bluuebunny/crossref_metadata_2025 huggingface dataset:
Gorham‐stout disease of costo‐vertebral localization: radiographic, scintigraphic, computed tomography, and magnetic resonance imaging findings
Authors: Ceroni D. , De Coulon G. , Regusci M. , Kaelin A.
Published: June 2004

Gorham‐Stout disease is a clinical, radiographic, and histological entity characterized by progressive osteolysis as a result of a histologically benign vascular proliferation involving bone. We present a case involving the cervical and thoracic spine and the osseous thorax, with attention to the clinical, radiographic, scintigraphic, computed tomography, and magnetic resonance imaging findings. These subjects are discussed in the light of the literature.
Evaluation of tumor angiogenesis using dynamic enhanced magnetic resonance imaging: comparison of plasma vascular endothelial growth factor, hemodynamic, and pharmacokinetic parameters
Authors: Ikeda O. , Nishimura R. , Miyayama H. , Yasunaga T. , Ozaki Y. , Tuji A. , Yamashita Y.
Published: June 2004

Purpose: To assess whether tumor angiogenesis of breast cancers can be predicted on the basis of dynamic magnetic resonance imaging (MRI).

Material and Methods: Seventy‐one patients with 71 breast cancers underwent Gd‐DTPA enhanced dynamic MRI. Two regions of interest measurements were obtained in the periphery and in the center of the breast cancers. Hemodynamic parameters obtained by dynamic MRI included peak time, contrast enhancement ratio (CE ratio), and washout ratio. The triexponential concentration curve of Gd‐DTPA was fitted to a theoretical model based on compartmental analysis. The transfer constant (or permeability surface product per unit volume of compartment “k”) was obtained using this method. Tumor angiogenesis was assessed by plasma vascular endothelial growth factor (P‐VEGF).

Results: The P‐VEGF was positive in 28 of 71 tumors (39%). The CE ratio, washout ratio, and k in the periphery in P‐VEGF positive breast cancers (mean 178%, 18%, and 1.5×10−2 (s−1)) were significantly greater ( P<0.01, P<0.05, and P<0.03)) than those for P‐VEGF negative breast cancers (mean: 151%, 14%, and 1.1×10−2 (s−1)). The peak time in the periphery in P‐VEGF positive breast cancers was more marked than for P‐VEGF negative breast cancers, but this difference was not significant.

Conclusion: The hemodynamic and pharmacokinetic analysis of MRI provides valuable information about angiogenesis of breast cancers.
Duplex sonography of the carotid arteries in patients with pure aortic regurgitation: pulse waveform and hemodynamic changes and a new indicator of the severity of aortic regurgitation
Authors: Kervancioglu S. , Davutoglu V. , Ozkur A. , Soydinc S. , Adaletli I. , Sirikci A. , Bayram M. M.
Published: June 2004

Purpose: To determine the changes of multiple hemodynamic parameters and pulse wave contour in pure aortic regurgitation (AR) and to present a new indicator of the severity of AR (shrink ratio of proximal common carotid artery).

Material and Methods: The sonograms of 42 patients (31 M, 11 F; 16–68 years) with pure AR and 18 control subjects (15 M, 3 F; 20–47 years) were assessed for velocities and indices, and change of pulse wave contour (bisferious pattern, zero level and retrograde diastolic flow) in each carotid artery. Shrink ratio (maximum diameter–minimum diameter/maximum diameter) of each proximal common carotid artery was calculated.

Results: Bisferious waveforms seen in patients with AR grade 1, grade 2, and grade 3–4 were 66%, 83%, and 88%, respectively. Diastolic reversed flow was determined in 7 (39%) of 18 patients with AR grade 3–4. Three patients (25%) with AR grade 2 and 4 patients (22%) with AR grade 3–4 had zero level diastolic flow in the common carotid artery. Statistically significant changes of decreased end‐diastolic velocity, increased peak systolic velocity/end‐diastolic velocity, resistivity index, and pulsatility index were revealed, especially in AR grade 3–4 compared to controls. Significantly increased shrink ratio was seen only in AR grade 3–4.

Conclusion: Increased shrink ratio or changes in hemodynamics or pulse waveform can be used in recognition of AR.
Arachnoid cyst of the craniospinal junction: a case report and review of the literature
Authors: Cakirer S.
Published: June 2004

Arachnoid cysts are benign intra‐arachnoid collections of cerebrospinal fluid and comprise around 1% of the intracranial masses. Unless complicated with hemorrhage, they are similar to cerebrospinal fluid in signal intensity in most cases. Diffusion‐weighted magnetic resonance imaging (MRI) reveals that they have no water restriction and distinguishes them from epidermoid cysts, which show water restriction. Arachnoid cysts of the craniospinal junction are rare lesions, with only seven cases reported in the literature. Imaging findings of all craniospinal arachnoid cysts reveal a large posterior fossa arachnoid cyst extending through the foramen magnum to the level of the upper spine. We present MRI findings of a 27‐year‐old female patient with a craniospinal arachnoid cyst.
Value of helical computed tomography in the management of upper esophageal foreign bodies
Authors: de Lucas E. Marco , Sádaba P. , García‐Barón P. Lastra , Ruiz‐Delgado M. L. , Sánchez F. González , Ortiz A. , Pagola M. Á.
Published: June 2004

Purpose: To analyze the utility of helical computed tomography (CT) in the diagnosis of suspected upper esophageal foreign bodies.

