bluuebunny/crossref_metadata_2025 huggingface dataset:
Buoyancy of Convective Vertical Motions in the Inner Core of Intense Hurricanes. Part II: Case Studies
Authors: Eastin Matthew D. , Gray William M. , Black Peter G.
Published: March 2005

This is the second of two papers on the buoyancy of convective vertical motions in the inner core of intense hurricanes. This paper uses extensive airborne radar, dropwindsonde, and flight-level observations in Hurricanes Guillermo (1997) and Georges (1998) to illustrate typical azimuthal distribution of buoyant convection and demonstrate that the low-level eye can be an important source region for buoyant eyewall convection.

In both hurricanes, eyewall vertical velocity and radar reflectivity are asymmetric and exhibit persistent relationships with the direction of the environmental vertical wind shear. Mesoscale vertical motions exhibit a wavenumber-1 structure with maximum ascent downshear and weak descent upshear. The mesoscale reflectivity maxima are located left-of-shear. Buoyant eyewall updraft cores and transient convective-scale reflectivity cells are predominantly downshear and left-of-shear. Most eyewall downdraft cores that transport significant mass downward are located upshear. Negative buoyancy was most common in left-of-shear downdrafts, with positive buoyancy dominant in upshear downdrafts. Inward-spiraling rainbands located outside the eyewall exhibit upband/downband asymmetries. Upband segments contain more convective reflectivity cells and buoyant updraft cores than the more stratiform downband segments. Equal numbers of downdraft cores are found upband and downband, but the majority exhibit negative buoyancy.

Several buoyant updraft cores encountered in the midlevel eyewall exhibit equivalent potential temperatures (θe) much higher than the θe observed in the low-level eyewall, but equivalent to the θe observed in the low-level eye. Asymmetric low-wavenumber circulations appear responsible for exporting the high-θe eye air into the relatively low-θe eyewall and generating the locally buoyant updraft cores.

Implications of these results upon conceptual models of hurricane structure are discussed. Three mechanisms, whereby an ensemble of asymmetric buoyant convection could contribute to hurricane evolution, are also discussed.
Low-Frequency Atmospheric Acoustic Energy Associated with Vortices Produced by Thunderstorms
Authors: Bedard A. J.
Published: March 2005

An infrasonic observatory collocated with the Colorado State University CHILL radar during the summer of 1995 permitted unique comparisons between severe storm kinematics and detected acoustic energy at subaudible frequencies near 1 Hz. Radar observations of a velocity couplet aloft (evolving into a tornado) showed a circulation maximum descending for about 30 min while moving to the east. The detected infrasound followed the trend of these observations. A model of sound radiated from vortex systems predicts frequencies in the range observed. These data are interpreted in the context of past infrasonic observations. An ongoing study comparing regional tornado and funnel sightings with archived infrasonic data has identified over 100 cases to date where the infrasonic signals occurred at the time of, and from the direction of, the vortices. For some of these cases, the distances were greater than 100 km. The author and his associates continue to collect datasets to permit further evaluation of infrasonic detection methods.
Chronic Care Initiatives for the Elderly: Can They Bridge the Gerontology-Medicine Gap?
Authors: Lynch Marty , Estes Carroll L. , Hernandez Mauro
Published: March 2005

The authors describe initiatives designed to meet the chronic health needs of the elderly. These programs include demonstration programs such as Program of All-Inclusive Care for Elderly, Social Health Maintenance Organization, and state programs for Medicare-Medicaid-eligible elders that focus on integrating medical care with home and community-based services, disease- or disability-focused care management/coordination initiatives, and recent population-based disease management programs focused on improving adherence to evidence-based protocols, self-care management, and the use of innovative practices such as group visits to improve health outcomes. These initiatives have the potential to improve outcomes and reduce costs, but also highlight tensions between medical model disease management and functionally oriented home and community service programs. The authors suggest that optimal chronic care for elders would require the integration of advances in medically oriented disease management with the best of home and community-based service programs. Medicare policy should promote such integration.
Correlates of Change in Perceptions of Nursing Facilities Among Volunteers
Authors: Keith Pat M.
Published: March 2005

The image of nursing facilities by the public is largely negative. Change in perceptions of nursing facilities is not often studied. The author investigated whether individuals would change their views of nursing facilities in response to volunteer activities in an ombudsman program and identified factors associated with transitions in perceptions as well as qualitative types of change. More than 60% of 778 men and women attributed their altered views of nursing facilities to volunteering. Factors associated with changes in perceptions were markedly different for men and women. Identification of correlates of change may assist administrators of volunteer programs in addressing experiences that may encourage more positive perceptions of settings in which volunteers work.
Reproducibility of Physical Performance and Physiologic Assessments
Authors: Wolinsky Fredric D. , Miller Douglas K. , Andresen Elena M. , Malmstrom Theodore K. , Miller J. Philip
Published: March 2005

We evaluate the test-retest stability of physical performance and physiologic assessments used in epidemiologic research. Method: Eighty subjects aged 50 to 65 were randomly selected from a probability sample of African Americans for test-retest assessments 5 to 45 days after baseline. Physical performance assessments included grip strength, chair stands, gait speed, and four standing-balance measures. Physiologic assessments included systolic and diastolic blood pressure, height, weight, body fat, and peak expiratory flow. Results: Intraclass correlations coefficients (ICCs) were .81 for grip strength, .72 for chair stands, .56 for gait speed, .60 for one-leg stand, .52 for semitandem stand, .58 for tandem stand with eyes closed, and .27 for tandem stand with eyes open. Except for blood pressure (ICCs of .51 and .55 for systolic and diastolic), the physiologic assessments had ICCs > .89. Discussion: Additional interviewer training may improve the reproducibility of the tandem stand with eyes open.
Synthesis of Polysiloxaneimide with Piezoelectric Response
Authors: Simionescu Mihaela , Sacarescu Liviu , Ardeleanu Rodinel , Sacarescu Gabriela
Published: March 2005

