bluuebunny/crossref_metadata_2025 huggingface dataset:
Necrophylactic periderm formation in the roots of western larch and Douglas‐fir trees infected with Armillaria ostoyae. I. The response to abiotic wounding in non‐infected roots
Authors: Robinson R. M. , Jensen G. D. , Morrison D. J.
Published: March 2004

The sequence of events leading to necrophylactic periderm formation was studied throughout the year following the abiotic wounding of the non‐infected roots of 10‐ and 27‐year‐old western larch (Larix occidentalis) and 11‐ and 25‐year‐old Douglas‐fir (Pseudotsuga menziesii) trees that were infected with Armillaria ostoyae. The sequence was the same for both ages and species of trees. Wound repair was more rapid in the summer compared with the spring and autumn. Following cell hypertrophy, a zone of lignified impervious tissue was in the initial stages of formation within 10 days of wounding in the summer and 14 days in the spring or autumn. The new phellogen produced a layer of phellem three to four rows of cells thick after 20 days in the summer or 40 days in the spring. Modified cells abutting the inner boundary of the impervious zone frequently developed thick lignified abaxial walls and thin suberized adaxial walls. A typical exophylactic periderm in healthy root bark tissue of both western larch and Douglas‐fir consisted of stone phellem one to four rows of cells thick and a layer of thin‐walled phellem three to six rows of cells thick in western larch and two to three rows thick in Douglas‐fir, a single row of phellogen cells and one to three rows of phelloderm cells. Mature thin‐walled phellem cells had pigmented contents, red in western larch and light brown in Douglas‐fir. In response to wounding, 27‐year‐old western larch and 25‐year‐old Douglas‐fir developed necrophylactic periderms with annual bands of phellem. The bands included a layer of phellem that was six to 12 and nine to 15 rows of cells thicker than the layer of phellem observed in the respective naturally developed exophylactic periderms. Fifty days following wounding in the summer, stone phellem, one to three rows of cells thick, was observed in the necrophylactic periderm of 10‐year‐old trees. When fully developed, the necrophylactic periderm in 27‐year‐old western larch also had a layer of stone phellem three to five rows of cells thick in each band. Stone phellem development was only sporadic in 25‐year‐old Douglas‐fir. Wounds in the winter showed no signs of activity associated with repair until dormancy broke in the spring.
The perceived needs of Jordanian families of hospitalized, critically ill patients
Authors: Al‐Hassan Musa Ali , Hweidi Issa M
Published: March 2004

The purpose of this study was to identify needs of Jordanian families of hospitalized, critically ill patients. The Critical Care Family Needs Inventory was introduced to 158 family members who were visiting their hospitalized, critically ill relatives. The findings revealed that ≥ 80% of the family members perceived 16 need statements as important or very important. The participants ranked order needs for assurance, information and proximity the highest and needs for support and comfort the lowest. Specifically, the most important needs of the families were to receive information about the patients, to feel that the hospital personnel care about the patients and to have the information given in understandable terms. Results of this study indicated that Jordanian families had specific and identifiable needs. Providing families of critically ill patients clear, simple and updated information about the patients, and assuring them about the quality of care the patients receive, should be essential components of the critical care nursing delivery system.
Anxiety and depression in community‐dwelling, Italian Alzheimer's disease caregivers
Authors: Sansoni Julita , Vellone Ercole , Piras Giovanni
Published: March 2004

Family caregiving for those who suffer from Alzheimer's disease is an important but understudied area in Italian nursing. Population ageing and the existing burden of care for family caregivers indicate that there will be enormous pressure on families in the future to provide adequate and culturally appropriate care. This study attempted to redress this situation by examining anxiety and depression among 34 female Italian Alzheimer's caregivers over a total of 816 caregiving days. A descriptive, repeated measures design was used, using three instruments to survey caregiving: a General Questionnaire about Caregiving, the Spielberg State‐Trait Anxiety Inventory and the Geriatric Depression Scale. Findings indicated that caregivers suffered high levels of anxiety (76%) and depression (42%). Statistical analyses showed that the anxiety and depression scores were positively correlated with hours of care, physical and psychological illness scores, and negatively correlated with level of education and time for leisure activities. However, no significant correlations were found with the Mini Mental State Examination scores, demonstrating that the burden of care is large, irrespective of the extent of mental impairment. Implications of the findings suggest that support and assistance given to Italian caregivers might be inadequate, particularly with respect to respite services and educational support.
Selected single blastocyst transfers maintained pregnancy outcome and eliminated multiple pregnancies
Authors: Kuramoto Takeshi , Boediono Arief , Egashira Akiyoshi , Motoishi Mutsuro , Sugioka Michiyo , Fukuda Kimiko , Higashijima Toki , Yoshioka Naomi , Rajamahendran Rajadurai
Published: March 2004

Background:  Transfer of more than one embryo following in vitro fertilization/intracytoplasmic sperm injection cycles have increased pregnancy rate at the cost of increasing the incidence of triplets and twins. It has been proposed that prolonged culture to the blastocyst stage would automatically result in the selection of good quality embryos for transfer and minimize the incidence of triplets and twins.