Material and Methods: A prospective study was performed on 36 patients (26 F, 10 M, mean age 70 years) with a history of foreign body impaction. All had negative findings at indirect laryngoscopy. Radiologic assessment included unenhanced helical CT and a barium contrast study. Patients with positive findings were taken to esophagoscopy. All patients had a posterior clinical surveillance.

Results: Twenty patients had both normal CT and barium study and satisfactory clinical outcome. In 12 patients a foreign body was noted in the cervical esophagus by CT, barium study, and endoscopy. In one patient a fish bone was detected by CT (and not by barium) confirmed with esophagoscopy. Another patient had a fish bone esophageal perforation which was observed only by CT and confirmed at surgery. Two patients with normal barium and endoscopy presented a false‐positive CT result.

Conclusion: Barium swallow is currently the first radiologic study, but may involve a risk of aspiration and can impede a subsequent esophagoscopy. Esophagoscopy is an invasive technique with a certain risk of serious complications that can be avoided with a satisfactory radiologic assessment. CT is easy, fast, has 100% sensitivity and is therefore the first choice technique for diagnosing suspected upper esophageal foreign bodies not expected to be visible on plain radiographs.
Re‐expansion pulmonary edema
Authors: Murat A. , Arslan A. , Balcı A. E.
Published: June 2004

Re‐expansion pulmonary edema (REPE) is an uncommon complication following re‐expansion of the lung as treatment of conditions such as hemopneumothorax, large pleural effusion, and after lobectomy, pneumothorax, or even during single‐lung ventilation. The majority of REPE complications are associated with treatment of spontaneous pneumothorax. The etiology of REPE remains speculative, although it is thought to be caused by increased pulmonary capillary permeability. Risk factors, including young age, a large pneumothorax, and long duration of collapse, may help predict the patients that might encounter this complication.
Sonographically guided 11‐g directional vacuum‐assisted breast biopsy as an alternative to surgical excision: utility and cost study in probably benign lesions
Authors: Alonso‐Bartolomé P. , Vega‐Bolívar A. , Torres‐Tabanera M. , Ortega E. , Acebal‐Blanco M. , Garijo‐Ayensa F. , Rodrigo I. , Muñoz‐Cacho P.
Published: June 2004

Purpose: To evaluate the utility and economic costs of the 11‐G vacuum‐assisted biopsy probe under ultrasound (US) guidance as an alternative to surgical excision in patients with probably benign lesions.

Material and Methods: US‐guided 11‐G vacuum‐assisted biopsy was performed in 102 probably benign breast lesions in 97 women who refused radiological follow‐up. Complete removal of the lesion was intended in all cases. Open biopsy was done if questionable pathologic findings were present. Treatment was indicated if the diagnosis was malignant. Economic costs were estimated taking into consideration monetary expenses generated to the public health system, as well as expenses for the patients receiving percutaneous and open surgical biopsy.

Results: Median patient age was 42 years (range 18–77). Median lesion size was 14.7 mm (range 6–30 mm). Complete removal of the lesion seen at imaging was achieved in 72.5% of cases. Adequate tissue samples for histopathological evaluation were obtained in all cases. Surgical biopsy was recommended in nine cases. One patient diagnosed with mucinous carcinoma underwent immediate surgical treatment. The remaining 87 women with 92 lesions were included in a follow‐up program. Economic cost of the 11‐G vacuum‐assisted percutaneous biopsy was 82% lower than the surgical biopsy (total savings in this series: €136,402.84). Time spent for the patient was 71% less in percutaneous biopsy than in surgery.

Conclusion: Ultrasound‐guided 11‐G directional vacuum‐assisted breast biopsy is an accurate and less expensive procedure that can be used as an alternative to open surgical excision in a selected group of patients.
Short‐term reproducibility of computed tomography‐based lung density measurements in alpha‐1 antitrypsin deficiency and smokers with emphysema
Authors: Shaker S. B. , Dirksen A. , Laursen L. C. , Maltbaek N. , Christensen L. , Sander U. , Seersholm N. , Skovgaard L. T. , Nielsen L. , Kok‐Jensen A.
Published: June 2004

Purpose: To study the short‐term reproducibility of lung density measurements by multi‐slice computed tomography (CT) using three different radiation doses and three reconstruction algorithms.

Material and Methods: Twenty‐five patients with smoker's emphysema and 25 patients with α1‐antitrypsin deficiency underwent 3 scans at 2‐week intervals. Low‐dose protocol was applied, and images were reconstructed with bone, detail, and soft algorithms. Total lung volume (TLV), 15th percentile density (PD‐15), and relative area at −910 Hounsfield units (RA‐910) were obtained from the images using Pulmo‐CMS software. Reproducibility of PD‐15 and RA‐910 and the influence of radiation dose, reconstruction algorithm, and type of emphysema were then analysed.

Results: The overall coefficient of variation of volume adjusted PD‐15 for all combinations of radiation dose and reconstruction algorithm was 3.7%. The overall standard deviation of volume‐adjusted RA‐910 was 1.7% (corresponding to a coefficient of variation of 6.8%). Radiation dose, reconstruction algorithm, and type of emphysema had no significant influence on the reproducibility of PD‐15 and RA‐910. However, bone algorithm and very low radiation dose result in overestimation of the extent of emphysema.

Conclusion: Lung density measurement by CT is a sensitive marker for quantitating both subtypes of emphysema. A CT‐protocol with radiation dose down to 16 mAs and soft or detail reconstruction algorithm is recommended.
Volume rendering compared with maximum intensity projection for magnetic resonance angiography measurements of the abdominal aorta
Authors: Persson A. , Dahlström N. , Engellau L. , Larsson E.‐M. , Brismar T. B. , Smedby Ö.
Published: June 2004

Purpose: To compare the volume rendering technique (VRT) with maximum intensity projection (MIP) for aortic diameter measurements in MR angiography (MRA) data sets.

