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Biomedical subjects

G Koukoulis

Publications and source records attributed to G Koukoulis.

31 records · Page 2Linked to original sources
PubMed1994

Primary amyloidosis and severe intrahepatic cholestatic jaundice.

Liver involvement in systemic amyloidosis is frequent but is rarely of clinical importance. Five patients with severe cholestatic jaundice are described and an additional 20 from published reports are reviewed. The most frequent presenting symptoms were lethargy and abdominal pain, which were present for a median of 11 months before the onset of jaundice. Hepatomegaly, usually marked, was present in 92%, with ascites in 56% of the cases. The serum bilirubin concentration was noticeably high and the serum globulin low. Histology of the liver showed considerable perisinusoidal deposition with a slight predilection for the periportal area. Two patients presented with predominant centrilobular deposition. Congo red staining was not uniformly positive. A variety of treatment regimens was tried but median survival was only three months from the onset of jaundice.

Aged↗
PubMed1993

Hepatocyte growth factor induces proliferation and morphogenesis in nonparenchymal epithelial liver cells.

Hepatocyte growth factor is the most potent mitogen known for hepatocytes, and increasing evidence suggests that hepatocyte growth factor plays an important role in liver regeneration. However, hepatocytes are not the only liver epithelial cell population that proliferates during regeneration. Experimental and clinical data indicate that the regenerative liver response also includes the participation of nonparenchymal epithelial cells. The possible role of hepatocyte growth factor in this nonparenchymal epithelial cell regenerative response has not been explored. We studied the effects of hepatocyte growth factor with a model of two normal mouse nonparenchymal epithelial cell-derived cell lines with varying differentiation potentials. Addition of hepatocyte growth factor induced mitogenesis and scattering of colonies growing on culture dishes in both cell lines. Furthermore, hepatocyte growth factor was found to exert a profound morphogenic effect on cells growing in collagen matrixes. Hepatocyte growth factor-treated embryonic BNL CL.2 cell colonies developed elaborately branching elongated cords with only minimal tubularization. Hepatocyte growth factor-treated postnatal NMuLi cell colonies developed a network of anastomosing tubules with wide lumens. These morphological changes were not inhibitable by transforming growth factor-beta and were not induced by other hepatocellular growth factors including epidermal growth factor, transforming growth factor-alpha, acidic fibroblast growth factor and insulin. Histological sections of the hepatocyte growth factor-treated BNL CL.2 cell colonies resembled neocholangioles, believed to include facultative stem cells, which proliferate after submassive and massive hepatic necrosis. Sections of hepatocyte growth factor-treated NMuLi colonies resembled ductules proliferating in biliary tract obstruction from a wide variety of causes. This work represents the first examples of hepatocyte growth factor-induced mitogenesis, scattering and morphogenesis in the same cell lines. More important, our data suggest that hepatocyte growth factor mediates liver response to injury not only by acting on hepatocytes but also by exerting mitogenic and morphogenic influences on nonparenchymal epithelial cell components.

Animals↗
PubMed1992

Liver transplantation for fulminant hepatic failure and late-onset hepatic failure in children.

The mortality rate of fulminant hepatic failure (FHF) and late-onset hepatic failure (LOHF) in childhood has remained between 70 and 95 per cent despite recent improvements in medical therapy. Liver transplantation has become an important therapeutic option in adults with this condition but has been performed infrequently in children. Between March 1988 and August 1991, 12 children aged between 1 month and 14 years with FHF or LOHF received 13 liver transplants. The aetiology was viral hepatitis in eight children (non-A non-B in six, A in two), drug hepatotoxicity (carbamazepine) in two, autoimmune hepatitis in one and congenital haemochromatosis in one. Reduced-size livers were used for ten of the 13 transplants. Morbidity after operation included infective complications and abdominal bleeding. Two patients died from graft versus host disease, one from brain aspergillosis and another from graft infarction after portal vein thrombosis. Eight patients survive after a median follow-up of 18 months. Liver transplantation should be the therapeutic choice for children with FHF and LOHF for whom the chances of recovery are poor.

Adolescent↗
PubMed1992

Immunolocalization of regenerating cells after submassive liver necrosis using PCNA staining.

