varied among three ethnic/racial groups.

Methods: The study population consisted of 53 Asian‐, 69 African‐ and 62 Hispanic‐Americans. Clinical measurements included probing depth, attachment level, gingival erythema, bleeding upon probing, suppuration and plaque. Disease progression was defined as a >2 mm loss of attachment 2 months post baseline. The demographic variables examined included occupational status, report of a private dentist, years resident in the United States and smoking history.

Results: The rate of attachment loss for the entire population was 0.04 mm or 0.24 mm/year. No significant differences were found among the three ethnic/racial groups. Variables associated with subsequent attachment loss for the entire population were age, male gender, mean whole‐mouth plaque, erythema, bleeding upon probing, suppuration, attachment loss and probing depth, and belonging to the “unskilled” occupational group. No differences in risk profiles were found among the 3 ethnic/racial groups. Using stepwise logistic regression analysis, a model was developed to relate the clinical and demographic variables examined with subsequent attachment loss. The model indicated that prior attachment loss, gingival erythema, suppuration, being a current smoker and belonging to the “unskilled” occupational group conferred high risk of >1 site of attachment loss of >2 mm.

Conclusions: The results of this study suggest that variables associated with ethnicity/race, such as occupational status, are largely responsible for the observed disparity in destructive periodontal disease progression in these populations.
Demonstration of Feline Foamy Virus in Experimentally Infected Cats by Immunohistochemistry
Authors: Weikel J. , Löchelt M. , Truyen U.
Published: November 2003

Foamy viruses (FV) are complex retroviruses which are commonly isolated from cats, cattle and non‐human primates. The infection is persistent and infected animals have a sustained antibody response. The role of FV in diseases remains unclear, in cats, a possible association with uncharacterized renal symptoms remains to be confirmed. To demonstrate feline FV (FFV) in tissues of experimentally infected cats three polyclonal monospecific antisera from rabbits against three different viral proteins, the structural Gag and the non‐structural Bel 1 and Bet proteins were tested for their applicability in immunohistochemistry with paraffin sections. Only the Bet antiserum allowed detection of FFV‐specific proteins, the antibodies against Gag and Bel 1 did not work even after pre‐treatment of the slides with proteinase K or cooking in a pressure cooking pot. The Bet‐reactive antibodies were detected using a commercial streptavidin kit and revealed Bet in the cytoplasm of cells from different lymphoid tissues like lymphnodes, tonsils, thymus and spleen. The method described opens new ways to explore the in vivo replication and tissue specificity of FFV and its possible role in disease.
Emerging Legal Orders. Formalism and the Theory of Legal Integration
Authors: Schäfer Burkhard , Bankowski Zenon
Published: November 2003

Using analogies from research in simulation and artificial societies and borrowing from Weinrib's Philosophy of Private Law, we show how a “private law” model of law and legal integration does not need to presuppose the state as a regulatory framework. Rather, the state emerges as a “second order property” from the private law interaction of individuals. We apply this to the debate about harmonisation in Europe. We show how a form of unity in diversity can be built up starting with such individual interactions, extended later to interactions between member states. But this does not need to end up in an individualistic and neo‐liberal model, as in Weinrib, if we understand the underlying exchange relation in terms of Wilhelmsson's social contract law.
Retrospective analysis of 1312 patients with haemophilia and related disorders in a single Chinese institute
Authors: Zhang L. , Li H. , Zhao H. , Zhang X. , Ji L. , Yang R.
Published: November 2003

Summary.  With 1.3 billion people, China has the largest population in the world, and therefore has the largest population of persons with haemophilia (PWH). As there is no national registry for haemophilia, it is difficult to ascertain how many PWH have actually been diagnosed. Between January 1983 and June 2002, 1312 patients with coagulation disorders were referred to our hospital, and 1190 patients were evaluable. Among them, 1069 (89.8%) patients had haemophilia, 68 had vWD, 20 had factor XI deficiency, 10 had acquired factor VIII inhibitor and 23 had other coagulation disorders. Of the 1069 PWH, 14.7% were unclassified, 38.4% severe, 35.7% moderate and 11.1% mild. If the unclassified cases were excluded, 45.1% were severe, 41.9% moderate and 13.0% mild. Twenty‐nine of the 68 vWD patients had vWF:Ag <5%, and subcategorized as type 3 vWD. Because vWF multimer analysis was not performed in our centre, the remaining vWD patients were not subdivided.
In vitro efficacy of l‐asparaginase in childhood acute myeloid leukaemia
Authors: Okada Shuichi , Hongo Teruaki , Yamada Sayuri , Watanabe Chieko , Fujii Yuji , Ohzeki Takehiko , Horikoshi Yasuo , Ito Tsuyoshi , Yazaki Makoto , Komada Yoshihiro , Tawa Akio
Published: November 2003

