Serum prohepcidin levels in chronic hepatitis C,alcoholic liver disease,and nonalcoholic fatty liver disease

Background/Aims

Patients with various chronic liver diseases frequently have increased body iron stores. Prohepcidin is an easily measurable precursor of hepcidin, which is a key regulator of iron homeostasis. This study investigated the serum prohepcidin levels in patients with various chronic liver diseases with various etiologies.

Methods

Serum prohepcidin levels were measured in patients with chronic hepatitis C (CH-C) (n=28), nonalcoholic fatty liver disease (NAFLD) (n=24), and alcoholic liver disease (ALD) (n=22), and in healthy controls (n=25) using commercial ELISA. Serum interleukin 6 (IL-6) levels and blood iron indices were also measured.

Results

The serum levels of both prohepcidin and IL-6 were significantly higher in CH-C patients than in healthy controls, and there was a positive correlation between the IL-6 and prohepcidin levels (r=0.505, p=0.020). The prohepcidin levels in ALD patients did not differ from those in controls, despite their significantly elevated IL-6 levels. There was a tendency for a negative correlation between serum prohepcidin levels and transferrin saturation in ALD patients (r=-0.420, p=0.051). Neither prohepcidin nor IL-6 was significantly elevated in the NAFLD group, despite the presence of elevated serum iron and ferritin levels.

Conclusions

The role of prohepcidin may differ in different human liver diseases. In the setting of CH-C, both the serum prohepcidin and IL-6 levels were significantly elevated and were positively correlated with each other.     

Sustained elimination of hepatitis B virus from serum induced in a patient with chronic hepatitis B and advanced human immunodeficiency virus infection

A 48-year-old male patient was admitted with acquired immunodeficiency syndrome (stage III, Centers for Disease Control 1993) and viremic hepatitis B. Blood CD4 count was 15/l. Discontinuation of prednisolone, previously prescribed by the patient's family practitioner because of elevated liver enzymes, resulted in severe hepatitis (alanine aminotransferase > 300U/1). Administration of interferon-, (9 × 10⁶U s.c. 3 × weekly) was initiated. Serum markers of viral replication disappeared, and aminotransferase levels returned to normal within a few weeks. The patient's serum was found negative for HBsAg after 3 months. Immunohistochemical analysis of liver biopsies before and during interferon therapy showed disappearance of all hepatitis B virus antigens and a marked reduction in inflammatory activity. Hepatitis B virus seroconversion remained stable until the patient died from the syndrome 2 years later. This case shows that in spite of severe HIV-associated immune deficiency with CD4 counts constantly below 100/l, interferon- can lead to sustained serological and histological improvement of viremic hepatitis B. Previous administration and discontinuation of cortisone may have helped to reach this effect.Abbreviations HBV hepatitis B virus - HIV human immunodeficiency virus - IFN interferon Correspondence to: G. Gerken     

Implantation: Clinical evidence for a detrimental effect on uterine receptivity of high serum oestradiol concentrations in high and normal responder patients

This study was undertaken to investigate an empirical observationthat ‘high responder patients have poorer in-vitro fertilization(IVF) outcome than normal responder patients’. The aimof our study was to analyse the effect of high serum oestradioland progesterone concentrations at the day of human chorionicgonadotrophin (HCG) administration on endometrial receptivityand oocyte—embryo quality in high and normal responderpatients. The IVF patients were divided into two groups: 59high responder patients who voluntarily donated some of theiroocytes, and a control group consisting of 105 normal responderpatients. Both groups were compared in terms of the number andquality of oocytes retrieved, embryos transferred, fertilization,implantation and gestation rates, serum oestradiol and progesteroneconcentrations and the oestradiol: progesterone ratio on theday of HCG injection. To ascertain oocyte—embryo quality,a second control group of 96 women undergoing oocyte donation(receiving oocytes from high responder patients) was considered.To assess the impact of steroid concentrations on endometrialreceptivity, high responder patients were divided into two subgroupsaccording to oestradiol concentration, above or below the minimaloestradiol and progesterone concentrations (mean – SD)in this group. The normal responder patients were divided intotwo subgroups according to oestradiol concentration, above orbelow the maximal oestradiol and progesterone concentrations(mean + SD) in this group. To assess further the relevance ofoestradiol concentration on endometrial receptivity, patientswere divided into different subgroups according to increasingoestradiol concentration, regardless of whether they were highor normal responders. High responder patients had significantlydecreased implantation and pregnancy rates per cycle comparedwith normal responder patients (33.3 versus 16.3 and 11.1 versus5.4% respectively; P < 0.05). The results of 108 embryo transfersin 91 recipients who received oocytes from the high respondergroup showed normal embryo quality. Implantation rates and pregnanciesper cycle were significantly lower in high responder patientswith serum oestradiol concentrations > 1700 pg/ml comparedwith those having oestradiol concentrations 1700 pg/ml, as wellas in normal responder patients with serum oestradiol concentrations2200 pg/ml compared with those having oestradiol concentrations<2200 pg/ml. Considering all the patients together, significantdecreases in pregnancy and implantation rates were observedwhen oestradiol concentrations were >2500 pg/ml comparedwith patients having lower oestradiol concentrations. Our clinicalresults demonstrate that high serum oestradiol concentrationson the day of HCG injection in high and normal responder patients,regardless of the number of oocytes retrieved and the serumprogesterone concentration, are detrimental to uterine receptivitywithout affecting embryo quality.     