A new segmented polysiloxaneimide was synthesized by solution polycondensation of N, N bis(hydroxyethyl)benzophenontetracarboxylic diimide with siloxane diacid chloride. The copolymer was obtained with good yield and high molecular weight. The characterization by IR and 1H-NMR spectrometry and a study of the properties such as solubility and thermal behaviour of this copolymer are presented. A corona poling study was performed to obtain information about the piezoelectric behaviour of polysiloxaneimide. The remanent dielectric constants of the polarized samples were compared with those of well-known piezoelectric polymers.
Synthesis and Characterization of Optically Active Polyimidothioethers
Authors: Cianga Luminita
Published: March 2005

New optically active polyimidothioethers derived from chiral bismaleimides and 1 5-pentandithiol were synthesized by Michael-type polyaddition. Chiral bismaleimides were obtained by the reaction of 4-maleimidobenzoic acid or its acid chloride with (L)-cystine, (L)-lysine or (R)-2-amino-1-butanol, and they are prochiral monomers too. The polyaddition proceeds with a quite low stereoselectivity in terms of asymmetric induction on the configuration of the newly formed chiral centers. The structures of the new polymers were confirmed by elemental analysis and spectral methods (IR and 1H-NMR). The molecular weights of the polymers were estimated by gel permeation chromatography and a correlation with viscometric data was found. Optical activity was evidenced by polarimetric measurements. Thermal behavior was investigated by thermogravimetric analysis and differential scanning calorimetry. The X-ray diffractograms revealed an amorphous structure of polymers due to a low degree of stereoregularity originated by the presence of randomly distributed constitutional repeating units having different diastereomeric configurations.
Liquid Crystalline Polymers. 15. Synthesis and Thermal Behavior of Some Aromatic Polyethers Containing Different Spacers
Authors: Alazaroaie Silvia , Catanescu Carmen Otilia , Pavel Dumitru , Scutaru Dan , Romanic Mihaela , Toader Violeta , Simionescu Cristofor I. , Hurduc Nicolae
Published: March 2005

A series of aromatic homo- and copolyethers containing 6, 7 or 8 methylenic groups as spacers are presented. The polymers were synthesized by phase-transfer catalysis and they were characterized by using 1H-NMR, polarized light microscopy, differential scanning calorimetry and thermogravimetric analyses. All copolymers have low molecular weight, situated within the oligomer domain. They have high transition temperatures except for the case when bent or semi-flexible bisphenols were used as comonomers. Only 4,4 -dihydroxyazobenzene-based polymers showed liquid crystalline properties with a mesophase range over 50° C, and with the clearing temperatures situated near their thermal decomposition limit. The insertion of kink or flexible bisphenols was not favorable to mesophase formation (it induced too high a disorder in the system), but it lowered the transition temperatures, as expected. Few exceptions occurred in the case of bisphenol A and 4,4 -dihydroxybenzophenone. The biphasic nature of these copolyethers is most probably due to both the polydispersity and the chemical heterogeneity of the samples. Some of the semi-crystalline copolymers may exhibit virtual mesophase that can be uncovered by increasing their molecular weight or by raising the free energy of the isotropic liquid state.
Some Aspects of the Cure of RP-46, a Nadic End-capped Polyimide, and Phenyl Nadimide and Bis-Nadic-3,4'-ODA Model Compounds
Authors: Simone Christopher D. , Xiao Youming , Sun X. D. , Scola D. A.
Published: March 2005

Infrared studies of the initial cure and post-cure of RP-46 resin, a nadic end-capped polyimide and a model bisnadimide compound N, N' -(oxydi-3,4 phenylene) di-5,6-norbornene-2,3-dicarboximide (Bis-nadic-3,4'-ODA) were conducted at 316, 325 and 350° C for various time periods. Infrared studies of another model compound, N-phenylnadimide, were conducted at lower temperatures, from 100 to 270° C. N-Phenylnadimide cures at much lower temperatures than Bis-nadic-3,4 -ODA and RP-46. The crosslinking reaction was followed by monitoring the absorption peaks at 841 and 785 cm-1, the endo and exo bands in the 2,3 positions of the nadic end caps and cyclo-aliphatic and cyclo-olefinic peaks on the region 1000 to 600 cm-1 associated with the nadic end-cap curing reaction. Weight losses and changes in the glass transition temperature of the RP-46 resin due to cure and post-cure, were also examined. The infrared changes suggest that complete cross-linking requires a temperature of 325° C or above, and that several new infrared bands are generated in the process. The simple thermally induced reverse Diels–Alder cyclopentadiene N-substituted maleimide recombination reaction or norbornene to norbornene, norbornene to cyclopentadiene or norbornene to substituted maleimide addition reactions may adequately define the cross-linked products derived from the initial cross-linking reaction at 316° C for 1 to 2 h. However, postcure of RP-46 resin or the nadic-3,4 -ODA model compound at 325 or 350° C for several hours generates additional infrared bands in the cyclo-aliphatic and cyclo-olefinic regions (1000–600 cm-1), which are absent in material cured at 316° C for 1 to 2 h. Therefore, completely cured resin consists of simple addition reaction products from the initial cure at 316° C and more complex products from the elevated temperature post-cures. A post-cure at 325° C for about 8 h or at 350° C for 2 h is required for a maximum Tgof 391° C. This is accompanied by a stabilization weight loss of about 2–3%. The weight loss and Tgdata are supporting evidence for the infrared studies.
Emergent autoimmunity in graft-versus-host disease
Authors: Tivol Elizabeth , Komorowski Richard , Drobyski William R.
Published: March 2005