Summary.  To explore the potential efficacy of l‐asparaginase treatment in acute myeloid leukaemia (AML) patients, we studied the in vitro resistance of French–American–British (FAB) subtypes of childhood AML to l‐asparaginase using a methyl–thiazol–tetrazolium assay. We tested leukaemic cells obtained from 177 common acute lymphoblastic leukaemia (cALL) and 228 AML children at diagnosis. The median 70% lethal dose of l‐asparaginase (LD70asp) (U/ml) was 0·46 in the cALL and 6·70 in the AML samples. The median LD70asp among each FAB subtype of AML was 0·76 (M0), 0·46 (M1), 10·00 (M2), 10·00 (M3), 1·18 (M4), 1·35 (M5) and 10·00 (M7). Type M3 samples had the highest LD70asp. The LD70asp of the M2 samples was significantly higher than that of the M1, M4 and M5 samples. When the LD70asp values were classified as low (0·016–0·159), intermediate (0·16–1·59) or high (1·6–10·00), the frequency of low, intermediate or high LD70asp among the M1 samples were similar to those among the cALL samples. In conclusion, cells from AML types M1, M4 and M5 were relatively sensitive to l‐asparaginase, and M1 cells were as sensitive as those of cALL, suggesting that l‐asparaginase treatment may be effective for these subtypes of AML.
Brief exposures of resting fibroblasts to okadaic acid stimulate DNA synthesis
Authors: Setkov N. A. , Epifanova O. I.
Published: November 2003

To study further the factors providing for cellular quiescence, we used okadaic acid (OA) at concentrations (0.1, 1, 10 or 100 nM) inhibiting type 1 and/or type 2A protein phosphatases in mammalian cell cultures. Brief (2 h) exposure of resting (0.2% serum for 72 h) NIH 3T3 mouse fibroblasts to OA with subsequent incubation of cells in a medium with 0.2% serum, stimulated DNA synthesis at all concentrations studied. Maximal stimulation was observed following pre‐incubation of resting cells with 10 nM OA. Treatment of cycling cells (10% serum) with OA (2 h pulses at 12 h intervals for 72 h) prevented their exit to the resting state on transfer to a medium with 0.2% serum. Brief exposures of resting cells to OA did not affect the rate of protein synthesis. OA pulses in the late pre‐replicative period had no effect on the entry of serum‐stimulated cells into the S phase.

Cell fusion experiments with resting (serum‐deprived) and proliferating (serum‐stimulated) NIH 3T3 cells, using radioautography with a double‐labelling technique, revealed that pre‐incubation of resting cells with OA for 2 h before and after fusion abrogates their ability to suppress the onset of DNA synthesis in the nuclei of proliferating cells in heterodikaryons. The results indicate that protein phosphatases of type 1 and/or 2A may be involved in the growth‐arrest machinery that provides for cellular quiescence.
Serum deprivation induces SV40 early promoter activity
Authors: Tzen C.‐Y. , Scott R. E. , Robinson F. D.
Published: November 2003

Proliferation and the expression of proliferation‐associated genes are modulated by changing the serum concentration in the media of cultured cells. To determine if activity of the SV40 early promoter is modulated by serum, we examined the expression of SV40 early promoter driven marker genes in murine BALB/c 3T3T cells following serum deprivation or serum stimulation. SV40‐promoter‐regulated β‐galactosidase and chloramphenicol acetyl transferase genes were studied following either transient or stable transfection. The results show that serum deprivation of growing cells induces SV40 promoter activity while serum stimulation of quiescent G0 cells suppresses it. Kinetic analyses show a significant induction of the SV40 promoter activity during the first 2 days of serum deprivation which is maintained at a high level for 15 days. The induction of reporter gene expression by serum deprivation was selective for the SV40 early promoter because such an effect was not observed using the Rous sarcoma viral promoter. Nuclear run‐off assays further show that the transcription controlled by the SV40 early promoter is ∼ twofold greater in cells rendered quiescent by serum deprivation for 72 h than in growing cells cultured in medium containing serum. These results suggest that one reason SV40 T transformed cells commonly fail to undergo quiescence following serum deprivation is that the SV40 promoter is induced.
Child protection services and parental reactions to children’s behaviour
Authors: Thorpe David , Jackson Maureen
Published: November 2003