Behavior of soluble HLA class I antigens in patients with chronic hepatitis C during interferon therapy: An early predictor marker of response?

Soluble HLA class I antigens (sHLA-I), ₂-microglobulin ( ₂-.) and alanine aminotransferase (ALT) serum levels have been evaluated in 16 patients affected by chronic hepatitis C treated for six months with recombinant interferon- (rIFN-, 3 MU three times a week). The predictor role of sHLA-I and ALT modifications with respect to the response to rIFN- therapy was also evaluated. Six patients responded (group 1), five patients relapsed following an initial response (group 2), and five did not respond to rIFN- treatment (group 3). The baseline serum levels of sHLA-I and ₂- were significantly higher in all three groups of HCV-positive patients with respect to HCV-negative controls (P<0.05). A significant increase of sHLA-I serum level with respect to baseline value (P<0.001) was observed in group 1 patients after two weeks of rIFN- treatment. sHLA-I serum level then decreased, although remaining steadily and significantly increased with respect to baseline (P values ranging from 0.05 to 0.01) in the following five months and then returned to baseline one month after the end of rIFN- administration. No significant variations of ₂- serum levels were detected throughout the observation period. In group 1 patients ALT serum levels significantly decreased after two weeks of rIFN- treatment (P<0.001) and then remained in the normal range throughout the observation period. In the other two groups of patients no relevant variations of sHLA-I and ₂- serum levels were found during and after rIFN- therapy. The modifications of sHLA-I serum levels discriminate, as a single marker, group 1 patients from group 2 and 3 patients after two weeks of rIFN- treatment (P<0.003). The association of sHLA-I and ALT modifications improves the discriminant power and leads to a complete differentiation of the three groups of patients after four weeks of rIFN- treatment (P<0.0001). If confirmed in a larger series of patients, these results will provide a useful marker to predict which patients affected by chronic hepatitis C will respond to treatment and will help to avoid their ineffective treatment with an expensive and potentially harmful drug.     

Andrology: Pituitary-testicular axis in men with {beta}-thalassaemia major

Delayed puberty and hypogonadism are frequently observed inpatients with homozygous -thalassaemia. We evaluated the pituitary-testicularaxis in 30 thalassaemic men, aged from 17 to 35 years who wereregularly trans fused and underwent chelation therapy, whileemphasis was given to pituitary reserves of gonadotrophins andthe correlation of hormones with serum ferritin (SF). The investigationincluded endocrinological examination, evaluation of serum basallevels of follicle stimulating hormone (FSH), luteinizing hormone(LH), free testosterone and gonadotropbin-releasing hormone(GnRH) test and also spermiograms. According to the results,patients were divided into three groups: group A, which included18 eugonadal patients with moderately elevated SF, group B whichincluded six patients who had hypogonadotrophic hypogonadismand excessive elevation of SF, and group C, which included sixpatients characterized as intermediate, with regard to sexualmaturation and SF levels. In conclusion, -thalassaemia majorleads to variable pituitary iron overload and thus hypophysealdamage. This endocrine disturbance is becoming less frequentnowadays with early and intensive chelation therapy.     