Methods and Results:  The objectives of the present retrospective analysis were to examine the pregnancy outcome, multiple pregnancy and related data following: (i) single blastocyst transfer (BT) and double BT; (ii) single BT in patients belonging to different age groups; and (iii) good, fair or poor quality of BT. A total of 260 BT were carried out between August 1998 and July 2002 and they are included in the current study. Sixty of the 260 BT patients received a single BT, and 41 of them received selected single good quality BT (SSBT). The implantation rate has no significant difference between following single BT (53.3%) and double BT (42.8%). No multiple pregnancy occurred following single BT, while significantly higher (P < 0.05) multiple pregnancy rate was observed following a double BT (45.8%). The clinical pregnancy and implantation rates following a single BT were similar (P > 0.05) in patients belonging to <30 years (62.5%), 30–34 years (57.9%) and 35–39 years old (35.8%).

Conclusion:  Selected single good quality BT maintained pregnancy and avoided multiple pregnancies. It is recommended for patients with a risk for high‐order multiple pregnancy. (Reprod Med Biol 2004; 3: 13–18)
Effects of low‐dose metformin in Japanese women with clomiphene‐resistant polycystic ovary syndrome
Authors: Kurabayashi Takumi , Suzuki Mina , Kashima Katsunori , Banzai Junichi , Terabayashi Kyoko , Fujita Kazuyuki , Tanaka Kenichi
Published: March 2004

Background and Aims:  The aim of the present prospective observational study was to evaluate the effects of low‐dose, short‐term metformin, in combination with clomiphene (CC), in CC‐resistant infertile Japanese women with polycystic ovary syndrome (PCOS).

Methods:  Metformin therapy was administered orally (one 250 mg tablet, twice daily) to 15 CC‐resistant infertile patients with PCOS, beginning on the third day of progestin‐induced withdrawal bleeding, and was continued for 14 days in the first cycle. In the event of anovulation, 100 mg/day of CC was given during subsequent cycles on days 5–9, in addition to the aforementioned dose of metformin. Hormonal and metabolic parameters were measured on the second or third days of the first cycle and also the fourth cycle, following an overnight fast.

Results:  None of the 15 women successfully ovulated during the first cycle with metformin treatment alone. After two subsequent cycles with the combination of CC and metformin, ovulation was confirmed in 17 of 29 cycles (61%) and in 13 of 15 patients (87%). Two women became pregnant within 2 months of therapy (13%). There were no cases of ovarian hyperstimulation syndrome. Following three cycles of metformin therapy, a slight reduction in serum levels of luteinizing hormone (LH), free testosterone, androstenedione, dehydroepiandrosterone sulfate, hemoglobin A1c and total cholesterol was seen, while serum LH/follicle‐stimulating hormone ratio and serum level of low‐density lipoprotein cholesterol were significantly decreased. Although there were no significant differences between the responder (n = 11) and non‐responder (n = 2) groups at baseline, the levels of plasma fasting insulin was significantly higher and fasting glucose/insulin ratio was significantly lower in the non‐responder group compared with the responder group after three cycles.

Conclusion:  Low‐dose, short‐term metformin, combined with CC, can improve ovulation rates in CC‐resistant infertile Japanese women with PCOS. (Reprod Med Biol 2004; 3: 19–26)
Surgery results using different uterine wall incision directions in laparoscopic myomectomy of the intramural myoma
Authors: Morita Mineto , Asakawa Yasuyuki , Uchiide Ichiro , Nakakuma Masahito , Kubo Harumi
Published: March 2004

Objective:  To study clinical outcomes for different uterine wall incision directions, comparing vertical incision and transverse incision in laparoscopic myomectomy of the intramural myoma.

Methods:  Laparoscopic myomectomies were performed on 50 women with intramural myomas. Using a table of random numbers, they were randomly divided into a vertical incision group (25 women) and a transverse incision group (25 women) according to the direction of incisions in the uterine wall. The numbers of enucleated myoma, operation duration, amount of bleeding, and numbers of sutures were compared. The Mann–Whitney U‐test was used for analysis.

Results:  For the transverse incision group, the amount of bleeding (137.6 ± 88.1 mL) was a significantly lower value (P = 0.0426) than for the vertical incision group (235.8 ± 169.4 mL). In addition, in cases where the maximum myoma nucleus diameter was 7 cm or larger, operation duration (129.0 ± 32.5 min) and amount of bleeding (158.9 ± 87.1 mL) showed significantly lower values (P = 0.0067 and P = 0.0002, respectively) for the transverse incision group than did operation duration (362.3 ± 147.3 min) and amount of bleeding (362.3 ± 147.3 mL) for the vertical incision group.

Conclusion:  Transverse incision of the uterine wall is useful to reduce the amount of bleeding in the laparoscopic myomectomy of the intramural myoma. Transverse incision also shortens operation duration in cases where the myoma nuclei are large. (Reprod Med Biol 2004; 3: 33–37)
Low well‐being, cognitive impairment and visual impairment associated with functional disabilities in elderly Japanese patients with diabetes mellitus
Authors: Araki Atsushi , Nakano Tadasumi , Oba Kenzo , Ito Chikako , Mori Seijiro , Ishibashi Shun , Umeda Fumio , Abe Ryuzo , Kojima Hideto , Kikkawa Ryuichi , Kawamori Ryuzo , Ito Hideki
Published: March 2004

Background:  The objective of this study is to examine the important factors associated with functional disabilities in elderly patients with diabetes mellitus.

Methods:  This was a multicenter cross‐sectional study. A total of 1135 elderly diabetic outpatients aged over 65 years in 10 hospitals participated in our study. Functional disabilities were assessed with questionnaires on the instrumental activity of daily livings (IADL), intellectual activity and social role using the Tokyo Metropolitan Institute of Gerontology Index of Competence. Cognitive function and well‐being were assessed by the mini‐mental state examination and morale scale, respectively.