Little data exist on the proliferative state of liver cells and its relationship with various morphological findings in acute liver failure (ALF) in man. In this study we used the monoclonal antibody NCL-PCNA (clone PC-10) against the proliferating cell nuclear antigen (PCNA) to detect cycling cells in paraffin sections of 3 normal livers, 14 post-mortem needle-specimens of submassive hepatic necrosis (SHN) due to paracetamol overdosage (POD), and 10 hepatectomy specimens obtained at transplantation in patients with acute or subacute liver failure of presumed viral aetiology. In normal livers, only occasional sinusoid-lining cells were stained, whereas in SHN following POD or presumed viral hepatitis, hepatocytes of variable morphology showed significant immunoreactivity. Following POD, immunoreactivity was higher in samples taken within 5-6 days than in those obtained at 9-11 days, a pattern reminiscent of the decrease in the rate of regeneration, previously documented after partial hepatectomy in humans. Immunolabelled hepatocytes were aggregated in multiacinar 'nodules' in cases with a map-like distribution of collapsed and non-collapsed parenchyma. Ductules demonstrated comparatively less staining, but extensive labelling was exceptionally found in areas of complete hepatocellular dropout. In these areas, small elongated cells with strongly PCNA-positive ovoid nuclei, forming periportal sprouting cords or incorporated into the lining of ductules, were most remarkable in that they closely resembled 'oval cells' described in animal studies.

Acetaminophen↗
PubMed1992

Syncytial giant-cell hepatitis--a specific disease entity?

Syncytial giant-cell hepatitis was recently reported to be related to a paramyxovirus and carried a poor prognosis. Twelve patients with syncytial giant-cell hepatitis seen in an 8 1/2-year period in our institute were reviewed. Seven patients had an identifiable aetiological cause: two had autoimmune chronic active hepatitis, one had primary sclerosing cholangitis and autoimmune chronic active hepatitis, two presented with prolonged jaundice after acute hepatitis A and B, one had chronic Epstein-Barr virus infection and the remaining patient was seropositive for antibody to hepatitis C virus. One patient with autoimmune chronic active hepatitis who had frequent syncytial giant cells in the liver responded promptly to corticosteroid treatment and a repeated biopsy 3 years later showed histological improvement with a marked decrease in the number of syncytial giant cells. Of the remaining five patients, three ran a clinical course of fulminant hepatic failure and two had severe chronic active hepatitis. These data indicate that syncytial giant-cell hepatitis is unlikely to be related to only one single aetiological agent and that syncytial giant-cell hepatitis does not always carry an ominous prognosis.

Adolescent↗
PubMed1989

Assessment of sperm motion characteristics from fertile and infertile men using a fully automated computer-assisted semen analyzer.

Sperm curvilinear velocity (Vc) and linearity (L) were analyzed in semen from 20 fertile men and from 53 patients with unexplained infertility by a computer-assisted semen analyzer (CASA). Because the frequency distribution of Vc from patient's spermatozoa showed a nongaussian distribution, comparison of mean values of Vc and L between men with unexplained infertility and fertile men is inappropriate. As an alternative, the authors compared the cumulative distribution of the percent of cells measured at increasing intervals of Vc and L, and observed a significant difference between patients and fertile men from the level of Vc30 through Vc70 micron/sec for curvilinear velocity and L2 through L6 for linearity (P less than 0.001). Furthermore, the authors coanalyzed these two parameters at the greatest point of difference (Vc40 and L3) and observed that their patient population can be differentiated into four subpopulations of subjects accordingly to their Vc40 and L3 values. In this study, 43 of the 53 patients had a motility disorder characterized by having a higher percent of cells being substantially slower and less directional than cells from normal men. However, in some patients, motion characteristics were indistinguishable from those in normal men.

Diagnosis, Computer-Assisted↗
PubMed1989

Sperm motion characteristics in men with isolated hypogonadotropic hypogonadism treated with gonadotropin.

