bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Progesterone Prior to GnRH‐PGF2α Treatment on Induction of Oestrus and Pregnancy in Anoestrous Awassi Ewes
Authors: Husein MQ , Kridli RT
Published: May 2003

Contents

An experiment was conducted to examine the effect of progesterone prior to a GnRH‐PGF2α treatment on oestrus and pregnancy in seasonally anoestrous Awassi ewes. Twenty‐four ewes were randomly assigned to three groups to be pre‐treated with 60 mg medroxyprogesterone acetate sponges (group A), 600 mg progesterone sponges (group B) or blank sponges (group C) for 4 days. All ewes were injected with 100 μg of GnRH 24 h after sponge removal followed, 5 days later, by 20 mg PGF2α injection. Ewes were exposed to three fertile rams at the time of PGF2α injection (day 0, 0 h) and were checked for breeding marks at 6‐h intervals for 5 days. Blood samples were collected from all ewes 1 day (day −10) prior to sponge insertion, at the time of sponge removal (day −6), 1 day following sponge removal (day −5, at the time of GnRH injection) and at the time of PGF2α injection (day 0) for analysis of progesterone. Progesterone concentrations on days −10 and −5 were basal and averaged 0.2 ± 0.04 and 0.2 ± 0.2 ng/ml, respectively. Progesterone concentrations on day −6 were elevated only in group B ewes and were higher (p < 0.0001) than those of groups A and C. Progesterone concentrations on day 0 were higher (p = 0.002) in groups A and B than group C. Oestrous responses occurred only in ewes of groups A and B (p > 0.05). Induced oestrus conception rate was greater (p < 0.01) in group A than groups B and C. Ewes returned to oestrus 17–20 days following day 0 were two of eight, six of eight and three of eight of groups A, B and C, respectively, all of which eventually lambed. The overall lambing rate was 82% in progesterone‐primed ewes compared with only 38% non‐progesterone‐primed ewes (p < 0.05). Progesterone priming apparently sensitizes GnRH‐PGF2α‐treated seasonally anoestrous ewes and increases their response in oestrus and pregnancy rates.
24‐Hour Secretion Patterns of Plasma Oestradiol 17β in Pony Mares in Late Gestation
Authors: O'Donnell LJ , Sheerin BR , Hendry JM , Thatcher MJ , Thatcher WW , LeBlanc MM
Published: May 2003

Contents

The mare exhibits nocturnal uterine contractions in the last 6 days of gestation. It is hypothesized that estradiol 17β (O17β) may be associated with the nightly increase in uterine contractions. The 24‐h secretion pattern of plasma O17β was measured in 3 pony mares in late gestation to identify changes in release as the mare neared parturition. Blood was collected weekly at 08:00 hours beginning on day 240 and every third day from day 330 until delivery. Serial blood samples were collected from each mare every 30‐min for 24‐h beginning on gestation day 310 and every sixth day thereafter until parturition. Concentrations of O17β were elevated at night with lowest concentrations occurring directly before sunset (p < 0.01). The natural log of the variance was increased at sunset (p < 0.01) and was decreased during the 6‐h period immediately after sunrise. This pattern was especially evident in the 6 days that preceded parturition. The contrast between nocturnal and daytime concentrations of O17β in the last 6 days of gestation may contribute to night‐time delivery in the mare.
Expression of Osteopontin (OPN) mRNA in Bovine Ovarian Follicles and Corpora Lutea
Authors: Brunswig‐Spickenheier B , Mukhopadhyay AK
Published: May 2003

Contents

The matricellular protein osteopontin (OPN) plays a role in various physiological processes, including angiogenesis and tissue remodelling. As these processes are essential for the maintenance of ovarian physiology, the aim of the study was to investigate the expression of OPN (mRNA) in ovarian cells and to evaluate whether it can be regulated by gonadotrophins. Using conventional RT‐PCR and real‐time PCR, we have detected and quantified OPN mRNA as well as glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) mRNA expression in bovine granulosa, theca and luteal cells. In all cells examined, both genes were found in equal amounts and no striking variations in the expression could be observed between granulosa, theca and luteal cells. Furthermore, no effect on either OPN or GAPDH mRNA expression was evident after culturing ovarian cells in the presence of gonadotrophic hormones, although the cells were still highly responsive in terms of cAMP formation. Although neither variations between different cell types nor a regulation of OPN mRNA expression by gonadotrophic hormones could be detected, the high and unambiguous mRNA expression in steroidogenic cells suggests that OPN should be added to the growing list of intraovarian factors which may be involved in ovarian physiology.
Effects of Short‐Term High Carbohydrate or Fat Intakes on Leptin, Growth Hormone and Luteinizing Hormone Secretions in Prepubertal Fat‐Tailed Tuj Lambs
Authors: Yildiz S , Blache D , Celebi F , Kaya I , Saatci M , Cenesiz M , Guven B
Published: May 2003