Uselessness of liver biopsy in patients with hepatitis C virus chronic infection and persistently normal aminotransferase levels

This case-control study evaluated the real need for liver biopsy in subjects with persistently normal aminotransferase values over a long period by comparing the histological features of these subjects with those of patients with abnormal aminotransferase values. We considered as "Cases" all 32 consecutive anti-HCV/HCV-RNA positive subjects with at least eight normal serum ALT values during the last twelve months; for each "Case", we selected as a "Control" one anti-HCV/HCV-RNA positive patient with at least two abnormal serum ALT values during the last twelve months. The Cases and Controls were matched for age ( 5 years) and sex. In the Case group, 1 subject showed normal liver tissue, 18 minimal chronic hepatitis (CH) and 13 mild CH. In the Control group, 7 subjects showed minimal CH, 19 mild CH, 3 moderate CH, 1 severe CH and 2 cirrhosis. The subjects in the Control group showed a significantly higher HAI score (5.39+2.81) than those in the Case group (2.96+1.62, p < 0.001). The subjects in the Control group more frequently showed a fibrosis score greater than 1 (28.1%) compared to the Case group (9.4%; p<0.05). Finally, steatosis was more frequent and more severe in the Control group than in the Case group (respectively, 78.1% vs 50%, p < 0.05; and 1.47+1.16 vs 0.6+0.71, p < 0.001). The HAI and fibrosis scores did not correlate with the ALT value, HCV genotype or HCV viral load in either the Case or Control group. Our findings showed that the subjects with a persistently normal serum ALT value had minimal or mild chronic hepatitis, thus demonstrating that a liver biopsy is not indicated for these subjects.     

Oxidative Stress Level in Circulating Neutrophils Is Linked to Neurodegenerative Diseases

Alzheimers and Parkinsons diseases are the most common neurodegenerative conditions. Oxidative lesions are a hallmark of both diseases, but the respective roles of systemic and cerebral dysfunction are not elucidated. As circulating neutrophils are the most powerful sources of reactive oxygen species, we measured oxidative stress levels in resting neutrophils from 44 Alzheimers and Parkinsons disease patients and compared them to 40 healthy counterparts. Significantly increased oxidative stress levels were observed in patients groups, while control groups had very similar levels irrespective of age. One-third of the neurodegenerative patients presented with oxidative stress levels higher than those of any healthy donor. This increase was not due to an elevated production of reactive oxygen species during the neutrophil oxidative burst. Mitochondrial mass and activity were altered in neutrophils of the Parkinsonian group compared to controls, but not in those from Alzheimers disease group. To our knowledge, this is the first report linking oxidative stress and mitochondrial parameters in circulating neutrophils from neurodegenerative and normal donors. Our results indicate that oxidative stress levels in circulating neutrophils are of interest for further mechanistic studies of neurodegenerative diseases and might open the perspective of a diagnostic tool.     

Suppressed thyroid-stimulating hormone secretion in patients treated with interleukin-2 and interferon-α2b for metastatic melanoma

Recent reports suggest that combined therapy with recombinant interleukin (IL)-2 and interferon (IFN) alb may result in autoimmune-induced thyroid dysfunction. We prospectively analyzed thyroid function for 6 weeks in two groups of patients with progressive metastatic melanoma treated according to two different protocols. In group I (n =17) three treatment cycles were given, each with three weeks of subcutanous administration of rIL-2 and INF-_2b at different doses. In group 11 (n=13) the chemotherapeutic agent dacarbazine was given in addition. In group 1 three patients developed frank hyperthyroidism, which required antithyroid drug therapy in one case. Autoantibodies against thyroid microsomal antigen, thyroglobulin, and the thyroid-stimulating hormone (TSH) receptor were not significantly elevated in any of these patients. However, the remaining 14 patients showed a significant decrease in TSH after 6 weeks of treatment, from 1.8 ± 0.9 to 0.7 ± 0.7 U/ml (P < 0.02). Thyroid hormones (triiodothyronine, thyroxine, free thyroxine) also increased during the observation time, but this did not parallel the drop in TSH levels. Only thyroxine increased above the upper limit of normal, while triiodothyronine and free thyroxine stayed within the normal range. In group 11, 6 of 13 patients (46%) had a decreased TSH after 6 weeks of treatment. Mean TSH was 1.5±1.4 before and 0.8 ± 0.6 U/ml after 6 weeks and was totally suppressed in three cases. None of these patients showed ouvert hyperthyroidism. Hypothyroidism was not observed in either group. We conclude that treatment with rIL-2 and INF-_2b may not only be associated with autoimmune thyroiditis and hyperthyroidism but also results in suppression of TSH levels while the patients remain euthyroid.Abbreviations IL interleukin - INF interferon - TSH thyroid-stimulating hormone - T3 triiodothyronine - T₄ thyroxine - fro free thyroxine Correspondence to: H. Mönig     