The authors compared curvilinear velocity (Vc) and linearity (L) of sperm from fertile oligospermic men with isolated hypogonadotropic hypogonadism (IHH) to Vc and L of sperm from fertile normal men in order to determine if sperm motion analysis is better than sperm density as an indicator of fertility potential. Nine fertile men with IHH treated with exogenous gonadotropins and 20 fertile normal men were studied. Sperm density was significantly lower in the men with IHH compared with normal men (15.5 +/- 4.8 x 10(6)/ml versus 92.4 +/- 9.7 x 10(6)/ml; mean +/- standard error of the mean [SEM]; P less than 0.01) as was percent motility (51.4 +/- 4.7 versus 73.4 +/- 3.1; P less than 0.01). While a small but significant difference in Vc was noted between the groups at the 40 micron/second cumulative distribution point (P less than 0.01), no difference in L was found between the two groups. When the men with IHH were subgrouped according to sperm density (greater than 20 x 10(6)/ml versus less than or equal to 20 x 10(6)/ml, no differences in Vc were found between the subsets, but for L sperm were somewhat less directional for the subgroup with a density less than or equal to 20 x 10(6)/ml (P = 0.05). Coanalysis using both Vc and L parameters indicated that sperm from IHH patients were distributed similarly to sperm from normal men. However, sperm motion characteristics in men with unexplained infertility were different from values measured in normal men and IHH patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis, Computer-Assisted↗
PubMed1989

In vitro-perifused rat testes secrete beta-endorphin and dynorphin: their effect on testosterone secretion.

Leydig cells of many species synthesize and secrete opioid peptides, but the Sertoli and possibly the peritubular cells are the only intratesticular cells having opiate receptors. It is known that Sertoli and peritubular cells can modify the secretion of testosterone from Leydig cells. To test the hypothesis that testicular opioid peptides participate in a Leydig-Sertoli-peritubular-Leydig cell feedback loop that can regulate the intratesticular concentration of testosterone, we have developed a method for the in vitro perifusion of rat testicular fragments in which the intratesticular structure and thus the paracrine feedback loop remains intact. Our data show that both immunoreactive (IR)-beta-endorphin and IR-dynorphin were present in the testicular perifusion effluent; gel chromatography of pooled perifusion effluent show that the bulk of the secreted IR-beta-endorphin had the apparent mol. wt. of synthetic rat beta-endorphin whereas most of the secreted IR-dynorphin was composed of smaller than 4000 mol. wt. forms. On the other hand, the bulk of IR-dynorphin present in rat testicular tissue homogenates eluted in two higher mol. wt. peaks. The effect of mu and kappa opioid agonists and naloxone (a universal opioid antagonist) on both basal and gonadotropin-stimulated testosterone secretion from perifused testicular fragments was then examined; no stimulatory or inhibitory effect of the opioid receptor agonists or naloxone was found on basal and gonadotropin-stimulated testosterone secretion. Parallel experiments with Leydig cells in culture gave similar results.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Computer-assisted semen analysis: evaluation of method and assessment of the influence of sperm concentration on linear velocity determination.

Semen samples from 77 men were used to estimate the accuracy and precision of measurements of sperm density, percent motility, and motion characteristics using a new, fully automated, computer-assisted semen analyzer (CASA). Results are compared with traditional semen analysis methodology. Acceptable precision for count and percent motility was obtained using three to nine random fields of observation when there were more than 10 cells per high-power microscopic field. A highly significant correlation (P less than 0.01) was found between the two methods in the assessment of sperm concentration and percent motility, but CASA overestimated concentration significantly (P less than 0.01) by about 30% when there were less than 60 cells per high power field. This overestimation seemed to be due to the number of nonsperm particles in semen that are confused with spermatozoa by the program. Linear velocity determination was influenced by the number of tracking points as well as by the concentration of cells present in the counting chamber. More representative linear velocity estimations in semen were obtained when sperm concentration was less than 40 x 10(6) cells/ml and 20 tracking points were used in the determination. For semen specimens containing higher cell density, sperm concentration needed to be reduced by diluting the semen with the patient's own sperm-free seminal plasma before measuring motion characteristics.

Computers↗
PubMed1981

Characterization of cryofibrinogen isolated from patients plasma.

The cryofibrinogen of 27 patients was studied by SDS-polyacrylamide gel electrophoresis and immunochemical methods. Electrophoretic analysis of the isolated cryofibrinogens, as well as the proteins left after heat or thrombin defibrination, showed that cryofibrinogen is composed of two proteins, fibrin(ogen) and cold-insoluble globulin (CIg). A proportion of the fibrin(ogen) component formed stabilized oligomers interlinked through gamma-gamma dimerization. The degree of fibrin(ogen) proteolysis, as judged by measuring the alpha:gamma ratio of the reduced samples, was very similar to that of the fibrinogen of the original plasma. The CIg:fibrin(ogen) molar ratio in the cryofibrinogens was 0.04 +/- 0.018. The CIg and the fibrin(ogen) content of the cryofibrinogens were strongly correlated with the plasma CIg levels.

