Biomedical subjects

V Desmet

Publications and source records attributed to V Desmet.

At least 55 records · Page 3Linked to original sources

PubMed1995

Heparan sulfate proteoglycan expression in normal human liver.

Because increasing evidence implicates heparan sulfate proteoglycans (HSPGs) as essential cofactors in receptor-growth factor interactions, in cell-cell recognition systems, and in cell-matrix adhesion processes and yet little is known about their cellular distribution pattern and cellular sources in liver tissue, we used monoclonal antibodies specific for the core proteins of syndecan1, 2, 3, 4, glypican, and perlecan to investigate their immunohistochemical expression in normal adult human liver biopsy specimens. Syndecan1 was expressed in sinusoidal endothelial cells, whereas the endothelium of the portal tract vessels was negative. Hepatocytes showed a membranous staining pattern of the sinusoidal and intercellular domain. Bile duct epithelial cells showed basolateral membrane positivity. Immunoreactivity for syndecan2 was seen in mesenchymal cells, accentuated around bile ducts. Syndecan3 showed intense staining of hepatic arterial and portal venous endothelial cells, of mesenchymal cells, and of Ito cells. Immunohistochemistry for syndecan4 showed a granular staining pattern of hepatocytes at their bile canalicular pole. Glypican showed weak positivity in portal tract mesenchymal cells and clear positivity in nerve bundles. Perlecan was present in Disse's space, in endothelial cells, in basement membranes surrounding bile ducts and vessels, in vessel walls, and in mesenchymal cells. The highly differential expression of these HSPGs in the different cell compartments of the liver, as well as in basement membranes and in Disse's space, suggests that each of these proteoglycans has a specific function in the interplay of cells, matrix molecules, growth factors, and proteinases.

Cells, Cultured↗

PubMed1995

Intermittent subobstruction and cholestasis as complications of duodenal amyloid tumours.

Amyloidosis confined to the duodenum is uncommon. In the present report the history of an 83-year old patient, admitted for vomiting and heavy epigastric pain, is described. Radiographic and endoscopic investigation revealed two polypoid lesions in the duodenum (D2). Biopsies showed diffuse amyloid deposition in the lamina propria, muscularis mucosae and submucosa of the duodenum as well as vascular deposits. No other localisations were documented. Amyloid tumours of the gastrointestinal tract are rare but may lead to serious symptoms.

Aged↗

PubMed1994

Treatment of chronic hepatitis D with interferon alfa-2a.

BACKGROUND AND METHODS: Chronic hepatitis D is a severe and rapidly progressive liver disease for which no therapy has been proved effective. To evaluate the efficacy of treatment with interferon, we studied 42 patients with chronic hepatitis D who were randomly assigned to receive either 9 million or 3 million units of recombinant interferon alfa-2a (three times a week for 48 weeks) or no treatment. RESULTS: By the end of the treatment period, serum alanine aminotransferase values had become normal in 10 of 14 patients receiving 9 million units (71 percent), as compared with 4 of 14 treated with 3 million units (29 percent, P = 0.029) and 1 of 13 untreated controls (8 percent, P = 0.001). Seven patients treated with the higher dose of interferon (50 percent) had a complete response (normal levels of alanine aminotransferase and no detectable serum hepatitis delta virus [HDV] RNA), as compared with three of those who received the lower dose (21 percent, P = 0.118), and none of the controls (P = 0.004). Treatment with 9 million units of interferon was associated with a marked improvement in the histologic findings (reduced periportal necrosis and portal and lobular inflammation), whereas in the untreated controls there was considerable histologic deterioration. In 5 of the 10 patients treated with 9 million units of interferon whose alanine aminotransferase values became normal, the biochemical responses persisted for up to 4 years (mean, 39 months), but the effects of treatment on viral replication were not sustained. In contrast, none of those who received 3 million units and none of the untreated controls had a sustained biochemical or virologic response. CONCLUSIONS: In about half the patients with chronic hepatitis D treated with high doses of interferon alfa-2a (9 million units three times a week for 48 weeks), the serum alanine aminotransferase level becomes normal, HDV RNA becomes undetectable in serum, and there is histologic improvement. However, a relapse is common after treatment has been stopped.

