The N-terminal amino acid of apolipoprotein D is putatively covalently bound to 3-hydroxy-3-methyl hexanoic acid, a key odour compound in axillary sweat.

Axillary sweat is odourless when freshly collected at the surface of human skin, but it contains non-odoriferous precursors, which can be transformed into odorous substances by bacteria. E-3-methyl-2-hexanoic acid (3M2H) is one of the key odorous substances, but there are two contradictory reports about its precursor form. One report states that 3M2H linked non-covalently to apolipoprotein D (apoD) is the precursor, while a second report states that 3M2H-Gln identified in human axillary sweat is the precursor. Recently, 3-hydroxy-3-methyl hexanoic acid (HMHA) and 3-methyl-3-sulfanylhexane-1-ol (3M3T) have also been identified and reported as characteristic components found in apocrine sweat. To better understand the formation of axillary odours and the structural relationships between these compounds and apoD, we characterized the linkage between odorous substances and apoD in human axillary secretions. ApoD was purified from human axillary secretions collected from 50 healthy female volunteers and was then digested by trypsin and analysed by MALDI-TOF mass spectrometry. A Mascot search showed that 8 peaks identified in the trypsin-digested samples correspond to the masses calculated for theoretically digested apoD sequences and the purified protein was assigned as a precursor of apoD [Homo sapiens]. One spectrum corresponded to the theoretical peak of HMHA linked covalently to the N-terminal fragment of apoD. In contrast, no spectrum corresponded to the theoretical peak of a 3M2H adduct or to an unmodified N-terminal fragment of apoD. These results indicate a possibility that HMHA binds covalently to the N-terminal amino acid of apoD in human axillary secretions.

Knemidokoptiasis in a Wild Bird, the Little Spiderhunter ( Arachnothera longirostra cinereicollis), in Sumatra, Indonesia.

We report knemidokoptiasis in a wild male Little Spiderhunter ( Arachnothera longirostra cinereicollis; family Nectariniidae; order Passeriformes) from Jambi, Sumatra, Indonesia, in September 2017. Microscopic examination of a scraping from its leg lesion revealed the presence of Knemidocoptes jamaicensis as the cause of the condition.

Recombinant human interleukin 1 alpha is cytotoxic for and increases surface expression of HLA-A,B,C antigens of a human hepatoma cell line, PLC/PRF/5.

Our study was undertaken to determine whether human recombinant interleukin 1 alpha (rIL 1 alpha) has any effect on the proliferation and expression of HLA-A,B,C antigens of human liver cell lines. The addition of rIL 1 alpha reduced the cell number of the human hepatoma cell line, PLC/PRF/5. This effect was determined to be cytotoxic, but not growth inhibitory, rIL 1 alpha did not change the number of Chang cell or SK-Hep-1 at a concentration as, high as 25,000 U/ml. rIL 1 alpha enhanced the expression of HLA-A,B,C antigens on PLC/PRF/5, but had no effect on Change cell or SK-Hep-1. Receptor binding studies showed that 125I-rIL 1 alpha bound to PLC/PRF/5 in a specific and saturable manner, but did not bind to Chang cell or SK-Hep-1. Scatchard plot analysis of the binding to PLC/PRF/5 revealed a single type of high affinity binding site with an apparent dissociation constant of approximately 5 x 10(-5) M and the presence of approximately 150 binding sites per cell. These findings suggest that IL 1 alpha may play a role in host defense against some hepatomas as cytotoxic factor and may be an enhancer of expression of HLA-A,B,C antigens on tumor cells.

An outbreak of foodborne hepatitis A in a factory: a possible shift in age of patients in Japan.

We investigated extensively an outbreak of hepatitis A at a factory in suburban Nagoya. Epidemiological study indicated a foodborne outbreak by a supplier of lunches. Serologically, all the employees younger than 30 years of age had been susceptible to hepatitis A virus, but the highest morbidity was observed in the 40-44 age group. The age difference in morbidity from foodborne hepatitis and susceptible populations suggests a shift in mean patient age linked to a shift in antibody prevalence to hepatitis A virus. In communities where the prevalence started shifting after development of sanitary systems, effective prophylaxis for foodborne hepatitis A will be necessary to prevent the disease in an increasing number of older patients in a few decades.

Interferon-gamma receptors on T cells in patients with chronic liver disease.

