bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of three different mutations in the arginine vasopressin gene suggests genotype–phenotype correlation in familial neurohypophyseal diabetes insipidus kindreds
Authors: Siggaard Charlotte , Christensen Jane H. , Corydon Thomas J. , Rittig Søren , Robertson Gary L. , Gregersen Niels , Bolund Lars , Pedersen Erling B. 
Published: July 2005

SummaryObjective and study design  The autosomal dominant form of familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disease characterized by a severe and progressive deficiency of AVP secondary to mutations in the gene encoding the AVP precursor. Whereas a number of studies have investigated the pathogenetic mechanisms behind the disease only few studies have included detailed clinical characterization of the affected patients, thereby making genotype–phenotype correlations difficult. The aims of the present study were to investigate the cellular effects of three different adFNDI mutations (A19T, L81P and C110X) by heterologous expression in a neurogenic cell line and to correlate these findings to the corresponding clinical phenotype as determined by extensive clinical tests.Results  The clinical studies showed a later age of onset in the family carrying the A19T mutation (3·4 years, range 2–9 years) compared with families with the L81P and C110X mutations [0·75 year, range 0·5–1 year and 1·0 year (n = 1), respectively]. No other differences could be demonstrated in the clinical phenotype between families. Expression studies showed that each of the three mutant genes caused significant reduction of the amount of immunoreactive AVP in the cell culture medium and severe impairment of the intracellular trafficking and processing of the AVP prohormone, supporting the disease causing nature of all three mutations. However, the A19T mutation was associated with some capacity for processing and trafficking consistent with the clinical observations. Immunoflourescence studies provided evidence of reticular accumulation of protein within the ER in the A19T and C110X mutants but a unique accumulation of much larger aggregates in the L81P, which were localized both within and immediately outside the ER.Conclusion  The study suggests a genotype–phenotype correlation with regard to age of onset of diabetes insipidus symptoms and provides support by expression studies.
Ghrelin in preterm and term newborns: relation to anthropometry, leptin and insulin
Authors: Ng Pak C. , Lee Cheuk H. , Lam Christopher W. K. , Chan Iris H. S. , Wong Eric , Fok Tai F. 
Published: July 2005

SummaryAims  This study aimed to investigate (i) the plasma ghrelin concentration at birth, (ii) the relationship of ghrelin with metabolic hormones, including leptin and insulin, and (iii) its association with anthropometric parameters, in appropriately grown preterm (23–36 weeks gestation) and term (37–42 weeks gestation) newborns.Patients and methods  Blood samples for hormonal assay were obtained from preterm (n = 81) and term newborns (n = 40) within the first 2 h of life and before milk feeding or energy intake. The relationship between plasma ghrelin and other metabolic hormones or anthropometric parameters was evaluated.Results  Plasma ghrelin was detectable in all studied infants and the concentrations did not differ significantly between term and preterm infants [median (interquartile range): 1·21 (0·86–1·48) nmol/l vs. 1·04 (0·71–1·51) nmol/l, P = 0·52, respectively]. There was no overall significant correlation between plasma ghrelin and gestational age, anthropometric parameters and leptin or insulin. However, when term and preterm infants were analysed independently, plasma ghrelin was inversely correlated with birth weight (r = −0·31, P = 0·05) and body length (r = −0·33, P = 0·04) in the term infant group.Conclusions  Our findings suggested that plasma ghrelin concentrations were relatively constant at birth, between 23 and 42 weeks gestation, and ghrelin secretion did not appear to undergo gestational age‐related variations. An inverse relationship between plasma ghrelin and anthropometric indices in term infants raised the possibility that ghrelin might adopt its physiological role in regulating growth and metabolism at a late stage of gestation (≥ 37 weeks gestation). This phenomenon could be beneficial to term newborns by stimulating their appetite and maintaining an adequate blood sugar level at the most critical period when nutrients from mothers are abruptly terminated after birth.
The role of growth hormone in determining birth size and early postnatal growth, using congenital growth hormone deficiency (GHD) as a model
Authors: Mehta Ameeta , Hindmarsh Peter C. , Stanhope Richard G. , Turton James P. G. , Cole Tim J. , Preece Michael A. , Dattani Mehul T. 
Published: July 2005