Results:  The patients were divided into three age groups. The oldest (≥ 80 years) group reported significant high prevalence of functional disabilities (10% to 36%) compared to the youngest (65–69 years) group (4% to 20%). The number of vascular complications (≥ 4) was associated with a 5.5–8.8 fold increased risk of disabilities relating to the tasks on IADL (using public transportation, shopping, preparing meals and paying bills). Using multiple logistic regression analyses, low scores of morale scales (≤ 7) and mini‐mental state examination (≤ 23) were significantly associated with disabilities on the IADL, intellectual activity and social role after adjustment for age, gender, BMI, duration of diabetes, HbA1c, insulin treatment, microangiopathy and macroangiopathy. Insulin treatment and low visual acuity were also associated with the IADL after adjustment for the other variables.

Conclusions:  Older age, insulin treatment, low well‐being, cognitive impairment, and visual impairment were independently associated with the functional disabilities of elderly patients with diabetes mellitus.
Replacement of Factor XIII in an 89‐year‐old patient with persistent post‐extraction bleeding*
Authors: Saito Mika , Hirano Hirohiko , Yamaguchi Masatsune , Ueda Seigo
Published: March 2004

We had an 89‐year‐old patient with chronic disseminated intravascular coagulation who showed persistent post‐extraction bleeding and poor wound healing. A blood screening test revealed low plasma level of Factor XIII, which induces hemostasis with stabilization of fibrin and wound healing. The replacement of Factor XIII successfully produced hemostasis and wound healing in this case.
Distribution of acetylcholinesterase and cholineacetyl‐transferase activities in coronary vessels of younger and older adults
Authors: Cavallotti Carlo , Bruzzone Paolo , Mancone Massimo , Leali Francesca Mavia Tranguilli
Published: March 2004

Background:  The cholinergic nerve fibers of coronary arteries, capillaries and veins were studied in younger and older humans by staining of acetylcholinesterase and cholineacetyltransferase activities on autopsy samples of coronary vessels with the aim of investigating age‐related changes.

Methods:  Samples of human coronary vessels were harvested and exposed to the enzymatic staining for acetylcholinesterase, immunohistochemical staining for cholineacetyltransferase and quantitative analysis of images. Morphometric values were subjected to statistical analysis of data.

Results:  Our results demonstrated that both acetylcholinesterase and cholineacetyltransferase are localized in the coronary vessels of younger and older humans. Staining of these two enzymes showed specific age‐related changes. Structures resembling cholinergic nerve fibers were located in coronary vessels, in the extra‐parenchymal (large caliber) and intraparenchymal (small caliber) branches (arteries and veins), organized in a plexus. Coronary arterioles of large caliber (diameter > 150 µm) were found to have many cholinergic nerve fibers. The quantitative analysis of images and the statistical analysis of the data demonstrated that the cholinergic neurotransmitters of coronary vessels (especially the extra‐parenchymal branches of coronary arteries) strongly decrease with age.

Conclusions:  The age‐related changes of cholinergic nerve supply of the human coronary vessels may play a role in the control of coronary circulation. Further studies are needed in order to draw definite conclusions concerning the nervous control of coronary circulation under normal and/or pathological conditions.
Treatment of unresectable hepatocellular adenoma in dogs with transarterial iodized oil and chemotherapy with and without an embolic agent: A report of two cases
Authors: Cave T. A. , Johnson V. , Beths T. , Edwards R. , Argyle D. J.
Published: March 2004

Transarterial iodized oil with chemotherapy was evaluated in two dogs with large, surgically unresectable hepatocellular adenoma. A single cycle of therapy was used in each dog. Chemoembolic mixtures varied: doxorubicin emulsified with iodized oil radiographic contrast (case 1), doxorubicin and mitomycin C emulsified with iodized oil radiographic contrast (case 2). In addition, dog 2 underwent arterial embolization with polyvinyl alcohol granules. Response was assessed by computed tomography at 1 and 3 months after treatment. Superselective catheterization of the hepatic arterial branch supplying the tumour was not achieved in either case. In the immediate post‐operative period, both dogs developed mild clinical signs that may have been consistent with post‐embolization syndrome, but neutropenia and reduced liver function were not observed. Tumour response was minimal: stable disease at 1 month and progressive disease at 3 months was observed in both cases.
Influence of honey bee products on transplantable murine tumours
Authors: Oršolic̃ N. , Knez̆evic̃ A. , Šver L. , Terzic̃ S. , Hackenberger B. K. , Bašic̃ I.
Published: March 2004

