Two Autopsy Cases of Primary Leiomyosarcoma of the Liver Superiority of Muscle-specific Actin Immunoreactivity in Diagnosis

Two autopsy cases of leiomyosarcoma of the liver in a 49-year old female and 63-year-old male are reported. Both of the liver tumors showed electron microscopically dense patches in the cytoplasm and intermediate junctions between the tumor cells, suggesting a smooth muscle cell origin, irrespective of their different histological features. The nature of both tumors was confirmed by positive immunoreactivity for muscle-specific actin in the tumor cells, whereas desmin immunoreactivity was labile in both cases, showing a higher diagnostic value of the former compared with the latter in these leiomyosarcomas. Both cases, showed extensive distant metastases in spite of an evident difference in their mitotic indices, indicating that this index is not reliable for judging the metastatic potential of these tumors. Acta Pathol Jpn 41: 461–465, 1991.     

Reactivity of a monoclonal antibody produced to the histidine-rich protein of Plasmodium lophurae with Plasmodium falciparum

Monoclonal antibodies were produced against the histidine-rich protein of Plasmodium lophurae and tested for reactivity with Plasmodium falciparum antigens. One anti-histidine-rich protein monoclonal antibody showed immunological cross-reactivity with polypeptides of P. falciparum synthesized in vivo and in vitro.     

Monoclonal antibodies to three distinct epitopes on human IgE: their use for determination of allergen-specific IgE

Three different monoclonal antibodies (MAb) against human immunoglobulin E have been obtained which specifically bind to human myeloma and polyclonal IgE. The antibodies showed high avidities for soluble IgE (0.7 X 10(9) to 3.3 X 10(9) M-1). These MAb defined three distinct epitopes on IgE. A mixture of these antibodies in combination with an 125I-labelled anti-mouse Kappa chain MAb has been used to measure allergen-specific IgE. This determination was performed by a solid-phase radioimmunoassay using allergen extracts coated to either chemically activated paper discs or to polyvinyl chloride wells. This method is 4-10 times more sensitive than other previously reported procedures. A similar technique has also been applied to detect individual allergens in immunoblots of allergen extracts.     

Production of a monoclonal antibody for evaluation of hard red winter wheat cultivars to wheat streak mosaic virus

The monoclonal antibody technology has provided a means to produce a supply of highly specific uniform antibody which is useful in the detection of plant viruses and which facilitates disease resistance screening. Because of the specificity of a monoclonal antibody to an epitope, a monoclonal antibody may not react to a partially degraded protein. Wheat streak mosaic virus (WSMV) is a member of the potyvirus group and is transmitted by the wheat curl mite Eriophyes tulipae Keifer. The capsid protein of WSMV, like many potyviruses, is degraded in planta. Monoclonal antibodies produced to WSMV reacted to native as well as trypsin treated virions. The antibodies were also useful for evaluation of hard red winter wheat cultivars inoculated with WSMV in the fall or in the spring under field conditions.     

Primary and recurrent cytomegalovirus infections have different effects on human herpesvirus-6 antibodies in immunosuppressed organ graft recipients: absence of virus cross-reactivity and evidence for virus interaction.

The relationship between serum antibodies to human herpesvirus-6 (HHV-6) and cytomegalovirus (CMV) infection was studied in immunosuppressed adult organ graft recipients all of whom had IgG to both HHV-6 and Epstein-Barr virus capsid antigen (EBVCA) before operation and who had received an organ or organs from HHV-6 seropositive donors. In primary CMV infection the titre of IgG to HHV-6 rose substantially (between 32- and 512-fold) in eight out of eight patients whereas IgG to EBVCA only rose 32-fold in two patients. Moreover, the HHV-6 responses coincided closely with the CMV seroconversion. Serum absorption studies gave no evidence for antibody cross-reaction between CMV and HHV-6 because the CMV antibody titre could be reduced specifically without affecting HHV-6 antibody titres and vice versa. In recurrent CMV infection, HHV-6 antibody levels rose (32-fold) in three out of eight patients but these changes did not coincide with the CMV antibody response. Similarly, in the complete absence of CMV infection, five out of eight patients showed antibody rises to HHV-6 (between four- and 16-fold). IgG titres to EBVCA were stable in both these groups of patients. It is concluded that there is serological evidence (rising titre greater than or equal to four-fold) for genuine HHV-6 reactivation or, alternatively, for reinfection in 16 out of the 24 patients. This phenomenon was most frequent in primary CMV infection where the largest HHV-6 antibody responses were seen probably because of an, as yet, undetermined interaction between the two viruses.     