Material and Methods: Existing contrast‐enhanced 3‐dimensional MRA and digital subtraction angiography (DSA) data sets from 20 patients were analyzed. In each MRA data set, two aortic diameters were measured using MIP and VRT. Agreement with DSA measurements, dependence on rendering parameters, and interobserver agreement were assessed.

Results: Diameters measured on MIP with fixed parameters showed no significant difference compared with DSA and with freely selected parameters a slight overestimation relative to DSA. Diameters measured on VRT were larger than on DSA. For both MIP and VRT, the measurements depended on the chosen parameters. The error relative to DSA was larger for VRT than for MIP with fixed parameters but not with freely chosen parameters. Interobserver agreement did not differ significantly.

Conclusions: VRT is not suitable for diameter measurements of the abdominal aorta with fixed parameter settings but may be useful with user‐selected settings.
Decrease in Tumor Apparent Permeability‐Surface Area Product to a MRI Macromolecular Contrast Medium Following Angiogenesis Inhibition with Correlations to Cytotoxic Drug Accumulation
Authors: DALDRUP‐LINK HEIKE E. , OKUHATA YOSHITAKA , WOLFE ALLAN , SRIVASTAV SUDESK , ØIE SVEN , FERRARA NAPOLEONE , COHEN ROBERT L. , SHAMES DAVID M. , BRASCH ROBERT C.
Published: June 2004

Background: New strategies for cancer therapy include the combination of angiogenesis inhibitors with cytotoxins. However, angiogenesis inhibitors may alter tumor microvessel structure and transendothelial permeability thereby reducing tumoral delivery of cytotoxic agents. The aim of this study was to estimate quantitatively the apparent permeability‐surface area product (KPS) in tumors to a macromolecular contrast medium (MMCM), to follow changes in KPS induced by antibodies to vascular endothelial growth factor (anti‐VEGF), and to correlate the findings with tumor accumulation of cisplatin, a highly protein‐bound cytotoxin, and 5‐fluorouracil (5‐FU), a small unbound cytotoxin.

Methods: Dynamic MRI enhanced with a MMCM (albumin‐(Gd‐DTPA)30) was analyzed using a two‐compartment tumor tissue model (plasma and interstitial water) to quantitatively estimate KPS. These estimates of KPS were correlated with cytotoxic drug accumulations in the tumors.

Results: Anti‐VEGF treatment reduced KPS to MMCM in tumor tissue from 0.013 mL h−1 cm−3 (n = 9) at baseline to 0.003 mL h−1 cm−3 (n = 9) 24 h later (p < .05). The KPS values correlated significantly (r2 = .78; p < .0001) with the tumor cisplatin accumulation. No correlation (r2 = .001; p = .89) was found between KPS and tumor accumulation of the substantially smaller 5‐FU molecule.

Conclusions: MMCM‐enhanced MRI can be used to detect and estimate changes in KPS to this contrast agent following a single dose of anti‐VEGF antibody. The decline in KPS induced by this inhibitor of angiogenesis is associated with reduced tumor concentration of a protein‐bound cytotoxin, similar in molecular weight to the contrast agent. MRI assays of microvascular status as performed here may be useful to clinically monitor responses to anti‐angiogenesis drugs and to optimize the choice and timing of cytotoxic drug administration.
Effect of Venous Air Embolization on Pulmonary Microvascular Protein Permeability
Authors: STEWART RANDOLPH H. , ALLEN STEVEN J. , QUICK CHRISTOPHER M. , ROHN DOUGLAS A. , COX CHARLES S. , LAINE GLEN A.
Published: June 2004

Objective:An increase in pulmonary lymph flow and lymph protein clearance following pulmonary air embolization has been interpreted as evidence of increased pulmonary microvascular permeability. The authors hypothesized that air embolization does not alter the pulmonary microvascular permeability to protein and that this could be demonstrated by determining the effect of air embolization on the pulmonary solvent drag reflection coefficient (σf).

Methods:Anesthetized dogs were instrumented with left atrial balloon‐tipped catheters, pulmonary lymphatic cannulae, and inferior vena caval catheters. Values were determined for pulmonary lymph flow (QL) and the lymph‐to‐plasma protein concentration ratio (CL/CP) at baseline, after CL/CP was decreased to a filtration independent value by raising left atrial pressure via progressive balloon inflation and after 2 h of air embolization into the inferior vena cava with continued left atrial hypertension.

Results:QL increased and CL/CP decreased to a filtration‐independent value following induction of left atrial hypertension. Air embolization induced during left atrial hypertension resulted in no significant change in CL/CP. The authors were unable to demonstrate that σf changed following pulmonary air embolization.

Conclusions:Utilizing the washdown technique, the authors could not find any evidence that pulmonary microvascular protein permeability is altered by air embolization.
Independence of Connexin Expression and Vasomotor Conduction from Sympathetic Innervation in Hamster Feed Arteries
Authors: LOOFT‐WILSON ROBIN C. , HAUG SARA J. , NEUFER P. DARRELL , SEGAL STEVEN S.
Published: June 2004

Objective: Vasomotor responses can travel along the wall of resistance microvessels by two distinct mechanisms: cell‐to‐cell conduction through gap junctions or the release of neurotransmitter along perivascular nerves. It is unknown whether vascular innervation influences the expression of connexin molecules which comprise gap junctions, or the conduction of vasomotor responses. In feed arteries of the hamster retractor muscle (RFA), the authors tested whether sympathetic denervation would alter the expression of connexin isoforms and the conduction of vasomotor responses.