Contents

The aim of the current study was to evaluate the effects of high carbohydrate or fat diets, fed for 15 days at the end of breeding season, on leptin, GH and LH secretions in prepubertal fat‐tailed Tuj lambs. For that purpose, 9‐month‐old ram‐lambs were divided into three groups as control group (fed with basal ration, n = 4), high carbohydrate (HC) group, basal ration plus barley, n = 4), or high fat (HF) group (basal ration plus by‐pass fat, n = 4). For the measurement of leptin and GH, blood plasma samples were collected on days 1, 4, 9 and 14 of the experiment. For the measurement of LH pulse frequency, serial blood samples were collected every 15 min for 6 h on day 14. Lambs were weighed and body condition scored (BCS) on days 1 and 15. Body weight and BCS increased towards the end of the study (p < 0.05). The BCS was higher in high energy groups at the end of the experiment (p < 0.05). Diet affected plasma leptin concentrations (p = 0.002) but time did not. The GH concentrations were not affected by diet or time. The LH pulse frequency appeared to be higher in HC and HF groups but there were no statistical difference between the groups. There was a significant positive relationship between overall BCS and corresponding leptin concentrations (R2 = 0.263; p = 0.010) and between LH pulse frequency and leptin concentrations (R2 = 0.594; p = 0.003). In conclusion, the present study suggests that rather than type of energy, amount of energy intake and body energy reserves are much important regulators of plasma leptin concentrations and LH pulse frequency in fat‐tailed Tuj lambs.
The Effects of the Periodical Use of In‐feed Chlortetracycline on the Reproductive Performance of Gilts and Sows of a Commercial Pig Farm with a History of Clinical and Subclinical Viral and Bacterial Infections
Authors: Alexopoulos C , Fthenakis GC , Burriel A , Bourtzi‐Hatzopoulou E , Kritas SK , Sbiraki A , Kyriakis SC
Published: May 2003

Contents

The objective of this study was to assess the effects of in‐feed chlortetracycline (CTC) as a measure of preventing or minimizing infectious problems of reproductive failure in gilts and sows. In a farm of 400 Large White × Landrace gilts and sows with a clinical history of porcine respiratory and reproductive syndrome (PRRS) virus, the animals were treated with CTC. Treatment consisted of 10 g CTC sow/day for 15 days every 3 months. It improved the health status of sows by decreasing post‐farrowing clinical mastitis and vaginal discharges, abortions, return‐to‐oestrus and irregular return‐to‐oestrus rates. These beneficial effects had a positive impact on the performance of the litter. More piglets were born live and weaned. These positive effects improved with repeated use of CTC. The serological evidence of PRRS virus,Leptospiraspp. andChlamydiaspp. and the subsequent beneficial use of the antimicrobial agent indicate that reproductive failure, possibly resulting from the bacterial agents can be controlled with in‐feed use of broad spectrum antimicrobials.
Testicular Measurements and Daily Sperm Output of Tori and Estonian Breed Stallions
Authors: Kavak A , Lundeheim N , Aidnik M , Einarsson S
Published: May 2003

Contents

Evaluation of testicular measurements and daily sperm output (DSO) yields valuable information for predicting the reproductive capacity of stallions. The present study evaluated testicular measurements (height, length, width and circumference) and DSO of eight Tori and eight Estonian breed stallions. One ejaculate of semen was collected daily for 10 subsequent days from each stallion. The gel‐free volume of semen was measured with a graduated glass cylinder and the sperm concentration was assessed with a Chorjajev chamber. The volume of gel‐free fraction was multiplied by the sperm concentration to give the total number of spermatozoa (TSN). The DSO was calculated as mean TSN of collection on days 8–10 in Tori breed stallions and on days 4–10 in Estonian breed stallions. The DSO of Tori breed stallions was 12.9 × 109 spermatozoa and of Estonian breed stallions 4.5 × 109 spermatozoa (p < 0.001). Testicular measurements (in cm) 1 day after the last semen collection were as follows: left testis– height 7.3, length 10.4 and width 7.3 in Tori breed stallions, and 5.9, 8.1 and 5.9, respectively, in Estonian breed stallions; right testis– height 7.4, length 10.6 and width 7.4 in Tori breed stallions, and 5.5, 7.4 and 5.3, respectively, in Estonian breed stallions. All these testicular measurements were significantly smaller in Estonian than in Tori breed stallions (p < 0.001). Testicular circumference was 45.4 and 35.4 cm in Tori and Estonian breed stallions, respectively (p < 0.001). The testicular circumference was correlated with DSO in both Estonian (p < 0.05) and Tori breed stallions (p = 0.071). The results give us valuable information on the reproductive capacity of Tori and Estonian breed stallions.
Postnatal Hypothyroidism Does Not Affect Prepubertal Testis Development in Boars
Authors: Klobucar I , Kosec M , Cebulj‐Kadunc N , Majdic G
Published: May 2003

Contents

Young boars were treated with propiothiouracil to induce hypothyroidism to examine its effects on postnatal testicular development. Treatments with 0.1% 4‐propyl‐2‐thiouracil (PTU) in drinking water started after weaning, at 3 weeks of age and all boars were severely hypothyroid at 6  weeks of age as determined by measuring T3 and T4 in blood plasma. Boars were castrated at different ages up to 20 weeks and their testes used for histological and immunohistochemical analyses. Although small but significant reduction in testis weight was observed from 8 to 12 weeks of age, this was not accompanied by significant difference in testicular volume. By 20 weeks of age, at the beginning of puberty, the differences in testis weights between control and treated groups of boars disappeared suggesting there is no lasting effect of hypothyroidism on postnatal development of boar testis. Immunohistochemical staining was used to determine the presence of molecular markers in both Sertoli and Leydig cells. Again, there were no differences between testes from control and treated boars in the pattern or intensity of immunostaining using antibodies against 3β‐hydroxysteroid dehydrogenase, antimullerian hormone or proliferating cell nuclear antigen (PCNA). Immunostaining with antibodies against PCNA showed interesting results as it was observed that Sertoli cells still express this marker of proliferating cells at 14 weeks of age, later than previously suggested cessation of Sertoli cell proliferation. This study suggests that hypothyroidism in boars does not have similar effects on postnatal testis development as reported in some other species.
Conception Rates after AI in Swedish Red and White Dairy Heifers: Relationship with Progesterone Concentrations at AI
Authors: Båge R
Published: May 2003