Adjuvant-dependent modulation of Th1 and Th2 responses to immunization with beta-amyloid

The role of adjuvant on the T(h)1 and T(h)2 immune responses to Abeta-immunotherapy (Abeta(42 )peptide) was examined in wild-type mice. Fine epitope analysis with overlapping oligomers of the Abeta(42) sequence identified the 1-15 region as a dominant B cell epitope. The 6-20 peptide was recognized only weakly by antisera from mice administrated with Abeta(42) peptide formulated in complete Freund's adjuvant (CFA), alum or TiterMax Gold (TMG). However, mice immunized with Abeta(42) mixed with QS21 induced a significant antibody response to the 6-20 peptide. The only T cell epitope found was within the 6-28 sequence of Abeta(42). QS21 and CFA induced the strongest humoral response to Abeta, alum was intermediate, and TMG the weakest adjuvant. Analysis of antibody isotypes specific for Abeta indicates that alum induces primarily T(h)2-type immune response, whereas TMG, CFA and QS21 shift the immune responses toward a T(h)1 phenotype. Stimulation of splenocytes from Abeta-immunized mice with Abeta(40) peptide induced strikingly different cytokine expression profiles. QS21 and CFA induced significant IFN-gamma, IL-4 and tumor necrosis factor-alpha expression, whereas alum induced primarily IL-4 production. As T(h)1-type immune responses have been implicated in many autoimmune disorders, whereas T(h)2-type responses have been shown to inhibit autoimmune disease, the choice of adjuvant may be critical for the design of a safe and effective immunotherapy for Alzheimer's disease.     

Chronic mucocutaneous candidiasis. II. Class and subclass of specific antibody responses in vivo and in vitro

Patients with chronic mucocutaneous candidiasis (CMC) succumb to persistent infections with the opportunistic yeast Candida. Impaired cell-mediated responses to Candida have been repeatedly reported while antibody responses were mostly found to be normal. The underlying defect remains poorly understood. It has recently been shown that CMC patients are also susceptible to infections with encapsulated bacteria, and may have associated IgG2 and IgG4 deficiency. Our previous studies demonstrated altered cytokine production in CMC patients. As cytokines can influence production and isotype of specific antibody, in 10 patients with CMC we measured the levels and isotype distributions of serum antibodies to Candida antigens (CAg), pneumococcal polysaccharide (PPS) and tetanus toxoid (TT) antigens. Peripheral blood lymphocytes were also stimulated in culture and the antibodies made in vitro were measured. Our data demonstrated that in vivo, CMC patients had very high levels of IgG and IgA CAg-specific antibodies. CAg-specific and PPS-specific IgG1 was markedly higher than in controls. Children but not adults with CMC had significantly lower levels of IgG2-specific antibody to CAg and PPS compared with age-matched controls. Patients had significantly higher levels of IgG3-specific antibody to all three antigens tested. These findings were in accordance with increased total IgG and IgG3 levels seen in CMC patients. In vitro, CMC patients, particularly children, did not respond as frequently to antigen stimulation as did their healthy controls. The level of specific antibody produced was also lower to all antigens tested, as was the amount of total immunoglobulins following antigenic and particularly mitogenic stimulation. Addition of interferon-alpha (IFN-α) or IFN-γ to cultures had variable, sometimes marked, effects. Our results demonstrate that CMC patients manifest subtle alterations in specific antibody responses to CAg, PPS and TT, which are most pronounced in children. This may relate to altered cytokine production also seen in these patients.     

The prognostic value of Ki67 immunostaining in non-Hodgkin's lymphoma

The monoclonal antibody Ki67 recognizes an antigen expressed in all phases of the cell cycle except Go. It has been used in 141 biopsies from 138 patients with non-Hodgkin's lymphoma to identify proliferating cells in histological sections. A Ki67 index (the number of Ki67 positive tumour cells divided by the sum of Ki67 positive and negative tumour cells) has been derived by counting 1000 cells in each case. A correction for the presence of non-tumour cells has been incorporated by counting non-tumour cells in serial sections stained with a panel of other antibodies. A very strong correlation between a low Ki67 index (less than 20 per cent) and low grade histology and a high Ki67 index (greater than 20 per cent) and high grade histology was found (Chi2 = 98.0). Ninety-one patients could be analysed for survival and those with low grade lymphoma (n = 38) who had a relatively high Ki67 index (greater than 5 per cent) had a worse survival than those with an index of less than 5 per cent (p less than 0.05). In contrast, there was a trend for those patients with high grade disease with a very high Ki67 index (greater than 80 per cent) to have a better survival than those with a lower index (less than 80 per cent). The patients with high grade disease who achieved complete remission or good partial remission and had a Ki67 index of less than 80 per cent were more likely to relapse than those with an index of greater than 80 per cent (p less than 0.04). These findings could not be explained by the effect of other prognostic factors such as age, stage, or serum albumin. While the use of Ki67 immunostaining has potential drawbacks, it appears to be a simple and reproducible method of determining a tumour proliferative index which provides relevant clinical data.     

Maternal death associated with ovum donation twin pregnancy.

A case of maternal death due to sub-arachnoid haemorrhage in an ovum donation twin pregnancy complicated by hypertension is described. Attention is drawn to a forecasted increase in maternal morbidity and mortality in in-vitro fertilization (IVF) pregnancies, which occur in older women and are often multiple.