The effect of propolis [it is a water‐soluble derivative (WSDP)] and related polyphenolic compounds of propolis (caffeic acid, caffeic acid phenethyl ester and quercetin), honey, royal jelly and bee venom on tumour growth, metastasizing ability and induction of apoptosis and necrosis in murine tumour models (mammary carcinoma and colon carcinoma) was investigated. WSDP and related polyphenolic compounds showed significant anti‐metastatic effect (P < 0.01 and P < 0.001) given either before or after tumour‐cell inoculation. Oral or systemic application of WSDP or caffeic acid significantly reduced subcutaneous tumour growth and prolonged the survival of mice. Honey also exerted pronounced anti‐metastatic effect (P < 0.05) when applied before tumour‐cell inoculation (peroral 2 g kg−1 for mice or 1 g kg−1 for rats, once a day for 10 consecutive days). Royal jelly did not affect metastasis formation when given intraperitoneally or subcutaneously. However, intravenous administration of royal jelly before tumour‐cell inoculation significantly (P < 0.05) inhibited metastasis formation. When mice were given 105 tumour cells intravenously immediately after bee venom injection, the number of tumour nodules in the lung was significantly lower (P < 0.001) than in untreated mice or mice treated with bee venom subcutaneously. Local presence of bee venom in the tissue caused significant delay in subcutaneous tumour formation. These findings clearly demonstrate that anti‐tumour and anti‐metastatic effects of bee venom are highly dependent on the route of injection and on close contact between components of the bee venom and tumour cells. These data show that honey bee products given orally or systemically may have an important role in the control of tumour growth and tumour metastasizing ability.
Changing the way we think about global change research: scaling up in experimental ecosystem science
Authors: Osmond Barry , Ananyev Gennady , Berry Joseph , Langdon Chris , Kolber Zbigniew , Lin Gunghui , Monson Russell , Nichol Caroline , Rascher Uwe , Schurr Uli , Smith Stan , Yakir Dan
Published: March 2004

Scaling is a naturally iterative and bi‐directional component of problem solving in ecology and in climate science. Ecosystems and climate systems are unquestionably the sum of all their parts, to the smallest imaginable scale, in genomic processes or in the laws of fluid dynamics. However, in the process of scaling‐up, for practical purposes thewhole usually has to be construed as a good deal less than this. This essay demonstrates how controlled large‐scale experiments can be used to deduce key mechanisms and thereby reduce much of the detail needed for the process of scaling‐up. Collection of the relevant experimental evidence depends on controlling the environment and complexity of experiments, and on applications of technologies that report on, and integrate, small‐scale processes. As the role of biological feedbacks in the behavior of climate systems is better appreciated, so the need grows for experimentally based understanding of ecosystem processes.

We argue that we cannot continue as we are doing, simply observing the progress of the greenhouse gas‐driven experiment in global change, and modeling its future outcomes. We have to change the way we think about climate system and ecosystem science, and in the process move to experimental modes at larger scales than previously thought achievable.
Miscanthus biomass production for energy in Europe and its potential contribution to decreasing fossil fuel carbon emissions
Authors: Clifton‐brown John C. , Stampfl Paul F. , Jones Michael B.
Published: March 2004

Field trials throughout Europe over the past 15 years have confirmed the potential for high biomass production from Miscanthus, a giant perennial rhizomatous grass with C4 photosynthesis. However, policies to promote the utilization of biomass crops require yield estimates that can be scaled up to regional, national and continental areas. The only way in which this information can be reliably provided is through the use of productivity models. Here, we describe MISCANMOD, a productivity model, which was used in conjunction with a GIS to plot potential, non‐water‐limited yields across Europe. Modelled rainfed yields were also calculated using a water balance approach based on FAO estimates of plant available water in the soil. The observed yields were consistent with modelled yields at 20 trial sites across Europe. We estimate that if Miscanthus was grown on 10% of suitable land area in the European Union (EU15), 231 TWh yr−1 of electricity could be generated, which is 9% of the gross electricity production in 2000. Using the same scenario, the total carbon mitigation could be 76 Mt C yr−1, which is about 9% of the EU total C emissions for the 1990 Kyoto Protocol baseline levels.
Net primary production and net ecosystem production of a boreal black spruce wildfire chronosequence
Authors: Bond‐Lamberty Ben , Wang Chuankuan , Gower Stith T.
Published: March 2004

Net primary production (NPP) was measured in seven black spruce (Picea mariana(Mill.) BSP)‐dominated sites comprising a boreal forest chronosequence near Thompson, Man., Canada. The sites burned between 1998 and 1850, and each contained separate well‐ and poorly drained stands. All components of NPP were measured, most for 3 consecutive years. Total NPP was low (50–100 g C m−2 yr−1) immediately after fire, highest 12–20 years after fire (332 and 521 g C m−2 yr−1in the dry and wet stands, respectively) but 50% lower than this in the oldest stands. Tree NPP was highest 37 years after fire but 16–39% lower in older stands, and was dominated by deciduous seedlings in the young stands and by black spruce trees (>85%) in the older stands. The chronosequence was unreplicated but these results were consistent with 14 secondary sites sampled across the landscape. Bryophytes comprised a large percentage of aboveground NPP in the poorly drained stands, while belowground NPP was 0–40% of total NPP. Interannual NPP variability was greater in the youngest stands, the poorly drained stands, and for understory and detritus production. Net ecosystem production (NEP), calculated using heterotrophic soil and woody debris respiration data from previous studies in this chronosequence, implied that the youngest stands were moderate C sources (roughly, 100 g C m−2 yr−1), the middle‐aged stands relatively strong sinks (100–300 g C m−2 yr−1), and the oldest stands about neutral with respect to the atmosphere. The ecosystem approach employed in this study provided realistic estimates of chronosequence NPP and NEP, demonstrated the profound impact of wildfire on forest–atmosphere C exchange, and emphasized the need to account for soil drainage, bryophyte production, and species succession when modeling boreal forest C fluxes.
The Effects of MK‐0677, an Oral Growth Hormone Secretagogue, in Patients with Hip Fracture
Authors: Bach Mark A. , Rockwood Kenneth , Zetterberg Carl , Thamsborg Gorm , Hébert Réjean , Devogelaer Jean‐Pierre , Christiansen Jens Sandahl , Rizzoli René , Ochsner J.Lockwood , Beisaw Norman , Gluck Oscar , Yu Leisure , Schwab Thomas , Farrington Jeanne , Taylor Alice M. , Ng Jennifer , Fuh Vivian ,   for the MK 0677 Hip Fracture Study Group
Published: March 2004

Objectives:To evaluate the effects of MK‐0677, an orally active growth hormone (GH) secretagogue, on functional recovery from hip fracture in previously mobile older individuals.