Methods: Using intact vessels with sympathetic innervation and those 7–8 days following denervation surgery, mRNA expression was quantified using real‐time PCR, cellular localization of Cx protein was characterized using immunohistochemistry, and vasomotor responses to dilator and constrictor stimuli were evaluated in isolated pressurized RFA.

Results: Connexin protein localization and mRNA expression were similar between innervated and denervated vessels. mRNA levels were Cx43 = Cx37 > Cx45 ≫ Cx40. Vasodilation to acetylcholine conducted ≥2000 μ m along innervated and denervated vessels, as did the biphasic conduction of vasoconstriction and vasodilation in response to KCl. Vasoconstriction to phenylephrine conducted < 500 μ m and was attenuated (p < .05) in denervated vessels.

Conclusions: The profile of connexin expression and the conduction of vasomotor responses are largely independent of sympathetic innervation in feed arteries of the hamster retractor muscle (RFA).
Nitric Oxide Measurements in Rat Mesentery Reveal Disrupted Venulo‐Arteriolar Communication in Diabetes
Authors: NELLORE KAVITHA , HARRIS NORMAN R.
Published: June 2004

Objective: Arteriolar tone is partially controlled by diffusing mediators released by closely paired venules and is reported to depend on venular shear and venular leukocyte adherence. In healthy rat mesentery, venule‐initiated arteriolar dilation and consequent enhanced capillary flow appear to be tightly regulated by nitric oxide (NO). In contrast, diabetes inhibits NO‐dependent vasodilation and is associated with dysfunctional microcirculation. The objective of this study was to investigate venule‐dependent NO in diabetes.

Methods: Arteriolar and venular wall concentrations of NO were measured in control and diabetic (streptozotocin‐induced) rat mesentery with fluorescent diaminofluorescein‐2‐diacetate (DAF‐2‐DA); tissue NO was measured with DAF‐2. Venular leukocyte adherence and microvascular shear rates were also measured.

Results: Microvascular NO in diabetic rats was found to be significantly lower (< 50%) than in controls. In normal rats, arteriolar NO demonstrated a positive correlation with venular NO and venular shear, and a negative correlation with venular leukocyte adherence. Diabetes eliminated all these correlations. No correlation was present between arteriolar NO and arteriolar shear in either normal or diabetic rats.

Conclusions: Arteriolar NO appears to be enhanced by venular shear in normal but not in diabetic rats. This dysfunction could contribute to poor capillary perfusion in diabetes.
Contribution of Active Membrane Processes to Conducted Hyperpolarization in Arterioles of Hamster Cheek Pouch
Authors: CRANE GLENIS J. , NEILD TIMOTHY O. , SEGAL STEVEN S.
Published: June 2004

Objective: Conduction of vasodilation triggered by acetylcholine (ACh) in arteriolar networks reflects hyperpolarization and its spread from cell to cell along the vessel wall. The amplitude and distance of the vasomotor response appear greater than can be explained by simple passive decay of the electrical signal. The authors tested the hypothesis that the conduction of hyperpolarization involves active membrane processes as the signal travels along the arteriolar wall.

Methods: Intracellular recordings of membrane potential were made from either the smooth muscle or endothelial cell layer of arterioles of the hamster cheek pouch in vivo. Acetylcholine was delivered onto an arteriole using microiontophoresis at defined distances from the recording site, and transient hyperpolarizations were recorded. The area enclosed by the transients (voltage × time integral below baseline) was measured and compared to the area expected if the hyperpolarization was spreading passively.

Results:In 11 of 15 recordings from smooth muscle and 5 of 7 from endothelium, areas of the transients were larger than expected for purely passive spread of the electrical signal.

Conclusions: Conduction of hyperpolarization is enhanced by active membrane processes as the signal travels along the arteriolar wall. Signal augmentation will promote blood flow to tissue regions from which hyperpolarization of arterioles originates.
Functional Link Between ETB Receptors and eNOS Maintain Tissue Oxygenation in the Normal Liver
Authors: PAXIAN MARKUS , KELLER STEVE A. , BAVEJA RAJIV , KORNESZCZUK KATARZYNA , HUYNH TOAN T. , CLEMENS MARK G.
Published: June 2004

Objective: Endothelins and their receptors play a crucial role in regulating liver microcirculation in pathophysiological conditions. The authors investigated the functional significance of the coupling of ETB receptors and eNOS in maintaining regional perfusion and tissue oxygenation in the normal liver.

Methods: The effect of endothelin‐1 or the ETB agonist IRL1620 on oxygen consumption was determined in isolated perfused liver and isolated hepatocytes. Oxygen delivery to the liver tissue was determined in vivo. Following eNOS or iNOS blockade, either ET‐1 or IRL1620 was infused via the portal vein. Hepatic tissue oxygenation, redox state, and microcirculation were investigated by intravital microscopy. Injury was estimated by serum LDH.

Results: Although IRL1620 and endothelin‐1 increased oxygen consumption in isolated hepatocytes, in intact liver, endothelin decreased oxygen consumption while IRL1620 produced no change. In vivo, ETB stimulation modestly altered hepatic tissue PO2, redox potential, and microcirculation. eNOS inhibition and ETB activation dramatically reduced microcirculatory blood flow, oxygen supply, and increased LDH release. Inhibition of iNOS resulted in small but not significant changes in these parameters. Concomitant ETA/ETB receptor activation increased microcirculatory failure and decreased tissue oxygen even without NOS inhibition. In contrast, hepatocellular injury was significantly increased following eNOS inhibition.

