A Novel Variant in Triple A Syndrome.

Triple A syndrome is an autosomal recessive inherited multisystem disorder that was first described in 1978. Triple A syndrome has a high genotypic and phenotypic heterogeneity and has been linked with mutations in the AAAS gene, which has been identified on chromosome 12q13. A 14 years old male patient applied to outpatient clinic complaining of weakness and darkening of skin color since 4 months. On physical examination hyperpigmentation was observed on both the skin and mucosa. The morning cortisol level was 1.8 µg/dL and ACTH was >1250 ng/L. Schirmer test showed absence of tears. In the patient's esophagoscopy, mucosal paleness and stenosis of the cardia were observed. Molecular genetic analysis of AAAS gene confirmed the diagnosis of triple A syndrome caused by homozygous mutation: c.1368_1372delGCTCA (p.Gln456HisfsTer38). This variant is considered to be a possible pathogenic because it causes a frame shift that changes the protein structure. As a result of the genetic analysis of the patient's parents, the AAAS gene was detected as heterozygous in both parents for the c.1368_1372delGCTCA mutation. To the best of our knowledge, this is the first report of homozygous mutation: c.1368_1372delGCTCA (p.Gln456HisfsTer38).

Bcl-2 proto-oncogene expression in low- and high-grade prostatic intraepithelial neoplasia.

OBJECTIVE: To determine the incidence of bcl-2 protein expression in low- and high-grade prostatic intra-epithelial neoplasia (PIN) lesions, and to explore the role of bcl-2 in prostatic tumorigenesis. Materials and methods Immunoreactivity for bcl-2 was examined in 10 samples of benign prostatic hyperplasia (BPH), 13 of primary prostatic adenocarcinoma, 15 of high-grade PIN and 18 of low-grade PIN. All immunostaining results were scored for the approximate percentage of positive tumour cells and relative immunostaining intensity (score range 0-12). RESULTS: In all BPH samples, bcl-2 staining was detected consistently in the basal cell layer of the ducts and acini, but no staining was ever apparent in luminal cells. The immunoreactivity for bcl-2 was heterogeneous in the prostatic carcinomas and bcl-2 protein expression was present in six samples. In these six bcl-2-positive tumours, the mean (range) staining score was 1.15 (1-6). There was detectable expression of bcl-2 in low- and high-grade PIN in all cell layers; immunoreactivity was present in 10 of 15 high-grade PIN lesions, with a mean (range) score of 1.14 (1-4), and in 12 of 18 samples of low-grade PIN, with a mean (range) score of 1.77 (1-6). CONCLUSIONS: The high incidence of bcl-2 protein expression in low- and high-grade PIN lesions suggests that bcl-2 protein expression is associated with early prostate tumorigenesis.

Testicular effects of vasectomy in rats: an ultrastructural and immunohistochemical study.

OBJECTIVES: The correlation between infertility and morphofunctional alterations following vasal occlusion is not clearly understood. Although a correlation has been found between the expression of a high titer of antisperm antibodies and the status of infertility, the relationship between the immunoglobulin (Ig) depositions in the testis and ultrastructural alterations of the peritubular structures has not been clearly established. The objective of this study is to explain the etiopathogenesis of diffuse and focal testicular lesions caused by vasal obstruction. METHODS: Unilateral vasectomy was performed on adult male rats. Ultrastructural changes of testicular tissues and immunostaining affinity of peritubular structures with anti-actin, anti-vimentin, anti-laminin, and anti-immunoglobulin G (anti-IgG) antibodies were analyzed. RESULTS: In an ultrastructural study, vasectomized animals presented abundant collagen fibril accumulation in the peritubular area. In testis with intense IgG antibodies, staining revealed weak immunostaining of peritubular myoid cells with anti-actin antibodies, but intense immunostaining with anti-vimentin antibodies. The tubules of rats with no IgG deposition on peritubular structures revealed intense immunostaining with anti-actin antibodies but scant immunostaining with anti-vimentin antibodies. Anti-laminin deposits decreased severely in most of the tubules demonstrating intense IgG deposition. CONCLUSIONS: Our findings suggest that spermatogenesis deteriorates more severely in testes with dense IgG deposition. The sclerosis of the lamina propria in cases with vasal occlusion is secondary to alterations in the peritubular myoid cells. With the progressive changes that occur in the peritubular myoid cells or differentiation of the peritubular myoid cells that acquire active cell characteristics, collagen accumulation adjacent to these cells increases markedly. The alterations of the peritubular myoid cells reported here may be caused by alterations in basement membrane structures.

Image-directed color Doppler ultrasonography of kidney in systemic lupus nephritis.

We evaluated intrarenal arterial waveforms with image-directed color Doppler ultrasonography in 21 patients with systemic lupus erythematosus (SLE). The systolic-diastolic ratio, resistive index, and pulsatility index were compared with serum creatinine levels, creatinine clearance, and quantitation of urinary protein excretion, as well as with histopathologic scores of specimens obtained from 9 patients who underwent renal biopsy. Doppler parameters were in the normal ranges in all patients, without showing significant correlation with any of the histopathologic scores or laboratory parameters except creatinine levels. We conclude that image-directed color Doppler ultrasonography is of no practical value in the evaluation of lupus nephritis during the early stages of the disease.

Angioimmunoblastic lymphadenopathy with disproteinemia arising in a patient with rheumatoid arthritis.

Angioimmunoblastic lymphadenopathy with disproteinemia (AILD) is a systemic lymphoproliferative disorder characterized by constitutional symptoms such as generalized lymphadenopathy, hepatosplenomegaly and skin rash. In this article, we report on a patient with seronegative Rheumatoid Arthritis of 18 years duration who recently developed AILD.