Contents

Blood samples were collected from 211 dairy heifers at the time of field insemination [artificial insemination (AI)]. Heifers were defined as either first‐service heifers (n = 91) or third to eigth‐service heifers [presumed (third AI, n = 60)] or well‐defined repeat breeders (greater than the fourth AI, n = 60). Plasma progesterone concentrations at AI were evaluated in relation to oestrous behaviour at AI and conception rates post‐AI. Conception rates after third AI were good, but conception rates decreased markedly after fourth AI and onwards. Those heifers that did not become pregnant after AI had significantly higher basal progesterone concentrations (>0.5 nmol/l) at AI, so‐called suprabasal concentrations, compared with those which conceived after AI (irrespective of the number of AI practised). Relative risk for repeat breeding was 58% after AI performed at suprabasal progesterone concentrations, while it was 42% at basal (0.5) progesterone concentrations. Results from this field study confirm results obtained in earlier controlled studies of repeat‐breeder heifers (RBH), indicating that the current definition of repeat breeding should be retained. Analysis of suprabasal progesterone concentrations could be considered as a tool for identification of RBH, provided that heat detection and AI timing are optimal. Besides considering the direct costs involved in repeat breeding, it remains to be determined whether it would be economically beneficial to identify and exclude RBH from the breeding population.
Manipulated Mouse Embryos as Bioassay System for Water Quality Control
Authors: Elsheikh AS , Takahashi Y , Nagano M , Kanagawa H
Published: May 2003

Contents

Mouse pronuclear stage embryos with intact slit zona pellucida (manipulated) were cultured in vitro until the hatched blastocyst stage in simplex optimized medium with higher K+ concentration (KSOM) prepared with three different water types: tap, deionized reverse osmosis (D‐O) water and Milli‐Q system (M‐Q) water. The culture media were supplemented with or without protein and ethylenediaminetetraacetic acid (EDTA, disodium salt). The rates of hatched blastocysts were significantly affected (p < 0.01) by micromanipulation, protein supplement and water source. The water source has no influence (p > 0.05) on development in EDTA‐supplemented protein‐free culture media, whereas in EDTA‐ and protein‐free culture media, the water quality significantly (p < 0.001) affected the rates of development, with higher rates in media prepared with M‐Q water. The micromanipulated embryos showed higher sensitivity to the water quality (p < 0.01). It worth mentioning that the rates of hatched blastocysts in protein‐free culture media were very low (0–7.5%). Furthermore, the three different water types were analysed by measuring the electrical conductivity, inorganic ions, total organic carbon and endotoxins to evaluate the purity. M‐Q water showed the lowest levels of inorganic ion, total organic carbon and endotoxin concentrations. We concluded that manipulated mouse embryos are good system to evaluate the quality of water used in biological system.
Ovarian Follicular Dynamics in Buffalo Cows (Bubalus bubalis)
Authors: Ali A , Abdel‐Razek AK , Abdel‐Ghaffar S , Glatzel PS
Published: May 2003

Contents

Follicular growth in Egyptian buffalo cows was monitored using genital tracts from 200 buffalo cows collected immediately after slaughter. According to the morphological appearance of the corpus luteum (CL), the corresponding oestrous cycle was divided into four stages: A (days 1–4), B (days 5–10), C (days 11–17) and D (days 18–21). Within these stages the follicular population on the ovaries was evaluated and the dominant follicle (DF) determined in all recovered ovaries. The functional status of the DF and the largest sub‐dominant follicles was examined by histological examination in 31 cases, and Radio Immunoassay (RIA) analyses for estradiol‐17β (E2) and progesterone (P4) was performed in the follicular fluid in 23 of the DF. The results showed that DFs changed their endocrine character within the stages of the oestrous cycle. The DFs between days 5 and 10 were functionally active (E2‐dominant; non‐atretic) in most of the cases. Between days 11 and day 17 half of the DFs became functionally inactive (P4‐dominant; atretic). At days 18–21 all of the DF became functionally active and non‐atretic. In the specimens that carried two large follicles one of them was regularly atretic and P4‐dominant whereas the other was non‐atretic and E2‐dominant. Between days 18 and 21 all ovaries examined showed at least one large follicle. These findings suggest that in most of the cases follicular dynamics occurs in two wave‐like patterns in the Egyptian buffalo cows.
Secretory Patterns of Prolactin in Dogs: Circannual and Ultradian Rhythms
Authors: Corrada Y , Castex G , Sosa Y , Gobello C
Published: May 2003