SummaryObjective  The role of GH in early human growth is unclear. Congenital GH deficiency (CGHD) provides a useful tool to explore this putative role. We have assessed the effects of CGHD on birth size and early postnatal growth, and the further impact of the presence of additional pituitary hormone deficiencies and midline brain defects on these parameters.Design, patients and measurements  Weight, length and BMI expressed as standard deviation scores (SDS), over the first two years of life, were retrospectively compared in 44 GH‐deficient children (M:F 26 : 18). Thirty‐eight of 44 patients underwent GH provocation testing and all patients had neuro‐imaging of the brain. The patients were divided into three groups of increasing phenotypic complexity {group A [n = 12, isolated GHD, no midline defects], group B [n = 10, combined pituitary hormone deficiency (CPHD); no midline defects], group C (n = 22, CPHD with midline defects)}.Results  Mean birth weight, length and BMI SDS were −0·4, −0·9 and +0·1 SDS, respectively. The differences were significant for weight (P = 0·03) and BMI (P = 0·003), but not length (P = 0·3) SDS, between groups A and C. Of the three groups, group A had a lower weight and BMI SDS than group C. The prevalence of postnatal complications (n = 25) was significantly different in the three groups [group A (8%), group B (80%), group C (73%); P < 0·001] and particularly between patients with isolated GH deficiency (IGHD) (group A) and CPHD (groups B and C; P < 0·0001). No patients in group A presented with neonatal hypoglycaemia as compared with 70% of those in group B and 59% in group C (P = 0·001). A reduced length SDS was observed in all patients within 6 months of birth and the reduction was greatest in group B (P = 0·03). Group C remained significantly (P < 0·05) heavier at 12, 18 and 24 months compared to group A. BMI SDS was significantly (P < 0·05) greater at all study points in CPHD patients (groups B and C) as compared with IGHD. Serum GH concentrations at testing did not correlate significantly with birth length (r = −0·08, P = 0·7), birth weight (r = −0·08, P = 0·6) or the age at induction of GH treatment (r = 0·12, P = 0·5). There were no significant differences between peak serum GH concentrations in patients in groups A (7·8 ± 6·3 mU/l), B (3·9 ± 4·8 mU/l) or C (8·7 ± 5·4 mU/l).Conclusions  Length, weight and BMI data from our study groups suggest that GH per se has a minimal effect on intrauterine growth but a significant effect during the infancy period. Early growth may also be influenced by the complexity of the hypopituitary phenotype reflected by the presence of additional pituitary hormone deficiencies and midline forebrain defects.
Neural tumours of the neck presenting as thyroid nodules: a report of three cases
Authors: Aron M. , Kapila K. , Verma K. 
Published: July 2005

Objectives:  Neural tumours of the neck may at times secondarily involve the thyroid and manifest clinically as thyroid nodules. On cytological evaluation these nodules may be confused with other spindle lesions of the thyroid. We report two cases of schwannoma and one case of a malignant peripheral nerve sheath tumour (MPNST) of the neck, which presented as thyroid nodules and evaluate the role of cytology in identifying these tumours.Methods:  The thyroid nodules in all the three cases were sampled by the non‐aspiration technique using a 23‐gauge needle. Both alcohol‐fixed and air‐dried smears were prepared and stained by the Papanicolaou and May–Grünwald‐Giemsa stains. Cytology smears and histology sections from the resected specimens were reviewed, and the findings noted.Results:  Both the cases of schwannoma were correctly identified on cytology while the case of MPNST could only be typed as a spindle cell tumour. However, on cytology it was not possible to state whether the tumours were thyroidal or extrathyroidal in origin.Conclusions:  Schwannomas of the neck are easily identifiable on cytology compared with MPNST. However, cytology alone is not helpful in identifying the origin of these tumours. As primary neural tumours of the thyroid are rare, the possibility of a soft tissue neural tumour extending into the thyroid should always be ruled out while evaluating these cases.
Human papillomavirus DNA detection in women with primary abnormal cytology of the cervix: prevalence and distribution of HPV genotypes
Authors: Beerens E. , Van Renterghem L. , Praet M. , Sturtewagen Y. , Weyers S. , Temmerman M. , Depypere H. , Claeys P. , Cuvelier C. A. 
Published: July 2005