Sicam-1, sCD95 and sCD95L Levels in Chronic Liver Diseases of Different Etiology

Abstract

The release of soluble circulating molecules represents a prominent feature during the course of immune-mediated clinical conditions. To further assess the relationship between serum concentrations of adhesion or apoptotic-related soluble structures and liver diseases, we evaluated the levels of intercellular adhesion molecule-1 (sICAM-1), Fas receptor (CD95) and Fas ligand (sCD95L) in a group of patients affected by Hepatitis C Virus (HCV)induced chronic hepatitis (CH-C), HCV-positive liver cirrhosis with superimposed hepatocellular carcinoma (HCC), autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and alcoholic liver cirrhosis (ALC). Results show that sICAM-1 values were in all instances significantly elevated when compared to those seen in healthy donors. Similar findings were noted in subjects with liver diseases in terms of sCD95 concentrations, even if to a different degree of statistical significance. Finally, sCD95L amounts were augmented in AIH, PBC, ALC and CH-C in comparison to controls, while in the HCC counterpart sCD95L levels fell within normal range.

All together, these findings emphasize the occurrence of circulating soluble molecules in patients with various chronic liver diseases, likely reflecting the involvement of several pathogenetic mechanisms.     

194例慢性乙型肝炎病理及其与血清HBV DNA、HBeAg、ALT关系的研究

目的探讨慢性乙型肝炎病理及其与血清HBV DNA、HBeAg、ALT关系。方法对194例慢乙肝患者进行肝组织病理、HBV免疫组化检查,并检测肝功能、血清HBVM和HBV DNA。结果血清HBeAg阳性组的肝组织G2、G3~4、S2、S3~4发生率与阴性组比较差异有统计学意义,肝组织S0组与S1~4组比较差异有统计学意义,肝组织G0~1组与G2~4组、HBcAg阳性组与阴性组的HBV DNA含量比较差异亦有统计学意义,肝组织HBsAg表达为" "者与" ~ "者血清HBV DNA含量比较差异无统计学意义,肝组织达S1或(和)G2以上者血清ALT水平分别为:<40U/L组占28.57%,40~80U/L组占53.33%,81~400U/L占80.15%,>400U/L组占77.88%。结论血清HBV DNA与肝组织HBcAg表达有一致性,与肝内HBsAg无关,HBV DNA含量低可能是肝组织炎症活动度和纤维化程度高,ASC和轻度肝损害者应争取肝活检,以及时判断肝组织病理程度和治疗时机。     

sICAM-1, sCD95 and sCD95L levels in chronic liver diseases of different etiology

The release of soluble circulating molecules represents a prominent feature during the course of immune-mediated clinical conditions. To further assess the relationship between serum concentrations of adhesion or apoptotic-related soluble structures and liver diseases, we evaluated the levels of intercellular adhesion molecule-1 (sICAM-1), Fas receptor (CD95) and Fas ligand (sCD95L) in a group of patients affected by Hepatitis C Virus (HCV)induced chronic hepatitis (CH-C), HCV-positive liver cirrhosis with superimposed hepatocellular carcinoma (HCC), autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and alcoholic liver cirrhosis (ALC). Results show that sICAM-1 values were in all instances significantly elevated when compared to those seen in healthy donors. Similar findings were noted in subjects with liver diseases in terms of sCD95 concentrations, even if to a different degree of statistical significance. Finally, sCD95L amounts were augmented in AIH, PBC, ALC and CH-C in comparison to controls, while in the HCC counterpart sCD95L levels fell within normal range.

All together, these findings emphasize the occurrence of circulating soluble molecules in patients with various chronic liver diseases, likely reflecting the involvement of several pathogenetic mechanisms.     

