Recurrent bronchopneumonia and Morgagni hernia

The Morgagni hernia occurs behind the sternum and is a rare diaphragmatic defect although the late diagnosis may result in important clinic symptoms and poor prognosis. The authors present a case report of a child with 11 months and respiratory symptoms with chronic pulmonary infections and several hospitalizations without etiologic diagnosis. The conclusion was for the early Morgagni hernia diagnosis and the prevention of chronic complications.     

Age at starting smoking and number of cigarettes smoked in Catalonia, Spain

BACKGROUND: Few studies have investigated the association between age at starting smoking and the average number of cigarettes smoked per day in adulthood. To provide further evidence on this issue, we analyzed data from the Catalan Health Interview Survey (CHIS). METHODS: The CHIS was conducted in 1994 on a randomly selected sample (N = 15,000) of the population of Catalonia, Spain. A total of 4,897 current or exsmokers (3,276 males and 1,621 females) were included for analysis. Age-standardized proportions of subjects smoking <15, 15-24, and >/=25 cigarettes/day, age-standardized mean number of cigarettes smoked per day, and multivariate odds ratios (OR) of being a heavy smoker (>/=25 cigarettes/day) according to age at starting smoking (<15, 15-17, 18-19, >/=20 years) were computed. RESULTS: Men who started smoking before the age of 15 smoked on average 5.5 cigarettes more than those who started at age 19 or over. Women who started smoking early in life smoked, on average, 6.8 cigarettes/day more than women who started later. The proportion of smokers of <15 cigarettes/day was higher among subjects who started smoking later. Both for males and for females, the OR of being a heavy smoker significantly increased with decreasing age at starting smoking (OR = 2.4 for males and 4.5 for females who started at age <15 versus >/=20 years). The level of education did not modify the relationship in males, whereas the association with age at starting was only apparent for more educated women. CONCLUSIONS: This study confirms that age at starting smoking is inversely and strongly associated to the number of cigarettes smoked per day. Thus, actions aimed at the prevention or delay of smoking onset among adolescents would have an important beneficial effect.     

Detection of antibodies against pancreatic islet cells in clinical practice

Development of diabetes mellitus caused by pancreatic beta-cell destruction of autoimmune origin is the result of a long lasting process. The most easily examinable feature of this stage is the occurrence of the islet cell antibodies. The sera which are positive for islet cell cytoplasmic antibodies (ICA), examined by indirect immunofluorescence, contain a mixture of antibodies. The glutamic acid decarbocylase (GAD), the tyrosin phosphatase (IA2), the insulin, and the GM2-1 glycolipid can be the targets of these antibodies. One can routinely examine the ICA, the GADA, the IA2 antibodies. The detection of antibodies against insulin (IAA) and GM-2-1 glycolipid is not invented in the routine laboratory work. The aim of the authors was the evaluation of clinical significance of occurrence of islet cell antibodies: one hundred and eighteen nondiabetic children an adult human being without known diabetic first degree relatives and 366 type 1 diabetic children and adult patients served as controls. The authors evaluated the predictive value of the different islet cell antibodies to the development of type 1 diabetes mellitus in 596 nondiabetic children with type 1 diabetic first degree relatives. The authors looked for markers of beta-cell destruction among sera of 320 diabetics manifested after 30 years of age with at least half a year of non-insulin-dependency and in the sera of 68 females suffered from gestational diabetes after 0-14 years of the index pregnancy. Finally the authors report 7 cases in which the examination of islet cell antibodies helped the diagnosis and classification of diabetes mellitus. Indirect immunofluorescence method was used for the detection of ICA, radioimmunoassay for that of GADA and IA2 antibodies. There was no positive reaction for ICA and GADA in the nondiabetic population without diabetic first degree relatives. Among the freshly diagnosed type 1 diabetic children 39% were positive for only ICA, 44% for only GADA and 80% for any antibodies. Among the freshly manifested type 1 diabetic adults ICA positivity only was observed in 21%, GADA positivity only in 7.1% and 93% for any antibodies. From the 595 nondiabetic children with type 1 diabetic first degree relatives 23 were positive for ICA, from whom 5 became diabetic during a two years observation period. These diabetic children had multiplex autoantibodies besides ICA. One child from this group, who was negative for ICA became diabetic, too. Among type 2 diabetic patients 13% were positive for ICA alone, 17% were positive for GADA alone and 27% were positive for any antibodies. The insulin dependency manifested in a short time was associated with antibody positivity. Among the gestational diabetics 10 were found positive for ICA. From them, 7 were type 1 diabetics, and 3 were type 2 diabetics at the time of the detection of antibodies. The authors suggest the need of determination of islet cell antibodies in the group of nondiabetic first degree relatives of type 1 diabetic patients (ICA, GADA, IA2 and IAA), in the group of non-insulin-dependent diabetics (ICA and GADA) as a screening for later insulin dependency, and in gestational diabetes after delivery (ICA) as screening for type 1 diabetes mellitus.     

