3-Diazopyrroles. Part 5 (1). Antibacterial activity of 3-diazo-2-phenylpyrroles.

3-Diazo-2-phenylpyrroles 3a-g showed antimicrobial activity against Gram-positive bacteria, whereas against Gram-negative strains the inhibitory activity is limited to derivatives 3a and 3c. The substituents at 4 and 5 positions strongly influence the inhibitory activity, but the presence of the diazo group is crucial for appearance of activity.     

Spontaneous circadian fluctuations of prostate specific antigen and prostatic acid phosphatase serum activities in patients with prostatic cancer

Summary Spontaneous circadian variations of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP), determined simultaneously by radioimmunoassay (RIA), were investigated by multiple sampling, over a 24-hour period, in 32 patients with prostatic cancer. In 29/32 patients (91%), the coefficient of variation of 24-hour values, for either marker, was greater than that of the RIA method at the same range of values; stage D patients showed the greatest spontaneous variability. Fluctuations around the mean of 24-hour values ranged from-65% to +85% for PAP, from-72% to +190% for PSA, occurring random and independently for each marker. Variability was about 20% greater for PSA than for PAP. The existence of spontaneous fluctuations should be considered in multiple marker evaluation of prostatic cancer patients.Preliminary results of this study have been presented at the International Symposium on Hormonal Therapy of Prostatic Diseases —Basic and Clinical Aspects, April 6–8, 1987, Milan, Italy     

Evoked potentials in patients with non-neurological Wilson's disease

Summary In Wilson's disease neurological manifestations result from the damage in the basal ganglia, even if a widespread degeneration of the brain occurs. The few studies performed using evoked potentials with the aim of identifying subclinical dysfunction in the three major sensory pathways have never shown abnormalities in patients without neurological manifestations. To verify this observation we studied 12 patients suffering from Wilson's disease in a pre-neurological stage by using pattern visual evoked potentials (VEPs), somatosensory evoked potentials (SEPs) to median nerve stimulation and brainstem auditory evoked potentials (BAEPs). Four of these patients had not yet been treated with penicillamine or trientine (triethylenetetramine dihydrochloride), while the remaining 8 patients were on treatment for at least 1 year. In 3 patients of this second group and in 1 patient of the first group we observed a significant (3 SD over the mean) increase in P100 wave latency, while SEPs and BAEPs were found to be abnormal in only 1 patient, respectively.     

Lead accumulation in the bones of aging male mice.

The lead content of mouse femurs increased by 83% between 76 and 958 days of age with values ranging from 0.192 to 1.78 ng Pb/mg dry weight. These values are remarkably lower than in previous reports for the lead content of bone. The lead content of mouse liver showed no aging-related trend with values ranging from 0.00823 to 0.0149 ng/mg dry weight. Bone density, calcium and collagen content were not related to the lead content. We conclude that while bone lead content is very low in mice, it increases with aging but does not appear to be related to the osteopenia which develops in the C57BL/6J male mouse.     

Superior Transseptal Approach for Surgical Removal of Left Atrial Myxoma

A bstract Eight patients (4 men, 4 women), mean age 51 years, referred to our Institution for left atrial myxoma underwent removal of the tumor through a superior transseptal approach. All patients in sinus rhythm with normal conduction time. The myxomas were localized in the fossa ovalis (3 cases), interatrial septum (2 cases), left appendage (2 cases), and mitral annulus (1 case). One patient died in hospital after emergency operation for low-output syndrome complicated by septic shock. All other patients had an uneventful postoperative course. Atrial arrhythmias did not represent a major postoperative complication. Transient PR interval elongation was occasionally seen. Electrophysiological studies showed normal sinus node function. At 6 months following operation, patients were evaluated with transeso-phageal echocardiography. There was no tumor recurrence. There were no episodes of arrhythmia in 24-hour electrocardiographic monitoring, and all patients were in NYHA Class I. We believe that the superior transseptal approach gives optimal exposure of the left atrial cavity, overcoming all difficulties related to a small left atrium which is an usual pattern in left atrial myxomas.     

Trimethylaminuria in a girl with Prader-Willi syndrome and del(15)(q11q13)

We report on an individual with trimethyl-aminuria, Prader-Willi syndrome, and del(15) (q11q13). To our knowledge, such an association has never been reported. Skin sores secondary to choline-rich foods and amenable to dietary control have not been described in trimethylaminuria, although they are seen in some patients with Prader-Willi syndrome. Pathogenesis, clinical diagnosis, and management of reported cases with trimethylaminuria are reviewed. Serious social and behavioral problems may result from strong body odor. Amelioration of the “fish odor” by dietary choline restriction makes trimethylaminuria detection important. Association of trimethylaminuria with Prader-Willi syndrome and del(15) (q11q13) in this patient is of particular interest. It may represent a contiguous gene syndrome, or deletion of the normal allele leading to expression of a single recessive trimethylaminuria gene, or an unrelated association, such as in Noonan syndrome. However, recent development of mapping of flavin-containing monooxygenase 2 (FMO2), the likely enzyme that is defective in fish odor syndrome, to chromosome 1q probably excludes pathogenetic association of fish odor syndrome with the Prader-Willi syndrome. © 1993 Wiley-Liss, Inc.     

Myocardial ANP expression in Pompe's disease: An immunohistochemical study

The expression of atrial natriuretic peptide (ANP) was analyzed in the atrial and ventricular myocardium in three cases of Pompe's disease (glycogen storage disease of the myocardium), using an immunoperoxidase technique. The cytoplasm of almost all atrial myocytes and some subendocardial myocytes from the right and left ventricles were ANP-positive, excluding the typical central vacuole, which was occupied by glycogen. Ventricular ANP expression was usually more prominent in left ventricular samples, and its distribution was similar to that described in dilated, hypertrophic, restrictive, or ischemic heart disease; however, the enlargement of the myocytes in Pompe's disease is not caused by hypertrophy. We conclude that the atrial myocytes in Pompe's disease maintain ANP expression, despite severe cytoplasmic vacuolization. These results suggest that ventricular ANP expression may be related to mechanical stimuli, such as the increase in wall stress, and not directly related to myocyte hypertrophy.     

Antibody for detecting p53 protein by immunohistochemistry in normal tissues.

AIMS--To establish whether PAb248 recognises human p53 as well as murine p53 and if so, to determine its distribution in normal tissues. METHODS--The ability of PAb248 to recognise human p53 was established by analysis of the human osteosarcoma derived Saos-2 cell line, which lacks the p53 gene, before and after transfection with p53 cDNA, using western blotting and immunoprecipitation. Immunostaining on normal tissues and cell lines was carried out using an immunoperoxidase technique. The two anti-p53 antibodies PAb 240 and DO-7 were used as controls. RESULTS--The anti-p53 PAb248 monoclonal antibody stained the Saos-2 cell line after, but not before, transfection with p53 cDNA. Both western blots and immunoprecipitations performed with this antibody revealed a 53,000 molecular weight band. With immunostaining, this antibody detects p53 protein in most lymphoid and human epithelial cells in a cytoplasmic-perinuclear localisation that has not been described before. In the same tissues nuclear staining could be seen in a few scattered cells using the PAb240 antibody. The topographical distribution of wild type p53 was not related to proliferating areas but, rather, to short-lived populations of cells. CONCLUSIONS--Immunostaining of wild type p53 is demonstrable not only in its nuclear form using antibody PAb240 but also in it common cytoplasmic-perinuclear localisation in normal tissues using the PAb248 monoclonal antibody. This opens up new possibilities for its study in both physiological and pathological conditions.