Contents

The objectives of the present study were to characterize in dogs circannual and ultradian prolactin (PRL) secretory patterns and also to compare gender differences in the ultradian period of study in the Southern hemisphere. Blood samples were collected at 15‐min intervals for 2.5 h from seven male and seven female dogs and a single monthly sampling, over a 1‐year time span, from six male dogs for the ultradian and circannual studies, respectively. Plasma PRL was measured by a homologous enzyme immunometric assay. The ultradian study evidenced PRL elevations suggesting pulsatile secretion in both genders. Significantly higher mean smoothed baseline (ng / ml [7.02 ± 1.2 vs 1.23 ± 1.0, p < 0.01]) and AUC (ng/ml * 2.5 h [25.2 ± 3.8 vs 4.4 ± 3.8, p < 0.01]) were found in females when compared with males. In the circannual study, plasma PRL concentrations did not statistically differ among the months of the year. When grouped together the 3 months with a longer daylight had significantly higher PRL concentrations than the 3 months with the shortest (2.31 ± 0.37 vs 0.96 ± 0.37, p < 0.01). The correlation between length of daylight and PRL concentrations was 0.24, p < 0.05. It is concluded that PRL does have a circannual rhythmicity and that there are ultradian gender‐related differences in the period under study in these groups of dogs. This study also demonstrates plasma PRL elevations suggesting pulsatile secretion in male dogs.
Apoptosis of Granulosa Cells: A Review on the Role of MAPK‐signalling modules
Authors: Peter AT , Dhanasekaran N
Published: May 2003

Contents

Recent studies suggest that ovarian follicular atresia is associated with DNA fragmentation and degeneration of granulosa cells, the hallmark of programmed cell death or apoptosis. Apoptosis of granulosa cells play a major role in follicular atresia. These studies have also demonstrated the involvement of tumour suppressors, apoptotic proteins and survival factors. These factors contribute to the developmental decision as to whether the ovarian follicles mature or undergo atresia. However, the precise temporal and molecular events involved in the apoptotic pathways in this process need to be elucidated. The present report summarizes the role of Jun N‐terminal kinase (JNK), p38 mitogen activated protein kinase (p38 MAPK), and extracellular‐signal regulated kinase (ERK)‐signalling module in the regulation of pro‐ and anti‐apoptotic factors of the granulosa cells in regulating follicular atresia. The findings presented here suggest that the loss of tropic hormone support is translated into the attenuation of Raf‐1‐MAPK/ERK kinase (MEK)‐ERK‐signalling pathway of the granulosa cells and this results in the decreased phosphorylation of the pro‐apoptotic BAD.
Working community as the basis of the quality of care
Authors: Koivula Meeri , Paunonen‐Ilmonen Marita , Laippala Pekka
Published: May 2003

Nursing takes place in a working community and the working community influences the quality of nursing. The purpose of this study was to find out the effects of nurses’ individual characteristics, working conditions, and the ward sisters’ management skills on working climate and team spirit. Thirty‐seven wards of two Finnish hospitals took part in the study, and 717 nurses answered the questionnaire. Statistical analyses indicate that the ward sister’s management skill is the best predictor of the climate and team spirit of the wards as perceived by nurses. The nurses’ age, education, and working experience have no direct effect on the working community. Nurses who work by the day, who have plenty of further education and permanent employment, are most likely to be dissatisfied with the climate. According to the results, it is important that the ward sister provides sufficient opportunities for professional development, especially for those who are highly motivated to advance their careers. The ward sister can influence the ward’s team spirit also by furthering operational preconditions of the ward.
Feeding outcomes and influences within the Neonatal Unit
Authors: Wheeler Jan , Chapman Claire , Johnson Maree , Langdon Rachel
Published: May 2003

This study examined the feeding intention of mothers (n = 100), and the
factors and beliefs, and changes in those factors or beliefs that influenced their
choices, in the challenging environment of the neonatal unit. Mothers’ experience
and the frequency of nurse‐assisted feeding activities were examined in mothers intending
and not intending to breast‐feed on discharge. Eighty‐one per cent of mothers were
either partially or fully breast‐feeding or intending to do so on discharge. The
most important factors identified as influencing this feeding choice included personal
choice, with other influences being special benefits, more natural and feeling closer
to the baby. Experiences such as infants receiving their first sucking feed from
either the breast or bottle (inclusive of breast milk) and mothers expressing breast
milk more frequently, were found to be significantly different and increased in frequency,
in mothers intending to breast‐feed. Differences in the mean weighted total daily
nurse‐assisted feeding score confirmed that these activities varied with gestational
age (≤32 weeks [2.57], 32 to less than 35 weeks [3.86], and ≥35 weeks [4.91];
F = 7.04, d.f. 55, P = 0.002), although there was insufficient power to determine differences between breast‐feeding and non‐breast‐feeding mothers. The use of the Feeding Activities Calendar may have contributed to increased activity and high levels of breast‐feeding in this preterm group.
Reflections on the role of the nursing development facilitator in clinical supervision and reflective practice
Authors: Maggs Christopher , Biley Anna
Published: May 2003

The notions of clinical supervision and reflective practice are attracting considerable interest across the spectrum of nursing. This paper focuses upon how the two were linked together and, with the support of an independent survey, were used to evaluate the nursing development facilitator role. It is argued that reflective practice, as a model of clinical supervision, may provide a forum for nurses to explore the value of their actions. Linked to this, the personal knowledge that is revealed may mirror reality and as a result it is argued that there is benefit in evaluating practice through reflection.
The Ottawa Charter—from nursing theory to practice: Insights from the area of alcohol and other drugs
Authors: Smith Morgan , Cusack Lynette
Published: May 2003