Conclusions: Coupling between ETB receptor stimulation and eNOS activation decreases sinusoidal constriction and plays a functionally important role in maintaining microcirculation and tissue oxygenation in the normal liver.
From private to public: Alba de Céspedes' agony column in 1950s Italy
Authors: Morris Penny
Published: June 2004

A unique, if problematical, historical source for the study of the ‘private sphere’, the problem page has, as yet, been the subject of little serious attention. This article initially considers the problem page in general terms, and with particular reference to 1950s Italy, a time when a notable feature of the changing patterns of cultural consumption was the emergence and upsurge in popularity of the weekly magazine. The rest of the paper is devoted to an analysis of best-selling author Alba de Céspedes' agony column, ‘Dalla parte di lei’, published in the magazine Epoca. The article shows that the column provides intriguing insights into the state of family and marriage during a time of transition. It discusses the idea of the agony column as a commodity, but also highlights de Céspedes' aim of providing a kind of compendium of lay morals, arguing that any attempt to provide an alternative to the Catholic Church, and the prevailing conservative attitudes of the time, was a matter of careful negotiation.
Natural mothers: teaching morals and parent-craft in Italy, 1945–60
Authors: Bernini Stefania
Published: June 2004

At the end of the Second World War, politicians and social observers apprehensively considered the condition of the family and its destiny and role in post-war Italy. As well as informing political discourses and sociological examinations, the family became a privileged terrain for medical and psychological enquiry, with particular attention given to parenthood and the maternal role of women. The article explores the role played by religious and medical authorities in shaping narratives of parental responsibilities during the post-war years. The interplay of biology and morality in medical discourse and Catholic teaching is discussed in the context of debates about motherhood and the management of childbirth. Particular attention is given to discussions about the use of pain relief in labour and the reception by Italian Catholic gynaecologists of the so-called ‘natural childbirth method’, advocated during the post-war period by a number of European and American practitioners.
The redefinition of gender roles and family structures among Istrian peasant families in Trieste, 1954–64
Authors: Nemec Gloria
Published: June 2004

From 1942 to the late 1950s, about 240,000 Italians fled from Istria and Dalmatia, territories included in the new Yugoslav Federal Republic. The last movement of population took place after the London Memorandum in 1954, when the portion of territory closest to Italy (‘Zone B’) was given to Yugoslavia. About 40,000 Italians took part in this last exodus, and most of them were peasants wishing to settle in Trieste. The article describes the adaptation of social behaviours and gender roles among Istrian peasants as they faced new urban realities and modernization in the exodus. Oral sources, personal memoirs, literature and other documents are used to reconstruct the process by which rural communities moved from pre-war stability to change and transformation as they integrated within urban society in Trieste. In this process, gender and familial roles were significantly affected and redefined.
The Italian family from the 1960s to the present
Authors: Saraceno Chiara
Published: June 2004

The family in Italy lies at the centre of an apparent paradox. On the one hand, it appears stronger in its traditional form based on marriage and on intergenerational solidarity than in most European countries. The normal way of living for couples is marriage, marriage instability is lower than the European average, and births out of wedlock are scarce. On the other hand, with its low fertility and long permanence of children in their parents’ household, Italy appears to be a country where the forming of new families and the reproduction of families is most difficult. This article explores the reasons for this paradox, many of which lie in the persistent gender division of labour and in the lack of supportive family policies. At the same time the article shows that despite the apparent stability of the family many changes are under way, some of them dating back to the early 1960s: not only because of fertility decline, but also due to women's changing patterns of behaviour and expectations.
Making connections: family and relatedness in clinics of assisted conception in Italy
Authors: Bonaccorso Monica
Published: June 2004

This article explores contemporary notions of Italian kinship—procreation, the family, biological and social relatedness—as they are shaped by programmes of gamete donation (these are programmes that require the use of third-party egg and semen to achieve conception). The research was carried out in Italian clinics of assisted conception and presents the views of heterosexual couples suffering from impaired infertility. The overall material reveals the power of kinship as a cultural form.
The Sicilian mafia: a profile based on judicially confirmed evidence
Authors: Forte Guido Lo
Published: June 2004

This article reports the main findings of a paper first presented in May 1996 at a study conference organized by the Reform Commission of the Higher Council for the Judiciary (Consiglio Superiore della Magistratura, CSM). That presentation was published in full in Quaderni del Consiglio Superiore della Magistratura, 1, 99, 1998, pp. 1–84. For reasons of space, most of the evidential materials are omitted here.
Metallothionein as an Adaptive Protein Prevents Diabetes and its Toxicity
Authors: Cai Lu
Published: June 2004