Interferon-gamma (IFN-gamma) appears to be important for the activation of T cells, and its binding to IFN-gamma receptors on T cells is an essential step for its actions. We investigated the expression of IFN-gamma receptors on T cells in chronic liver disease using radioiodinated recombinant interferon-gamma binding assay, and by Scatchard analysis. The mean numbers of IFN-gamma receptors on T cells from controls, asymptomatic hepatitis B virus carriers (ASC), patients with chronic active hepatitis (CAH), and patients with liver cirrhosis (LC) were 2,205 +/- 497, 2,494 +/- 1,074, 1,925 +/- 735, and 1,666 +/- 653, respectively. The numbers of IFN-gamma receptors on T cells from the patients with LC were significantly smaller than those of controls (P less than 0.05). Kids of IFN-gamma receptor on T cells from control and patient groups were 2.3 4.8 x 10(-9) M, and there was no significant difference among the groups. The percentage of T cells reactive with OKT3, OKT4, or OKT8 was similar in control and patient groups. These findings suggest that the decrease in IFN-gamma receptors in LC is not related to the activity of the liver damage, but is associated with the severity of the underlying disease. The normal expression of IFN-gamma receptors on T cells from CAH may provide a reasonable basis for IFN-gamma therapy to type B CAH.

Serum levels of alpha-interferon and gamma-interferon in patients with acute and chronic viral hepatitis.

We measured activities of alpha- and gamma-interferon simultaneously in 198 sera of 70 patients with acute and chronic viral hepatitis using specific and sensitive enzyme immunoassay and immunoradiometric assay. The results were compared with those in patients with influenza and in healthy controls. Twelve out of 28 patients with acute viral hepatitis showed positive alpha-IFN and/or gamma-IFN activities. alpha-IFN was detectable throughout the clinical course while gamma-IFN levels rose in the convalescent phase regardless of etiology. Conversely, in patients with influenza, both alpha-IFN and gamma-IFN levels of initial samples tended to be higher than those of late samples. Six out of 12 patients with chronic active type B hepatitis showed increased alpha-IFN and/or gamma-IFN values during acute deterioration with marked elevation of serum alanine aminotransferase. However, the two interferons did not always appear simultaneously, although either was detectable in both acute and chronic hepatitis. Enhanced alpha-IFN or gamma-IFN activity was not found in asymptomatic chronic hepatitis B carriers or in patients with chronic persistent hepatitis and liver cirrhosis with chronic hepatitis B virus infection, with the exception of 2 cases. Our results indicated that circulating multiple IFN species were present during the clinical course in some patients with acute and chronic viral hepatitis.

A patient with chronic hepatitis C who obtained sustained response by retreatment of interferon after decrease of viral load and mutation in interferon sensitivity determining region.

A 44-year-old man with chronic hepatitis C received three courses of interferon (IFN) therapy. HCV genotype was 1b, viral load was 1,200 kcopies/ml and interferon sensitivity determining region (ISDR) was the intermediate type before the 1st IFN therapy. The 1st and 2nd IFN therapies resulted in failure to yield a sustained response. Seven years after from the 1st therapy, viral load had decreased to 15 kcopies/ml and ISDR had changed to mutant type. The 3rd IFN therapy yielded sustained response. Thus, we should consider retreatment with IFN when a decrease of the viral load and change of ISDR to mutant type are observed.

Giant hepatic angiomyolipoma associated with disseminated intravascular coagulation.

We report a case of giant hepatic angiomyolipoma in a 68-year-old woman who had an increase in the fibrinolytic activity concomitant with disseminated intravascular coagulation (DIC). The presence of the tumor was confirmed by ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen and the selective arteriography of the liver via the superior mesenteric artery. Following treatment with heparin and gabexate mesilate, abnormal hemostatic values were corrected. Furthermore, the surgical removal of the huge hepatic angiomyolipoma completely normalized the alternations of the clotting system. These findings suggest that giant hepatic angiomyolipoma was profoundly associated with DIC.

Profiles of progesterone- and estradiol-like substances in the hemolymph of female Pandalus kessleri during an annual reproductive cycle.

The changes in GSI and HSI of Pandalus kessleri were monitored during an annual reproductive cycle. GSI reached a peak when ovaries were composed of yolky oocytes and decreased sharply during the spawning season. HSI followed a similar pattern. The changes in the concentrations of progesterone- and estradiol-17 beta-like substances in the hemolymph were also investigated. Progesterone levels increased at the onset of vitellogenesis and decreased during vitellogenesis. In contrast, estradiol concentrations rose during the peak of vitellogenesis and dropped after the release of mature eggs from the gonad.

Interleukin 1 alpha production by peripheral blood monocytes from patients with chronic liver disease and effect of sera on interleukin 1 alpha production.