This article aims to assist nursing services to use the Ottawa Charter as a framework for nursing practice. Incorporation of the Ottawa Charter for Health Promotion into a nursing structure constitutes an innovation in nursing practice that was evaluated as a quality improvement exercise in a health‐care organization responsible for providing services in the area of alcohol and other drugs. The evaluation consisted of two stages and sought to identify the degree to which the framework was effective in practice. This involved identifying issues surrounding the implementation of the Ottawa Charter as a framework for nursing practice as well as identifying the means by which quality improvements could occur. The evaluation involved an initial questionnaire to all nursing staff, followed by a series of focus groups. The data collected was both informative and enlightening and revealed a range of pertinent issues such as staff understanding and interpretation of the Ottawa Charter, expansion of the nurse’s role and suggestions for organizational change. The Ottawa Charter strategies are discussed in relation to their relevance to the organization under evaluation and also expanded into recommendations to assist those contemplating using the Ottawa Charter as a framework for nursing practice. There was considerable agreement among the respondents that the Ottawa Charter provided a useful framework for nursing practice, but was on occasions problematic.
‘The day of the soft towel?’: Comparison of the current bed‐bathing method with the Soft Towel bed‐bathing method
Authors: Hancock Irene , Bowman Alexandra , Prater David
Published: May 2003

The impressions of 200 patients (both medical and surgical) and 200 nursing staff (registered, enrolled and trainee enrolled nurses) in relation to two bed‐bathing methods were compared by means of questionnaires and semi‐structured interviews. Data regarding costs were obtained from appropriate cost centre managers. The results of the study found the soft towel bed‐bathing method to be more cost effective and provide more patient and nurse satisfaction than the current bed‐bathing method.
From rituals to reason: Creating an environment that allows nurses to nurse
Authors: Tonuma Maie , Winbolt Margaret
Published: May 2003

From rituals to reason is a description of the journey that one unit is taking to overturn traditional nursing culture and create an environment that will enable nurses to care for people. In our experience the reality of day‐to‐day nursing practice does not always correspond to the nursing rhetoric of individualised holistic nursing care for each person. We identified that traditional nursing culture, with a focus on task orientation, rigid hierarchical structures and resultant disempowerment of staff, is an impediment to delivery of patient‐centered care. We introduced changes to management structures, care delivery models and staff behaviours with the aim of overturning this traditional nursing culture. Changing clinical practice to focus on client outcomes and provide a relaxed and patient‐centered environment was easier to achieve than staff empowerment and their full involvement in decision making and innovation.
Primary small cell carcinoma of the stomach
Authors: KUSAYANAGI SATOSHI , KONISHI KAZUO , MIYASAKA NOBUO , SASAKI KATSUMI , KURAHASHI TOSHINORI , KANEKO KAZUHIRO , AKITA YASUSHI , YOSHIKAWA NOZOMI , KUSANO MITSUO , YAMOCHI TOSHIKO , KUSHIMA MIKI , MITAMURA KEIJI
Published: May 2003

Abstract  We report on an 80‐year‐old man with primary gastric small cell carcinoma (SmCC). He was admitted to hospital with hematemesis. An upper gastrointestinal examination revealed an irregularly ulcerated tumor, 60 mm in diameter, on the lesser curvature of the stomach body extending to the cardia. An endoscopic biopsy revealed a solid proliferation of intermediate‐sized tumor cells with hyperchromatic nuclei and scanty cytoplasm. Immunohistochemically, the neoplastic cells were positive for neuron‐specific enolase and chromogranin A, but negative for carcinoembryonic antigen. No tumor was detected on examination of the chest. Therefore, primary gastric SmCC was diagnosed preoperatively. To date, only 38 cases of primary gastric SmCC, including our case, have been reported. By using endoscopic biopsy, approximately two‐thirds of cases have been diagnosed incorrectly. In the reported cases of gastric SmCC, the endoscopic findings frequently indicated a submucosal tumor. Gastric SmCC is clinically aggressive and has an extremely poor prognosis, even when discovered at an early stage. Most patients with gastric SmCC die within 1 year of diagnosis. Although a standard treatment for gastric SmCC has not been established, intensive chemotherapy should be considered to promote long‐term survival. We believe that careful examination, including immunohistochemical investigation, is necessary for determining the therapeutic strategy whenever gastric SmCC is suspected during endoscopy.
Alterations in the DNA binding activity of transcriptional factors activator protein‐1, Sp1, and hepatocyte nuclear factor‐1 in rat jejunum during starvation and refeeding
Authors: IHARA TAKASHI , TSUJIKAWA TOMOYUKI , FUJIYAMA YOSHIHIDE , BAMBA TADAO
Published: May 2003

Background: The molecular processes leading to mucosal atrophy, regrowth, and functional changes with starvation and refeeding are largely unknown. There are many transcriptional factors that might be related to mucosal atrophy and proliferation. In contrast, we previously reported that H+/peptide transporter and aminopeptidase N messenger RNA in the intestinal mucosa were upregulated during starvation. Therefore, we selected and studied three transcriptional factors: activator protein (AP)‐1, Sp1, and hepatocyte nuclear factor (HNF)‐1, which not only play important roles for enterocytes proliferation, but also exist in promoter lesions of the brush border enzymes and peptide transporter.

Methods: In the present study, we performed electrophoretic mobility shift assays employing AP‐1, Sp1, and HNF‐1, and evaluated the changes in the DNA binding activities in rat jejunum during starvation and refeeding.

Results: Two days after starvation, the Sp1 binding activity was significantly decreased to 61.8% as compared with the control level, whereas AP‐1 was 121.4% and HNF‐1 was 77.5%. Two hours after refeeding, the AP‐1 activity was significantly increased to 175.0% as compared with the control level, and the HNF‐1 activity was significantly increased to 180.2%. In contrast, the decreased SP1 level did not recover until 24 h after refeeding.