Adolescent↗

PubMed1994

Hepatitis C virus and its genotypes in patients suffering from chronic hepatitis C with or without a cryoglobulinemia-related syndrome.

Recently, evidence has been presented for a possible association between hepatitis C virus (HCV) infection and essential mixed cryoglobulinemia (EMC). Eleven consecutive patients with EMC and two with cryoglobulinemia type I were examined for the presence of markers of HCV infection. Eleven of 13 patients (10 with EMC and 1 with type I cryoglobulinemia) had anti-HCV antibodies (as determined by a second generation anti-HCV assay) and HCV-RNA in plasma or serum. HCV-RNA was also detected in liver biopsies of five patients. Genotyping showed that HCV genotype 1 was found in 10 of 11 patients with HCV-RNA (9 genotype 1b and 1 genotype 1a) and only one patient had HCV genotype 2. However, a similar high prevalence of genotype 1b (100%) was found in a group of 14 consecutive patients with chronic hepatitis C, who had no clinical evidence of cryoglobulinemia. Concomitant infection was present in three patients with genotypes 2, 3 and 4, respectively. These findings stress the high prevalence of HCV infection in patients with EMC and further study shows that a difference in genotype prevalence was not found between HCV-related EMC and chronic hepatitis C without clinical manifestations of EMC.

Adult↗

PubMed1994

Clinical aspects of incomplete septal cirrhosis in comparison with macronodular cirrhosis.

BACKGROUND/AIMS: Incomplete septal cirrhosis (ISC) is a form of macronodular cirrhosis characterized by slender, incomplete septa that demarcate inconspicuous nodules. Its clinical features have not been investigated in a large series. The aims of this study were to review the clinical symptoms and evolution of ISC in 42 patients. METHODS: Forty-two patients with at least one liver biopsy strongly suggestive of ISC were selected for the study covering a period between 1968 and 1987. Data for these patients were compared with the evolution of 49 patients with classical macronodular cirrhosis after chronic active hepatitis type B or C. RESULTS: Possible etiological factors for ISC were alcohol abuse, arsenic treatment, and hepatitis B infection. In three cases, a genetic factor could not be excluded. Patients with ISC had significantly lower serum concentrations of transaminases and bilirubin at diagnosis. Compared with macronodular cirrhosis, bleeding varices were more frequent (57% vs. 22%) in ISC. Ten-year survivals in the ISC and the macronodular cirrhosis groups were 54% and 57%, respectively. CONCLUSIONS: ISC represents a relatively stable burnt-out form of macronodular cirrhosis with an unusually high incidence of variceal bleeding. This could be explained by a superimposed insufficiency of the portal vascular supply.

Adolescent↗

PubMed1994

Detection of hepatitis C virus antigen by immuno-histochemical staining: a histological marker of hepatitis C virus infection.

Hepatitis C virus has been recognized as a major cause of non-A, non-B viral hepatitis. Although serologic tests have been commercialized, no specific histological or immuno-histochemical markers for hepatitis C virus infection are available for routine use. In an effort to detect hepatitis C virus antigen in liver tissue we investigated the immuno-reactivity to monoclonal antibodies on frozen liver tissue from a chimpanzee and patients with chronic non A, non B hepatitis. Monoclonal antibodies were developed in mice immunized with a synthetic peptide derived from hepatitis C virus core antigen. One monoclonal antibody was reactive and showed typical cytoplasmic granules in chimpanzee hepatocytes. Using this monoclonal antibody a similar staining pattern was found in the liver biopsies of 21 out of 28 chronic non-A, non-B hepatitis patients, positive for hepatitis C virus-RNA and anti-HCV. The granular immuno-reactivity was abolished after pre-incubation of this monoclonal antibody with infected chimpanzee liver or with hepatitis C virus synthetic peptide but not with normal chimpanzee or human liver tissue. There was no reactivity in four patients with hepatitis C virus-RNA-negative, anti-HCV-positive chronic non-A, non-B hepatitis, in 11 patients with chronic type B hepatitis or in 12 hepatitis C virus-RNA-negative, anti-HCV-negative patients with various liver diseases. However, staining was found in three out of four additional chronic type B hepatitis patients suspected of co-infection with non-A, non-B agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1994

Pleuropulmonary blastoma (pulmonary blastoma of childhood): genetic link with other embryonal malignancies?