We investigated the role of interleukin 1 alpha (IL 1 alpha) in the pathogenesis of chronic liver disease. IL 1 alpha production by peripheral blood monocytes was measured with a specific, sensitive double-antibody radioimmunoassay. When monocytes were cultured for two days with bacterial lipopolysaccharide (LPS), IL 1 alpha production in asymptomatic hepatitis B virus carrier (ASC) and patients with chronic active hepatitis (CAH) was equivalent to that of controls (168 +/- 31 U/ml, mena +/- SD), while IL 1 alpha levels generated by monocytes from liver cirrhosis (LC) (117 +/- 45 U/ml, p less than 0.01) were significantly lower than controls. When normal monocytes were cultured together with LPS and IFN gamma, mena IL 1 alpha production was 297 +/- 56 U/ml. IL 1 alpha production in ASC did not differ from controls. On the other hand, IL 1 alpha production in patients with CAH (241 +/- 58 U/ml, p less than 0.05) and LC (189 +/- 70 U/ml, p less than 0.01) were significantly diminished in comparison with controls although there was considerable overlap. Serial study demonstrated that IL 1 alpha production rose significantly during acute deterioration of illness with marked rise in serum alanine aminotransferase. The addition of sera to normal monocytes cultures resulted in significantly enhanced suppression (p less than 0.05) for IL 1 alpha production in comparison with that of control sera. These findings indicate that decreased monocyte function and serum inhibitor(s) for IL 1 alpha production could contribute to the pathogenesis of chronic liver disease.

Interleukin 2 receptor bearing T lymphocytes in patients with chronic liver disease.

We investigated the role of interleukin 2 receptor expression (IL 2R) on T cell in chronic liver disease. IL 2R was determined by analysing T cell surface Tac antigen with anti-Tac, a monoclonal antibody that binds at or near the binding site for IL 2, using a fluorescence-activated cell sorter. The percentage of Tac+ cells in T cell fraction from peripheral blood mononuclear cells in unstimulated cultures was 7.9 +/- 2.1% (+/- SD) in controls. A similar value was obtained in asymptomatic carriers of HBsAg (ASC), in patients with chronic active hepatitis (CAH) and liver cirrhosis (LC). Upon stimulatin with recombinant IL 2, there was a small but significant increase in Tac+ cells. The percentages of Tac+ cells in IL 2-stimulated cultures were significantly lower in ASC (P less than 0.01), patients with CAH (P less than 0.01) and LC (P less than 0.05) as compared to controls (16.4 +/- 4.4%). Percentages of Tac+ cells after stimulation with phytohemagglutinin P (PHA-P) in ASC and CAH did not differ from controls (74.9 +/- 5.9%). Only patients with LC showed diminished Tac+ cells (P less than 0.01) compared to controls. During a 4-wk course of recombinant IL 2 therapy, a serial study on 5 HBeAg-positive patients with CAH was done, and the results showed that Tac+ cells were significantly diminished 2 wk (P less than 0.01) and 4 wk (P less than 0.05) after starting therapy in comparison with pretreatment levels in IL 2-stimulated cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies against liver cell membrane antigens detected by enzyme-linked immunosorbent assay in acute and chronic liver disease.

An enzyme-linked immunosorbent assay was developed to detect serum antibody binding to liver membrane antigen derived from human hepatoma cell line SK-Hep-1. When we tested sera from 214 patients with this assay, IgM antibodies were detected in 100% of patients with acute type A, but not with type B or non-A, non-B hepatitis. IgM antibodies were also found in highest frequency (76%) and titer in patients with autoimmune chronic active hepatitis (CAH) among chronic liver disease groups. IgG antibodies occurred in over 50% of patients with acute type A hepatitis, type B chronic active liver disease (CALD), and autoimmune CAH. IgA antibodies were present in 43% of the patients with alcoholic liver disease, but were also seen in other patient groups. When freshly isolated rat hepatocytes were used as target cells, prevalences and titers similar to those obtained with SK-Hep-1 were found. The levels of serum membrane binding antibody were significantly reduced by the addition of human liver-specific membrane lipoprotein in all patient groups. In particular, IgM antibodies became negative in over 50% of patients with CALD (both type B and non-A, non-B) and autoimmune CAH, whereas in acute hepatitis over 50% lost their positivity for IgG antibody. These results indicate that circulating liver membrane binding autoantibodies are heterogeneous, occurring in hepatitis virus-induced acute and chronic liver disease as well as in autoimmune CAH.