Objectives:  In this study, we focus on the prevalence and occurrence of different anogenital human papillomavirus (HPV) genotypes in a first abnormal cervical screening test, and correlate HPV genotyping with the cytological diagnosis on thin‐layer liquid‐based preparations in routine gynaecological screening.Methods:  Out of 780 abnormal smears, 513 tested positive for HPV. All 25 different HPV types were identified by Line Probe Assay.Results:  The prevalence of high‐risk HPV types increased from 72% in atypical squamous cell of undetermined significance to 94.5% in high‐grade intra‐epithelial lesion (HSIL). Co‐infection with multiple HPV types was predominantly found in HSIL (35.8%). In the HSIL group the most common HPV types were 16, 52, 51 and 31; type 18 was rarely present.Conclusion:  The role of types 31, 51 and 52 should be considered in future studies on vaccine development.
Differentiating keratoacanthoma from squamous cell carcinoma by the use of apoptotic and cell adhesion markers
Authors: Slater M , Barden J A 
Published: July 2005

Aims : Keratoacanthomas (KA) are well‐differentiated squamoproliferative skin lesions that grow rapidly and regress spontaneously. In contrast, squamous cell carcinomas (SCC) can have variable differentiation, inexorably progress and on occasion metastasize. Distinguishing between KA and SCC using haematoxylin and eosin‐stained sections from an initial biopsy can often be difficult. There is also some debate as to whether KA is simply a variety of well‐differentiated SCC or a distinct entity.Methods and results : Initial biopsy sections from 25 cases of SCC and 20 of KA were labelled with markers for both the initiation (the cytolytic receptor P2X7) and end‐stage (terminal deoxynucleotidyl transferase biotin–dUTP nick end labelling) of apoptosis, telomerase‐associated protein (TP1) and the cell adhesion protein E‐cadherin. As this was a retrospective study, the clinical outcome of each case was known. This resulted in a unique labelling pattern of each marker for SCC and KA, allowing a differential diagnosis between the two conditions. The simplest marker to use for this purpose was anti‐P2X7. Sections from five cases that were initially very difficult to diagnose were correctly identified as SCC using this method.Conclusions : These results support the view that KA has a different pathogenesis and biochemistry from that of SCC, and is a distinct entity. Anti‐P2X7 labelling, using routine immunohistochemical techniques, provides a method for differentially diagnosing these conditions.
Pathological response following long‐course neoadjuvant chemoradiotherapy for locally advanced rectal cancer
Authors: Ryan R , Gibbons D , Hyland J M P , Treanor D , White A , Mulcahy H E , O'Donoghue D P , Moriarty M , Fennelly D , Sheahan K 
Published: July 2005

Aims : To standardize the pathological analysis of total mesorectal excision specimens of rectal cancer following neoadjuvant chemoradiotherapy for locally advanced disease (T3/T4), including tumour regression.Methods and results : Standardized dissection and reporting was used for 60 patients who underwent total mesorectal excision following long‐course chemoradiotherapy. Tumour regression was scored by two pathologists (K.S., D.G.) using both an established 5‐point tumour regression grade (TRG), and a novel 3‐point grade. Both scores were evaluated for interobserver variability. A complete or near‐complete pathological response (3‐point TRG 1) was found in 10 patients (17%). Using the 5‐point TRG, there was good agreement between both pathologists (κ = 0.64). Using the 3‐point grade, agreement was excellent (κ = 0.84). No disease recurrence has been reported in patients with a complete, or near complete pathological response (3‐point TRG 1), after a mean follow‐up of 22 months.Conclusion : Tumour regression grade is a useful method of scoring tumour response to chemoradiotherapy in rectal cancer. TRG 1 and 2 can be regarded as a complete pathological response (ypT0). A modified 3‐point grade has the advantage of better reproducibility, with similar prognostic significance.
Usefulness of epithelial membrane antigen (EMA) to discriminate between perineural invasion and perineural indentation in prostatic carcinoma
Authors: Tsuzuki T , Ujihira N , Ando T 
Published: July 2005

