Bifunctional antibody: a binary radiopharmaceutical delivery system for imaging colorectal carcinoma.

In clinical studies we have evaluated a unique monoclonal antibody-based drug delivery system, a bifunctional antibody designed to deliver imaging or therapeutic agents, such as radioisotopes, drugs, or biologics, to tumor cells, while minimizing the dose to normal tissue. The bifunctional antibody, with one specificity to a tumor-associated antigen (carcinoembryonic antigen) and another specificity to a hapten, is injected and allowed to localize at a tumor site for 4 days. A hapten, tagged with a radioisotope, is subsequently injected for delivery to and capture by the prelocalized antibody at the tumor site. In studies reported here, the sulfhydryl groups of Fab' fragments of ZCE-025 and CHA-255 were linked with bis-maleimidomethyl ether to form an F(ab')2 bifunctional antibody coupled by a stable thioether linkage. EOTUBE, a hydroxyethylthiourido derivative of benzyl EDTA, was used as the hapten carrier of 111In. Fourteen patients 62-82 years old with recurrent or metastatic adenocarcinoma of the colon were studied. Twenty of 21 known lesions were imaged, and eight of nine new lesions were confirmed. With this fundamentally new approach to drug delivery, clearance from normal tissue is rapid, and high tumor:normal tissue ratios are expeditiously achieved.     

Carcinome lobulaire à cellules pléomorphes du sein. Difficultés diagnostiques: à propos d’un cas avec revue de la littérature

We report a case of a 27-years-old woman with a lesion at the right breast, incidentally noted. The patient underwent tumour resection followed by a right mastectomy type “Patey”. Microscopic analysis of the tumour had recognised an invasive pleomorphic lobular carcinoma. Invasive pleomorphic lobular carcinoma (PLC) is a distinctive aggressive subtype of invasive lobular carcinomas (ILC). It has the typical infiltrating pattern of classical ILC of diffuse single cell spread but the nuclei aremore pleomorphic. Histological differential diagnosis with ductal carcinoma may be difficult, but it is important for this difference to be done. E-cadherine is a trans-membrane glycoprotein, typically expressed in ductal carcinoma, and loss of E-cadherine expression characterises invasive and in situ lobular carcinoma.     

New mutations of Darier disease in Tunisian patients

Darier’s disease (DD, MIM 124200) also known as Darier-White disease and keratosis follicularis, is a rare autosomal dominant skin disorder characterized by warty papules and plaques in the seborrheic area (central trunk, flexures, scalp, and forehead). Pathogenic mutations in the ATP2A2 gene encoding the sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase (SERCA) 2 gene underlie the disease. In the present study, we performed genetic investigation of three unrelated Tunisian families affected by DD. Mutation screening was performed by direct sequencing of the coding region and exon/intron boundaries of the ATP2A2 gene. Patients in the 3 studied families exhibited classical DD phenotype. DD was associated with neurological and cardiac disorders in one family. Two novel mutations were identified: a missense mutation (R559Q) and a frameshift mutation (1713-1714 del 2A). Both pathogenic mutations are located in exon 13 of the ATP2A2 gene and affected the ATP-binding site of the SERCA2 protein. In one family, no mutation was found within the coding region and exon/intron boundaries of the ATP2A2 gene. Our findings provide further evidence for the genetic heterogeneity of DD in Tunisia and that most mutations involved in this disease are family specific.     

Acute myocarditis and myocardial infarction induced by Paraphenylenediamine poisoning. Interest of angiocoronarography

We present 2 cases of myocardial damage induced by Paraphenylenediamine (PPD) poisoning in young patients without any history of cardiovascular disease. ECG findings revealed the presence of localized ST segment elevation in precordial leads (V1-V4) in the first case and (V3-V6) in the second associated to an increase of the serum troponine T level at 23 ng/ml (case 1) and 29.7 ng/ml (case 2). The transthoracic echocardiography was in favour of diffuse myocarditis in the first case and of localized myocarditis or septo-apical myocardial infarction in the second. The angiocoronarography performed for the first time in the second case conclude on a septo-apical hypokinesia of the left ventricular resulting of a coronary spasm of the anterior interventricular artery.     

Mouse primase initiation sites in the origin region of simian virus 40.

The sites of initiation of DNA synthesis by purified mouse DNA primase in the origin-of-replication region of simian virus 40 (SV40) were examined. Using as template the separated strands of a cloned fragment of SV40 approximately equal to 300 base pairs (bp) long that includes the origin, we observed specific sites of initiation on the two strands. On the early strand that is the template for early mRNA synthesis, the primary starts are at four positions within 10 nucleotides of each other around nucleotide 5215 and an additional site around nucleotide 5147 that is used at one-sixth the frequency of the major sites. The major start sites on the early strand are within the 65-bp minimal origin of replication and lie between tumor antigen binding sites I and II. On the late strand that is the template for late mRNA synthesis, six major initiation sites were observed, each within the 3' C-C-C-G-C-C 5' sequence in the template that is repeated twice within each of the three 21-bp repeats that lie adjacent to the minimal origin, on its late side. A 6-bp deletion in the 65-bp minimal origin that eliminates its function as an origin reduced the major initiations around nucleotide 5215 on the early strand by 90% but did not affect initiations at the minor start site on the early strand or initiations on the late strand. Mouse DNA primase is able to recognize specific regions on the SV40 DNA. Those on the early strand are within the minimal origin of replication and those on the late strand are within the 21-bp repeat region necessary for maximum replication.     

