Synpolydactyly (type II syndactyly) with aplasia/hypoplasia of the middle phalanges of the toes: Report on a family with eight affected members in four generations

We describe a new family with synpolydactyly (syndactyly type II) with 8 affected members in 4 generations. Aplasia/hypoplasia of the middle phalanges of the toes was also noted. In our opinion, this anomaly represents a frequent manifestation of synpolydactyly. No other major skeletal or extraskeletal malformations were present. © 1995 Wiley-Liss, Inc.     

A novel genetic locus for low renin hypertension: familial hyperaldosteronism type II maps to chromosome 7 (7p22)

Familial hyperaldosteronism type II (FH-II) is caused by adrenocortical hyperplasia or aldosteronoma or both and is frequently transmitted in an autosomal dominant fashion. Unlike FH type I (FH-I), which results from fusion of the CYP11B1 and CYP11B2 genes, hyperaldosteronism in FH-II is not glucocorticoid remediable. A large family with FH-II was used for a genome wide search and its members were evaluated by measuring the aldosterone:renin ratio. In those with an increased ratio, FH-II was confirmed by fludrocortisone suppression testing. After excluding most of the genome, genetic linkage was identified with a maximum two point lod score of 3.26 at θ=0, between FH-II in this family and the polymorphic markers D7S511, D7S517, and GATA24F03 on chromosome 7, a region that corresponds to cytogenetic band 7p22. This is the first identified locus for FH-II; its molecular elucidation may provide further insight into the aetiology of primary aldosteronism.


Keywords: chromosome 7; aldosterone; familial hyperaldosteronism type II; hypertension     

Clinical and biochemical analysis of two families with type I and type II mannosidosis

We report on two unrelated patients with different presentations of mannosidosis. One patient was affected in early childhood with a severe phenotype characteristic of type I mannosidosis. The other was diagnosed with type II mannosidosis only after the onset of progressive neurologic deterioration in late adulthood. Both were detected by non-invasive urinary screening of oligosaccharides. Lymphoblasts transformed from both patients' blood cells had markedly reduced lysosomal α-mannosidase activity. Kinetic analyses showed that α-mannosidase from the type I patient had a 400-fold reduction in affinity while that from the type II patient was reduced 40-fold. Lymphoblasts from all 4 parents had reduced α-mannosidase activity, but there were overlapping activities among these type I and type II obligate heterozygotes. We conclude that screening urinary oligosaccharides will detect mannosidosis over a wide range of phenotypes, that lymphoblasts transformed from affected heterozygotes have decreased enzymatic activity, and that the severity of clinical expression is related to the degree of enzyme impairment. © 1995 Wiley-Liss, Inc.     

Delayed diagnosis of familial hypercholesterolemia: A case report of two patients from Egypt

Two young Egyptian women with homozygous familial hypercholesterolemia (HoFH) were diagnosed after the appearance of vascular complications despite the presence of family history and suggestive clinical features. The first patient was treated by repeated surgical excisions of disfiguring tendon xanthomas diagnosed as “lipomas”. The second patient, presenting with embolic ischemia, had an amputation of the forearm and repeated reconstructive surgical procedures. Each patient was diagnosed as HoFH after presenting with typical angina to a cardiologist. The first patient had severe aortic stenosis, left main and multi-vessel coronary artery disease, and died at age 21 years. The second patient had multivessel coronary artery disease that was treated by Percutaneous Coronary Intervention (PCI) with drug-eluting stents. These cases demonstrate that the delayed diagnosis of xanthomas and familial inheritance characteristic of HoFH leads to atherosclerosis and aortic stenosis early in life.     

Effect of an angiotensin II type 1 receptor blocker on caveolin-1 expression in prostate cancer cells

Introduction

Caveolin-1, the major structural protein of caveolae, interacts directly with the AT1 receptor. The biological functions of caveolin-1 in cancer are compound, multifaceted, and depend on cell type, tumour grade and cancer stage. The AT1-R-caveolin complex in caveolae may coordinate angiotensin II (Ang II) induced signalling. The aim of this study was to determine the effect of the angiotensin II receptor type 1 blocker candesartan on caveolin expression in human metastatic prostate adenocarcinoma cells PC-3.