Blastic transformation of mantle cell lymphoma: genetic evidence for a clonal link between the two stages of the tumour

AIMS: The blastic variant of mantle cell lymphoma (MCL-BV) may develop through histological transformation of mantle cell lymphoma (MCL). However, the clonal link between the tumour cells of MCL and transformed MCL-BV has not been established at the genetic level. To investigate this link longitudinal molecular genetic studies have been performed in two cases of MCL that showed morphological transformation to MCL-BV. METHODS AND RESULTS: Polymerase chain reaction (PCR) and nucleotide sequence analyses of the complementary determining region 3 (CDR) of the immunoglobulin (Ig) heavy chain (H) gene were performed to identify clone-specific rearrangements. In both cases, nucleotide sequence analysis revealed common clone-specific IgH gene rearrangements in MCL and subsequent MCL-BV. CONCLUSIONS: These results provide genetic evidence for the common clonal origin of MCL and subsequently developed MCL-BV.     

Contribution of kinases and the CD45 phosphatase to the generation of tyrosine phosphorylation patterns in the T-cell receptor complex zeta chain

The zeta subunit of the T-cell receptor complex plays a crucial role in coupling the antigen binding alphabeta and gammadelta heterodimers to the downstream activation pathways. Three tandem amino acid sequence motifs containing pairs of exactly spaced Tyr-X-X-Leu/Ile sequences, designated as Immunoreceptor Tyrosine-based Activation Motifs (ITAMs), control this function. The phosphorylated forms of ITAMs serve as docking sites for several src homology 2 (SH2) domain containing signaling proteins. The composition of the assembled signaling complex and the outcome of cell activation depends on the tyrosine phosphorylation pattern of the zeta polypeptide. The mechanism that conducts the generation of various phosphorylated forms has not yet been well established. In this study we have analyzed the ability of src family tyrosine kinases and the CD45 tyrosine phosphatase in determining the phosphorylation state of the different ITAMs and the individual tyrosine residues of the TCR zeta chain. The intracellular part of the zeta chain was phosphorylated by src family tyrosine kinases, p56lck and p59fyn in vitro. Synthetic oligopeptides representing full-length or half-sized ITAMs with a single tyrosine residue were also phosphorylated by both p56lck and p59fyn. In contrast, an additional membrane proximal tyrosine residue in the human zeta chain, located outside of the ITAMs, was not phosphorylated. We also examined the activity of the CD45 phosphatase, using a panel of ITAM derivatives, in which one or both tyrosines were phosphorylated. The efficiency of ITAM dephosphorylation by CD45 was dependent on the primary sequence of the oligopeptides and the position of the phosphotyrosine residues. The in vitro data suggest that the CD45 phosphatase rather than the tyrosine kinase(s) may control the generation of specific phosphorylation patterns of the zeta chain during cell activation.     

Lectin histochemistry of pathological bones

Our present knowledge of the structure and function of glycoproteins in bone tissue is very limited. The introduction of lectins into histology offered principally a new approach for studying the presence and chemical structure of glycoproteins in tissue sections. In this paper these highly specific carbohydrate binding molecules have been used to characterize glycoproteins in the cellular elements of normal bone and benign bone lesions. We retrospectively examined 35 benign bone lesions (7 fibrous dysplasias, 5 foreign body granulomas, 5 epulis, 8 osteoid osteomas, 10 giant cell tumors) together with 25 normal bone samples. In normal bone samples and all cases of benign bone lesions, two characteristic types of PNA binding were found after neuraminidase digestion in osteoclasts. In osteoclasts which did not adhere to bone surface, diffuse intracytoplasmic PNA binding was seen, and following the adherence to the bone surface, it disappeared, and the resorption zone became stainable. We assume that this PNA binding glycoprotein is formed in the cytoplasm of osteoclasts, then, after the activation of osteoclasts, the glycoprotein gets accumulated at the resorption zone of the cytomembrane where it plays a significant role in the bone resorption.     

Effects of intrathecal nocistatin on the flexor reflex and its interaction with orphanin FQ nociceptin

We studied the effects of intrathecal (i.t.) nocistatin, a peptide identified from the precursor of orphanin FQ/nociceptin (OFQ) on the spinal nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats and its interaction with i.t. OFQ. Nocistatin induced a moderate, non-dose-dependent facilitation of the flexor reflex without producing reflex depression whereas i.t. OFQ induced a biphasic dose-dependent facilitatory and inhibitory effect. The facilitatory effect of low dose (0.55 pmol) OFQ was significantly increased by nocistatin. On the other hand, the duration, but not magnitude, of reflex depression induced by a high (550 pmol) dose of OFQ was significantly shortened by 5.5 nmol nocistatin. Thus, nocistatin interacts with OFQ in a complex fashion, increasing excitation and reducing inhibition. No evidence was obtained for an antinociceptive effect of nocistatin in rat spinal cord.