Donor T-cell recognition of host alloantigens presented by host antigen-presenting cells (APCs) is necessary for the induction of graft-versus-host disease (GVHD), but whether direct alloreactivity is sufficient for the propagation of GVHD is unknown. In this study, we demonstrate that GVHD cannot be effectively propagated through the direct pathway of allorecognition. Rather, donor T-cell recognition of antigens through the indirect pathway is necessary for the perpetuation of GVHD. Furthermore, GVHD results in the breaking of self tolerance, resulting in the emergence of donor T cells that can cause autoimmune disease in syngeneic recipients. Notably, GVHD-induced autoreactivity is donor APC dependent, transferable into secondary hosts, and involves cells of the innate immune system. These results indicate that donor T-cell--mediated pathologic damage during GVHD becomes donor APC dependent and provide a mechanistic explanation for the long-standing observation that GVHD is associated with autoimmune clinical manifestations. (Blood. 2005;105:4885-4891)
The role of mast cells in the pathogenesis of pain in chronic pancreatitis
Authors: Hoogerwerf Willemijntje A , Gondesen Kelly , Xiao Shu-Yuan , Winston John H , Willis William D , Pasricha Pankaj J
Published: March 2005

Background

The biological basis of pain in chronic pancreatitis is poorly understood. Mast cells have been implicated in the pathogenesis of pain in other conditions. We hypothesized that mast cells play a role in the pain of chronic pancreatitis.

We examined the association of pain with mast cells in autopsy specimens of patients with painful chronic pancreatitis. We explored our hypothesis further using an experimental model of trinitrobenzene sulfonic acid (TNBS) -induced chronic pancreatitis in both wild type (WT) and mast cell deficient mice (MCDM).

Methods

Archival tissues with histological diagnoses of chronic pancreatitis were identified and clinical records reviewed for presence or absence of reported pain in humans. Mast cells were counted.

The presence of pain was assessed using von Frey Filaments (VFF) to measure abdominal withdrawal responses in both WT and MCDM mice with and without chronic pancreatitis.

Results

Humans with painful chronic pancreatitis demonstrated a 3.5-fold increase in pancreatic mast cells as compared with those with painless chronic pancreatitis.

WT mice with chronic pancreatitis were significantly more sensitive as assessed by VFF pain testing of the abdomen when compared with MCDM.

Conclusion

Humans with painful chronic pancreatitis have an increased number of pancreatic mast cells as compared with those with painless chronic pancreatitis. MCDM are less sensitive to mechanical stimulation of the abdomen after induction of chronic pancreatitis as compared with WT. Mast cells may play an important role in the pathogenesis of pain in chronic pancreatitis.
JTE-522, a selective COX-2 inhibitor, inhibits growth of pulmonary metastases of colorectal cancer in rats
Authors: Kobayashi Hirotoshi , Uetake Hiroyuki , Higuchi Tetsuro , Enomoto Masayuki , Sugihara Kenichi
Published: March 2005

Background

Epidemiological studies have shown that individuals who regularly consume NSAIDs have lower rates of mortality associated with colorectal cancer. Because COX-2 inhibitors prevent tumor growth through some mechanisms, we assessed the effect of JTE-522, a selective COX-2 inhibitor, on pulmonary metastases of colon cancer in a rat model.

Methods

A suspension of 5 × 106 RCN-9 (rat colon cancer cells) was injected into the tail vein of 24 anesthetized male F344/DuCrj rats. Oral JTE-522 (0, 3, 10, or 30 mg/kg/day) was administered from the day before RCN-9 injection until the end of the study. Twenty-four days later, the lungs were removed from sacrificed rats and weighed. Pulmonary metastatic tumors were microscopically evaluated in the largest cross sections. We also performed immunohistochemical staining for both COX-2 and VEGF.

Results

JTE-522 dose-dependently decreased lung weight (p = 0.001) and the size of pulmonary metastatic tumors (p = 0.0002). However, the differences in the number of metastatic tumors among 4 groups were insignificant. Significant adverse effects of JTE-522 were undetectable. Immunohistochemical staining showed high levels of both COX-2 and VEGF in pulmonary metastatic tumors.

Conclusion

JTE-522 dose-dependently decreased the size, but not the number of pulmonary metastases. COX-2 inhibitors might block metastatic tumor growth, but not actual metastasis. Selective COX-2 inhibitors might be useful as therapeutic agents that inhibit the growth of metastatic tumors, as well as the tumorigenesis of colorectal cancer.
Clinical outcome of endonasal KTP laser assisted dacryocystorhinostomy
Authors: Ressiniotis Thomas , Voros Gerasimos M , Kostakis Vasilios T , Carrie Sean , Neoh Christopher
Published: March 2005

Background

To evaluate the clinical outcome of primary endonasal laser assisted dacryocystorhinostomy (ENL-DCR) using the potassium-titanyl-phosphate laser.