Material and methods

WST-1 and BrdU assays were used as indicators of cell viability and proliferation after angiotensin II and/or candesartan stimulation. Real-time RT–PCR and western blot were used to study the effect of Ang II and/or candesartan on the expression of Cav-1 and AT1-R in PC-3 cells

Results

We found that the expression of caveolin-1 mRNA in the PC-3 cells treated with CV was significantly decreased in comparison with the control (2.9 ±0.17, 4.7 ±0.6, p < 0.05), whereas a higher caveolin-1 mRNA expression was observed in those after Ang II treatment (6.0 ±0.43, 4.7 ±0.6, p < 0.05). Protein analysis indicate that the expression of caveolin-1 protein in the PC-3 cells treated with candesartan was significantly decreased when compared with the control (0.69 ±0.05, 1.6 ±0.12, p < 0.05), whereas higher caveolin-1 protein expression was observed after Ang II treatment (2.5 ±0.20, 1.6 ±0.12, p < 0.05).

Conclusions

These results provide new information on the action of candesartan and may improve the knowledge about AT1 receptor inhibitors, which can be potentially useful in prostate cancer therapy.     

Cribriform adenocarcinoma of minor salivary gland: A report of two cases with an emphasis on cytology

Cribriform adenocarcinoma of minor salivary gland (CAMSG) is a recently characterized low grade salivary gland malignancy that most commonly presents as a mass in the base of the tongue, frequently with regional lymph node metastasis. Given its relative rarity and overlapping cytomorphology, CAMSG may be confused with polymorphous low grade adenocarcinoma (PLGA) in minor salivary gland sites and papillary thyroid carcinoma (PTC) in cervical metastasis, in both fine‐needle aspiration and excisional specimens. As there are no cytology reports in the literature, we present two new cases of CAMSG and describe the aspiration cytology of the tumor taken from bench top aspirates, compare it with the histomorphology, and discuss the features that may help one avoid misdiagnosis of PTC in the setting of cervical lymph node metastasis. We found that like PTC, aspirates of CAMSG contain polymorphic fragments of epithelial cells arranged in monolayer sheets, papillary fronds and tips, and occasional cribriform configurations, and metachromatic stromal fragments, which may be misinterpreted as colloid. A background of myxoid/mucoid material also reminiscent of colloid was prominent. Differentiation from PLGA is more difficult based strictly on cytology. A review of the most current literature in relation to the molecular and immunohistochemical profiles, therapeutic options, and prognosis is also presented. It is critical for pathologists and clinicians to be aware of this tumor when presented with patients having a cervical lymph node mass in the absence of a primary tumor. Diagn. Cytopathol. 2014;42:1085–1090. © 2014 Wiley Periodicals, Inc.     

Papillary adenocarcinoma of lung with psammoma bodies: report of a case derived from type II pneumocytes

A 52-year-old woman underwent thoracotomy for the removal of a mass in the middle lobe of the right lung. Light microscopy showed a tumour with the morphology of a papillary adenocarcinoma with numerous psammoma bodies. Electron microscopy revealed the tumour cells to possess the lamellated intracytoplasmic inclusions characteristic of normal and neoplastic type II pneumocytes. Psammoma bodies have not previously been reported in type II cell carcinoma of the lung. Alveolar cell carcinoma should be considered in the differential diagnosis of a papillary adenocarcinoma with psammoma bodies occurring in the lung.     

Two unrelated families with variable expression of Fraser syndrome due to the same pathogenic variant in the FRAS1 gene

We report on two unrelated families of Polish origin with variable expression of Fraser syndrome (FS; MIM#219000) due to homozygosity for the same pathogenic variant, c.6963_6964dup, of FRAS1. In one family, the disorder presented with perinatal and prenatal lethality. One affected female from family 2 who was followed‐up for 32 years, represented a relatively favorable long‐term outcome. She displayed the typical craniofacial dysmorphism, including right cryptophthalmos, cutaneous syndactyly, abnormalities of the stomathognatic system, bilateral atresia of the external ear canals resulting in conductive hearing loss, and malformations of the larynx, spleen, kidney, and genitourinary tract. Her intellectual capacities were normal. Our observations illustrate that expression and severity of FS, even when caused by the same pathogenic variant, may be quite different ranging from a lethal disorder to a condition with multiple physical malformations but normal psychomotor development. In addition, we propose that the FRAS1 c.6963_6964dup variant may be a founder mutation in the Polish population. Therefore, it would be reasonable to test specifically for this variant first in any FS1 patient of Polish ancestry.     

The effect of treatment with interferon-gamma on type II collagen-induced arthritis.

We have investigated the effects of recombinant murine interferon-gamma (rIFN-gamma) on type II collagen-induced arthritis (CA) in DBA/l mice. Therapeutic as well as prophylactic treatment with subcutaneous rIFN-gamma, at 10(5) U/mouse six times a week, inhibited the development of CA without any obvious side effects. The accompanying suppression of anti-CII antibody responses may partly explain the inhibition of CA by rIFN-gamma. The possible role of the anti-inflammatory effect of systemic IFN-gamma in the inhibition of CA is discussed.     