Design:Placebo‐controlled, randomized, double‐blind trial.

Setting:Thirteen medical centers in England, Sweden, Denmark, Belgium, Switzerland, Canada, and the United States. Patients were recruited between 3 and 14 days postoperatively, or no more than 18 days postfracture, at acute care hospitals and rehabilitation centers.

Participants:One hundred sixty‐one hip‐fracture patients were enrolled. Entry criteria included consenting hip‐fracture patients who were aged 65 and older and who were ambulatory before their fracture, medically stable postoperatively, and mentally competent. Patients were excluded if they had multiple fractures or severe trauma, diabetes mellitus, cancer, uncontrolled hypertension, congestive heart failure, or total hip replacement in the involved extremity.

Intervention:Random assignment to 6 months of daily treatment with MK‐0677 or placebo. Patients were followed for an additional 6 months after completion of therapy.

Measurements:Change from Week 6 to Week 26 in a panel of functional performance measures. Additional outcome measures included change in the Sickness Impact Profile for Nursing Homes (SIP‐NH), the ability to live independently, and insulin‐like growth factor I (IGF‐I) levels.

Results:MK‐0677 treatment increased serum IGF‐I levels by 84% (95% confidence interval (CI)=63–107), compared with an increase of 17% (95% CI=8–28) on placebo. There were no significant differences between MK‐0677 and placebo in improvement in functional performance measures or in the overall SIP‐NH score. Although MK‐0677 patients showed greater improvement relative to placebo in three of four lower extremity functional performance measures, in the physical domain of the SIP, and in the ability to live independently, these differences were not statistically significant.

Conclusion:Although MK‐0677 treatment increased serum IGF‐I, it is uncertain whether clinically significant effects on physical function were achieved. Measuring function in clinical trials in hip‐fracture patients is difficult because of the lack of validated outcome measures, high variability, and the lack of a baseline assessment. Present functional performance measures may not be sufficiently responsive for use as the primary endpoint of small intervention studies; alternatively, stimulation of GH may not result in significant functional improvement.
Living Alone and Outpatient Care Use by Older Veterans
Authors: Guzman Jenice S. , Sohn Linda , Harada Nancy D.
Published: March 2004

In nonveteran older adults, living alone influences outpatient care use, but its importance in the veteran population has not been well studied. The aims of this study are to describe the use of outpatient care by older veterans who live alone versus those who live with others and determine whether living alone influences outpatient use by older veterans. The data come from the 2001 Veteran Identity Program Survey designed to measure Department of Veterans Affairs (VA) and non‐VA outpatient care use. Univariate and bivariate analyses were conducted to examine distributional properties, associations, and subgroup differences in outpatient care use. Poisson regression was used to assess the role of living alone on outpatient care use, controlling for predisposing, other enabling, and need factors. Results found that older veterans who use the VA, whether they live alone or not, have similar numbers of VA outpatient visits. Older veterans who use VA and non‐VA facilities and who live alone have greater total outpatient visits than those who live with others. Regression results indicate that living alone is a predictor of VA routine medical visits, VA prescription refill visits, and total VA and non‐VA outpatient visits but does not influence VA emergency room visits. These findings suggest that living alone is associated with differences in outpatient care use by older veterans. It is important for the VA to understand this relationship with the aim of developing interventions to improve access, effectiveness, and efficiency of health services for older veterans.
Effect of thyroidectomy on the histology of rat sublingual gland
Authors: ONCU M. , KANTER M. , GOKCIMEN A. , KAVAKLI D. , ONCU M. , URAL M. , KARAOZ E.
Published: March 2004

This study was carried out to investigate the effect of thyroidectomy on the histology of rat sublingual gland. Twenty‐eight male Wistar albino rats, aged 4 weeks and weighing between 45–55 g, were used. The rats were divided into two experimental groups (control and thyroidectomy), each containing 14 animals. Total thyroidectomy of rats was performed under ether anesthesia in thyroidectomy group. The rats in the control group were sham operated without having the thyroidectomy. Seven rats randomly selected from both groups were fixed using the perfusion fixation technique 2 and 6 weeks after thyroidectomy, and their sublingual glands were harvested for histological investigation. No histological difference was observed between the two groups 2 weeks after thyroidectomy. However, 6 weeks after thyroidectomy considerable cytoplasmic vacuolization of the epithelial cells of the mucous tubules was seen in the thyroidectomy group compared to the controls. Enlargement of mucous tubules was also observed, and the lumina in most of the tubules was quite dilated. In the stroma surrounding the parenchymal tissues, increased lipid tissue mass was observed. In addition, increased connective tissue mass and mononuclear cell infiltrations were evident. Furthermore, the number of mast cells was significantly higher in the thyroidectomy group than in the controls 6 weeks after thyroidectomy. It was concluded that the thyroid gland and hormones might have an influence on the histology of the sublingual gland.
Thioredoxin is associated with proliferation, p53 expression and negative estrogen and progesterone receptor status in breast carcinoma
Authors: TURUNEN NINA , KARIHTALA PEETER , MÄNTYNIEMI ANNE , SORMUNEN RAIJA , HOLMGREN ARNE , KINNULA VUOKKO L. , SOINI YLERMI
Published: March 2004