Methods

We retrospectively reviewed all primary ENL-DCRs performed within a period of twelve months by the same combined Ophthalmology and Otorhinolaringology team in Freeman Hospital, Newcastle upon Tyne, UK. The main outcome measure for success was resolution or significant improvement of epiphora. Details of surgery, intraoperative and postoperative complications, as well as pathology associated with failure were also studied. Patients were followed up for at least 12 months.

Results

A total of 41 consecutive ENL-DCRs on 29 patients (22 females, 7 males, mean age 75 years) were analysed. All patients had bicanalicular silicone intubation for at least 4 months. The success rate at 12 months postoperatively was 78.1%. Pathology associated with failure included: intranasal pathology (12.2%), mucocele (7.3%), and systemic sarcoidosis (2.4%). No significant intra-operative complications were recorded.

Conclusion

The ENL-DCR with potassium-titanyl-phosphate laser can be considered as a safe and efficient primary procedure for the treatment of nasolacrimal duct obstruction.
The efficacy of playing a virtual reality game in modulating pain for children with acute burn injuries: A randomized controlled trial [ISRCTN87413556]
Authors: Das Debashish A , Grimmer Karen A , Sparnon Anthony L , McRae Sarah E , Thomas Bruce H
Published: March 2005

Background

The management of burn injuries is reported as painful, distressing and a cause of anxiety in children and their parents. Child's and parents' pain and anxiety, often contributes to extended time required for burns management procedures, in particular the process of changing dressings. The traditional method of pharmacologic analgesia is often insufficient to cover the burnt child's pain, and it can have deleterious side effects [1, 2]. Intervention with Virtual Reality (VR) games is based on distraction or interruption in the way current thoughts, including pain, are processed by the brain. Research on adults supports the hypothesis that virtual reality has a positive influence on burns pain modulation.

Methods

This study investigates whether playing a virtual reality game, decreases procedural pain in children aged 5–18 years with acute burn injuries. The paper reports on the findings of a pilot study, a randomised trial, in which seven children acted as their own controls though a series of 11 trials. Outcomes were pain measured using the self-report Faces Scale and findings of interviews with parent/carer and nurses.

Results

The average pain scores (from the Faces Scale) for pharmacological analgesia only was, 4.1 (SD 2.9), while VR coupled with pharmacological analgesia, the average pain score was 1.3 (SD 1.8)

Conclusion

The study provides strong evidence supporting VR based games in providing analgesia with minimal side effects and little impact on the physical hospital environment, as well as its reusability and versatility, suggesting another option in the management of children's acute pain.
Quality of sleep in patients with schizophrenia is associated with quality of life and coping
Authors: Hofstetter John R , Lysaker Paul H , Mayeda Aimee R
Published: March 2005

Background

While sleep disturbance is widespread in schizophrenia it is less clear whether sleep disturbance is uniquely related to impaired coping and perceived quality of life.

Methods

We simultaneously assessed sleep quality, symptoms, and coping in 29 persons with schizophrenia or schizoaffective disorder in a post acute phase of illness. Assessment instruments included the Pittsburgh Sleep Quality Index; the Positive and Negative Symptom Scale; the Heinrichs Quality of Life Scale; and the Ways of Coping Scale. Multiple regressions were performed predicting quality of life and coping from sleep quality controlling for age and symptom severity. On a subset of seven subjects non-dominant wrist actigraphy was used as an objective check of their self-reported poor sleep.

Results

Analyses revealed that poor sleep quality predicted low quality of life (r = -0.493; p = .022) and reduced preference for employing positive reappraisal when facing a stressor (r = -0.0594; p = 0.0012). Actigraphy confirmed poor sleep quality in a subset of subjects. They had shorter sleep duration (p < .0005), shorter average sleep episodes (p < .005) and more episodes of long awakening (p < 0.05) than community norms.

Conclusion

The results are consistent with the hypotheses that poor sleep may play a unique role in sustaining poor quality of life and impaired coping in patients with schizophrenia. These associations may hold for community controls as well.
A case of invasive aspergillosis in CGD patient successfully treated with Amphotericin B and INF-γ
Authors: Mamishi Setareh , Zomorodian Kamiar , Saadat Farshid , Gerami-Shoar Mohsen , Tarazooie Bita , Siadati Seyad Ahmad
Published: March 2005

Background

Chronic granulomatous disease (CGD) is a rare disorder of phagocytes in which absence of superoxide and hydrogen peroxide production in phagocytes predisposes patients to bacterial and fungal infections. The most common fungal infections in these patients are caused by Aspergillus species.

Case presentation

Here, we describe Aspergillus osteomyelitis of the ribs and hepatic abscess in a 5-year-old boy. The patient was successfully treated with Amphotericin B and INF-γ.

Conclusion

With respect to the high frequency of aspergillosis in the CGD patient, immune deficiency should be investigated in patients with invasive aspergillosis. Moreover, using antifungal drugs as prophylaxis can improve the quality of life in these patients.
Increased daily physical activity and fatigue symptoms in chronic fatigue syndrome
Authors: Black Christopher D , O'Connor Patrick J , McCully Kevin K
Published: March 2005

Individuals with chronic fatigue syndrome (CFS) have been shown to have reduced activity levels associated with heightened feelings of fatigue. Previous research has demonstrated that exercise training has beneficial effects on fatigue-related symptoms in individuals with CFS.

Purpose

The aim of this study was to sustain an increase in daily physical activity in CFS patients for 4 weeks and assess the effects on fatigue, muscle pain and overall mood.