CD34 and microtubule-associated protein 2 expression in dysembryoplastic neuroepithelial tumours with an emphasis on dual expression in non-specific types

Sung C O, Suh Y‐L & Hong S‐C
(2011) Histopathology 59 , 308–317 CD34 and microtubule‐associated protein 2 expression in dysembryoplastic neuroepithelial tumours with an emphasis on dual expression in non‐specific types Aims: Three histological variants of dysembryoplastic neuroepithelial tumour (DNT) have been described, namely, simple, complex and non‐specific. However, the concept of non‐specific variants of DNT remains controversial, because they cannot be accurately distinguished by histological findings alone from ordinary gliomas. The aim was to characterize further the non‐specific histological forms of DNT. Methods and results: Forty‐one DNTs classified as three histological forms were investigated with CD34 and microtubule‐associated protein 2 (MAP2) immunohistochemistry. CD34 immunoreactivity was more frequently observed in non‐specific DNT types (16/18 cases; 88.9%) than in classic types (6/23 cases; 26.1%) (P < 0.001). Peritumoral CD34 expression of non‐neoplastic cells was significantly associated with CD34‐positive tumours (20/22 cases; 90.9%) than with CD34‐negative tumours (3/19 cases; 15.8%) (P < 0.001). MAP2 positivity in oligodendroglia‐like cells or glial elements was significantly different between classic types and non‐specific types (P = 0.025). CD34 and MAP2 immunoreactivities were significantly more frequent in non‐specific types (83.3%) than in simple (10%) and complex forms (30.8%) (P < 0.001). Conclusions: Non‐specific DNTs are glioneuronal tumours that have a heterogeneous population of cells with more immature neuronal and glial phenotypes. Furthermore, with regard to practical implications, combined analysis of CD34 and MAP2 is useful in distinguishing DNTs from particularly diagnostically challenging mimics.     

Oro-facial-digital syndrome II. Transitional type between the Mohr and the Majewski syndromes: report of two new cases

Two patients with the oro-facial-digital syndrome II or Mohr syndrome presented laryngeal anomalies and hallucal and postaxial polysyndactyly of the feet. Those rare malformations are typically observed in patients with the Majewski syndrome, a lethal, short rib-polydactyly skeletal dysplasia with orofacial findings almost identical to those of the Mohr syndrome. Phenotypic overlap between the Mohr and the Majewski syndromes has already been reported in the literature, and it has been suggested that the two syndromes may be mild and severe expressions of the same autosomal recessive disorder. Our two cases give further support to this hypothesis.     

口服鸡II型胶原治疗大鼠实验性类风湿性关节炎的研究

本文研究口服鸡II型胶原 (CCII)治疗大鼠类风湿性关节炎的作用。以CCII和完全弗氏佐剂免疫Wistar大鼠 ,建立大鼠的类风湿性关节炎 (RA )模型。用CCII进行口服 ,观察实验组和对照组动物关节炎的发病程度。并以ELISA法对发病大鼠血清中的抗CCII抗体的水平进行检测。结果表明 ,口服CCII可以减轻大鼠关节炎的发病程度。其中口服 6μg、 60 μgCCII的实验组大鼠关节炎指数均较对照组明显减低 ,且差异有显著性意义 (P <0 0 1;P <0 0 5 )。而口服 60 0 μgCCII的实验组大鼠关节炎指数虽较对照组大鼠降低 ,但二者相比 ,无显著性差异 (P >0 0 5 )。ELISA检测结果显示 :口服低剂量 (6μg和 60μg )可溶性CCII对大鼠体内抗CCII抗体的产生有一定的抑制作用。口服CCII对关节炎大鼠的发病程度有较明显的抑制作用 ,为应用口服耐受治疗RA等自身免疫性疾病提供了实验基础     

Co-existence of Hashimoto's thyroiditis with familial Mediterranean fever: is there a pathophysiological association between the two diseases?

Familial Mediterranean fever is an autosomal recessive disease characterized by periodic attacks of fever and polyserositis, while Hashimoto's thyroiditis is the most common cause of hypothyroidism. We suggest that common autoimmune mechanisms may underlie both disorders, describe their clinical co‐existence in a patient, and discuss a possible causal link between them.     