A commonly used expression in child protection is the term ‘physical abuse’. This paper consists of a quantitative and qualitative analysis of a 100% sample of ‘physical abuse’ child protection cases drawn from research in an Australian state child welfare agency, which shows that about 90% of these concerned incidents in which parents used physical punishment to control children. Resulting physical harms to children (where they occurred) were generally of a very minor nature. The paper examines these results in the light of research findings in the UK and Australia on patterns of physical punishment used by parents to control children. Such findings suggest that those child rearing practices that make frequent and systematic use of physical punishment are located largely amongst lower social class parents, who believe that such practices are an essential and normal component of effective parenting behaviour. One interpretation of child protection services in respect of these cases is that they are concerned primarily with the normalization of child rearing practices. The paper concludes with a discussion of the limited impact of the Swedish anti‐spanking law of 1979, which appears to have only reduced the use of physical punishment by those parents who may not necessarily have believed in such measures in the first place. However, legislation of this nature has the potential to criminalize a substantial sector of the population, but at least state intervention under the aegis of a specific criminal law provides a clearer mandate than does intervention under much looser, broader and subjectively interpreted child protection legislation.
Recombinant hGH replacement therapy and the hypothalamus–pituitary–thyroid axis in children with GH deficiency: when should we be concerned about the occurrence of central hypothyroidism?
Authors: Giavoli Claudia , Porretti Silvia , Ferrante Emanuele , Cappiello Vincenzo , Ronchi Cristina L. , Travaglini Pietro , Epaminonda Paolo , Arosio Maura , Beck‐Peccoz Paolo
Published: November 2003

objective  Recombinant hGH treatment may alter thyroid hormone metabolism and we have recently reported that 50% of patients with GH deficiency (GHD) due to organic lesions, previously not treated with thyroxine, developed hypothyroidism during treatment with recombinant human GH (rhGH). These results prompted us to evaluate the impact of rhGH treatment on thyroid function in children with GHD.

design  Open study of GH treatment up to 12 months. Investigations were performed at baseline, and after 6 and 12 months of GH therapy.

measurement and study subjects  Serum TSH, FT4, FT3, AbTg and AbTPO, IGF‐I, height and weight, were evaluated in 20 euthyroid children (group A) with idiopathic isolated GHD and in six children (group B) with multiple pituitary hormone deficiencies (MPHD) due to organic lesions. Among the latter, four already had central hypothyroidism and were on adequate LT4 replacement therapy, while two were euthyroid at the beginning of the study.

results  Serum IGF‐I levels normalized in all patients. In both groups, a significant reduction in FT4 levels (P < 0·01) occurred during rhGH therapy. No patient in group A had FT4 values into the hypothyroid range, while in four of six patients in group B, fell FT4 levels into the hypothyroid range during rhGH. In particular, the two euthyroid children developed central hypothyroidism during rhGH treatment, and their height velocities did not normalize until the achievement of euthyroidism through appropriate LT4 substitution. No variation in serum FT3 and TSH levels was recorded in either groups.

conclusion  Contrary to that observed in patients with MPHD, rhGH replacement therapy does not induce central hypothyroidism in children with idiopathic isolated GHD, further supporting the view that in children with MPHD, as in adults, GHD masks the presence of central hypothyroidism. Slow growth (in spite of adequate rhGH substitution and normal IGF‐I levels) is an important clinical marker of central hypothyroidism, therefore a strict monitoring of thyroid function is mandatory in treated children with MPHD.
Metabolic, inflammatory and haemostatic effects of a low‐dose continuous combined HRT in women with type 2 diabetes: potentially safer with respect to vascular risk?
Authors: McKenzie Joyce , Jaap Alan J. , Gallacher Stephen , Kelly Anne , Crawford Lynne , Greer Ian A. , Rumley Ann , Petrie John R. , Lowe Gordon D. , Paterson Kenneth , Sattar Naveed
Published: November 2003

background  Conventional hormone replacement therapy (HRT) containing conjugated equine oestrogen (CEE) and medroxyprogesterone acetate (MPA) increases triglyceride, C‐reactive protein (CRP) and coagulation Factor VII concentrations, potentially explaining their increased coronary heart disease (CHD) and stroke risk.