We investigated the expression of thioredoxin and thioredoxin reductase in a large set of breast invasive and in situ carcinomas by immunohistochemistry. Additionally, NF‐κB, p53 and proliferating cell nuclear antigen (PCNA) expression was studied. Thioredoxin and thioredoxin reductase expression was located in both cytoplasmic and nuclear compartments of the cell. Cytoplasmic thioredoxin positivity was found in 67 % and nuclear in 59 % of the cases, while thioredoxin reductase was found in 55 % and 6 % of cases, respectively. Ductal carcinomas showed stronger cytoplasmic thioredoxin immunoreactivity than lobular ones. Nuclear thioredoxin positivity was more often found in in situ lesions, and lobular carcinomas were more often negative than ductal ones. Both cytoplasmic and nuclear thioredoxin‐positive cases had a high proliferation measured by PCNA staining. Positive nuclear immunostaining was associated with negative estrogen and progesterone receptor status. Cases with high p53 expression showed significantly higher nuclear thioredoxin positivity, but lower thioredoxin reductase positivity. Whilst thioredoxin or thioredoxin reductase was not associated with patient survival, cases showing both cytoplasmic and nuclear thioredoxin reductase‐positive tumours had a shorter disease‐free interval than those with negative immunostaining.
Axonal Neuregulin-1 Regulates Myelin Sheath Thickness
Authors: Michailov Galin V. , Sereda Michael W. , Brinkmann Bastian G. , Fischer Tobias M. , Haug Bernhard , Birchmeier Carmen , Role Lorna , Lai Cary , Schwab Markus H. , Nave Klaus-Armin
Published: March 2004

In the nervous system of vertebrates, myelination is essential for rapid and accurate impulse conduction. Myelin thickness depends on axon fiber size. We use mutant and transgenic mouse lines to show that axonal Neuregulin-1 (Nrg1) signals information about axon size to Schwann cells. Reduced Nrg1 expression causes hypomyelination and reduced nerve conduction velocity. Neuronal overexpression of Nrg1 induces hypermyelination and demonstrates that Nrg1 type III is the responsible isoform. We suggest a model by which myelin-forming Schwann cells integrate axonal Nrg1 signals as a biochemical measure of axon size.
Best Practice No 176
Authors: Ellis I O , Bartlett J , Dowsett M , Humphreys S , Jasani B , Miller K , Pinder S E , Rhodes A , Walker R
Published: March 2004

This paper serves to update previously published guidance on rationale and methodology for HER2 laboratory testing following the recommendation for the use of HER2 targeted treatment in the management of advanced breast cancer in the UK. Emphasis is placed on the standardisation of methodology and assessment and strategies to achieve high quality performance. A two phase testing algorithm based on first line immunocytochemistry evaluation and second line fluorescence in situ hybridisation assessment of borderline cases is recommended. To ensure maintenance of expertise, an annual caseload volume of at least 250 cases is recommended for laboratories providing a testing service.
Tumour angiogenic activity and vascular survival ability in bladder carcinoma
Authors: Papadopoulos I , Giatromanolaki A , Koukourakis M I , Sivridis E
Published: March 2004

Background:Tumour angiogenic activity (TAA) is an important prognostic factor in many human tumours, including transitional cell carcinomas of the urinary bladder. The new tumour vessels are formed in the invading tumour front. This peripheral tumour area is internalised as soon as the growing tumour forms a new front.

Aims:To investigate and compare TAA with the ability of the tumour vasculature to survive (VSA) in inner tumour areas.

Methods:Fifty one cystectomy specimens with transitional cell carcinoma of the urinary bladder were studied. Sections were stained immunohistochemically for endothelial cells and proliferation activity, using the monoclonal antibodies CD31 and MIB-1, respectively. TAA was studied at the invading tumour edge—designated as the mean number of blood vessels in three “hot spots” at this site. VSA was assessed by comparing the vascular density in peripheral and inner tumour areas.

Results:High TAA at the invading tumour edge significantly correlated with lymph node involvement, but not with patient survival. Extensive lymphocytic infiltration was more frequent in tumours with high TAA. VSA was significantly higher in tumours of high proliferation index, high histological grade, advanced T stage, and poor prognosis. However, there was no association with metastasis to regional lymph nodes.

Conclusion:VSA and TAA provide a more complete profile of the tumour vasculature and are associated with aggressive tumour behaviour in transitional cell carcinomas of the urinary bladder. The qualitative information provided by VSA may be important for the identification of angiogenic tumours with differential responses to various antiangiogenic treatments.
Specificity of lymphoreticular accumulation of prion protein for variant Creutzfeldt–Jakob disease
Authors: Hilton D A , Sutak J , Smith M E F , Penney M , Conyers L , Edwards P , McCardle L , Ritchie D , Head M W , Wiley C A , Ironside J W
Published: March 2004

Background:Immunocytochemical accumulation of prion protein (PrP) in lymphoid tissues is a feature of variant Creutzfeldt–Jakob disease (vCJD) that has been used both to aid in the diagnosis of patients and as a basis of large scale screening studies to assess the prevalence of preclinical disease in the UK. However, the specificity of this approach is unknown.