Conclusions: The DNA binding activities of these three transcriptional factors were significantly changed in the rat jejunum during starvation and refeeding. Our results provide insight into the molecular mechanisms of the transcriptional regulations associated with mucosal atrophy, regrowth, and functional changes of the jejunal epithelium in response to starvation and refeeding.
Thermal ablative therapy for malignant liver tumors: A critical appraisal
Authors: NG KELVIN KWOK‐CHAI , LAM CHI‐MING , POON RONNIE TUNG‐PING , AI VICTOR , TSO WAI‐KUEN , FAN SHEUNG‐TAT
Published: May 2003

Abstract  The management of primary and secondary malignant liver tumors poses a great challenge to clinicians. Although surgical resection is the gold‐standard treatment, most patients have unresectable malignant liver tumors. Over the past decade, various modalities of loco‐regional therapy have gained much interest. Among them, thermal ablative therapy, including cryotherapy, microwave coagulation, interstitial laser therapy, and radiofrequency ablation (RFA), have been proven to be safe and effective. Despite the effective tumor eradication achieved within cryotherapy, the underlying freeze/thaw mechanism has resulted in serious complications that include bleeding from liver cracking and the ‘cryoshock’ phenomenon. Thermal ablation using microwave and laser therapy for malignant liver tumors is curative and is associated with minimal complications. However, this treatment modality is effective only for tumors <3 cm diameter. Radiofrequency ablation seems to be the most promising form of thermal ablative therapy in terms of a lower complication rate and a larger volume of ablation. However, its use is restricted by the difficulty encountered when using imaging studies to monitor the areas of ablation during and after the procedure. Moreover, the techniques of RFA need to be refined in order to achieve the same oncological radicality of malignant liver tumors as achieved by surgical resection. As each of the loco‐regional therapies has its own advantages and limitations, a multidisciplinary approach using a combination of therapies will be the future trend for the management of malignant liver tumors.
Differential, stage‐dependent expression of Hsp70, Hsp110 and Bcl‐2 in colorectal cancer
Authors: HWANG TAE SOOK , HAN HYE SEUNG , CHOI HYO KYOUNG , LEE YONG J , KIM YUN‐JEONG , HAN MI‐YOUNG , PARK YOUNG‐MEE
Published: May 2003

Background: The presence of hypoxic cells in solid tumors has been suggested to contribute to the malignant progression of various tumors. Recently, we reported an activation of heat shock transcription factor (HSF) and expression of heat shock proteins (Hsp) in murine tumor cells by hypoxia.

Methods: To search for a possible role of Hsp in the malignant progression of human tumors, we analyzed the expression profiles of Hsp family proteins in weakly and highly metastatic human colorectal cancer (CRC) cell lines. We also analyzed the expression profiles of Bcl‐2 family proteins because the altered expression of these proteins has been demonstrated in various solid tumors.

Results: In the present paper we showed among various Hsp and Bcl‐2 family proteins that the expression of Hsp70 and Hsp110 was elevated in highly metastatic CX‐1 and HT‐29 cells, while the expression of Bcl‐2 was elevated in weakly metastatic MIP‐101 and Clone A cells. Subsequent immunohistochemical analysis of 81 primary human CRC tissues demonstrated that the expression of Hsp70 and Hsp110 was highly correlated with the advanced clinical stages and positive lymph node involvement. The expression of Bcl‐2, in contrast, was correlated to the early clinical stage and negative lymphovascular invasion.

Conclusion: Taken together, our study demonstrated for the first time a differential, stage‐dependent expression of Hsp70, Hsp110 and Bcl‐2 in CRC. We suggest that the molecular mechanisms underlying the differential expression of Hsp and Bcl‐2 family members deserves a more rigorous future study, the results of which might offer novel modes of rationale and strategy to predict and manipulate the malignant progression of colorectal cancers.
Tumor progression in hepatocellular carcinoma: Relationship with tumor stroma and parenchymal disease
Authors: LOCKWOOD DAVID SR , YEADON TRINA M , CLOUSTON ANDREW D , CRAWFORD DARRELL G , FAWCETT JONATHAN , CALLAGHAN SHIRLEY A , GOTLEY DAVID C
Published: May 2003

Background: Encapsulation in hepatocellular carcinoma is associated with decreased invasiveness and improved survival in several series. Although active fibrogenesis by myofibroblasts has been demonstrated in the capsule, it is unclear if the capsule results from a general increase in peritumoral fibrosis, or an inherently less invasive tumor phenotype. The relationship between collagen deposition within tumor stroma, presence of cirrhosis and invasiveness also needs clarification.

Methods: We performed immunohistochemistry for collagens I, III, IV and VI on sections of encapsulated and non‐encapsulated hepatocellular carcinoma, arising in cirrhotic and non‐cirrhotic livers. Staining was graded semi‐quantitatively in tumor stromal elements and adjacent parenchymal sinusoids. The relationship of this staining with encapsulation, cirrhosis, and vascular invasion was analyzed.

Results: Formation of a discrete capsular layer was associated with reduced vascular invasion, but not with a pervasive increase in peritumoral fibrosis. Increased collagen I content of tumor stroma and adjacent parenchymal sinusoids was associated with non‐encapsulated tumors and vascular invasion. The presence of cirrhosis had little effect on capsule composition.