Methods

Six CFS and seven sedentary controls were studied. Daily activity was assessed by a CSA accelerometer. Following a two week baseline period, CFS subjects were asked to increase their daily physical activity by 30% over baseline by walking a prescribed amount each day for a period of four weeks. Fatigue, muscle pain and overall mood were reported daily using a 0 to 100 visual analog scale and weekly using the Profile of Mood States (Bipolar) questionnaire.

Results

CFS patients had significantly lower daily activity counts than controls (162.5 ± 51.7 × 103 counts/day vs. 267.2 ± 79.5 × 103 counts/day) during a 2-week baseline period. At baseline, the CFS patients reported significantly (P < 0.01) higher fatigue and muscle pain intensity compared to controls but the groups did not differ in overall mood. CFS subjects increased their daily activity by 28 ± 19.7% over a 4 week period. Overall mood and muscle pain worsened in the CFS patients with increased activity.

Conclusion

CFS patients were able to increase their daily physical activity for a period of four weeks. In contrast to previous studies fatigue, muscle pain, and overall mood did not improve with increased activity. Increased activity was not presented as a treatment which may account for the differential findings between this and previous studies. The results suggest that a daily "activity limit" may exist in this population. Future studies on the impact of physical activity on the symptoms of CFS patients are needed.
Preprandial ghrelin is not affected by macronutrient intake, energy intake or energy expenditure
Authors: Paul David R , Kramer Matthew , Rhodes Donna G , Rumpler William V
Published: March 2005

Background

Ghrelin, a peptide secreted by endocrine cells in the gastrointestinal tract, is a hormone purported to have a significant effect on food intake and energy balance in humans. The influence of factors related to energy balance on ghrelin, such as daily energy expenditure, energy intake, and macronutrient intake, have not been reported. Secondly, the effect of ghrelin on food intake has not been quantified under free-living conditions over a prolonged period of time. To investigate these effects, 12 men were provided with an ad libitum cafeteria-style diet for 16 weeks. The macronutrient composition of the diets were covertly modified with drinks containing 2.1 MJ of predominantly carbohydrate (Hi-CHO), protein (Hi-PRO), or fat (Hi-FAT). Total energy expenditure was measured for seven days on two separate occasions (doubly labeled water and physical activity logs).

Results

Preprandial ghrelin concentrations were not affected by macronutrient intake, energy expenditure or energy intake (all P > 0.05). In turn, daily energy intake was significantly influenced by energy expenditure, but not ghrelin.

Conclusion

Preprandial ghrelin does not appear to be influenced by macronutrient composition, energy intake, or energy expenditure. Similarly, ghrelin does not appear to affect acute or chronic energy intake under free-living conditions.
Distributional interaction: Interpretational problems when using incidence odds ratios to assess interaction
Authors: Campbell Ulka B , Gatto Nicolle M , Schwartz Sharon
Published: March 2005

It is well known that the incidence odds ratio approximates the risk ratio when the disease of interest is rare, but increasingly overestimates the risk ratio as the disease becomes more common. However when assessing interaction, incidence odds ratios may not approximate risk ratios even when the disease is rare. We use the term "distributional interaction" to refer to interaction that appears when using incidence odds ratios that does not appear, or appears to a lesser degree, when using risk ratios. The interpretational problems that arise from this discrepancy can have important implications in epidemiologic research. Therefore, quantification of the relationship between the interaction odds ratio and the interaction risk ratio is warranted.

In this paper, we provide a formula to quantify the differences between incidence odds ratios and risk ratios when they are used to estimate effect modification on a multiplicative scale. Using this formula, we examine the conditions under which these two estimates diverge. Furthermore, we expand this discussion to the implications of using incidence odds ratios to assess effect modification on an additive scale. Finally, we illustrate how distributional interaction arises and the problems that it causes using an example from the literature.

Whenever the risk of the outcome variable is non-negligible, distributional interaction is possible. This is true even when the disease is rare (e.g., disease risk is less than 5%). Therefore, when assessing interaction on either an additive or multiplicative scale, caution should be taken in interpreting interaction estimates based on incidence odds ratios.
Developmental Changes in the Pattern of Ghrelin’s Acyl Modification and the Levels of Acyl-Modified Ghrelins in Murine Stomach
Authors: Nishi Yoshihiro , Hiejima Hiroshi , Mifune Hiroharu , Sato Takahiro , Kangawa Kenji , Kojima Masayasu
Published: March 2005

Ghrelin is an acylated peptide hormone secreted primarily from endocrine cells in the stomach. The major active form of ghrelin is a 28-amino acid peptide with an n-octanoyl modification at Ser3 (n-octanoyl ghrelin), which is essential for its activity. In addition to n-octanoyl ghrelin, other forms of ghrelin peptide exist, including des-acyl ghrelin, which lacks an acyl modification, and other minor acylated ghrelin species, such as n-decanoyl ghrelin, whose Ser3 residue is modified by n-decanoic acid. Multiple reports have identified various physiological functions of ghrelin. However, until now, there have been no reports that explore the process of ghrelin acyl modification, and only a few studies have compared the levels of des-acyl, n-octanoyl, and/or other minor populations of acylated ghrelin peptides. In this study we report that the amount of n-octanoyl ghrelin in murine stomachs increases gradually during the suckling period to a maximal level at 3 wk of age and falls sharply after the initiation of weaning. However, the concentration (picomoles per milligram of wet weight tissue) of total ghrelin, which includes des-acyl and all acylated forms of ghrelin peptides with intact C termini in murine stomach, remains unchanged across this suckling-weaning transition. Prematurely weaned mice exhibited a significant decrease in the amount of n-octanoyl or n-decanoyl ghrelin in the stomach. Orally ingested glyceryl trioctanoate, a medium-chain triacylglyceride rich in milk lipids, significantly increased the level of n-octanoyl-modified ghrelin in murine stomach. Fluctuations in the proportion of this biologically active, acyl-modified ghrelin could contribute to or be influenced by the change in energy metabolism during the suckling-weaning transition.
Isolation and Identification of Histone H3 Protein Enriched in Microvesicles Secreted from Cultured Sebocytes
Authors: Nagai Ayako , Sato Takashi , Akimoto Noriko , Ito Akira , Sumida Michihiro
Published: March 2005