Aim:To assess the specificity of lymphoreticular accumulation of PrP for vCJD by examining a range of human diseases.

Methods:Paraffin wax embedded lymphoreticular tissues from patients with several reactive conditions (58 cases), tumours (27 cases), vCJD (54 cases), and other human prion diseases (56 cases) were assessed. PrP accumulation was assessed by immunocytochemistry using two different monoclonal anti-PrP antibodies and a sensitive detection system.

Results:All cases of vCJD showed widespread lymphoreticular accumulation of PrP; however, this was not seen in the other conditions examined.

Conclusion:Lymphoreticular accumulation of PrP, as assessed by immunocytochemistry, appears to be a highly specific feature of vCJD.
Prevalence and relevance of EBV latency in nasopharyngeal carcinoma in Israel
Authors: Bar-Sela G , Kuten A , Minkov I , Gov-Ari E , Ben-Izhak O
Published: March 2004

Background:Nasopharyngeal carcinoma (NPC) is frequently associated with Epstein-Barr virus (EBV). The incidence of NPC in Western countries is lower than in the Far East, and EBV latency in NPC is less prevalent. Israel, as a part of the Mediterranean area, is one of the countries with an intermediate risk for NPC.

Methods:Immunohistochemistry (IHC) for latent membrane protein 1 (LMP-1) and in situ hybridisation (ISH) for EBV encoded RNA (EBER) were used to evaluate the prevalence and possible prognostic value of EBV latency among Israeli patients with NPC. Forty five patients with different NPC histologies were studied.

Results:LMP-1 IHC was positive in six samples only, all with undifferentiated histology. EBER ISH was positive in 40 of the 45 samples. According to histological type, three of five patients with squamous cell carcinoma were EBV positive and 37 of 40 non-keratinising and undifferentiated carcinoma cases were positive. Although EBV was more prevalent in patients with non-squamous carcinoma, the difference was not significant, probably because of the small number of patients with keratinising carcinoma. With regard to the clinical categories and survival, no significant difference could be detected between patients who were positive or negative for EBER ISH. No association was found between EBV latency and patient sex, age, origin, stage, or survival.

Conclusions:NPC in Israel is highly associated with EBV latency as detected by EBER ISH. LMP-1 IHC is considerably less sensitive in detecting EBV latency in NPC among the same patient group.
Anomalous Magnetic Moments
Authors: Marciano William J.
Published: March 2004

The Dirac equation explained why the gyromagnetic ratio, g factor, is equal to 2 for fundamental spin [Formula: see text] particles. Quantum loop effects were subsequently shown to induce a small shift or anomaly, a≡(g-2)/2. Anomalous magnetic moment effects have been calculated and measured with extraordinary precision for the electron and muon. Here, the Standard Model's predictions for al=(gl-2)/2, l=e, μ are described and compared with experimental values. Implications for probing "New Physics" effects are also discussed.
P.A.M. Dirac and the Development of Modern General Relativity
Authors: Deser Stanley
Published: March 2004

I provide a very brief sketch of Dirac's Hamiltonian formulation of Einstein's theory, in its relation both to his own earlier work and to contemporary developments.
Time Variation of Fundamental Constants as a Probe of New Physics
Authors: Langacker Paul
Published: March 2004

Time variation of fundamental constants would not be surprising in the framework of theories involving extra dimensions. The variation of any one constant is likely to be correlated with variations of others in a pattern that is diagnostic of the underlying physics.
Fiber type conversion alters inactivation of voltage-dependent sodium currents in murine C2C12 skeletal muscle cells
Authors: Zebedin Eva , Sandtner Walter , Galler Stefan , Szendroedi Julia , Just Herwig , Todt Hannes , Hilber Karlheinz
Published: March 2004

Each skeletal muscle of the body contains a unique composition of “fast” and “slow” muscle fibers, each of which is specialized for certain challenges. This composition is not static, and the muscle fibers are capable of adapting their molecular composition by altered gene expression (i.e., fiber type conversion). Whereas changes in the expression of contractile proteins and metabolic enzymes in the course of fiber type conversion are well described, little is known about possible adaptations in the electrophysiological properties of skeletal muscle cells. Such adaptations may involve changes in the expression and/or function of ion channels. In this study, we investigated the effects of fast-to-slow fiber type conversion on currents via voltage-gated Na+ channels in the C2C12 murine skeletal muscle cell line. Prolonged treatment of cells with 25 nM of the Ca2+ ionophore A-23187 caused a significant shift in myosin heavy chain isoform expression from the fast toward the slow isoform, indicating fast-to-slow fiber type conversion. Moreover, Na+ current inactivation was significantly altered. Slow inactivation less strongly inhibited the Na+ currents of fast-to-slow fiber type-converted cells. Compared with control cells, the Na+ currents of converted cells were more resistant to block by tetrodotoxin, suggesting enhanced relative expression of the cardiac Na+ channel isoform Nav1.5 compared with the skeletal muscle isoform Nav1.4. These results imply that fast-to-slow fiber type conversion of skeletal muscle cells involves functional adaptation of their electrophysiological properties.
Stretch-induced nitric oxide modulates mechanical properties of skeletal muscle cells
Authors: Zhang Jingying Sarah , Kraus William E. , Truskey George A.
Published: March 2004