Metallothioneins (MTs) are a group of intracellular metal-binding and cysteine-enriched proteins and are highly inducible in many tissues in response to various types of stress. Although it mainly acts as a regulator of metal homeostasis such as zinc and copper in tissues, MT also acts as a potent antioxidant and adaptive (or stress) protein to protect cells and tissues from oxidative stress. Diabetes affects many Americans and other populations, and its development and toxic effect on various organs have been attributed to increased oxidative stress. Studies showed that zinc-induced or genetically enhanced pancreatic MT synthesis prevented diabetes induced by chemicals such as streptozotocin and alloxan, and zinc pretreatment also prevented spontaneously developed diabetes. Since diabetic complications are the consequences of organ damage caused by diabetic hyperglycemia and hyperlipidemia through oxidative stress, whether MT in nonpancreatic organs also provides a preventive effect on diabetic toxicity has been recently investigated. We demonstrated that overexpression of cardiac MT significantly prevented diabetes-induced cardiomyopathy. Likewise, overexpression of renal MT also prevented diabetes-induced renal toxicity. In addition, we also found that MT as an adaptive protein is overexpressed in several organs in response to diabetes. Therefore, the biological importance of diabetes-induced MT in diabetic complications and subsequent other pathogenesis was further explored. We found that diabetes-induced hepatic and renal MT synthesis was accompanied by a significant prevention of endotoxin-induced hepatic toxicity and cisplatin-induced renal toxicity. These studies suggest that MT as an adaptive protein can prevent both diabetes development and its complications or subsequent suffered other pathogenic injury.
Molecular Mechanisms of Anti-Aging Hormetic Effects of Mild Heat Stress on Human Cells
Authors: Rattan Suresh I. S. , Eskildsen-Helmond Yvonne E. G. , Beedholm Rasmus
Published: June 2004

In a series of experimental studies we have shown that repetitive mild heat stress has anti-aging hormetic effects on growth and various other cellular and biochemical characteristics of human skin fibroblasts undergoing aging in vitro. We have reported the hormetic effects of repeated challenge at the levels of maintenance of stress protein profile; reduction in the accumulation of oxidatively and glycoxidatively damaged proteins; stimulation of the proteasomal activities for the degradation of abnormal proteins; improved cellular resistance to ethanol, hydrogenperoxide, and ultraviolet-B rays; and enhanced levels of various antioxidant enzymes. We are now undertaking a detailed analysis of the signal transduction pathways to determine alterations in the phosphorylation and dephosphorylation states of extracellular signal-related kinase, c-Jun terminal kinase and p38 MAP-kinases as a measure of cellular responsiveness to mild and severe heat stress. Furthermore, we are also undertaking comparative studies using non-aging immortal cell lines, such as SV40-transformed human fibroblasts, spontaneous osteosarcoma cells, and telomerase-immortalized human bone marrow cells for establishing differences in normal and cancerous cells with respect to their responsiveness to mild and severe stresses.
Dose-Response Relationships in Expression of Biomarkers of Cell Proliferation in In Vitro Assays and Inhalation Experiments
Authors: Shukla Arti , Vacek Pamela , Mossman Brooke T.
Published: June 2004

Asbestos is a group of naturally occurring mineral fibers which are associated in occupational settings with increased risks of malignant mesothelioma (MM), lung cancers, and pulmonary fibrosis (asbestosis). The six recognized types of asbestos fibers (chrysotile, crocidolite, amosite, tremolite, anthophyllite, and actinolite) are different chemically and physically and may have different dose-response relationships in the development of various asbestos-associated diseases. For example, epidemiologic and lung fiber content studies suggest that the pathogenic potential and durability of crocidolite is much greater than chrysotile asbestos in the causation of human MM. We have used isolated mesothelial cells, the target cells of MM, as well as epithelial cells of the lung, the target cells of lung cancers, in vitro to elucidate the dose-response relationships in expression of early response protooncogenes and other genes critical to cell proliferation and malignant transformation in cells exposed to crocidolite and chrysotile asbestos, as well as a number of nonpathogenic fibers and particles. These studies reveal distinct dose-response patterns with different types of asbestos, suggesting a threshold for effects of chrysotile both in in vitro studies and inhalation experiments. The different patterns of gene expression have been confirmed in lungs of rats exposed by inhalation to these types of asbestos. Experiments also suggest no observed adverse effect levels after evaluation of lung injury, inflammation, and fibrosis at lower concentrations of both types of asbestos.
Effect of Low and Very Low Doses of Simple Phenolics on Plant Peroxidase Activity
Authors: Malarczyk Elżbieta , Kochmańska-Rdest Janina , Paździoch-Czochra Marzanna
Published: June 2004

Changes in the activity of horseradish peroxidase resulting from an addition of ethanol water dilutions of 19 phenolic compounds were observed. For each compound, the enzyme activity was plotted against the degree of dilution expressed as n = − log100 (mol/L) in the range 0 ≤ n ≥ 20. All the curves showed sinusoidal activity, more or less regular, with two to four peaks on average. Each analyzed compound had a characteristic sinusoidal shape, which was constant for samples of peroxidase from various commercial firms. This was clearly visible after function fitting to experimental results based on the Marquadt-Levenberg algorithm using the least-squares method. Among the 19 phenolics, the highest amplitudes were observed for phenol and iso- and vanillate acids and aldehydes. The specific character of each of the analyzed curves offers a possibility of choosing proper dilutions of phenolic compound for activating or inhibiting of peroxidase activity.
Spindle checkpoint regulates Cdc20p stability in Saccharomyces cerevisiae
Authors: Pan Jing , Chen Rey-Huei
Published: June 2004