Cold Temperature↗
PubMedDate not supplied

A bioequivalence study of levothyroxine tablets versus an oral levothyroxine solution in healthy volunteers.

Probably for genetic reasons a substantial part of the Greek population requires Levothyroxine treatment. Since commercially available Levothyroxine was first marketed, the manufacture and storage of the drug in tablet form has been complicated and difficult; and as cases of therapeutic failure have frequently been reported following treatment with this medicinal agent, quality control is an essential factor. Due to the unreliability of Levothyroxine-based commercial products, in the present study we decided to follow the Food and Drug Administration (FDA) guidelines*, and use a Levothyroxine solution as reference product. The bioavailability of the Levothyroxine sodium tablet formulation THYROHORMONE/Ni-The Ltd (0.2 mg/tab) and that of a reference oral solution (0.3 mg/100 ml) under fasting conditions were compared in an open, randomized, single-dose two-way crossover study. Twenty four healthy Caucasian volunteers (M/F=15/9, mean age=32.9+/-7.4yr) participated in the study. Bioavailability was assessed by pharmacokinetic parameters such as the area under plasma concentration-time curve from time zero up to the measurable last time point (AUC(last)) and the maximum plasma concentration (Cmax). Heparinized venous blood samples were collected pre-dose and up to a 48-hour period post-dose. Levothyroxine sodium in plasma samples was assayed by a validated electrochemiluninescent immunoassay technique. Statistical analysis showed that the post-dose thyrotropin-stimulating hormone (TSH) levels decreased significantly (p<0.05). Regarding Levothyroxine (T4), the point estimate of the test formulation to the reference formulation ratios (T/R) for AUC(last) and Cmax was 0.92 with 90% confidence limits (0.90, 0.94) and 0.93 with 90% confidence limits (0.91, 0.94), respectively. Regarding triiodo-L-thyronine (T3), the point estimate for the T/R ratios of AUC(last) and Cmax was 0.92 with 90% confidence limits (0.90, 0.95) and 0.94 with 90% confidence limits (0.92, 0.95), respectively. The 90% confidence limits for the pharmacokinetic parameters AUC(last) and Cmax lie within the acceptance limits for bioequivalence (0.80, 1.25), for both T3 and T4.

Administration, Oral↗
PubMedDate not supplied

Infantile liver giant cells: immunohistological study of their proliferative state and possible mechanisms of formation.

The mechanism of liver giant cell formation is not clarified. Some authors consider the giant cells regenerative, others, degenerative. Paraffin sections of 10 archival cases of idiopathic neonatal hepatitis (INH), 8 of extrahepatic biliary atresia (EHBA), and 5 normal liver samples were immunostained with two well-characterized cell proliferation markers: anti-PCNA monoclonal antibody (MAb) (clone PC-10) and MAb MIB-1, which detects Ki-67, a nuclear proliferation-related antigen. In addition, polyclonal antibody to carcinoembryonic antigen (CEA) was used to identify remnants of canalicular, therefore hepatocytic, membranes in giant cells. Quantitative analysis of immunostaining was done by estimating PCNA and Ki-67 indices separately in giant cells and in nongiant hepatocytes. In normal samples, mean PCNA and Ki-67 indices were 1. 22% and 0.74%, respectively. In the cases of INH and EHBA, only a small minority of giant cells showed PCNA or Ki-67 staining limited to occasional peripherally located nuclei. PCNA and Ki-67 indices were significantly higher in the non-giant cell compartment. CEA staining was seen only in rare giant cells as centrally located canalicular remnants bordered by polarized nuclei, suggesting that they had been formed from rosettes through dissolution of cell membranes. Other giant cells shared CEA-labeled canalicular membranes with mononuclear hepatocytes in rosettes. These findings indicate that the giant cells in INH and EHBA are not regenerative cells, they are not formed by amitotic division of nuclei in syncytia, and that fusion of rosette-forming hepatocytes is a possible mechanism of their formation.

Antigens, Nuclear↗