objective  To assess the metabolic effects of a continuous combined HRT containing 1 mg oestradiol and 0·5 mg norethisterone or matching placebo.

design  Double‐blind, randomized placebo‐controlled trial.

patients  Fifty women with type 2 diabetes.

measurements  Classical and novel risk factors for vascular disease.

results  Triglyceride concentration was not altered (P = 0·31, change in active arm relative to placebo) and low‐density lipoprotein (LDL) cholesterol concentration declined 13% (P = 0·018). IL‐6 concentration (mean difference −1·42 pg/ml, 95% CI: −2·55 to –0·29 IU/dl, P = 0·015), Factor VII (−32 IU/dl, −43 to −21 IU/l, P < 0·001) and tissue plasminogen activator antigen (by 13%, P = 0·005) concentrations fell, but CRP was not significantly altered (P = 0·62). Fasting glucose (P = 0·026) also declined significantly, but there are no significant effects on HBA1c, Factor IX or APC resistance.

conclusions  HRT containing 1 mg oestradiol and 0·5 mg norethisterone may avoid the adverse metabolic effects potentially implicated in the elevated CHD and stroke risk induced by conventional higher dose HRT. This type of preparation may therefore be more suitable than conventional HRT for women at elevated CHD risk such as those with type 2 diabetes. Large randomized controlled trials of such low dose preparations, powered for cardiovascular end points, are now needed.
Serum leptin levels in patients with premenstrual syndrome treated with GnRH analogues alone and in association with tibolone
Authors: Tommaselli Giovanni A. , Di Carlo Costantino , Bifulco Giuseppe , Di Spiezio Sardo Attilio , Pellicano Massimiliano , Nappi Carmine
Published: November 2003

objective  Leptin seems to regulate reproductive function and it has been hypothesised that its secretion may be induced by oestrogens. Changes in its levels has been advocated as a determinant in the pathogenesis of premenstrual syndrome (PMS). We evaluated serum leptin levels in patients affected by PMS and in controls to establish: (i) if induced hypoestrogenism has an impact on leptin concentrations; (ii) if the administration of tibolone modifies the effects of hypoestrogenism on serum leptin levels; and (iii) if the improvement in PMS symptomatology can be correlated to changes in serum leptin levels.

design  Prospective, randomized study.

patients  Twenty‐eight women affected by PMS and 20 unaffected controls. Affected patients were randomly assigned to two groups to receive leuprolide acetate (3·75 mg intramuscularly) plus tibolone (2·5 mg/day) (group A; n = 14) or plus placebo (group B; n = 14), at the onset of the vasomotor symptoms.

measurements  Serum leptin, oestradiol and progesterone levels, PMS signs and symptoms evaluated during a 2 months’ pretreament period and after 2 months of therapy.

results  No differences in leptin levels among the three groups and within the same group at all time evaluated were observed. Oestradiol and progesterone concentrations were significantly lower in all groups during treatment in comparison with pretreatment values. Before therapy, leptin levels were positively correlated both with oestradiol and progesterone in the follicular and luteal phase in all groups. This correlation was lost after treatment. All PMS patients showed a significant improvement of the symptomatology.

conclusions  Hypoestrogenism induced by GnRH analogues (GnRHa) does not seem to influence leptin levels in normal women and those with PMS, and the addition of tibolone does not impact on these levels. Because PMS symptomatology did significantly improve during treatment with GnRHa alone, or in associtation with tibolone, it is unlikely that changes in leptin levels could have an important role in the pathophysiology of PMS.
Acquired prolactin deficiency indicates severe hypopituitarism in patients with disease of the hypothalamic–pituitary axis
Authors: Mukherjee Annice , Murray Robert D. , Columb Breeda , Gleeson Helena K. , Shalet Stephen M.
Published: November 2003

objective  Prolactin deficiency has been the subject of many scientific studies, but there is a paucity of information regarding prolactin deficiency in humans. In this report, adults with disease of the hypothalamic–pituitary axis (HPA) were studied to determine the prevalence of severe acquired prolactin deficiency (APD) and the pathophysiological characteristics associated with it.