A case of pleuropulmonary blastoma (childhood variant of pulmonary blastoma) was examined using histological, immunohistochemical, ultrastructural and cytogenetic methods. The tumour consisted of undifferentiated 'blastematous' areas admixed with zones of rhabdomyoblastic and chondroid differentiation and fascicular areas. Desmin and S-100 protein immunoreactivity confirmed the myogenic and cartilaginous differentiation. Ultrastructurally only undifferentiated mesenchymal cells were present. The cytogenetic analysis revealed abnormalities of 2q. Involvement of 2q has also been described in hepatoblastoma and embryonal rhabdomyosarcoma. Although further confirmation is needed, our cytogenetic findings in pleuropulmonary blastoma suggest common genetic mechanisms in some paediatric embryonal malignancies.

Biopsy↗

PubMed1993

Treatment of decompensated viral hepatitis B-induced cirrhosis with low doses of interferon alpha.

Seven patients with decompensated posthepatitis B cirrhosis were treated with low doses of interferon alpha. The initial plasma level of HBV-DNA ranged from 3.0 to 189.3 pg/ml, and that of ALT from 37 to 156 IU/l. Liver biopsies demonstrated ongoing piecemeal necrosis. In sera of all but one patient, HBV-DNA became undetectable by hybridisation techniques within 10 to 28 weeks. Plasma HBeAg became negative in four and HBe-antibodies positive in three patients. Serum transaminase levels showed a marked initial rise 3 to 13 weeks after onset of therapy; they dropped to normal values later in all except one patient. Therapy was initiated at 1 MU (million units) three times a week for 2 weeks and was increased to 2.5 MU for 16 weeks. Later, this dosage was raised to 5 MU three times a week in some patients. Complications included variceal haemorrhage, aggravation of ascites or of encephalopathy, development of pneumonia, recurrence of spontaneous bacterial peritonitis or of gastric ulcer bleeding. One year after stopping the therapy, three patients are well and without any feature of liver decompensation. Three patients died before they could undergo a liver transplantation. In one patient treatment was interrupted because of marked exacerbation of liver cell necrosis. It thus seems possible to suppress HBeAg and HBV-DNA in patients with decompensated cirrhosis. This is important to prepare them for possible liver transplantation. Interferon should be initiated at low doses and the patients be very carefully monitored. Prophylactic therapy for bacterial peritonitis and for variceal haemorrhage is warranted.

Alanine Transaminase↗

PubMed1993

A multicentre randomized clinical trial of recombinant alpha-2a interferon therapy in patients with chronic hepatitis B.

Fifty six previously untreated patients who had been positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) for more than 1 year with detectable serum levels of hepatitis B virus DNA (HBV-DNA) and a liver biopsy performed in the 6 months before enrollment, were randomized to receive recombinant alpha-2a interferon at doses of 3MU intramuscolarly thrice weekly for 6 months or no treatment. Treated and untreated patients had similar clinical characteristics in terms of ALT elevation, HBV-DNA levels, and degree of liver damage. Twenty one had chronic persistent or lobular hepatitis; 28 had chronic active hepatitis and 7 had cirrhosis. The percentages of patients who lost HBeAg at month 6, 12 and 18 were 22%, 32% and 38% in the treated group, and 16%, 20% and 37% in the controls (differences = ns). At the same time intervals, HBV-DNA detected by dot spot hybridization, cleared off in 39%, 39% and 41% of treated patients as compared to 16%, 36% and 37% of controls (difference = p < 0.05 for HBV-DNA clearance at month 6). At the end of follow-up, 12 treated patients (41%, including 8 antiHBe seroconverters) and 10 untreated controls (42%, including 6 anti-HBe seroconverters) had normal aminotransferase levels. Conclusions show that in patients with chronic hepatitis B, clearance of HBV-DNA but not of HBeAg was hastened by a 6-month treatment with low doses of recombinant alpha-2a interferon.