Non-specific interstitial pneumonia (NIP): diagnosis and prognosis

The non-specific interstitial pneumonia (NIP) is an idiopathic diffuse interstitial pneumonia. It is recently reported by Katzenstein and Fiorelli in 1994. The clinical features are mild comparing with usual interstitial pneumonia and its histological features include a predominant degree of interstitial inflammation and a rare areas of honey combing, the lesions are temporally uniform. We reported a case of 32 year-old woman with non-specific interstitial pneumonia. The diagnosis was based on histological criteria. The authors discuses the diagnosis and the prognosis of this recent entity.     

The effects of ACTH on steroid metabolomic profiles in human adrenal cells

The adrenal glands are the primary source of mineralocorticoids, glucocorticoids, and the so-called adrenal androgens. Under physiological conditions, cortisol and adrenal androgen synthesis are controlled primarily by ACTH. Although it is well established that ACTH can stimulate steroidogenesis in the human adrenal gland, the effect of ACTH on overall production of different classes of steroid hormones has not been defined. In this study, we examined the effect of ACTH on the production of 23 steroid hormones in adult adrenal primary cultures and 20 steroids in the adrenal cell line, H295R. Liquid chromatography/tandem mass spectrometry analysis revealed that, in primary adrenal cell cultures, cortisol and corticosterone were the two most abundant steroid hormones produced with or without ACTH treatment (48 h). Cortisol production responded the most to ACTH treatment, with a 64-fold increase. Interestingly, the production of two androgens, androstenedione and 11β-hydroxyandrostenedione (11OHA), that were also produced in large amounts under basal conditions significantly increased after ACTH incubation. In H295R cells, 11-deoxycortisol and androstenedione were the major products under basal conditions. Treatment with forskolin increased the percentage of 11β-hydroxylated products, including cortisol and 11OHA. This study illustrates that adrenal cells respond to ACTH through the secretion of a variety of steroid hormones, thus supporting the role of adrenal cells as a source of both corticosteroids and androgens.     

Granulocytic sarcoma of the rectum: Report of one case that presented with rectal bleeding

Granulocytic sarcoma is an uncommon and localized extramedullary tumor composed of immature granulocytic cells. It may present in association with acute myeloid leukaemia, myelodysplastic syndrome and chronic myelogenous leukaemia. Granulocytic sarcoma may occur in any anatomical site but involvement of the gastrointestinal tract is rare, especially in the rectum. We report on the case of a 17 year old female who presented with rectal bleeding, abdominal pain and weight loss one mo prior to admission. Rectosigmoidoscopy revealed a rectal polypoid and ulcerated mass. The histological examination of the mass showed granulocytic sarcoma. Bone marrow examination was compatible with acute promyelocytic leukaemia (FAB type M3). This case report is a reminder of this peculiar sign of tumoral syndrome in acute myeloid leukaemia. We also discuss diagnostic methods and analyze the disease course.     

Evaluation of fine needle aspiration cytology in the diagnosis of cervical lymph node lymphomas

Purpose

Surgical biopsy examination is the gold standard for the diagnosis of lymph node lymphomas. Fine-needle aspiration cytology (FNAC) is a quick and safe method in the management of cervical lymph nodes. Its value in confirming recurrent or residual lymphoma is well established. However, its role in the primary diagnosis of lymph node lymphoma remains controversial. The aim of this study was to assess, in our experience, the reliability of FNAC in the diagnosis of cervical lymph node lymphomas.

Prognostic value of human erythrocyte acetyl cholinesterase in acute organophosphate poisoning

Acute organophosphate poisoning (OPP) such as dichlorvos may be monitored by the measurement of the erythrocyte acetyl cholinesterase (EAChE) and the serum cholinesterase (SChE) activities. The aim of this study was to look at correlation between the severity of the OPP judged by certain parameters such as coma, hemodynamic disturbances, respiratory failure, and the decrease of cholinesterases enzymes including EAChE and SChE at admission. Cholinesterase activity was determined upon admission and then on days 3 and 15 in the morning. Clinical effects, EAChE, and SChE activities data were investigated in 42 patients with OPP aged of 29.6 +/- 11.8 years with acute cholinergic crisis in all cases. They were comatose in 29% of cases, presenting both hypotension or shock and hypoxemia in 17% of cases. Fifteen of them (36%) required mechanical ventilation. The mean EAChE activity at admission was 24.3 +/- 11.6 micromol/mL per hour at 37 degrees C; it was 1260 +/- 2204 IU/L for SChE. There were no correlations between the EAChE and the SChE activities. The EAChE was decreased only in comatose patients and those presenting hypotension, hypoxemia, and bradycardia with a cutoff of 23.5 micromol/mL per hour at 37 degrees C. Death was observed in 2 patients with a deep decrease of the EAChE at 5 micromol/mL per hour at 37 degrees C in 1 case and 9 micromol/mL per hour at 37 degrees C in another. The kinetics of improvement of the EAChE activity below the cutoff showed the absence of statistical improvement of the EAChE activity on day 3 (16.6 +/- 9 vs 19.5 +/- 5.7 micromol/mL per hour at 37 degrees C); this improvement was remarkable on day 15 (16.6 +/- 9 vs 27.5 +/- 6.5micromol/mL per hour at 37 degrees C, P = .0004). In summary, the marked decrease of EAChE activity appears in this study as prognostic factor in acute OPP, and coma, respiratory failure, hemodynamic disturbances, and death are associated with a decrease of the EAChE of less than 23.5 micromol/mL per hour at 37 degrees C.