The spindle checkpoint arrests cells at the metaphase-to-anaphase transition until all chromosomes have properly attached to the mitotic spindle. Checkpoint proteins Mad2p and Mad3p/BubR1p bind and inhibit Cdc20p, an activator for the anaphase-promoting complex (APC). We find that upon spindle checkpoint activation by microtubule inhibitors benomyl or nocodazole, wild-type Saccharomyces cerevisiae contains less Cdc20p than spindle checkpoint mutants do, whereas their CDC20 mRNA levels are similar. The difference in Cdc20p levels correlates with their difference in the half-lives of Cdc20p, indicating that the spindle checkpoint destabilizes Cdc20p. This process requires the association between Cdc20p and Mad2p, and functional APC, but is independent of the known destruction boxes in Cdc20p and the other APC activator Cdh1p. Importantly, destabilization of Cdc20p is important for the spindle checkpoint, because a modest overexpression of Cdc20p causes benomyl sensitivity and premature Pds1p degradation in cells treated with nocodazole. Our study suggests that the spindle checkpoint reduces Cdc20p to below a certain threshold level to ensure a complete inhibition of Cdc20p before anaphase.
Hsp70 promotes TNF-mediated apoptosis by binding IKKγ and impairing NF-κB survival signaling
Authors: Ran Ruiqiong , Lu Aigang , Zhang Lu , Tang Yang , Zhu Hongyan , Xu Huichun , Feng Yuxin , Han Chun , Zhou Guoping , Rigby Alan C. , Sharp Frank R.
Published: June 2004

The major heat shock protein, Hsp70, can protect against cell death by directly interfering with mitochondrial apoptosis pathways. However, Hsp70 also sensitizes cells to certain apoptotic stimuli like TNF. Little is known about how Hsp70 enhances apoptosis. We demonstrate here that Hsp70 promotes TNF killing by specifically binding the coiled-coil domain of IκB kinase γ (IKKγ) to inhibit IKK activity and consequently inhibit NF-κB-dependent antiapoptotic gene induction. An IKKγ mutant, which interacts with Hsp70, competitively inhibits the Hsp70–IKKγ interaction and relieves heat-mediated NF-κB suppression. Depletion of Hsp70 expression with RNA interference rescues TNF-mediated cell death. Although TNF may or may not be sufficient to trigger apoptosis on its own, TNF-triggered apoptosis was initiated or made worse when Hsp70 expression increased to high levels to disrupt NF-κB signaling. These results provide significant novel insights into the molecular mechanism for the pro-apoptotic behavior of Hsp70 in death-receptor-mediated cell death.
The generation of proper constitutive G-tails on yeast telomeres is dependent on the MRX complex
Authors: Larrivée Michel , LeBel Catherine , Wellinger Raymund J.
Published: June 2004

The precise DNA arrangement at chromosomal ends and the proteins involved in its maintenance are of crucial importance for genome stability. For the yeast Saccharomyces cerevisiae, this constitutive DNA configuration has remained unknown. We demonstrate here that G-tails of 12–14 bases are present outside of S phase on normal yeast telomeres. Furthermore, the Mre11p protein is essential for the proper establishment of this constitutive end-structure. However, the timing of extended G-tails occurring during S phase is not affected in strains lacking Mre11p. Thus, G-tails are present on yeast chromosomes throughout the cell cycle and the MRX complex is required for their normal establishment.
Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration
Authors: Sansom Owen J. , Reed Karen R. , Hayes Anthony J. , Ireland Heather , Brinkmann Hannah , Newton Ian P. , Batlle Eduard , Simon-Assmann Patricia , Clevers Hans , Nathke Inke S. , Clarke Alan R. , Winton Douglas J.
Published: June 2004

Although Apc is well characterized as a tumor-suppressor gene in the intestine, the precise mechanism of this suppression remains to be defined. Using a novel inducible Ahcre transgenic line in conjunction with a loxP-flanked Apc allele we, show that loss of Apc acutely activates Wnt signaling through the nuclear accumulation of β-catenin. Coincidentally, it perturbs differentiation, migration, proliferation, and apoptosis, such that Apc-deficient cells maintain a “crypt progenitor-like” phenotype. Critically, for the first time we confirm a series of Wnt target molecules in an in vivo setting and also identify a series of new candidate targets within the same setting.
Multiple interactions between regulatory regions are required to stabilize an active chromatin hub
Authors: Patrinos George P. , de Krom Mariken , de Boer Ernie , Langeveld An , Imam A.M. Ali , Strouboulis John , de Laat Wouter , Grosveld Frank G.
Published: June 2004

The human β-globin locus control region (LCR) is required for the maintenance of an open chromatin configuration of the locus. It interacts with the genes and the hypersensitive regions flanking the locus to form an active chromatin hub (ACH) transcribing the genes. Proper developmental control of globin genes is largely determined by gene proximal regulatory sequences. Here, we provide the first functional evidence of the role of the most active sites of the LCR and the promoter of the β-globin gene in the maintenance of the ACH. When the human β-globin gene promoter is deleted in the context of a full LCR, the ACH is maintained with the β-globin gene remaining in proximity. Additional deletion of hypersensitive site HS3 or HS2 of the LCR shows that HS3, but not HS2, in combination with the β-globin promoter is crucial for the maintenance of the ACH at the definitive stage. We conclude that multiple interactions between the LCR and the β-globin gene are required to maintain the appropriate spatial configuration in vivo.
Mouse limb deformity mutations disrupt a global control region within the large regulatory landscape required for Gremlin expression
Authors: Zuniga Aimée , Michos Odyssé , Spitz François , Haramis Anna-Pavlina G. , Panman Lia , Galli Antonella , Vintersten Kristina , Klasen Christian , Mansfield William , Kuc Sylwia , Duboule Denis , Dono Rosanna , Zeller Rolf
Published: June 2004