In this study, we examined the hypothesis that stretch-induced (nitric oxide) NO modulates the mechanical properties of skeletal muscles by increasing accumulation of protein levels of talin and vinculin and by inhibiting calpain-induced proteolysis, thereby stabilizing the focal contacts and the cytoskeleton. Differentiating C2C12 myotubes were subjected to a single 10% step stretch for 0–4 days. The apparent elastic modulus of the cells, Eapp, was subsequently determined by atomic force microscopy. Static stretch led to significant increases ( P < 0.01) in Eapp beginning at 2 days. These increases were correlated with increases in NO activity and neuronal NO synthase (nNOS) protein expression. Expression of talin was upregulated throughout, whereas expression of vinculin was significantly increased only on days 3 and 4. Addition of the NO donor l-arginine onto stretched cells further enhanced Eapp, NOS activity, and nNOS expression, whereas the presence of the NO inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) reversed the effects of mechanical stimulation and of l-arginine. Overall, viscous dissipation, as determined by the value of hysteresis, was not significantly altered. For assessment of the role of vinculin and talin stability, cells treated with l-NAME showed a significant decrease in Eapp, whereas addition of a calpain inhibitor abolished the effect. Thus our results show that NO inhibition of calpain-initiated cleavage of cytoskeleton proteins was correlated with the changes in Eapp. Together, our data suggest that NO modulates the mechanical behavior of skeletal muscle cells through the combined action of increased talin and vinculin levels and a decrease in calpain-mediated talin proteolysis.
Regulation of intestinal phosphate cotransporter NaPi IIb by ubiquitin ligase Nedd4–2 and by serum- and glucocorticoid-dependent kinase 1
Authors: Palmada M. , Dieter M. , Speil A. , Böhmer C. , Mack A. F. , Wagner H. J. , Klingel K. , Kandolf R. , Murer H. , Biber J. , Closs E. I. , Lang F.
Published: March 2004

Serum and glucocorticoid-inducible kinase 1 (SGK1) is highly expressed in enterocytes. The significance of the kinase in regulation of intestinal function has, however, remained elusive. In Xenopus laevis oocytes, SGK1 stimulates the epithelial Na+ channel by phosphorylating the ubiquitin ligase Nedd4–2, which regulates channels by ubiquitination leading to subsequent degradation of the channel protein. Thus the present study has been performed to explore whether SGK1 regulates transport systems expressed in intestinal epithelial cells, specifically type IIb sodium-phosphate (Na+-Pi) cotransporter (NaPi IIb). Immunohistochemistry in human small intestine revealed SGK1 colocalization with Nedd4–2 in villus enterocytes. For functional analysis cRNA encoding NaPi IIb, the SGK isoforms and/or the Nedd4–2 were injected into X. laevis oocytes, and transport activity was quantified as the substrate-induced current ( IP). Exposure to 3 mM phosphate induces an IP in NaPi IIb-expressing oocytes. Coinjection of Nedd4–2, but not the catalytically inactive mutant C938SNedd4–2, significantly downregulates IP, whereas the coinjection of S422DSGK1 markedly stimulates IP and even fully reverses the effect of Nedd4–2 on IP. The effect of S422DSGK1 on NaPi IIb is mimicked by wild-type SGK3 but not by wild-type SGK2, constitutively active T308D,S473DPKB, or inactive K127NSGK1. Moreover, S422DSGK1 and SGK3 phosphorylate Nedd4–2. In conclusion, SGK1 stimulates the NaPi IIb, at least in part, by phosphorylating and thereby inhibiting Nedd4–2 binding to its target. Thus the present study reveals a novel signaling pathway in the regulation of intestinal phosphate transport, which may be important for regulation of phosphate balance.
NADPH oxidase-derived oxidant stress is critical for neutrophil cytotoxicity during endotoxemia
Authors: Gujral Jaspreet S. , Hinson Jack A. , Farhood Anwar , Jaeschke Hartmut
Published: March 2004

Neutrophils can cause liver injury during endotoxemia through generation of reactive oxygen species. However, the enzymatic source of the oxidant stress and the nature of the oxidants generated remain unclear. Therefore, we investigated the involvement of NADPH oxidase in the pathophysiology by using the NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI) in the galactosamine/endotoxin (700 mg/kg Gal:100 μg/kg ET) model of liver injury. In addition, we measured chlorotyrosine as indicator for hypochlorous acid formation by myeloperoxidase. Gal/ET treatment of male C3HeB/FeJ mice resulted in sinusoidal neutrophil accumulation and parenchymal cell apoptosis (14 ± 3% of cells) at 6 h. At 7 h, 35% of neutrophils had transmigrated. The number of apoptotic cells increased to 25 ± 2%, and the overall number of dead cells was 48 ± 3%; many of them showed the characteristic morphology of necrosis. Hepatocytes, which colocalized with extravasated neutrophils, stained positive for chlorotyrosine and 4-hydroxynonenal (4-HNE) protein adducts. In contrast, animals pretreated with DPI (2.5 mg/kg) were protected against liver injury at 7 h (necrosis = 20 ± 2%). These livers showed little chlorotyrosine or 4-HNE staining, but apoptosis and neutrophil accumulation and extravasation remained unaffected. However, DPI-treated animals showed serious liver injury at 9 h due to sustained apoptosis. The results indicate that NADPH oxidase is responsible for the neutrophil-derived oxidant stress, which includes formation of hypochlorous acid by myeloperoxidase. Thus NADPH oxidase could be a promising therapeutic target to prevent neutrophil-mediated liver injury. However, the long-term benefit of this approach needs to be investigated in models relevant for human liver disease.