Differences in immune recognition of cytochrome P4502D6 by liver kidney microsomal (LKM) antibody in autoimmune hepatitis and chronic hepatitis C virus infection

LKM-1 antibody, which characterizes a subtype of autoimmune hepatitis (AIH), is also found in some patients with chronic hepatitis C virus (HCV) infection. It has been suggested that HCV initiates autoimmunity through molecular mimicry, because there is partial identity between HCV and cytochrome P4502D6 (CYP2D6), the putative target of LKM-1. Whether CYP2D6 is the target of LKM-1 in HCV-related liver disease, however, is controversial. To clarify this issue, we have studied by phage plaque assay and Western blot the reactivity to recombinant CYP2D6, isolated from a human liver cDNA library, in 55 patients with LKM-1, 18 (14 females, median age 12 years) anti-HCV-negative, with classical AIH, and 37 (27 females, median age 52 years) anti-HCV-positive. Reactivity to CYP2D6 was found in 72% of the anti-HCV-negative, but only in 27% of the anti-HCV-positive patients (P < 0.001), although immunofluorescence LKM-1 titres were similar in the two groups. In addition, to investigate whether the antibody responsible for the LKM-1 fluorescent pattern also reacts with CYP2D6, we have determined the specificity of LKM-1 antibodies present in the supernatant of lymphoblastoid B cell lines obtained from two patients with LKM-1-positive AIH. An oligo/monoclonal antibody thus generated gave both the typical fluorescent pattern and reacted with CYP2D6. Our results show that whilst antibodies producing the characteristic LKM-1 fluorescent pattern can react with CYP2D6, not all LKM-1-positive sera do so, particularly if obtained from patients with chronic HCV infection. This suggests that LKM-1 in HCV infection recognizes epitopes or antigens different from those targeted in AIH.     

TINEA VERSICOLOR: HISTOLOGIC AND ULTRASTRUCTURAL INVESTIGATION OF PIGMENTARY CHANGES

A comparative histopathologic study is made between the hypopigmented and hyperpigmented skin lesions of pityriasis versicolor and normal skin areas utilizing histochemical stains and electron microscopy. There were no differences found between the population of Dopa-positive melanocytes within the hypopigmented and hyperpigmented lesions and the normal skin areas. The total epidermal pigmentation was diminished in hypopigmented lesions. The keratin layer was found to be significantly thicker in hyperpigmented lesions and contained more organisms. In hypopigmented lesions, melanocytes contained fewer and smaller melanosomes and exhibited signs of degenerative cellular changes.     

Effect of paced cycle length on sinus node effective refractory period before and after autonomic blockade in patients with sick syndrome

Effect of basic paced cycle length on sinus node effective refractoryperiod was studied in 22 patients with sick sinus syndrome.Sinus node effective refractory period was measured using threedifferent paced cycle lengths before and after pharmacologicautonomic blockade. Sinus node effective refractory period couldbe measured at one cycle length, at least, in 59% of the patientsbefore blockade, however, it could be measured at two or morecycle lengths in only 18% of patients because of the chaoticresponse of sinus node against premature stimuli. It could bemeasured after pharmacologic autonomic blockade in 68% of thepatients at two or more paced cycle lengths. On the other hand,the rest of the patients showed no measurable sinus node effectiverefractory period at any cycle length, for their sinus nodeeffective refractory periods were shorter than their right atrialeffective refractory periods. The comparison of sinus node effectiverefractory period at different paced cycle lengths was unsuccessfulbefore pharmacologic autonomic blockade, while the refractoryperiod was significantly prolonged as cycle length was shortenedafter blockade. We concluded that (1) sinus node effective refractoryperiod in humans is prolonged as paced cycle length decreases,(2) the autonomic reflex is the major disturbing factor in measuringsinus node effective refractory period, and pharmacologic autonomicblockade can be usefully employed to eliminate a chaotic sinusnodal response, (3) when sinus node effective refractory periodis shorter than right atrial effective refractory period, ashorter paced cycle length should be used for definite measurementof the former.     