Central Nervous System Toxoplasmosis with an Increased Proportion of Circulating γδ T Cells in a Patient with Hyper-IgM Syndrome

Hyper-IgM syndrome represents a diverse group of immunodeficiencies characterized by normal or high serum IgM concentrations with decreased or absent IgG, IgA, and IgE. The X-linked form of hyper-IgM syndrome is caused by mutations in the CD40 ligand gene, preventing its expression on activated T cells. The CD40 ligand–CD40 interaction is critical for effective isotype switching and for initiating antigen-specific T cell responses. In addition to recurrent pyogenic infections, patients with the CD40L defect also have opportunistic infections. An increased proportion of circulating T cells, shown to be important early during primary infections, has been demonstrated in numerous infectious diseases including toxoplasmosis. Here, we report a patient with hyper-IgM syndrome and CNS toxoplasmosis, who showed a marked increase in T cells in his peripheral blood and who has responded well to treatment of his toxoplasmosis and to high-dose immunoglobulin replacement therapy.     

Renin,aldosterone and arterial pressure responses to acute β-adrenergic receptor blockade in hypertensive patients

Summary The effect of acute (intravenous) -adrenergic blockade with propranolol or pindolol on arterial pressure (BP), plasma renin activity (PRA), and plasma concentration of aldosterone (PA) was evaluated in 20 essential hypertensive men. BP, PRA and PA were determined during continuous recumbency overnight (8 p.m. to 6 a.m.) every 30 min. Two groups of patients were observed. Patients of group I exhibited a characteristic day-night rhythm of PRA with low values before midnight and large increases early in the morning. Conversely, no rhythm and very low PRA values were observed in patients of group II. BP was higher in group II than in group I. In group I following intravenous propranolol or pindolol, BP fell within minutes and levels as well as rhythms of PRA were converted to those of group II without treatment. In group II day-night profiles of PRA and BP remained unchanged. Rhythm and concentration of PA in the two groups were not influenced by either drug. In 4 patients of group I infusion of angiotensin II inhibitor did not lower BP. The observations suggest that in the two groups dissimilarities in rhythms of PRA as well as in BP responses to -blockade may reflect differences in neuro-adrenergic tone.     

Anticonvulsant therapy and serumγ-glutamyl-transferase

Summary In 230 adult epileptic patients on long-term anticonvulsant therapy both serum drug levels and -glutamyl-transferase (GT) activities were determined and presented in groups according to the drug or drug combination in use. The GT activities measured never exceeded 250 U/l, there was a marked sex difference with lower values for females in all groups. The incidence of elevated GT values was between 90 and 100% for patients treated with diphenylhydantoin (DPH), phenobarbital (Pb), primidone (Prim) and combinations (Comb.), but lower for patients treated with carbamazepine (Cz). In this group with Cz-therapy mean value and standard deviation of GT values were also much lower than in the other groups. Only females with DPH alone and males with Pb alone showed a significant but slight correlation between drug levels and GT. These findings permit the assumption that serum GT is induced by treatment with DPH, Pb, Prim and Comb., to a lesser extent with Cz. Relating GT elevation to clinical data other than anticonvulsant drug therapy (e.g. age, type of seizures, duration of illness, history of intoxication) did not produce any subgroup with specific and consistent behaviour of serum GT. DPH-saturation did not appear to play an important part in GT elevation, rather the strongest stimulus for GT elevation seemed to derive from the initiation of anticonvulsant therapy and the highest levels of serum GT were reached between 1 and 4 weeks before the highest anticonvulsant levels. With long-term anticonvulsant therapy there appeared to be a direct relationship between serum GT and drug level for individual patients. Simultaneous estimations of serum drug levels and GT activities are helpful for monitoring patient compliance during long-term anticonvulsant therapy.     

