4'-N-methyl-5'-hydroxystaurosporine and 5'-hydroxystaurosporine, new indolocarbazole alkaloids from a marine Micromonospora sp. strain

Two new indolocarbazole alkaloids, 4'-N-methyl-5'-hydroxystaurosporine (2) and 5'-hydroxystaurosporine (3), were isolated together with the known staurosporine (1) from the culture broth of a marine Micromonospora sp. (strain L-31-CLCO-002). The fermentation, structural data and cytotoxic activities of these compounds against various tumor cell lines are given.     

Chairman's introduction--the importance of good quality surveillance data today

The Alexander Project is a continuing, international, multicenter, longitudinal study of the antimicrobial susceptibility of pathogens commonly associated with community-acquired lower respiratory tract infections (LRTI). The study began in 1992 to provide high-quality surveillance data, comparable between regions and through time. As antimicrobial resistance becomes more prevalent, reliable surveillance data are required for clinical decision-making. Accurate current susceptibility data are required to predict clinical success through the determination of pharmacodynamic breakpoints. The Alexander Project provides the information required for clinicians to improve the likelihood of microbiological and clinical cure in the antibiotic treatment of LRTI.     

Unchanged cardiac angiotensin II levels accompany losartan-sensitive cardiac injury due to nitric oxide synthase inhibition

Chronic nitric oxide synthase (NOS) inhibition results in hypertension and myocardial injury. In a rapid and severe model of chronic NOS inhibition, we determined the role of angiotensin II in these effects by using angiotensin II receptor blockade and by measuring cardiac angiotensin II concentrations before and during development of cardiac damage. Rats received either no treatment, the NOS inhibitor Nomega-nitro-L-arginine (L-NNA; 500 mg/l), the angiotensin AT(1) receptor antagonist losartan (400 mg/kg chow), or L-NNA plus losartan for 21 days. In the second protocol, five groups of rats received L-NNA (500 mg/l) for 0, 4, 7, 14 and 21 days, respectively. L-NNA increased systolic blood pressure (SBP) (227+/-8 versus 143+/-6 mm Hg; P<0.01), heart weight index (0.44+/-0.02 versus 0.32+/-0.01; P<0.01) and induced coronary vasculitis and myocardial necrosis. Co-treatment with losartan prevented all changes. L-NNA during 4 days decreased cardiac angiotensin II (23+/-4 versus 61+/-15 fmol/g; P<0.05). Although after 7 days, fresh infarcts and after 14 days organized infarcts were present, cardiac angiotensin II was only slightly increased after 21 days (100+/-10 fmol/g; P<0.05). In conclusion, losartan-sensitive cardiac damage due to chronic NOS inhibition is not associated with primary increase of cardiac angiotensin II, suggesting that chronic NOS inhibition increases cardiac sensitivity for angiotensin II.     

The radiographic manifestations of bone changes in copper deficiency

The bone changes in infants with copper deficiency are typified by osteopenia and the symmetrical appearance of sickle-shaped metaphyseal spurs. Four examples are demonstrated and the differential diagnosis is extensively discussed.     

Protracted diarrhoea: Secondary monosaccharide malabsorption and zinc deficiency with cutaneous manifestations during total parenteral nutrition

Protracted diarrhoea in early infancy gives rise to many diagnostic and therapeutic problems. Jejunal biopsy often reveals villous atrophy of varying degrees. Severe reduction of small intestinal absorptive area causes secondary monosaccharide malabsorption, as well as secondary disaccharide deficiency, consequences which are relevant in any attempts at oral feeding. Morphologic, metabolic, endocrinological and microbiological studies have to be undertaken in order to establish a definitive diagnosis in protracted diarrhoea, but these studies often fail to reveal the aetiology of the disease. Immunologic abnormalities like phagocyte dysfunction, thymic atrophy and hypoplasia of B-cell regions in lymph nodes might be secondary events, but some types of immunodeficiency are of primary importance in the development of protracted diarrhoea. Total parenteral nutrition in many cases has to be instituted, with all its implications and hazards: septicaemia is the most dangerous of these. Zinc deficiency and acrodermatitis enteropathica may occur during total parenteral nutrition, and zinc deficiency secondarily contributes to the symptoms of diarrhoea. Parenteral administration of zinc is able to overcome these effects.     

