Enzyme replacement therapy on hypophosphatasia mouse model.

Hypophosphatasia (HPP) is an inborn error of metabolism caused by deficiency of the tissue-nonspecific alkaline phosphatase (TNSALP), resulting in a defect of bone mineralization. Natural substrates for this ectoenzyme accumulate extracellulary including inorganic pyrophosphate (PPi), an inhibitor of mineralization, and pyridoxal 5-phosphate (PLP), a co-factor form of vitamin B6. Enzyme replacement therapy (ERT) for HPP by functional TNSALP is one of the therapeutic options.

Long circulating enzyme replacement therapy rescues bone pathology in mucopolysaccharidosis VII murine model.

Mucopolysaccharidosis (MPS) type VII is a lysosomal storage disease caused by deficiency of the lysosomal enzyme β-glucuronidase (GUS), leading to accumulation of glycosaminoglycans (GAGs). Enzyme replacement therapy (ERT) effectively clears GAG storage in the viscera. Recent studies showed that a chemically modified form of GUS (PerT-GUS), which escaped clearance by mannose 6-phosphate and mannose receptors and showed prolonged circulation, reduced CNS storage more effectively than native GUS.

Columnar cell lesions: a consensus study among pathology trainees.

Columnar cell lesions of the breast are a spectrum of lesions in the terminal duct lobular units, which include columnar cell change, columnar cell hyperplasia, and columnar cell change or columnar cell hyperplasia with atypia. The latter was designated by the World Health Organization as flat epithelial atypia. We studied a group of pathology trainees (pathology residents and fellows) as a model for the impact of a training tutorial on the ability to distinguish various types of columnar cell lesions.

Basal-like breast carcinoma: a phenotypically distinct entity.

Gene microarray profiling of human breast carcinomas has recently categorized invasive breast carcinomas into 5 distinct subtypes; luminal A, luminal B, normal breastlike, human epithelial growth factor receptor 2 (HER2) overexpressing, and basal-like. Basal-like breast carcinomas are characterized by high expression of basal cytokeratins; low or absent expression of estrogen receptor, progesterone receptor, and HER2/neu; and expression of epidermal growth factor receptor (EGFR) and/or c-kit, and they are frequently associated with breast cancer 1 (BRCA1) mutations and poor clinical outcome. Recent studies have begun to provide insights into the molecular genetics, biology, morphology, and clinical outcome of this subtype of breast carcinoma.

Number of lymph nodes examined and associated clinicopathologic factors in colorectal carcinoma.

Context: Nodal metastasis is one of the most important prognostic factors in colorectal carcinoma. The number of lymph nodes recovered and examined in resection specimens has been recently shown to be critical for proper staging and is associated with survival.

Objective: To assess the clinicopathologic factors that may be associated with the number of lymph nodes harvested from surgical resections.

Metastatic prostatic carcinoma to testis: histological features mimicking lymphoma.

We report a case of prostatic carcinoma with testicular metastasis, which mimicked malignant lymphoma of the testis. The patient was a 71 year-old man with a history of prostate adenocarcinoma of Gleason score 9 (4+5) diagnosed in 2001 for which he received hormonal therapy. Four years later, the patient developed multiple osteoblastic bone metastases.

Colorectal adenocarcinoma with micropapillary pattern and its association with lymph node metastasis.

Micropapillary carcinoma has been reported as an aggressive variant of carcinoma in several organs, where it is associated with frequent lymphovascular invasion and poor clinical outcome. This study explored the clinicopathological features of colorectal adenocarcinoma with a micropapillary carcinoma component and compared them with those of conventional colorectal adenocarcinoma. One hundred seventy-eight consecutive cases of surgically resected colorectal carcinomas were studied for tumor size, type, depth of invasion, nodal and distant metastases, tumor stage, and percentage and extent of micropapillary component.

Sexually dimorphic roles of steroid hormone receptor signaling in gonadal tumorigenesis.

Sex steroids control cellular phenotypes by binding to receptor proteins that in turn regulate downstream gene expression. They are important tropic factors in hormonally responsive tissues and have been implicated in the pathogenesis of both benign proliferations and malignancies at some of these sites. Knockout mice lacking inhibins, alpha:beta heterodimeric peptide hormones of the TGFbeta superfamily, develop gonadal tumors that produce sex steroids and depend on pituitary gonadotropin hormones.

Normal reproductive function in InhBP/p120-deficient mice.

The inhibins are gonadal transforming growth factor beta superfamily protein hormones that suppress pituitary follicle-stimulating hormone (FSH) synthesis. Recently, betaglycan and inhibin binding protein (InhBP/p120, also known as the product of immunoglobulin superfamily gene 1 [IGSF1]) were identified as candidate inhibin coreceptors, shedding light on the molecular basis of how inhibins may affect target cells. Activins, which are structurally related to the inhibins, act within the pituitary to stimulate FSH production.

Loss of holocytochrome c-type synthetase causes the male lethality of X-linked dominant microphthalmia with linear skin defects (MLS) syndrome.

Girls with MLS syndrome have microphthalmia with linear skin defects of face and neck, sclerocornea, corpus callosum agenesis and other brain anomalies. This X-linked dominant, male-lethal condition is associated with heterozygous deletions of a critical region in Xp22.31, from the 5' untranslated region of MID1 at the telomeric boundary to the ARHGAP6 gene at the centromeric boundary.