The sites of gene expression of atrial, brain, and C-type natriuretic peptides in mouse fetal development: temporal changes in embryos and placenta.

Atrial (ANP), brain (BNP), and C-type natriuretic peptide (CNP) belong to a family of hormones important in blood pressure and sodium homeostasis. Expression of ANP has been reported in embryo hearts, but BNP and CNP expression during development has not been described. We used in situ hybridization to identify the sites of gene expression of ANP, BNP, and CNP during development in mouse embryos at daily intervals from midgestation. Very intense expression of ANP and BNP was visible in the heart from 9.5 days gestation; levels of expression of both peptides in the ventricle exceeded those in atria throughout gestation. There was a major peak of atrial and ventricular ANP and BNP expression at 12.5 days, attaining levels similar to those in adult heart and then declining until birth. Cardiac expression of CNP was undetectable. Expression of ANP and CNP was also observed in distinct sites in the brain, and all three peptides were expressed in the spinal cord. In mouse placenta, strong CNP expression was seen in the decidua basalis around the large maternal blood vessels, and BNP message was detected at the peripheral margin of the decidual layer. This pattern of expression indicates that ANP and CNP are present during development of the mouse central nervous system and suggests that CNP and BNP participate in regulating the maternal blood supply to the developing embryo.

Ovine brain natriuretic peptide in cardiac tissues and plasma: effects of cardiac hypertrophy and heart failure on tissue concentration and molecular forms.

Whereas numerous studies have examined the cardiac tissue content and secretion of atrial natriuretic peptide (ANP), the response of brain natriuretic peptide (BNP) in states of experimental cardiac overload is less well documented. Our recent partial cloning of the ovine BNP gene has enabled us to study changes in cardiac tissue concentration, together with tissue and circulating molecular forms of ANP and BNP, in response to cardiac overload induced by rapid ventricular pacing (n = 7) and aortic coarctation (n = 6). In normal sheep, although highest levels of BNP were found in atrial tissue (15-fold those of the ventricle), the BNP/ANP concentration ratio in the ventricles was 10- to 20-fold higher than the ratio calculated for atrial tissue. Compared with normal sheep, significant depletion of both ANP and BNP concentrations within the left ventricle occurred after rapid ventricular pacing. Size exclusion and reverse phase HPLC analysis of atrial and ventricular tissue extracts from normal and overloaded sheep showed a single peak of high molecular weight BNP consistent with the proBNP hormone. In contrast, immunoreactive BNP extracted from plasma drawn from the coronary sinus was all low molecular weight material. Further analysis of plasma BNP using ion exchange HPLC disclosed at least 3 distinct immunoreactive peaks consistent with ovine BNP forms 26-29 amino acid residues in length. These findings show that BNP is stored as the prohormone in sheep cardiac tissues and that complete processing to mature forms occurs at the time of secretion. The capacity to process the prohormone at secretion is not impaired by chronic heart failure.

Increased accuracy and precision of heparin and protamine dosing reduces blood loss and transfusion in patients undergoing primary cardiac operations.

Individual aspects of heparin or protamine dosing have been better controlled than previously as useful tests have become available. Although many variables including drug potency, drug source, and individual patient response have been separately identified, there has not been an attempt to integrate them into a single management strategy. This study was undertaken to learn whether more precise control of drug variables and patient response would affect blood loss and transfusion requirements. Adult patients having primary cardiac operations were prospectively randomized into two groups. A control group received heparin and protamine by conventional methods. The test group received heparin and protamine according to in vitro predictive tests integrating drugs, tests, and patient response. Supplemental protamine was given in this group only if heparin was specifically found by testing. Anticoagulation in all patients was maintained at an activated coagulation time greater than 400 seconds, and any other treatment for bleeding was at the discretion of the clinical team caring for the patients. Testing and treatment for both groups followed routine practice after patient arrival in the intensive care unit. Test patients received slightly more heparin and a markedly lower dose of protamine than the control patients. Testing identified patients with decreased heparin sensitivity (preoperative heparin therapy) and correctly predicted the effective heparin dose. Supplemental protamine was given twice as often to control patients and frequently when no heparin was detectable (retrospectively). Test patients exhibited less 24-hour chest tube drainage (671 ml versus 1298 ml) and fewer patients received transfusion (9/22 versus 18/24) with fewer donor exposures (22/22 versus 101/24). The management strategy used for heparin and protamine added accuracy and precision, which was associated with improved hemostasis. Although the observation is valid, the mechanism or mechanisms are not completely clear. Nevertheless, it is reasonable to apply basic pharmacologic principles and establishment of consistent, predictable protocols that are beneficial. It is against this background that the efficacy of additional drugs or equipment should be assessed. It is quite possible that only marginal if any improvement in hemostasis may be found in patients having primary, uncomplicated cardiac operation with the addition of more costly drugs or equipment.