Phenotypic expression of natural killer cell associated membrane antigens in patients with chronic liver disease and hepatocellular carcinoma.

The function and phenotypes of peripheral blood natural killer (NK) cells from patients with chronic liver disease and hepatocellular carcinoma (HCC) were examined using a 4 hr 51Cr release NK assay and two-color flow cytometry utilizing anti-Leu-7 and anti-Leu-11 monoclonal antibodies. There was no significant difference between control and patient groups in the percent representation of a total of NK, Leu-7-11+ or Leu-7+11- cells except that the percent representation of Leu-7+11- cells was significantly increased in patients with liver cirrhosis (LC) in comparison with that of chronic active hepatitis (CAH). On the other hand, patients with LC and HCC had lower absolute numbers of a total of NK, Leu-7-11+ and Leu-7+11- cells than did controls or patients with CAH, reflecting the diminished peripheral blood lymphocyte count. Our data indicate that decreased in vitro NK activity in patients with LC and HCC observed in the present study may be due to a functional defect of NK cells.

Enhancement of antibody production to hepatitis B surface antigen by interleukin 2.

Studies were undertaken to determine whether induction of antibody to hepatitis B surface antigen (anti-HBs) production by cultured lymphocytes which had been conducted with pokeweed mitogen (PWM) could be replaced by interleukin 2 (IL 2). In cultures stimulated with purified HBsAg and IL 2, the comparable levels of anti-HBs production to those obtained in cultures stimulated with PWM alone occurred when peripheral blood mononuclear cells (PBMC) from patients positive for serum anti-HBs and recipients of HBsAg vaccine were used as effector cells. Detectable amounts of anti-HBs were produced only when IL 2 was added to the second-set cultures again. IL 2 or HBsAg alone, however, did not induce anti-HBs production. Anti-HBs production was not observed by the additions of these additives when PBMC from chronic HBsAg carriers and control individuals were used. These findings indicate that IL 2 could modulate the immune response to HBsAg.

Interferon-gamma production by peripheral blood mononuclear cells of patients with chronic liver disease.

We investigated the role of the interferon system in the pathogenesis of chronic liver disease. Interferon-gamma production by peripheral blood mononuclear cells was measured with an ELISA. While concanavalin A-stimulated and recombinant interleukin 2-stimulated production of interferon-gamma in patients with chronic active hepatitis and liver cirrhosis was significantly decreased when compared with that of controls (518 +/- 189 and 729 +/- 195 units per ml, mean +/- S.D.), there was also a lot of overlap. Addition of indomethacin to the cultures partially restored interferon-gamma production in patients with chronic active hepatitis and liver cirrhosis, indicating that suppressor function of monocytes was, in part, responsible for the diminished interferon-gamma production. Serial studies showed that interferon-gamma production rose during acute deterioration of illness, during treatment with interleukin 2 and with the improvement of clinical course. Interferon-gamma production was not different among hepatitis B e antigen or antibody positive, and non-A, non-B patients with chronic active hepatitis and liver cirrhosis. Our findings suggest that diminished interferon-gamma production is associated with disease severity in chronic liver disease, irrespective of the hepatitis B virus carrier state. It would be interesting to compare the efficacy of treatment with interferon-gamma or interferon-gamma inducers such as interleukin 2 in chronic hepatitis B patients with and without decreased in vitro interferon-gamma production.

Proliferation and immunoglobulin synthesis of peripheral blood mononuclear cells from patients with chronic liver disease stimulated by Staphylococcus aureus Cowan 1 and interleukin 2.

Proliferation and IgG synthesis of peripheral blood mononuclear cells (PBMC) in response to stimulation with recombinant interleukin 2 (IL-2) and Staphylococcus aureus Cowan 1 (SAC) were evaluated in 32 patients with chronic persistent hepatitis (CPH), chronic active hepatitis (CAH) and liver cirrhosis (LC). Eleven patients had serum HBe antigen, 10 presented with HBe antibody and 11 had non-A, non-B hepatitis. IgG synthesis of PBMC induced with the two stimuli was significantly decreased in patients with CAH and LC when compared with that of controls. However, the generated amounts of IgG were not associated with the HB virus carrier state. B cells and T4+ cells were responsible for the diminished IgG synthesis in patients with CAH and LC when assessed by coculture experiments. On the other hand, proliferative response of PBMC to IL-2 and SAC were similar in controls and patient groups. These findings indicate that IgG production level of PBMC stimulated with IL-2 and SAC can reflect the severity of the underlying disease in chronic hepatitis patients.