Echographic Detection of Latent Severe Thrombotic Stenosis of the Superior Vena Cava and Innominate Vein in Patients with a Pacemaker: Integrated Diagnosis Using Sonography, Pulse Doppler, and Color Flow

Thrombosis of the innominate vein and SVC is a serious complication in patients with pacemakers, inducing puhnonary embolism or SVC syndrome. Venography is the definitive method for its diagnosis; however, it is too invasive for related studies. The purpose of this study was to validate sonography, pulse Doppler, and color flow in detecting noninvasively innominate vein or SVC thrombosis in patients with pacemakers. In 53 patients with pacemakers, the 1 severe SVC stenosis and 18 severe innominate vein stenoses due to thrombosis were diagnosed by digital subtraction angiography. Sonography accurately showed the severe SVC stenosis due to thrombosis, but had limitations on the innominate vein thrombosis. Color flow demonstrated mosaic flow, indicating poststenotic turbulence due to stenosis of the innominate vein and SVC caused by thrombosis in 15 of 16 patients, and pulse Doppler disclosed absence of flow due to complete occlusion of the innominate vein in 2 of 2 patients. Sensitivity and specificity for detecting severe innominate vein stenosis due to thrombosis using combined color flow and pulse Doppler was 94% and 100%, respectively. In conclusion, sonography, pulse Doppler, and color flow allow accurate detection of severe innominate vein or SVC stenosis due to thrombosis, and are therefore useful for the follow-up of patients with a pacemaker.     

Determinant of QT Dispersion in Patients with Hypertrophic Cardiomyopathy

KAWASAKI, T., et al. : Determinant of QT Dispersion in Patients with Hypertrophic Cardiomyopathy. QT dispersion is thought to reflect a regional difference in repolarization process although QT interval is composed of depolarization and repolarization. This study was designed to investigate the effect of depolarization and repolarization on QT dispersion in hypertrophic cardiomyopathy. Standard 12-lead ECG was recorded in 70 hypertrophic cardiomyopathy patients with anteroseptal wall hypertrophy (HC-As), 8 patients with lateral wall hypertrophy (HC-L), 8 patients with diffuse hypertrophy (HC-D), and 46 normal controls. QRS, JTc, maximum and minimum QTc, and QTc dispersion were compared. The maximum QTc was greater in HC-As and HC-L than in the control; the minimum QTc was similar in all 3 groups; consequently, QTc dispersion was greater in HC-As and HC-L. In HC-D, the maximum QTc and the minimum QTc were greater than the control, which produced QTc dispersion similar to that in the control. JTc did not differ among 4 groups. In hypertrophic cardiomyopathy, both QTc and QRS duration were increased in the leads coinciding with the left ventricular portion of localized hypertrophy. We conclude that QTc dispersion depended on the heterogeneity of QRS duration or depolarization rather than repolarization, which in fact may be ascribed to the regionally different hypertrophy of the left ventricle in hypertrophic cardiomyopathy. (PACE 2003; 26[Pt. I]:819–826)     

Vasoactive intestinal peptide immunoreactive nerve fibres are deficient in intestinal and nasal mucosa affected by cystic fibrosis

Cystic fibrosis (CF) is the most common lethal or debilitating inherited disease amongst Caucasians, with estimates of its frequency of occurrence in this population ranging from 1: 2000 to 1: 15 000 live births. It is characterized by disorders of exocrine secretions, primarily of the skin, respiratory tract and digestive system. The secretory processes of these tissues are influenced by autonomic nerve fibres, many of which contain regulatory peptides. The innervation of the intestinal and respiratory mucosa of CF patients has been investigated in order to determine if there is any derangement of the peptide-containing nerve fibres that supply these tissues. The present work demonstrates that, in CF, there is a deficiency of vasoactive intestinal peptide immunoreactivity (VIP-IR) in nerve fibres in the nasal and intestinal mucosa. There is not a generalized loss of fibres that are immunoreactive for this peptide, however, since VIP-IR fibres innervating the intestinal muscle are largely unaffected. Moreover, other types of nerve fibres innervating the nasal mucosa and the mucosa of the intestinal villi appear to be unaffected in CF patients. Physiological evidence indicates that vasoactive intestinal peptide is contained in secretomotor neurons and is a powerful stimulant of secretion; loss of function restricted to these neurons is consistent with the clinical manifestations of CF.