patients and methods  APD was defined as a serum prolactin level persistently below the detection limit of the assay, i.e. less than 50 mU/l (normal range: male 85–444, female 85–530). Patients with a diagnosis of acromegaly, prolactinoma or with congenital or drug induced prolactin deficiency were excluded. Three hundred and sixty‐nine patients (190 women, age range 17–79 years) with disease of the HPA, meeting the specified criteria were identified.

results  Twenty‐two (13 women, age range 29–76 years), showed evidence of APD. Thirteen of the 22 patients with APD had been treated for Cushing's disease. In all, 62 patients treated for Cushing's disease were identified, resulting in a prevalence of APD in treated Cushing's disease of 20·97%. Excluding treated Cushing's disease, the prevalence of APD in the remainder of the cohort was 2·93%. Nineteen patients with APD (86·4%) and 183 without APD (52·7%) underwent surgery in the region of the HPA (P = 0·0042). In contrast, nine patients with APD (40·9%) and 283 without APD (80·4%) had received radiotherapy, with fields which included the HPA (P < 0·001). No patient with isolated APD was identified. All patients with APD had evidence of severe GH deficiency (GHD) with a peak GH response to provocative stimuli of < 1·6 mU/l and a median IGF‐I standard deviation score (SDS) of −4·85 (quartiles −9·56 to −2·80). Of the 13 patients with APD and Cushing's disease, all were gonadotrophin and TSH‐deficient, six were adrenocorticotropic hormone (ACTH)‐deficient and six (46·1%) had cranial diabetes insipidus (CDI). Of the remaining nine patients with APD, total anterior pituitary hormone failure was present in all and CDI was present in two (22·2%).

conclusions  The presence of APD indicates severe hypopituitarism in adults with HPA disease. It is universally associated with severe GHD. It is more common after surgery to the HP region. It has a low overall prevalence except in patients surgically treated for Cushing's disease.
Reduced exercise capacity in untreated adults with primary growth hormone resistance (Laron syndrome)
Authors: Ben‐Dov Issahar , Gaides Mark , Scheinowitz Mickey , Wagner Rivka , Laron Zvi
Published: November 2003

objective  Primary IGF‐I deficiency (Laron syndrome, LS) may decrease exercise capacity as a result of a lack of an IGF‐I effect on heart, peripheral muscle or lung structure and/or function.

methods  Eight patients (six females) who had never received treatment with IGF‐I, with mean age of 36 ± 10 (SD) years (range 21–48), weight 47 ± 9 kg (31–61), height 126 ± 12 cm (112–140) and body mass index of 29 ± 4 kg/m2 (24–34), and 12 age‐matched controls, underwent lung function tests and incremental cycling to the limit of tolerance (CPX, MedGraphics). Predicted values for the patients were derived from adult equations based on height.

results  In LS patients, lung function was near normal; vital capacity was 84 ± 11% of expected (66–103). Peak exercise O2‐uptake and the anaerobic threshold were reduced, 57 ± 20% of predicted and 33 ± 9% of predicted peak (P = 0·005 vs. controls), despite normal mean exercise breathing reserve. All parameters were normal in the controls.

conclusion  Exercise capacity in untreated adults with LS is significantly reduced. The limitation for most patients was not ventilatory but resulted either from low cardiac output and/or from dysfunction of the peripheral muscles. However, the relative contribution of each of these elements and/or the role of poor fitness needs further study.
Molecular characterization of arrestin family members in the malaria vector mosquito, Anopheles gambiae
Authors: Merrill C. E. , Pitts R. J. , Zwiebel L. J.
Published: November 2003