Conclusions: Encapsulation of hepatocellular carcinoma reflects reduced invasiveness, rather than increased peritumoral collagen synthesis, which may instead enhance invasion. Increased intratumoral collagen I protein is also associated with increased tumor invasiveness. Pre‐existing cirrhosis has little effect on tumor progression, possibly because the characteristics of cirrhosis are overwhelmed by tumor‐induced changes in the adjacent parenchyma.
Effects of interferon alpha therapy on the catalytic domains of the polymerase gene and basal core promoter, precore and core regions of hepatitis B virus
Authors: CHEN ROBERT YUNG MING , BOWDEN SCOTT , DESMOND PAUL VINCENT , DEAN JO , LOCARNINI STEPHEN A
Published: May 2003

Aims: The aim of the present study was to examine the catalytic domains of the polymerase gene, the basal core promoter and the precore and core regions of the hepatitis B virus (HBV) genome for specific mutations. These may account for the response to interferon alpha (IFN‐α) treatment, which may have prognostic value.

Methods: Multiple serum samples were collected prospectively from 30 patients with chronic active hepatitis B who were treated with IFN‐α. Patients were assigned to one of three groups: group A (n = 11) and group B (n = 10) individuals were hepatitis B e antigen (HBeAg)‐positive prior to treatment. Group A patients underwent HBeAg seroconversion after treatment while group B patients did not. Group C (n = 9) patients were HBeAg‐negative prior to treatment. The HBV DNA was extracted from the sera collected before, during and after treatment and the various genomic regions were amplified, sequenced and examined for mutations.

Results: During IFN‐α therapy, multiple changes were found in the catalytic domains of the HBV polymerase gene in all groups. The frequency of mutations and associated amino acid changes were highest in virus from group C patients and lowest in group A patients. The interdomain regions of the viral polymerase were the most affected. Multiple mutations were also found in the precore, core and core promoter regions. However, no specific mutations were associated with clinical response or outcome.

Conclusions: During IFN‐α treatment, multiple mutations occurred in the HBV genome, including the catalytic domains of the polymerase gene. Changes that did occur could not be correlated to the clinical response or treatment outcome. However, no mutations were found that have been linked to lamivudine escape, indicating that lamivudine therapy would be effective in IFN‐α non‐responder patients.
Gross appearance of hepatocellular carcinoma reflects E‐cadherin expression and risk of early recurrence after surgical treatment
Authors: INAYOSHI JUN , ICHIDA TAKAFUMI , SUGITANI SOICHI , TSUBOI YASUNORI , GENDA TAKUYA , HONMA NOBUYUKI , ASAKURA HITOSHI
Published: May 2003

Background and Aims: Correlation between the gross classification of hepatocellular carcinoma (HCC) and its vascular invasion or intrahepatic metastasis has been reported previously. Because E‐cadherin‐mediated epithelial cell‐to‐cell adhesion is thought to suppress cancer cell invasion, the present study was performed to analyze the correlation between E‐cadherin expression and the gross classification of HCC.

Methods: Thirty‐six resected solitary HCC <6 cm in diameter were each classified as single nodular type (type 1), single nodular with extranodular growth type (type 2) or contiguous multinodular type (type 3), and the clinicopathological and prognostic differences between type 1 HCC and the other types were analyzed. The expression of E‐cadherin in each tumor was examined by immunoblotting and immunohistochemical analysis.

Results: Vascular invasion and microscopic intrahepatic metastasis were observed more frequently in types 2 and 3 (61%) than in type 1 (13%) HCC. Immunoblot analysis indicated that the relative level of E‐cadherin expression in cancerous tissue was significantly lower in type 2 and 3 (0.75 ± 0.49) than in type 1 (1.46 ± 0.79) HCC. Immunohistochemical examination revealed decreased and partially absent E‐cadherin expression in the tumorous area of type 2 and 3 HCC. The recurrence‐free survival rate was higher for patients with type 1 HCC than for those with the other types.

Conclusions: Types 2 and 3 HCC have marked metastatic and invasive potential and reduced expression of E‐cadherin, predicting a high risk of recurrence after surgical treatment.
Role of elevated platelet‐associated immunoglobulin G and hypersplenism in thrombocytopenia of chronic liver diseases
Authors: SANJO AKIRA , SATOI JUJIN , OHNISHI AKIHIRO , MARUNO JUNKO , FUKATA MASAYUKI , SUZUKI NAOKI
Published: May 2003

Background and Aim: Thrombocytopenia typically worsens with the progression of liver disease and can become a major clinical complication. Several mechanisms that contribute to thrombocytopenia have been proposed, including hypersplenism accompanied by increased platelet sequestration, platelet destruction mediated by platelet‐associated immunoglobulins (PAIgG), and diminished platelet production stimulated by thrombopoietin (TPO). The purpose of the present study was to evaluate the role of each of these mechanisms in patients with liver disease‐associated thrombocytopenia.

Methods: Twenty‐nine patients with liver cirrhosis (LC), 20 of whom were hepatitis C virus (HCV)‐seropositive, 29 chronic hepatitis (CH) patients, 24 of whom were HCV‐seropositive, and 16 control patients without liver or hematopoetic disease were enrolled in this study. Serum TPO levels, PAIgG, and liver‐spleen volumes were determined and correlation analyses were performed.

Results: No differences in serum TPO levels were observed among the three groups. The PAIgG levels were significantly elevated in CH and LC patients (mean ± SD: 56.5 ± 42.3 and 144.6 ± 113.6 ng/107 cells, respectively) compared with the controls (18.9 ± 2.5 ng/107 cells, P < 0.001 for both). Spleen volume was significantly higher only in LC (428 ± 239) compared with CH (141 ± 55) and control (104 ± 50 cm3) (P < 0.001), while liver volume was not significantly different between the three groups. Correlation analyses demonstrated a significant negative correlation between platelet count with PAIgG (r = − 0.517, P < 0.001) and spleen volume (r = − 0.531, P < 0.001), and no relationship between platelet count and serum TPO level (r = 0.076).