Adolescent↗

PubMed1992

[Chronic hiccups].

We report 18 cases of chronic hiccup (defined as lasting for more than 48 hours) in adults. Among the numerous possible causes, reflux esophagitis proved to be by far the most frequent (50% of the cases). However, hiccup often initiated a self-perpetuating vicious circle. This is possibly because hiccup per se can give esophageal dyskinesia, which in turn leads to gastro-esophageal reflux. The treatment was difficult and whenever possible has been directed chiefly towards the cause. However hiccup remained intractable in many cases even after a possible cause had been adequately cured (e.g., successful Nissen procedure in reflux cases). Central nervous system depressants and myorelaxing drugs were not very helpful, except for baclofen (initial response rate = 60%).

Adult↗

PubMed1992

Whipple's disease: a histological, immunocytochemical and electronmicroscopic study of the immune response in the small intestinal mucosa.

Whipple's disease is a multisystem disorder with protean manifestations and with poorly understood aetiopathogenesis. It is unclear how the immune system reacts, whether it functions normally or not, whether it protects the organism or is defeated in one way or another by the 'Whipple bacillus'. The purpose of our study was to assess humoral and cellular immunity at the level of the intestinal mucosa. This histochemical, immunocytochemical and electronmicroscopic study, based on 16 cases, has shown that the changes in components of the mucosal immune system in Whipple's disease are quite different from normal. The phagocytic capacity of the macrophages, assessed microscopically, is abnormal, the number of intra-epithelial lymphocytes is increased, the CD 4/CD 8 cell ratio is decreased and the IgM positive cells in the lamina propria outnumber the IgA positive cells. These changes may be inter-dependent.

Adult↗

PubMed1992

Granulomatous gastritis and Whipple's disease.

Granulomatous gastritis is an uncommon morphological diagnosis. An etiopathogenetic diagnosis can be reached only by combining the morphological examination with clinical and laboratory investigations. The diagnosis of Whipple's disease in our patient was based upon a classical clinical picture and upon the likewise classical morphological appearance of the small intestinal mucosal biopsy. To our knowledge, this case report is the first to describe granulomatous gastritis in a patient with Whipple's disease.

Gastritis↗

PubMed1992

Ultrastructural characteristics of novel epithelial cell types identified in human pathologic liver specimens with chronic ductular reaction.

Previous immunohistochemical studies on human liver biopsies with chronic ductular reaction revealed the presence of "small cells" with bile-duct type cytokeratin profile in the periportal area. This study identified similar cells by electron microscopy. The authors studied 13 human liver specimens with various liver diseases, but all characterized by chronic ductular reaction. In all specimens, variable numbers of "small cells" with common epithelial characteristics were identified in the periportal area. They could be classified into three types. Type I cells showed an oval cell shape and oval nucleus, early or established formation of junctional complexes with adjacent cells, a full assortment of cytoplasmic organelles, and bundles of tonofilaments. Type II cells showed features of bile-duct cell differentiation, including lateral interdigitations, apical microvilli, basal pinocytotic vacuoles, and basement membrane formation. In contrast, type III cells displayed additional features indicating hepatocellular differentiation, such as a more prominent nucleus, formation of a hemicanaliculus, and glycogen rosettes. It is concluded that these small cells of epithelial nature display variable differentiation characteristics of either bile-duct type cells or hepatocytes. These findings support the existence of bipotential progenitor epithelial cells in human liver. They may have implications for liver regeneration and carcinogenesis.

Cholestasis↗

PubMed1991

True histiocytic neoplasm of Langerhans' cell type.

Malignant histiocytic neoplasms of dendritic cell lineage are rare and most are derived from the dendritic cells of the T-cell and B-cell areas of the lymph node, respectively. Only one case of a malignant histiocytic neoplasm of Langerhans' cells, the dendritic cell of the skin, has been reported. We report the occurrence of a true histiocytic neoplasm of Langerhans' cell type in a 23-year-old female patient. The diagnosis of this highly aggressive neoplasm is supported by histochemical, immunohistochemical, ultrastructural, and genotypic analysis--techniques which allow differentiation from malignant melanoma and large cell anaplastic lymphoma.