The characterization of ovine genes for atrial, brain, and C-type natriuretic peptides.

The natriuretic peptides (NPs) play an important role in the homeostasis of blood pressure and sodium balance in all mammals studied to date. Their combined actions on the vasculature, kidneys, and adrenals reduce blood pressure and intravascular volume. In order to provide sequence information about the ovine NP genes for our physiological studies in sheep, we have determined the genomic DNA sequence of each of the NPs; atrial NP, brain NP (BNP), and C-type NP using an ovine genomic library. Strong homology with other species was found for ovine peptide and genomic sequences of atrial NP and for C-type NP. Further, despite previous reports of poor conservation of BNP across species, the peptide sequence for ovine BNP was found to be identical to both the 26 amino acid-residue porcine BNP, and the 35 amino acid peptide known as bovine aldosterone secretion-inhibitory factor. This data also revealed strong homology of BNP mature forms in dog, cow, pig, and sheep, thus permitting the use of porcine antisera to study BNP-level changes in sheep models of cardiac failure. This conservation of the BNP gene sequence suggests that BNP, like the other NPs, plays an important role in mammalian physiology.

[Grover's acantholytic dermatosis (transient acantholytic dermatosis) (author's transl)]. / Dermatose acantholytique de Grover. A propos de deux observations.

The authors report two cases of Grover's transient acantholytic dermatosis. These two cases exhibit some unusual features. Case no. 1 is that of a 39-year-old female with typical lesions on chest, neck, back and upper limbs. The course was cyclic with spontaneous regressions. This condition had been present for 4 years. Case no. 2 was that of a 46-year-old man with a large erythemato-squamous plaque of the left chest wall exhibiting a vesicular lining. In both instances the histologic findings revealed a picture similar to that of Hailey-Hailey's familial benign pemphigus. In spite of these unusual data, long duration and atypical clinical aspects, these two cases are consistant with the diagnosis of Grover's disease as evidenced by description found in the literature.

[Subcutaneous localizations of Castleman's pseudolymphoma. Review of the literature apropos of a case]. / Les localisations sous-cutanées du pseudo-lymphome de Castleman. Revue de la littérature à propos d'une observation.

The angiofollicular lymphoid hyperplasia, first described in 1954 by Castleman in the mediastinum, is a quite rare pseudolymphoma where there are few subcutaneous localizations. Since 1954, more than 300 observations were published including mediastino-pulmonary forms (about 60 p. 100 of the cases) intra-abdominal forms (15 p. 100 of the cases) and superficial forms which represent 25 p. 100 of the cases and associate superficial ganglionic, intra-muscular and subcutaneous localizations. The authors report the observation of a 44-year-old negro who had a subcutaneous tumefaction of the left elbow which appeared recently without a functional sign nor a biological change. The histological findings allowed the diagnosis of Castleman's pseudolymphoma in a hyalino-vascular form or Flendrig's type II. The evolution was marked a few weeks later by a local recurrence of which a second surgery has secured the recovery. The detailed study of the 76 cases of Castleman's superficial pseudo-tumours published in the literature allows us to recall the features of this disease which affects especially the young adult without prevalence of sex at about 25 years old. The circumstances of discovery are univocal, isolated palpable subcutaneous tumefaction in most of the cases. The localizations are distributed by decreasing incidence as following: latero-cervical, axillary, sus-clavicular, inguinal, vulvar, abdominal wall, shoulder, arm, forearm with a few bifocal forms. The histological aspect associated a predominant lymphoid population and vessels with fibro-hyalinous wall which morphological variations have permitted to individualize three forms: a plasmocytic form or Flendrig's type I which should be a stage of beginning often associated with hematological changes, a hyalino-vascular form or Flendrig's type II more frequent and a mixed form or intermediary type. The immunofluorescence, histo-enzymology and immunohistochemistry studies reveal a changeable polyclonal plasmocytosis and a predominance of T-suppressors in the lymphocytic population. The histological differential diagnosis of the superficial forms of the Castleman's pseudolymphoma is rarely set with certain lymphoma in case of ganglionic localization. On the other hand isolated subcutaneous localizations must be distinguished of the Kimura's disease and of the angiolymphoid hyperplasia with eosinophils where the vessels have a different morphology. The evolution is favorable in most of the cases and surgical exeresis insures the recovery.(ABSTRACT TRUNCATED AT 400 WORDS)