Secretion of microvesicles, defined as sebosomes, containing lipid particles were discovered for the first time in cultured sebocytes. After reaching confluency, hamster-cloned sebocytes released bubble-like microvesicles with a diameter range of 0.5–5.0 μm. They had a complex structure containing multiple Oil Red O-stainable particles. The lipid components of the microvesicles were large amounts of squalene both of hamster-cloned and rat primary cultured sebocytes. The microvesicles contained a concentrated 17-kDa cationic protein, which was soluble in sulfate buffer including Nonidet P-40 at pH 1.5. As the protein bound tightly to heparin-Sepharose and eluted with 1.5 m NaCl, it was further purified from a SDS-PAGE gel. Peptide sequencing identified the protein to be histone H3. Polyclonal antibodies against the purified protein detected the antigen in the microvesicles both in the hamster-cloned and rat primary cultured sebocytes. The antibodies demonstrated a distribution of the protein within the nucleus, cytoplasm, and precursor microvesicles. When a gene construct encoding histone H3-enhanced green fluorescent protein was transfected to the sebocytes, fluorescence of the fusion proteins was detected within both the nucleus and the precursor microvesicles of the cytoplasm. The distribution of heparan sulfate was evident in the microvesicles, and it suggested the possibility that the histone H3 protein was recruited and then condensed to the secreted microvesicles by the molecules. In addition, the 14-3-3 protein, which was detected in the microvesicles, also may help incorporate the histone H3 protein in the microvesicles because it can bind to both histone and lipid particles.
The Antiangiogenic Factor, 16-kDa Human Prolactin, Induces Endothelial Cell Cycle Arrest by Acting at Both the G0–G1 and the G2–M Phases
Authors: Tabruyn Sébastien P. , Nguyen Ngoc-Quynh-Nhu , Cornet Anne M. , Martial Joseph A. , Struman Ingrid
Published: March 2005

The 16-kDa N-terminal fragment of human prolactin (16K hPRL) is a potent antiangiogenic factor that has been shown to prevent tumor growth in a xenograph mouse model. In this paper we first demonstrate that 16K hPRL inhibits serum-induced DNA synthesis in adult bovine aortic endothelial cells. This inhibition is associated with cell cycle arrest at both the G0–G1 and the G2–M phase. Western blot analysis revealed that 16K hPRL strongly decreases levels of cyclin D1 and cyclin B1, but not cyclin E. The effect on cyclin D1 is at least partially transcriptional, because treatment with 16K hPRL both reduces the cyclin D1 mRNA level and down-regulates cyclin D1 promoter activity. This regulation may be due to inhibition of the MAPK pathway, but it is independent of the glycogen synthase kinase-3β pathway. Lastly, 16K hPRL induces the expression of negative cell cycle regulators, the cyclin-dependent kinase inhibitors p21(cip1) and p27(kip1). In summary, 16K hPRL inhibits serum-induced proliferation of endothelial cells through combined effects on positive and negative regulators of cell cycle progression.
A Monoclonal Antibody with Potential for Aiding Non-invasive Prenatal Diagnosis: Utility in Screening of Pregnant Women at Risk of Preeclampsia
Authors: Fernández Alejandra , Prieto Belén , Escudero Ana , Ladenson Jack H. , Alvarez Francisco V.
Published: March 2005

The development of a non-invasive method of prenatal diagnosis in maternal blood has been the goal of our investigations during the last years. We have developed several anti-CD71 monoclonal antibodies and optimized a protocol for the isolation of nucleated red blood cells (NRBC) from peripheral maternal blood. The enhanced traffic of fetal erythroblasts into the maternal circulation in preeclampsia has been investigated by several groups. In this study, we compared one of our antibodies, 2F6.3, with a commercial anti-CD71 antibody in blood samples from pregnant women suffering pregnancy-induced hypertension (PIH) and in a control group of pregnant women without clinical features suggestive of an increased risk of developing preeclampsia. The mAb 2F6.3, developed by our group, has succeeded in isolating a significantly higher number of erythroblasts with less maternal cell contamination than the commercial antibody in both women with PIH and in the control group ( p<0.01; Wilcoxon Signed Ranks Test). Florescence in situ hybridization analysis also demonstrated that 2F6.3 is a better antibody for the isolation of fetal NRBC in maternal blood than the commercial anti-CD71 antibody.
The Variation of Aneuploidy Frequency in the Developing and Adult Human Brain Revealed by an Interphase FISH Study
Authors: Yurov Yuri B. , Iourov Ivan Y. , Monakhov Viktor V. , Soloviev Ilia V. , Vostrikov Viktor M. , Vorsanova Svetlana G.
Published: March 2005