Adult↗

PubMed1991

Intrahepatic cholestasis induced by amoxicillin/clavulanic acid (Augmentin): a report on two cases.

Two patients who developed a severe but reversible cholestatic jaundice during and after treatment with an amoxicillin/clavulanic acid preparation (Augmentin) are described. The diagnosis of drug-induced intrahepatic cholestasis was based on the clinical course, biochemical pattern and on histological findings. Since amoxicillin alone does not induce liver injury, the combination of amoxicillin and clavulanic acid or clavulanic acid alone could be responsible for this adverse reaction, probably through a metabolic idiosyncrasy or a hypersensitivity mechanism. Although more than 100 cases of hepatotoxic reactions have been reported to the pharmaceutical company (Beecham Laboratories) and several reports have been published, the incidence of hepatotoxicity of this antibiotic is relatively rare, since this antibiotic has been widely used. However, recognition of this benign and reversible cholestatic syndrome is important to avoid unnecessary, expensive and invasive diagnostic procedures.

Aged↗

PubMed1991

Histiocytes in Sweet's syndrome.

The histological features of biopsies from 18 previously unreported cases of Sweet's syndrome are reported. The dermal infiltrate in the majority of the cases contained numerous histiocytes that at first sight appeared to mimic neutrophils. The immunophenotype of these histiocytes was consistent with monocytes that have freshly infiltrated into the lesions. Only two of the cases in this series, associated with leukaemia, displayed the histological features of Sweet's syndrome with a predominant neutrophilic infiltration. We suggest that the initiating mechanisms in Sweet's syndrome are that monocyte/histiocyte-derived cytokines such as the interleukins IL-1 and IL-8, secreted either by infiltrating histiocytes in the non-leukaemia-associated cases of Sweet's syndrome or by tumoural myelomonocytic cells in those associated with leukaemia, are responsible for the systemic manifestations and the infiltration with neutrophils in the skin lesions.

Adult↗

PubMed1991

Cells with neuroendocrine features in regenerating human liver.

Regeneration of liver tissue in man after submassive necrosis is reflected by replicating features in hepatocytes, and by a remarkably increased number of bile duct structures that are thought to transdifferentiate into true functioning hepatocytes. Similar to the bile ductule-related "oval cells" in rats, human bile ductular cells may therefore serve as "facultative stem cells" that become activated when hepatocyte regeneration is insufficient or inhibited. Our recent demonstration of neuroendocrine features in proliferating bile ductules in cholestatic liver disease prompted us to perform a similar immunohistochemical and electron microscopical study on regenerating human liver tissue after submassive liver necrosis. In the earliest stages of regeneration, bile ductular cells and small, singular cells in the periportal area expressed chromogranin-A and contained dense-cored, secretory granules. It is tempting to speculate that the scattered singular cells represent the human equivalent of the bipotential progenitor cells in the rat. In later stages of regeneration, these singular cells were no longer evident, suggesting their differentiation into other cell types. In these cases, neuro-endocrine cells corresponded to proliferating bile ductules and to scattered, typical hepatocytes, located near portal tracts and in regenerating nodules. In all cases, proliferating bile ductules displayed the neural cell adhesion molecule (NCAM). These data further support our hypothesis that the substance(s) produced in the dense cored secretory granules may play a role in the growth and/or differentiation of liver cells through an autocrine and or paracrine pathway.

Antibodies, Monoclonal↗

PubMed1990

Alagille syndrome (arteriohepatic dysplasia) and del(20)(p11.2)

We report on a boy with Alagille syndrome. Chromosome analysis on a peripheral blood lymphocyte culture showed a de novo deletion of the short arm of chromosome 20 with a 46,XY,del(20)(p11.2) chromosome constitution. This is the second report of a del(20p) in a patient with Alagille syndrome. The possible localisation of this autosomal dominant syndrome on 20p is discussed.

Abnormalities, Multiple↗