Conclusions: Serum TPO level may not be directly associated with thrombocytopenia in patients with chronic hepatitis and liver cirrhosis. In contrast, spleen volume and PAIgG are associated with thrombocytopenia in such patients, suggesting that hypersplenism and immune‐mediated processes are predominant thrombocytopenic mechanisms.
Tolerance to famotidine and ranitidine treatment after 14 days of administration in healthy subjects without Helicobacter pylori infection
Authors: KOMAZAWA YOSHINORI , ADACHI KYOICHI , MIHARA TAKAFUMI , ONO MASAHIRO , KAWAMURA AKIRA , FUJISHIRO HIROFUMI , KINOSHITA YOSHIKAZU
Published: May 2003

Background and Aim: The attenuated antisecretory activity observed during continuous administration of ranitidine has been described as tolerance. However, it remains unclear whether a similar phenomenon occurs with other histamine H2 receptor antagonists (H2RA). We investigated whether tolerance to famotidine, a stronger H2RA than ranitidine, occurs during long‐term administration.

Methods: Seven healthy male Japanese subjects without Helicobacter pylori infection participated in a randomized cross‐over study in which ranitidine and famotidine were administered for 14 days with a 4‐week wash‐out period. We performed 24‐h intragastric pH monitoring on the first and 14th days of administration of each drug, and measured serum gastrin and plasma drug concentrations on the first, seventh and 14th days.

Results: The acid‐inhibiting activity of ranitidine and famotidine declined during continuous administration. In particular, the potent nocturnal pH‐increasing effect of the H2RA, which was observed on day 1, declined on day 14. Serum gastrin concentrations on day 14 were significantly lower than those on day 7, although plasma drug concentrations remained unchanged.

Conclusion: Tolerance to famotidine occurs during continuous administration for 14 days, as previously shown in ranitidine studies.
Nutritional benefits of enteral alanyl‐glutamine supplementation on rat small intestinal damage induced by cyclophosphamide
Authors: SATOH JIN , TSUJIKAWA TOMOYUKI , FUJIYAMA YOSHIHIDE , BAMBA TADAO
Published: May 2003

Background: Glutamine is the principal fuel used by the small intestine. Although the parental administration of glutamine promotes intestinal mucosal growth, it is controversial whether enteral glutamine is effective against small intestinal damage caused by chemotherapy. To further evaluate the benefits of enteral supplementation, peptide and amino acid transporter functions must be considered.

Method: Rats were given cyclophosphamide (CPM) intraperitoneally (300 mg/kg). Expression of the amino acid transporter, B0 and peptide transporter (PepT1) in the jejunal mucosa was initially examined by northern blot analysis. Rats received a bolus oral supplement of an alanine (1.22 g/kg/day) plus glutamine (2.0 g/kg/day) mixture, alanyl‐glutamine (2.972 g/kg/day) or saline as a control, for 7 days after CPM administration.

Results: Levels of B0 mRNA remained unchanged at both 3 and 7 days after CPM administration. Conversely, PepT1 mRNA increased significantly after CPM administration, and reached 200% of the initial level 7 days later. In rats given alanyl‐glutamine, the mucosal wet weight and protein content increased significantly with increasing villus height at 3 and 7 days, compared with the alanine plus glutamine mixture. The plasma glutamine concentration in the alanyl‐glutamine group, but not the alanine plus glutamine mixture group, increased significantly compared with that in the saline group.

Conclusion: Enteral supplementation with an alanyl‐glutamine but not alanine plus glutamine mixture prevents intestinal damage, as demonstrated by increased peptide transport expression and an elevated plasma glutamine concentration after CPM administration.
Autonomic nervous dysfunction in patients with liver cirrhosis using 123I‐metaiodobenzylguanidine myocardial scintigraphy and spectrum analysis of heart‐rate variability
Authors: IGA AKIKO , NOMURA MASAHIRO , SAWADA YUKI , ITO SUSUMU , NAKAYA YUTAKA
Published: May 2003

Background: It has been reported that nitric oxide (NO) synthase is induced in patients with liver cirrhosis (LC), and that an excessive production of NO enhances sympathetic nervous function. The present report describes a study of the feasibility of evaluation of abnormalities of autonomic nervous function by 123I‐metaiodobenzylguanidine (MIBG) myocardial scintigraphy and heart‐rate variability in patients with LC.

Methods: Low‐frequency (LF) power, high‐frequency (HF) power, LF/HF, and 1/f fluctuations of heart rate variability were examined in 50 patients with LC (LC group), and 50 normal subjects (N group). Echocardiogram, urinary nitrite and nitrate, and cathecholamines were examined.

Results: Fractional shortening was observed for the hyperdynamic state of patients in the LC group according to Child's A–C classification. Washout rate of MIBG, LF/HF, and blood levels of norepinephrine increased and HF power decreased with the progression of LC. However, the urinary secretion of nitrite and nitrate were significantly increased only in cirrhotic patients with Child C.

Conclusions: The present results indicate that autonomic abnormalities appear early in LC, and that these abnormalities can be detected by MIBG myocardial scintigraphy and analysis of heart‐rate variability. We consider these methods to be clinically useful for the quantitative detection of hyperdynamic circulation of liver cirrhosis.