Despite the lack of direct cytogenetic studies, the neuronal cells of the normal human brain have been postulated to contain normal (diploid) chromosomal complement. Direct proof of a chromosomal mutation presence leading to large-scale genomic alterations in neuronal cells has been missing in the human brain. Large-scale genomic variations due to chromosomal complement instability in developing neuronal cells may lead to the variable level of chromosomal mosaicism probably having a substantial effect on brain development. The aim of the present study was the pilot assessment of chromosome complement variations in neuronal cells of developing and adult human brain tissues using interphase multicolor fluorescence in situ hybridization (mFISH). Chromosome-enumerating DNA probes from the original collection (chromosomes 1, 13 and 21, 18, X, and Y) were used for the present pilot FISH study. As a source of fetal brain tissue, the medulla oblongata was used. FISH studies were performed using uncultured fetal brain samples as well as organotypic cultures of medulla oblongata tissue. Cortex tissues of postmortem adult brain samples (Brodmann area 10) were also studied. In cultured in vitro embryonic neuronal brain cells, an increased level of aneuploidy was found (mean rate in the range of 1.3–7.0% per individual chromosome, in contrast to 0.6–3.0% and 0.1–0.8% in uncultured fetal and postmortem adult brain cells, respectively). The data obtained support the hypothesis regarding aneuploidy occurrence in normal developing and adult human brain.
Fluorescence In Situ Hybridization and Spectral Imaging Analysis of Human Oocytes and First Polar Bodies
Authors: Weier Heinz-Ulli G. , Weier Jingly F. , Renom Maria Oter , Zheng Xuezhong , Colls Pere , Nureddin Aida , Pham Chau D. , Chu Lisa W. , Racowsky Catherine , Munné Santiago
Published: March 2005

We investigated the frequencies of abnormalities involving either chromosome 1, 16, 18, or 21 in failed-fertilized human oocytes. Although abnormalities involving chromosome 16 showed an age-dependent increase, results for the other chromosomes did not show statistically significant differences among the three age groups, <35 years, 35–39 years, and >39 years. The scoring of four chromosomes is likely to underestimate the true rate of aneuploid cells. Therefore, for a pilot study investigating a more-comprehensive analysis of oocytes and their corresponding first polar bodies, we developed a novel eight-probe chromosome enumeration scheme using fluorescence in situ hybridization and spectral imaging analysis.
The Usefulness of Calyculin A for Cytogenetic Prenatal Diagnosis
Authors: Srebniak Malgorzata I. , Trapp Gizela G. , Wawrzkiewicz Angelika K. , Kaźmierczak Wojciech , Wiczkowski Andrzej K.
Published: March 2005

An increased number of chromosome plates can be obtained by use of calyculin A (CLA). CLA is an inhibitor of protein phosphatases (type 1 and type 2A serine/threonine). Inactivation of these phosphatases leads to premature chromosome condensation (PCC) in all phases of the cell cycle; thus, it is possible to investigate both metaphase and G2-PCC chromosomes. Amniotic fluid (AF) cultures were treated with calyculin A (CLA). GTG banding was obtained. Using this method it is possible to investigate all cell cycle phases, GTG banding, chromosomal breaks, and rates of PCD on the same preparation. Analyses of AF cultures treated with CLA allow complex studies on fetal genetic material. This work presents potential usefulness of CLA for cytogenetic prenatal diagnosis.
Polar Body Diagnosis for Hemophilia A Using Multiplex PCR for Linked Polymorphic Markers
Authors: Tomi Diana , Griesinger Georg , Schultze-Mosgau Askan , Eckhold Juliane , Schöpper Beate , Al-Hasani Safaa , Diedrich Klaus , Schwinger Eberhard
Published: March 2005

Preimplantation genetic diagnosis (PGD) is usually performed on blastomeres. In Germany, the only possibility to perform PGD is by analysis of polar bodies. We performed PGD using polar bodies in a woman who is a carrier of hemophilia A. Multiplex PCR followed by nested fluorescent PCR for five linked polymorphic markers was established. From 11 analyzed polar bodies, only 1 showed alleles linked to the mutation. The corresponding oocyte was transferred and no pregnancy was established. As seen in other investigations, the rate of heterozygous first polar bodies is surprisingly high.
Rapid Prenatal Diagnosis of Aneuploidy Using Quantitative Fluorescence-PCR (QF-PCR)
Authors: Ogilvie Caroline Mackie , Donaghue Celia , Fox Susan P. , Docherty Zoe , Mann Kathy
Published: March 2005

Molecular cytogenetic aneuploidy testing for pregnant women at increased risk of chromosome abnormality leads to rapid reassurance for those with normal results and earlier decisions on pregnancy management in the case of abnormality. We tested 9080 prenatal samples using a one-tube QF-PCR test for trisomies 13, 18, and 21; the abnormality rate was 5.9%. There were no misdiagnoses for non-mosaic trisomy. A sex chromosome multiplex was developed that detects structural sex chromosome abnormalities as well as aneuploidies. The sex chromosome test was targeted at pregnancies (272) with specific abnormalities suggestive of Turner syndrome; 13.2% showed 45,X, confirmed by follow-up analysis.
New Aspects of Laser Microdissection in Research and Routine
Authors: Burgemeister Renate
Published: March 2005

Laser microdissection has opened a window to new technologies. The scientific fields of genomics, transcriptomics, and proteomics need pure samples for rendering reliable results. Homogeneous sample preparation is a prerequisite for modern molecular analyses, both qualitative and quantitative. Laser microdissection and pressure catapulting (LMPC) is a tool for isolating specific cells from complex tissues in a non-contact and contamination-free manner. Because LMPC technology is an optimal method for obtaining fast and reliable access to single cells, the possibility of automatic isolation of single fetal cells has the promise of being a big step forward in developing protocols for non-invasive prenatal diagnosis.
First Systematic CGH-based Analyses of Ancient DNA Samples of Malformed Fetuses Preserved in the Meckel Anatomical Collection in Halle/Saale (Germany)
Authors: Tönnies H. , Gerlach A. , Klunker R. , Schultka R. , Göbbel L.
Published: March 2005