β2-microglobulin and other proteins in serum and urine during preeclampsia

Summary Serum and urine samples of 5 patients with preeclampsia, an equal number with preeclampsia superimposed upon chronic pyelonephritis, and 20 normal pregnant women were analysed for fibrin split products (immunoelectrophoresis) and other proteins (Oudin-method) including ₂-microglobulin (radioimmunoassay).No fibrin split products could be detected in normal pregnant women or those with preeclampsia superimposed upon chronic pyelonephritis. Distinctly abnormal values were found, however, in the patients with preeclampsia (split D, 27.2±5.1 mg% (S.D.) in serum and 162±55mg/24 h (S.D.) in urine; split E, 0.3±0.1 mg% (S.D.) in serum and 4.2±3.1 mg%/24 h (S.D.) in the urine; fibrinogen in serum 532±146 mg% and in urine 340±78 mg/24 h (S.D.).Mean total protein excretion of patients with preeclampsia (1951±322 mg S.D./24 h) was not different from the value of patients with preeclampsia superimposed upon chronic pyelonephritis (1781±289 mg S.D./24 h).Urinary ₂-microglobulin excretion of patients with simple preeclampsia (glomerular filtration rate 100 ml/min) was 4 to 5-fold increased at term but more than 100-fold in patients whose preeclampsia was superimposed upon chronic pyelonephritis (glomerular filtration rate 30–70 ml/min).The transient urinary excretion of fibrin split products and other proteins in patients with preeclampsia and normal glomerular filtration rate is an indication of a reversible glomerular lesion, whereas the increased ₂-microglobulin excretion in this group of patients is due to a tubular lesion. In patients with preeclampsia superimposed upon chronic pyelonephritis the excretion of ₂-microglobulin is further increased which may be explained by an additional lesion of the already impaired tubular function during delivery.In serum, prealbumin was decreased to about 55% and albumin to 60% in the patients with preeclampsia and preeclampsia superimposed upon chronic pyelonephritis which cannot be explained by renal loss alone but is very likely due to an inhibition of protein synthesis in the liver cell.Contains parts of the Doctoral Thesis of D. Prüfer     

Treatment of chronic hepatitis C with cirrhosis with recombinant human granulocyte colony-stimulating factor plus recombinant interferon-alpha

Interferon therapy in cirrhotic patients with hepatitis C virus infection is not efficient. In an attempt to improve the response rate, a pilot study using recombinant human granulocyte colony-stimulating factor (rhG-CSF) alone, and in combination with recombinant interferon-alpha (rIFN), was carried out. Fifteen cirrhotic patients with hepatitis C virus infection were randomly allocated into 3 groups to receive treatment: 0.5, 1, or 1.5 μg/kg of rhG-CSF daily for 4 weeks, followed by a 4 week resting period, and by the same dose of rhG-CSF daily, plus 6 MU of rIFN 3 times weekly for 4 weeks. They then continued to receive 6 MU of rIFN alone for 4 weeks, followed by 3 MU of rIFN for 16 weeks. After the 4 weeks of treatment with rhG-CSF alone, no changes in ala-nine aminotransferase (ALT) levels were observed. No changes occurred during the resting period. Three of 10 patients who ended the rhG-CSF plus rIFN treatment period had normal ALT values. During the treatment with rIFN alone, two responders suffered a relapse. The other responder had normal ALT until the first month of follow-up. In summary, the combination of rhG-CSF and rIFN seems promising for the treatment of patients with chronic hepatitis C and liver cirrhosis. © 1995 Wiley-Liss, Inc.     

Variations with age of immunoreactive serum trypsin: Higher reference ranges in “Healthy” elderly people

Summary According to the literature, the mean values of immunoreactive serum trypsin (IRT) (RIA-gnost Hoechst) in controls vary considerably between 150 and 283 ng/ml. The reasons for these variations are unknown. The purpose of the present investigation was to study the variations of IRT in relation to age in adults. We studied 124 hospital controls, who were without evidence of pancreatic disease or renal insufficiency and who varied in age between 17 and 84 years. Utilizing the kit of Hoechst, IRT was determined in fasting serum specimens. The mean (±SD) in patients over 60 years was 469.6±197.4 ng/ml, in contrast to 309.1±118.9 ng/ml (30–59 years) and 209.7±80.7 (<30 years). Of cases over 60 years 36.5% had elevated IRT levels above 500 ng/ml. In 25 cases over 60 years no correlation was found between IRT levels and creatinine clearance and in eight of ten cases of this group with high IRT (>500 ng/ml) the serum pancreatic isoamylase levels were normal. The data indicate that in the diagnosis of pancreatic disease the higher reference ranges in the elderly people have to be taken into account. The age-related higher reference ranges seem not to be due to subclinical renal disease nor to clinically evident pancreatic disease.The RIA-gnost Trypsin was kindly supplied by Hoechst Pharma, Frankfurt/M, and the Isoamylase Test by Pharmacia, Uppsala     