[Langerhans cell histiocytosis and myelomonocytic leukemia: a non-fortuitous association]. / Histiocytose langerhansienne et leucémie de la lignée myélomonocytaire: une association non fortuite.

BACKGROUND: Langerhans cell histiocytosis is an uncommon clonal disorder. Its reactional or genetic nature is debated. CASE REPORT: Three patients aged 71, 75 and 73 years with Langerhans cell histiocytosis also developed myelomoncytic leukemia (AML4, AML5, and chronic myelomonocytic leukemia). In two cases, there was no prior treatment which could potentially induce leukemia. In the third case, AML4 occurred shortly (10 months) after initiation of a vinblastin treatment. DISCUSSION: This pathogenic association suggests a common origin for these two conditions, corresponding to an anomalous pluripotent stem cell line. These cases provide further evidence favoring the hypothesis of a genetic origin rather than a reactional origin for Langerhans cell histiocytosis.

Nutrition and diabetes: putting guidelines into practice.

Dietary recommendations for the management of diabetes have changed over the past 10 years. There is now a reduced emphasis on the importance of carbohydrate in the diabetic diet. The first move away from carbohydrate restriction came in 1982 when the British Diabetic Association published its 'Dietary recommendations for diabetics for the 1980s'. This document suggested that the diet for people with diabetes should be based on a high intake of complex carbohydrate and fibre, with a restriction of fat intake. This article discusses the impact of these recommendations on different nutrients, and demonstrates, through the use of a case study, how these can be put into practice.

Direct monitoring of UV-induced free radical generation in HaCaT keratinocytes.

BACKGROUND: Ultraviolet radiation (UVR) is one of the most important aetiological factors in the development of skin cancer, with an estimated 100,000 new cases of nonmelanoma skin cancer (NMSC) diagnosed each year in the UK. To date, little work has been carried out to investigate the role of UVR in the increased production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) following exposure of skin cells to simulated solar UVR. AIM: To monitor directly the effects of simulated solar UVR on ROS and RNS generation in HaCaT keratinocytes. METHODS: This study reports the use of electrochemical monitoring techniques for the direct, real-time detection of two highly reactive free radical species, superoxide (O2-) and nitric oxide (NO), from HaCaT keratinocyte cells that had been exposed to a source of UVR designed to simulate the doses of UVA and UVB found in solar light. RESULTS: An increase in both O2- and NO generation was observed in HaCaT cells that had been exposed to UVR. No detectable increase in either species was observed in cells that had not been exposed to UVR. The specificity of the electrochemical methods for O2- or NO was confirmed through the scavenging or inhibition of these species. CONCLUSION: The findings of this study demonstrated that exposure of HaCaT cells to relatively low doses of UVR resulted in the immediate generation of both O2- and NO, therefore potentially leading to the downstream generation of highly damaging metabolites and the development of a number of pathologies, including cancer.

Optical image-forming system for T-type correlation antennas.

This paper describes an optical processor capable of forming real-time visible images of the radio sky directly from the output signals of a low-frequency T-type antenna array. Current modulator and light-valve technology could accommodate an array with 50-element crossbar and 25-element stem. Experimental confirmation of the correlator principle is described.

One-bit optical correlator.

A real-time optical correlator based on the principle of one-bit correlation, often used to facilitate the construction of real-time digital signal processors, is shown to have a greater immunity to mechanical noise than a comparable analog optical correlator. One-bit quantization also avoids some of the difficulties encountered with nonlinear light modulators. The one-bit optical correlator was studied by means of a computer simulation and an experimental system. Application of the technique to a multichannel correlator is discussed.