We present the first data on our comparative genomic hybridization (CGH)–based strategy for the analysis of ancient DNA (aDNA) samples extracted from fetuses preserved in the Meckel Anatomical Collection in Halle, Germany. The collection contains numerous differently fixed ancient samples of fetal malformations collected from the middle of the 18th to the early 19th century. The main objective of this study is to establish a “standard” aDNA extraction and amplification protocol as a prerequisite for successful CGH analyses to detect or exclude chromosomal imbalances possibly causative for the malformations described for the fetuses.
A Highly Complex Chromosomal Rearrangement between Five Chromosomes in a Healthy Female Diagnosed in Preparation for Intracytoplasmatic Sperm Injection
Authors: Kuechler Alma , Ziegler Monika , Blank Cornelia , Rommel Birgit , Bullerdiek Joern , Ahrens Jochen , Claussen Uwe , Liehr Thomas
Published: March 2005

We report a case of a de novo complex chromosomal rearrangement among five chromosomes found in a clinically healthy woman. The only indication for chromosome analysis was a planned intracytoplasmatic sperm injection. Physical examination, including internal and external genitals, and ovaries and hormone status were normal. Banding cyto-genetics showed a rearrangement among chromosomes #3, #4, #7, #9, and #17. Twenty-four-color fluorescence in situ hybridization and multicolor banding were applied to characterize the translocations and breakpoints more precisely. This confirmed the involved chromosomes and revealed two breakpoints in chromosome #4. This six-breakpoint rearrangement [der(3)t(3;4), der(4)t(17;4;7), der(7)t(3;7), der(9)t(4;9), and der(17)t(9;17)] seemed to be balanced on a molecular cytogenetic level, although submicroscopic deletions or duplications close to the breakpoints cannot be excluded.
QF-PCR Examination of Parental and Meiotic Origin of Trisomy 21 in Central and Eastern Europe
Authors: Machatkova Marina , Brouckova Martina , Matejckova Milada , Krebsova Alice , Sperling Karl , Vorsanova Svetlana , Kutsev Sergei , Zerova Tatiana , Arbuzova Svetlana , Krejci Roman , Petersen Michael , Macek Milan
Published: March 2005

Study of parental/meiotic origin of free trisomy 21 in nuclear families from Russia (70 cases), Ukraine (32 cases), and 22 from Germany revealed maternal nondisjunction in 77.3% (Germany), 93.8% (Ukraine), and 91.4% (Russia), paternal origin in 13.6%, 6.2%, and 8.6%, respectively. Maternal meiosis I errors were found in 84.4% (Ukraine), 77.1% (Russia), paternal origin in 3.1% (Ukraine), 2.9% (Russia). Maternal meiosis II errors occurred in 9.4% and 14.3% and paternal in 3.1% and 5.7% in Ukraine and Russia, respectively. No significant differences were found in maternal/paternal origin among Ukraine, Russia, Germany, and published data from other European regions.
Technology for Automated, Rapid, and Quantitative PCR or Reverse Transcription-PCR Clinical Testing
Authors: Raja Siva , Ching Jesus , Xi Liqiang , Hughes Steven J , Chang Ronald , Wong Wendy , McMillan William , Gooding William E , McCarty Kenneth S , Chestney Melissa , Luketich James D , Godfrey Tony E
Published: March 2005

Background: PCR-based assays can improve clinical care, but they remain technically demanding and labor-intensive. We describe a new instrument, the GeneXpert®, that performs automated nucleic acid isolation, reverse transcription, and fluorescence-based quantitative PCR in ∼35 min.

Methods: Yield and integrity of RNA isolated on the GeneXpert were compared with Qiagen-based extraction for parallel samples (5-μm frozen tissue sections). The reproducibility of automated RNA isolation, reverse transcription, and quantitative PCR was determined by replicate (n = 10) analysis of 10 tissues, using duplex (target and endogenous control) reverse transcription-PCR reactions for two gene combinations. The GeneXpert was then used to perform rapid analysis of lymph nodes from melanoma, breast cancer, and lung cancer patients and analysis of melanoma metastatic to the lung, primary lung adenocarcinoma, and healthy lung tissue.

Results: On the GeneXpert, RNA was recovered in slightly over 6 min, and the yield was ∼70% of that from parallel Qiagen reactions. The RNA integrity was comparable to that of Qiagen-isolated RNA as determined by gel electrophoresis. For the melanoma samples, the 95% prediction interval for the ΔCt for a new measurement was ±1.54 cycles, and for breast cancer samples, the interval for a newly observed ΔCt was ±1.40 cycles. GeneXpert assays successfully detected the presence of metastatic melanoma, breast cancer, and lung cancer in lymph nodes and also differentiated among metastatic melanoma, lung adenocarcinoma, and healthy lung.

Conclusions: RNA yield and integrity on the GeneXpert are comparable to benchtop methods. Reproducibility of the GeneXpert data is similar to that seen with manual methods in our hands but may need improvement for some applications. The GeneXpert can perform RNA isolation, reverse transcription, and quantitative PCR in ∼35 min and could therefore be used for intraoperative testing when applicable.