Achondrogenesis: A review with special consideration of achondrogenesis type II (langer-saldino)

We describe two dwarfed infants with large head, short neck and chest, prominent abdomen, and short limbs. Both died neonatally. Radiographic and morphologic characteristics identified the Langer-Saldino form of achondrogenesis (type II). Review of type II achondrogenesis documented distinctive clinical and anthropometric manifestations (fewer stillbirths, longer survival time and gestational period, larger size of the baby, longer limbs, and characteristic craniofacial features) as compared with type I achondrogenesis (Parenti-Fraccaro).     

Nasal glomus tumors: report of two cases with emphasis on immunohistochemical features and differential diagnosis.

We describe 2 cases of nasal glomus tumor that presented as nasal polyps. Grossly, each of the polypectomy specimens consisted of small fragments of polypoid soft tissue with glistening mucosa. Histopathological examination of each of the specimens showed sheets and nests of monomorphic round cells intimately associated with capillary-sized blood vessels. The tumor cells were strongly cytoplasmic positive for vimentin, smooth-muscle specific actin, muscle-specific actin, and CD34. Collagen IV showed pericellular positivity. Nasal glomus tumors are extremely rare and represent less than 0.5% of nasal nonepithelial tumors. Nasal polyps are common surgical pathological specimens, with the majority of nasal polyps being inflammatory polyps or a respiratory epithelial proliferation. Histologically, many nasal polyps show vascular proliferation with an inflammatory cell infiltrate, which may be confused with the rare glomus tumor. In addition, other nasal vascular tumors, in particular nasal hemangiopericytoma and neural tumors, may histologically mimic nasal glomus tumors.     

Insulin-like growth factor II mRNA-binding protein 3 (IMP3) expression in hepatocellular carcinoma. A clinicopathological analysis with emphasis on diagnostic value

Wachter D L, Kristiansen G, Soll C, Hellerbrand C, Breuhahn K, Fritzsche F, Agaimy A, Hartmann A & Riener M‐O
(2012) Histopathology  60, 278–286
Insulin‐like growth factor II mRNA‐binding protein 3 (IMP3) expression in hepatocellular carcinoma. A clinicopathological analysis with emphasis on diagnostic value Aims: Patients with hepatocellular carcinoma (HCC) usually present with advanced disease and rarely qualify for curative therapy. Immunohistochemical markers that help to discriminate benign from malignant processes early, and that have prognostic significance, would be useful. Expression of the oncofetal protein insulin‐like growth factor II mRNA‐binding protein 3 (IMP3) in malignant cells of different tumour types correlates with reduced overall survival. Methods and results: Tissue microarrays (TMAs) containing 55 normal liver samples, 365 HCCs (122 with corresponding non‐tumorous liver), 10 hepatocellular adenomas, 13 focal nodular hyperplasias and nine dysplastic nodules from western European patients were stained for IMP3. IMP3 was analysed in 61 core needle biopsies and findings were compared to glypican‐3 and CD34. HCCs in TMAs were strongly positive for IMP3 in 18.4% of cases compared to absent expression in normal and non‐tumorous liver tissue and benign liver tumours. Patients with IMP3 expression in HCCs showed significantly poorer overall survival in multivariate analysis (P = 0.044). Of the 61 core needle biopsies analysed, 32 (52.5%) of the HCCs were IMP3‐positive. Conclusions: In core needle biopsies, IMP3 expression seems to be of limited use as a single marker for the diagnosis of HCC, given a sensitivity of 52%, but it may be helpful in combination with other markers.     

Inflammatory fibroid polyp of the ileum causing intussusception: report of two cases with emphasis on cytologic diagnosis

Inflammatory fibroid polyp (IFP) of the gastrointestinal tract is a type of inflammatory pseudotumor or inflammatory myofibroblastic tumor that occurs most commonly in the stomach but also in the small and large bowel. Small-bowel IFP usually presents with intussusception. The purpose of the current study is to describe cytological features of this lesion with differential diagnoses since pathologists may be called on to render a diagnosis on fine-needle aspiration. Two cases of IFP are described with diagnostic features on imprint smears. Both were middle-aged obese women with a history of prior intra-abdominal surgical procedures who presented with signs of intestinal obstruction and were found to have a tumor causing intussusception. At intraoperative consult, scrape cytology specimens showed cellular smears with a heterogeneous population of myofibroblasts, inflammatory cells and vessels. The features together with clinical history are sufficient to suggest the diagnosis. IFP is a lesion with a characteristic morphology. The differential diagnosis includes several other lesions, hence triage of cytological specimen for culture, electron microscopy, and immunohistochemistry is important in facilitating a correct diagnosis. Although a surgical procedure may still be necessary once a diagnosis of IFP is made, treatment may be tailored for a less aggressive process.