Serum antibodies against gliadin and reticulin in a family study of coeliac disease

The familial occurence of coeliac disease is well known. In every day practice, however, diagnosis of coeliac disease is not frequently established in the relatives of patients. As it did not seem practicable to biopsy all relatives, several tests were investigated in selecting individuals for intestinal biopsy in a family study. 55 index patients out of 54 families with biopsy-proven coeliac disease and 165 of their first grade relatives underwent the study. Immunofluorescent gliadin and reticulin antibodies were determined, and additionally laboratory tests were done. These included haemoglobin, serum iron, serum protein and albumin, serum immunoglobulins and blood xylose. The immunofluorescent gliadin antibody assay using red cells coated with gliadin proved to be superior to the other methods. False negatives came to 8.7%, and false positives 10.9%, in healthy relatives. Gliadin antibodies could be found five times more frequently in healthy relatives than in normal controls. This finding indicates a genetic predisposition to the formation of gliadin antibodies in coeliac families.Ninety-one percent of index coeliac children had IgG-antigliadin in their sera while on a normal diet. During gluten-free diet, and in adult patients, results were less convincing. All relatives with antigliadin titres greater than 8 have been biopsied, and all with titres above 64 were shown to have coeliac disease. The prevalence of coeliac disease found in this study was 5.5%. In the active state of coeliac disease in children, gliadin antibody determination thus is a valuable diagnostic tool but in selecting relatives for biopsy there are limitations to the wide application of the test. Although reticulin antibodies are more specific for coeliac disease than gliadin antibodies, determination of antireticulin proved to be much less sensitive.Supported by Deutsche Forschungsgemeinschaft Gr 278/6 and Ste 305/1     

The activities of alanine aminopeptidase,leucine aminopeptidase,proline dipeptidase and prolyl dipeptidase in the mucosa of the small intestine

Alanine aminopeptidase (EC 3.4.11.2), leucine aminopeptidase (EC 3.4.11.1), proline dipeptidase (EC 3.4.13.9), and prolyl dipeptidase (EC 3.4.13.8) have been investigated in small intestinal mucosa homogenates of normal children and children suffering from different degrees of villous damage. The activities of proline dipeptidase and prolyl dipeptidase could be shown to be significantly decreased in cases of subtotal and total villous atrophy, whereas the activities of alanine aminopeptidase and leucine aminopeptidase were not influenced. The results are discussed in view of the subcellular distribution of these enzymes.     

Transfer factor and cellular immune response in urinary tract infections in children.

Cellular immune responses in vivo and in vitro were studied in 20 children with chronic or relapsing urinary tract infections. Skin tests revealed decreased immune responses to PPD in cases with chronic or recurrent pyelonephritis and to OM, in these cases and in cases of lower urinary tract infections. Blast transformation responses to PPD, OM and PHA were at least as high as in controls. Administration of chromatographically purified fraction from human leucocyte transfer factor resulted in a positive skin reaction with antigen concentration, which before TF administration had caused a negative reaction. The results suggest that the action of the transfer factor component used in this study is based on an immunologically nonspecific stimulation of the cellular immune response.     

Unusual bone involvement in congenital syphilis mimicking the battered child syndrome

Congenital syphilis is re-emerging in modern society. The pediatric radiologist may contribute to its early diagnosis. A case of unusual bone involvement with fracture of the olecranon and facial bone lesions is described; the condition had to be differentiated from the “battered child syndrome”. The problem of congenital syphilis as an infectious disease versus bone dystrophy is also discussed.