An α-fetoprotein producing pancreatic cystadenocarcinoma

An autopsy case of an 83-year-old Japanese woman with pancreatic cancer with significantly elevated serum -fetoprotein levels is reported. The pancreatic tumor was a mucinous cystadeno-carcinoma with multiple metastasis to the liver. The immunohistochemistry for -fetoprotein revealed positive reactivity in the cytoplasm of cancer cells in the primary and liver metastatic lesions. The current case is the first reported in which mucinous cystadenocarcinoma of the pancreas produced -fetoprotein.Abbreviations AFP -fetoprotein - ETA enzyme immunoassay - RIA radioimmunoassay - PAS periodic acid-Schiff     

Endogenous α-melanotropin and central dopamine systems in physical and psychological stress

Summary The response of central dopamine (DA) systems to physical stress (10 s footshock, 0.5 mA, to naive rats) or psychological stress (10 s stay in experimental chamber 1 day after footshock) was studied in male rats in view of possible interactions between these neuron groups and endogenous -MSH. Three hours before stress, part of the animals were injected i.v. or intraventricularly with antiserum against -MSH or with inactivated normal rabbit serum (NRS).Characteristic response patterns were observed in different DA neuron groups by histochemical microfluorimetry: In substantia nigra, increased fluorescence intensity of DA neurons indicating increased neuronal activity, was seen on the first day (1) 5 min after physical stress or (2) 30 min after a first transfer to the experimental chamber without footshock, and on the second day (3) immediately after the psychological stress in rats given a footshock on the previous day, or (4) 5 min after the second stay in the experimental chamber in animals previously exposed to the chamber without shock. Hence, the reaction appears to occur faster the second day. No significant intensity changes were detected in the ventromedial tegmental DA neurons (A10). The arcuate DA neurons which i.a. control -MSH secretion, responded to physical stress or control manipulations in a complex way, while no significant reaction was seen after psychological stress. Differences between physical and psychological stress were also seen in serum levels of -MSH (determined by RIA).Intravenous antiserum against -MSH enhanced the response of nigral DA neurons to physical stress and led to elevated intensity levels 5 min after psychological stress when values were again decreasing in uninjected rats. Moreover, a marked rise in intensity was elicited after psychological stress in the A10 DA neurons where no change was detected in the absence of antiserum. Anti--MSH also affected the arcuate DA neurons in psychological stress. Intraventricular antiserum did not display any specific effects.These data point to a modulatory influence of circulating -MSH on the functional state of central DA systems. They further reveal different temporal response patterns of nigral and also arcuate DA neurons in relation to the two stress situations and to other types of manipulations considered to be less stressful.The investigation was supported by grants from the Swiss National Science Foundation (3.231-0.77 and 3.547-0.79), the Hartmann-Müller Stiftung and the Jubiläumsspende of the University of Zürich     

Acute ethanol consumption synergizes with trauma to increase monocyte tumor necrosis factor α production late postinjury

The hypothesis that acute ethanol uptake plus trauma can synergize to increase immunosuppression was tested. We found that, unlike non-alcohol-exposed patients, patients with acute alcohol use prior to trauma have a transient decrease in monocyte tumor necrosis factor (TNF) production during the very early postinjury (0–3 days) period. However, TNF production by these alcoholexposed patients' monocytes (MØ) became hyperelevated late postinjury (>9 days). Consequently, these massively elevated MØ TNF levels can contribute to posttrauma immunosuppression after acute alcohol use. We also demonstrate that normal monocyte activation with the superantigen,Staphylococcus enterotoxin B (SEB), results in a preferential induction of cellassociated MØ TNF production, described as characteristic of immunosuppressed trauma patients. Acutein vitro ethanol treatment down-regulated the elevated TNF production by trauma patients' MØ after either SEB, muramyl-dipeptide (MDP), interferon- plus MDP, or lipopolysaccharide (LPS) stimulation. Both SEB- and LPS-induced TNF mRNA induction was inhibited by acute alcohol treatment in normal MØ, indicating that ethanol can regulate cytokine gene expression. An additional immunosuppressive effect of acute ethanol's stimulation was suggested by its induction of elevated transforming growth factor production in trauma patients' activated MØ.