The mouse limb deformity (ld) mutations cause limb malformations by disrupting epithelial–mesenchymal signaling between the polarizing region and the apical ectodermal ridge. Formin was proposed as the relevant gene because three of the five ld alleles disrupt its C-terminal domain. In contrast, our studies establish that the two other ld alleles directly disrupt the neighboring Gremlin gene, corroborating the requirement of this BMP antagonist for limb morphogenesis. Further doubts concerning an involvement of Formin in the ld limb phenotype are cast, as a targeted mutation removing the C-terminal Formin domain by frame shift does not affect embryogenesis. In contrast, the deletion of the corresponding genomic region reproduces the ld limb phenotype and is allelic to mutations in Gremlin. We resolve these conflicting results by identifying a cis-regulatory region within the deletion that is required for Gremlin activation in the limb bud mesenchyme. This distant cis-regulatory region within Formin is also altered by three of the ld mutations. Therefore, the ld limb bud patterning defects are not caused by disruption of Formin, but by alteration of a global control region (GCR) required for Gremlin transcription. Our studies reveal the large genomic landscape harboring this GCR, which is required for tissue-specific coexpression of two structurally and functionally unrelated genes.
Father Love and Child Development
Authors: Rohner Ronald P.
Published: June 2004

Six types of studies show that father love sometimes explains as much or more of the variation in specific child and adult outcomes as does mother love. Sometimes, however, only father love is statistically associated with specific aspects of offsprings' development and adjustment, after controlling for the influence of mother love. Recognition of these facts was clouded historically by the cultural construction of fatherhood and fathering in America.
Learning and Representing Verbal Meaning
Authors: Landauer Thomas K.
Published: June 2004

Latent semantic analysis (LSA) is a theory of how word meaning—and possibly other knowledge—is derived from statistics of experience, and of how passage meaning is represented by combinations of words. Given a large and representative sample of text, LSA combines the way thousands of words are used in thousands of contexts to map a point for each into a common semantic space. LSA goes beyond pair-wise co-occurrence or correlation to find latent dimensions of meaning that best relate every word and passage to every other. After learning from comparable bodies of text, LSA has scored almost as well as humans on vocabulary and subject-matter tests, accurately simulated many aspects of human judgment and behavior based on verbal meaning, and been successfully applied to measure the coherence and conceptual content of text. The surprising success of LSA has implications for the nature of generalization and language.
Cognitive Development in Social and Cultural Context
Authors: Gauvain Mary
Published: June 2004

The development of thinking is discussed from a sociocultural perspective. Three features of the social and cultural context that play important roles in organizing and directing cognitive development are presented and illustrated empirically: (a) activity goals and values of the culture, (b) material and symbolic tools for satisfying cultural goals and values, and (c) higher level structures that instantiate cultural goals and values in everyday practices. The article concludes with a discussion of the utility of this approach for advancing understanding of human intellectual growth.
De novo germline mutation in the serine–threonine kinase STK11/LKB1 gene associated with Peutz–Jeghers syndrome
Authors: Hernan I , Roig I , Martin B , Gamundi M J , Martinez‐Gimeno M , Carballo M
Published: June 2004

Peutz–Jeghers syndrome (PJS) is an autosomal dominant disease, characterized phenotypically by mucocutaneous pigmentation and hamartomatous polyposis. Affected patients are at an increased risk of developing gastrointestinal and other malignancies. Mutations in the STK11/LKB1 (LKB1) gene, which encodes for a serine–threonine kinase, have been identified as a genetic cause of PJS. Molecular analysis of the LKB1 gene in a simplex case of PJS revealed a substitution of cytosine (C) for guanine (G) at codon 246 in exon 6, resulting in the Tyr246X mutation. The nucleotide substitution leads to a premature stop codon at the 246 residue, predicting a truncated protein and presumed loss of kinase activity. Analysis of DNA from both parents of the PJS patient did not show this mutation, which is therefore a de novo mutation. We isolated DNA from microdissected gastrointestinal hamartomatous polyps in the PJS patient and investigated the loss of heterozygosity (LOH) at the LKB1 locus by real‐time fluorescence polymerase chain reaction genotyping using a fluorescent resonance energy transfer technique. The results suggest a different mechanism from LOH in the formation of hamartomatous polyps.
Three new families with X‐linked mental retardation caused by the 428–451dup(24bp) mutation in ARX
Authors: Partington MW , Turner G , Boyle J , Gécz J
Published: June 2004

Three families with X‐linked mental retardation caused by a 24 base‐pair duplication in ARX[428–451dup(24 bp)] are reported. The clinical features in these and six other published families are reviewed. In general, the clinical picture is variable. Mental retardation ranges from mild to severe. Infantile spasms (West syndrome) occurred in 12.5% and other less severe forms of seizures in 37.5%. Characteristic dystonic movements of the hands were seen in 63% and dysarthria in 54%. The focal dystonia, in association with mental retardation, may prove to be diagnostic of this mutation.
Familial iridogoniodysgenesis and skeletal anomalies: a probable new autosomal recessive disorder
Authors: Rodríguez‐Rojas LX , García‐Cruz D , Mendoza‐Topete R , Barba LB , Barrios MT , Patiño‐García B , López‐Cardona MG , Nuño‐Arana I , García‐Ortiz JE , Cantú JM
Published: June 2004

Three sibs with congenital glaucoma, skeletal anomalies, and peculiar facial appearance were studied. At birth, enlarged eyes and corneae were present in the proposita and her two brothers due to congenital glaucoma secondary to iridogoniodysgenesis (IGD). The purpose of this article is to describe the second familial case with IGD and skeletal anomalies as the family previously described by García‐Cruz et al. in 1990, corroborating this new distinct dysmorphic syndrome with probable autosomal recessive inheritance.