Olfaction influences many insect behaviours including mate seeking and host selection. The molecular machinery underlying insect olfactory systems is a G protein‐coupled receptor pathway that, in addition to activation, requires adaptation for olfactory sensitivity and discrimination. We have previously identified ARR1 (henceforth AgARR1), a sensory arrestin from the malaria vector mosquito Anopheles gambiae that has been postulated to modulate olfactory adaptation. This report describes three additional arrestin family members including ARR2 (henceforth AgARR2), which is similar to previously characterized insect sensory arrestins and is expressed at significantly higher levels in the antennae of male vs. female A. gambiae mosquitoes. This finding is consistent with the hypothesis that AgARR2 may be important for the regulation of olfactory‐driven behaviours particular to male mosquitoes.
Synthesis of peptide sequences related to thrombospondin: factors affecting aspartimide by‐product formation
Authors: Cebrián J. , Domingo V. , Reig F.
Published: November 2003

Abstract:  Aspartimide formation is one of the most common secondary reactions on solid phase peptide synthesis. In the present work, we describe the optimization of the synthesis of two thrombospondin fragments containing an Asp‐Gly sequence that show a strong tendency to form cyclic aspartimide derivatives in an unusual high percentage. Several different strategies were applied changing type of resin, Fmoc‐deprotection reagents, coupling additives, resin cleavage cocktails and the use of Hmb‐Gly derivative to minimize the extension of this byproduct. Best results were obtained with cross‐linked ethoxylate acrylate (CLEAR®‐cross‐linked ethoxylate Acrylate Resin)‐type resin and pip/dimethylformamide deprotection. Besides, as in biological assays the aspartimide containing sequence resulted to be more active than the linear one, the optimization of its synthesis was also carried out.
Attempt to map the receptor binding sites of human follicle‐stimulating hormone using disulfide peptides of its β‐subunit indicates major involvement of the regions around disulfide bonds Cys28–Cys82 and Cys32–Cys84 in receptor binding of the hormone
Authors: Jetly N.M. , Iyer K.S. , Mahale S.D. , Hosur M.V.
Published: November 2003

Abstract:  Follicle‐stimulating hormone (FSH) is a heterodimeric glycoprotein hormone secreted by the anterior pituitary. It plays a very important role in folliculogenesis in females and is responsible for spermatogenesis in males. The α‐subunit which is common within a species and the β‐subunit which is hormone‐specific are held together by noncovalent association. This association is very essential for the biological activity of the hormone. Each of these subunits are highly cross‐linked by disulfide bonds which appear to stabilize the tertiary structures required for the noncovalent association of the subunits to generate hormonal activity. This study was initiated to delineate the role of the disulfide bonds of hFSHβ in receptor binding of the hormone. Five intermolecular and one intramolecular disulfide peptides corresponding to the disulfide bonds found in hFSHβ were synthesized and screened along with their linear counterparts, for their ability to competitively inhibit the radiolabelled [125I]hFSH from binding to the FSH receptor containing membranes from the testis of immature rats. The disulfide peptides Cys28–Cys82 and Cys32–Cys84 were found to be the most potent in inhibiting radiolabelled hFSH from binding to its receptor. The results suggest the involvement of the regions around disulfide bonds Cys28–Cys82 and Cys32–Cys84 in receptor binding of the hormone. The studies also suggest the involvement of βL2 and βL3 loop regions in receptor binding of the hormone. This study is the first of its kind to use disulfide peptides rather than linear peptides to map the receptor binding regions of hFSH.
The influence of dietary fish oil vs. sunflower oil on the fatty acid composition of plasma cholesteryl‐esters in healthy, adult cats
Authors: Plantinga E. A. , Beynen A. C.
Published: November 2003

The question addressed was whether the fatty acid composition of plasma cholesteryl esters (CEs) in cats reflects the intake of fatty acids. Diets containing either fish oil or sunflower oil were fed to six healthy, adult cats in a cross‐over trial. The dry cat foods contained approximately 18.5% crude fat, of which two‐third was in the form of the variable oil. Blood samples were collected at the end of each 4‐week feeding period, and the fatty acid composition of plasma CEs and plasma concentrations of lipoproteins were determined. Consumption of the diet with fish oil was associated with significantly greater proportions of eicosapentaenoic acid, arachidonic acid,α‐linolenic acid, oleic acid, palmitic acid and myristic acid in plasma CEs. The intake of fish oil instead of sunflower oil reduced the percentage of linoleic acid in CEs. The plasma concentrations of total cholesterol, high‐density lipoprotein cholesterol, phospholipids and triglycerides were not affected by fish oil vs. sunflower oil feeding.
Evaluation of loss of heterozygosity before and after interferon therapy in patients with hepatitis C virus infection who developed hepatocellular carcinoma during follow up
Authors: SUZUKI SEIJI , KONDO YUTAKA , HIRASHIMA NOBORU , KATO HIDEAKI , SUGAUCHI FUMINAKA , TANAKA YASUHITO , ORITO ETSURO , YANG YING , SHEN YU , SAKAKIBARA KENJI , UEDA RYUZO , MIZOKAMI MASASHI
Published: November 2003