Aims : Perineural invasion (PNI) is one of the few unequivocal criteria to diagnose adenocarcinoma of the prostate. Distinguishing PNI from perineural indentation (PNIn), however, is sometimes difficult. The aim of this study was to discriminate between PNI and PNIn using EMA immunohistochemistry.Methods and results : We selected representative sections from 87 prostatectomies with prostatic adenocarcinoma. Normal peripheral nerves were continuously encircled with perineurium, which was immunoreactive for EMA. We identified 1319 PNI by carcinomas, 368 PNIn by carcinomas, and 303 PNIn by benign glands. We categorized the EMA immunoreactivity patterns into three classes: samples that displayed discontinuity or complete loss of the perineurium (Type A), samples where there were carcinomas or benign glands in the perineural space or peripheral nerves (Type B) and samples that showed no changes in the perineurium (Type C). For PNI we observed Type A, Type B, and Type C patterns in 55.3%, 24.8% and 19.9% of carcinomas, respectively. The incidence of each of those patterns in PNIn by carcinomas was 32.1%, 14.9% and 53.0%, respectively. Cases of PNIn by benign glands showed Type A or Type C patterns. They did not, however, exhibit Type B patterns.Conclusion : EMA immunostaining will aid the diagnosis of prostatic adenocarcinoma.
Expression of GCDFP‐15 and AR decreases in larger or node‐positive apocrine carcinomas of the breast
Authors: Honma N , Takubo K , Akiyama F , Sawabe M , Arai T , Younes M , Kasumi F , Sakamoto G 
Published: July 2005

Aims : Apocrine carcinoma of the breast is typically, though not always, positive for gross cystic disease fluid protein‐15 (GCDFP‐15). In order to clarify the clinical significance of GCDFP‐15 in apocrine carcinomas, GCDFP‐15 expression was examined in apocrine carcinomas of different stages and compared with clinicopathological factors. Apocrine lesions reportedly exhibit an unusual immunohistochemical status, expressing androgen receptors (AR) instead of oestrogen receptors (ER), progesterone receptors (PR), or bcl‐2. Their expression was also examined.Methods and results : Fifty‐two apocrine carcinomas were examined immunohistochemically. Thirty‐nine (75%) and 29 (56%) were positive for GCDFP‐15 and AR, respectively. GCDFP‐15 positivity was significantly lower in infiltrating carcinomas than intraductal carcinomas (P = 0.0111). In infiltrating carcinomas, GCDFP‐15 positivity was significantly low in tumours ≥ 15 mm (P = 0.0005) and node‐positive tumours (P = 0.0004). Similar phenomena were observed for AR. Rare cases were positive for ER (3.8%), PR (5.8%), and bcl‐2 (1.9%).Conclusions : GCDFP‐15 positivity is transient and should not be considered a definitive marker of apocrine carcinomas. Cases which have apocrine features but lack GCDFP‐15 expression should rather be considered as advanced apocrine carcinomas. ER/PR/bcl‐2 negativity will sometimes be helpful to confirm the diagnosis of apocrine carcinoma, because it is more consistent than GCDFP‐15/AR positivity.
Dermal non‐neural granular cell tumour (so‐called primitive polypoid granular cell tumour): a distinctive entity further delineated in a clinicopathological study of 11 cases
Authors: Chaudhry I H , Calonje E 
Published: July 2005

Aims : Cutaneous and soft tissue granular cell tumour is a well‐characterized benign neoplasm of neural origin. However, there remains a subcategory of granular cell tumour, first described by Le Boit as ‘primitive polypoid granular cell tumour’, that shows no obvious line of differentiation. The aim of this study is to further the characterization of this lesion by undertaking a clinicopathological review.Methods and results : Eleven cases of dermal non‐neural granular cell tumour were retrieved from one of the authors referral archives (E.C.) and both the histology and immunohistochemistry reviewed. Clinical data with follow‐up were obtained from the referring pathologists. The lesions most commonly occurred in young to middle‐aged adults (nine cases, median = 33 years, age range 6–56 years), with a slight female predominance. They presented as painless nodules, mainly on the extremities or face. Local excision was the treatment of choice and up to date follow‐up reveals no sign of recurrence. Histologically, eight cases were polypoid, while three cases were endophytic. The tumours were composed of elongated spindle‐shaped to polygonal or round cells with prominent granular cell change, and tumour nuclei showing mild focal atypia to rare moderate atypia. Mitotic activity ranged from one to nine mitoses per 10 high‐power fields (median = 2, mean = 3.8). Immunohistochemical labelling of the tumour cells demonstrated expression for NKI‐C3 (n = 11), focal, weak positivity for CD68 (n = 10) and FXIIIa (n = 2). There was negative staining for S100 protein, smooth muscle actin, Melan‐A, CD34, desmin and cytokeratin.Conclusions : This analysis of 11 cases contributes to the characterization of this recently described entity, which despite some atypical histological features and no obvious line of differentiation, behaves in a completely indolent fashion.
Microvessel density for melanoma prognosis
Authors: Depasquale I , Thompson W D 
Published: July 2005

Aims : Two‐hundred and four accessible cases of malignant melanoma from the Grampian region of Scotland, collected over a period of 4 years, were studied for standard prognostic indicators for comparison with microvessel density.Methods and results : The range of tumour thickness varied from in‐situ melanoma to 14.8 mm. Microvessel density was assessed using the Chalkley technique on sections immunostained with CD31 antibody to identify endothelium. Vessel counts were performed in the peritumoral host tissue of all specimens. Strong correlation was observed between microvessel density at the tumour edge and tumour thickness (P < 0.001). Multifactorial regression analysis confirms Chalkley estimation as a reliable predictor of the risk of recurrence of melanoma (P < 0.005). The predictive value was found to be superior to the Breslow score, for tumours more than 2 mm thick.Conclusions : Microvessel assessment of primary melanoma using the Chalkley score technique provides reliable prognostic information on the risk of recurrence of the tumour, particularly for melanomas deeper than 2 mm. It remains to be seen whether this methodology can predict response to novel anti‐angiogenic therapies currently entering trials.
Galectin‐3 expression in papillary microcarcinoma of the thyroid
Authors: Cvejic D , Savin S , Petrovic I , Paunovic I , Tatic S , Krgovic K , Havelka M 
Published: July 2005

Aims : Galectin‐3 is a β‐galactoside binding protein, recently recognized as a promising molecular marker of thyroid malignancy. As reported in several studies, galectin‐3 is highly expressed in papillary thyroid carcinoma, but its expression has not been investigated in papillary microcarcinoma, which is a variant of papillary thyroid carcinoma.Methods and results : Using a monoclonal antibody to galectin‐3 and the avidin–biotin–peroxidase complex (ABC) immunohistochemical technique, we analysed galectin‐3 expression in 63 cases of papillary microcarcinoma. The results showed immunohistochemical reactivity for galectin‐3 in 51 (80.9%) cases. Intensity of staining varied from strong or moderate to weak. Galectin‐3 localization was mostly cytoplasmic, but also membranous or nuclear in some cells. Immunohistochemical expression of galectin‐3 was not found in 12 (19.1%) cases. Most galectin‐3 negative microcarcinomas (10/12) were of the non‐classical type, i.e. without papillary architecture. Neither the frequency nor the intensity of a positive reaction was related to tumour size.Conclusions : Galectin‐3 gene is expressed at the protein level in most papillary microcarcinomas, although with slightly lower frequency than that reported for clinically evident papillary thyroid carcinoma. The presence of galectin‐3 in clinically silent microcarcinomas may indicate that galectin‐3 is not related to growth or aggressiveness of papillary thyroid microcarcinomas but rather plays some other role in thyroid tumour biology.
Ki67 expression in different epithelial types in columnar lined oesophagus indicates varying levels of expanded and aberrant proliferative patterns
Authors: Olvera M , Wickramasinghe K , Brynes R , Bu X , Ma Y , Chandrasoma P 
Published: July 2005

Aims : To evaluate proliferative patterns in metaplastic columnar epithelia of the oesophagus, classified as oxynto‐cardiac (n = 43), cardiac (n = 45) intestinal without dysplasia (n = 41), dysplastic intestinal epithelium (n = 25), and adenocarcinoma (n = 15) by Ki67 immunohistochemistry.Methods and results : Abnormal patterns of Ki67 immunoreactivity were classified into (i) expanded proliferation, characterized by increased levels of Ki67 expression in the deep and mid third of the foveolar pit; and (ii) aberrant proliferation, characterized by positive staining in the surface epithelium and superficial third of the foveolar pit. A significant step‐wise increase in the frequency of expanded proliferation was seen in oxynto‐cardiac, cardiac, intestinal and dysplastic intestinal epithelium indicative of increasing levels of damage. Aberrant proliferation was absent in oxynto‐cardiac mucosa, present at a low and similar level in cardiac, intestinal and low‐grade dysplastic epithelia and at a significantly increased frequency in high‐grade dysplasia.Conclusions : These findings suggest that oxynto‐cardiac mucosa occurs in a low damage environment and intestinal metaplasia in a high damage environment along the length of the columnar lined oesophageal segment. Aberrant proliferative patterns with Ki67 staining are not useful in differentiating reactive epithelia from low‐grade dysplasia, but may prove useful in the diagnosis of high‐grade dysplasia.