Background and Aim:  The aim of the present study was to determine whether evaluating the status of loss of heterozygosity (LOH) before interferon (IFN) therapy is predictive for development of hepatocellular carcinoma (HCC) in chronic hepatitis and liver cirrhosis patients.

Methods:  Eighteen patients with hepatitis C virus were studied, nine of whom developed HCC (HCC group) after IFN therapy and nine whom did not (non‐HCC group). Samples before IFN therapy from both groups (pre‐IFN‐N and pre‐IFN‐H samples from the non‐HCC and HCC groups, respectively) were analyzed for LOH using 12 microsatellite markers. To evaluate the LOH incidence in different steps in HCC patients, paired samples of cancerous tissue (CT) and adjacent non‐CT (ANCT) obtained from the HCC group were also analyzed.

Results:  Frequency of LOH in the pre‐IFN‐H samples was significantly higher than that in the pre‐IFN‐N samples regardless of the response to IFN therapy. Interestingly, in the HCC group, there is no significant difference in the frequency of LOH among the pre‐IFN‐H, ANCT and CT samples.

Conclusions:  The present results suggest the theory that genetic instability, such as LOH, had already accumulated at stages before the development of HCC. The authors propose that the status of LOH in chronic hepatitis and liver cirrhosis patients before IFN therapy could be a potential predictor for the development of HCC.
A grounded theory study of the role that nurses play in increasing clients’ willingness to access community mental health services
Authors: McCann Terence V. , Clark Eileen
Published: November 2003

ABSTRACT:  lients and caregivers frequently encounter difficulties in accessing mental health services. Early intervention to care and treatment is essential to recovery as delays can adversely affect the severity and the duration of the illness. This paper reports the factors that encouraged and deterred young adults with schizophrenia and their caregivers when trying to seek early access to community mental health services, and examines how community mental health nurses made themselves accessible to these individuals in order to increase their access to services. The findings showed that several factors simultaneously encouraged and inhibited individuals initiating contact at community mental health centres, and these had serious implications for care and treatment, and recovery. There were two client access pathways to care: a direct access pathway where an individual recognized signs of being unwell and sought help early; and an indirect access pathway where others, such as caregivers, general practitioners, police, and inpatient facilities initiated contact on an individual's behalf. Nurses used three strategies to enhance client and caregiver access to services: ‘promoting favourable experiences to enhance approachability’, ‘using technology to promote access’ and ‘being available’. The findings have significance for nursing practice because they reinforce the importance of having good relationships with clients and caregivers, and the need to take account of the needs of caregivers. They highlight the benefits and drawbacks of using telecommunications to enhance accessibility, and why it is necessary to analyse nurses’ workloads and time management skills.
Morphology of step‐wise S–N curves depending on work‐hardened layer and humidity in a high‐strength steel
Authors: NAKAJIMA M. , TOKAJI K. , ITOGA H. , KO H.‐N.
Published: November 2003

The present paper describes the effects of work‐hardened layer and humidity on the fatigue response of high strength steel, JIS SNCM439 (AISI4340). Tests were conducted in laboratory air and in dry air using cantilever‐type rotating bending fatigue testing machines. The dew point of dry air was −60 °C. Specimens with two different surface conditions were prepared, i.e., buff‐finished and electro‐polished specimens. In the buff‐finished specimens, a stepwise S–N curve was seen in both environments, but the transition stress below which subsurface crack initiation occurred shifted to a higher stress level in dry air than in laboratory air. In the electro‐polished specimens, stepwise S–N curve was not observed in laboratory air, but seen in dry air. At stress levels where cracks initiated at the surface, the fatigue lives of the electro‐polished specimens were shorter than those of the buff‐finished specimens. At stress levels where subsurface cracks initiated, the fatigue lives of both specimens were the same, irrespective of surface finishing condition and humidity.