Immunological unresponsiveness and apoptotic cell death of T cells in measles virus infection

The phenotypic alterations associated with T cells during measles virus infection have been demonstrated and an attempt has been made to show programmed cell death (PCD) of T cells activated in vivo. During the acute phase of illness, activated T cells increased rapidly. Memory T cells (CD45RO⁺), especially CD8⁺ memory T cells also tend to increase. During the recovery phase, CD8⁺ T cells declined rapidly, and naive (CD45RA⁺) T cells increased in numbers. The anti-CD3 monoclonal antibody-induced expression of interleukin-2 receptor (CD25) was suppressed. However, the addition of phorbol 12-myristate 13-acetate (PMA) caused the significant recovery of CD25 expression. In addition, PCD of activated T cells from measles patients was induced in culture. After triggering of the T cell receptor-CD3 complex, cells became more susceptible to PCD. Interestingly, the addition of PMA could inhibit PCD of activated T cells. Taken together, these data suggest unresponsiveness and activation-induced cell death of T cells during the primary response to measles virus antigens, depending on the activation status of protein kinase C.     

An infantile case of cytomegalovirus induced idiopathic thrombocytopenic purpura with predominant proliferation of CD10 positive lymphoblast in bone marrow

An infant with cytomegalovirus infection (CMV) developed idiopathic thrombocytopenic purpura (ITP) at 4 months of age. A bone marrow (BM) aspiration showed a remarkable increase of immature megakaryocytes and prominent proliferation of lymphoblasts. Flow cytometric analysis of the bone marrow cells showed that the predominant cells in the lymphocyte cluster were of B-lineage (CD19) with CD10 (common acute lymphoblastic leukemia antigen) positive. Virus study showed a high titer of CMV antibody. Cytomegalovirus DNA was detected by the polymerase chain reaction (PCR) method in urine, peripheral cells and marrow cells. Low-grade fever, diarrhea and petechiae were accompanied by mild liver dysfunction. Complete remission was made with intravenous high-dose immunoglobulin (IVIg) without progression to overt acute leukemia. The percentage of CD10⁺/CD19⁺ lymphocytes in bone marrow also diminished. We postulated that the proliferation of immature lymphocytes and megakaryocytes in bone marrow was caused by maturation arrest that might result from CMV infection.     

Clinical features of measles in immunocompromised children

Measles is often fatal for immunocompromised hosts. Protective immunity against measles has been studied but is still not completely understood. Recently, five cases of measles were encountered in immunocompromised children. Two of these were allogeneic bone marrow transplanted cases (one common variable immunodeficiency and one severe aplastic anemia) in remission, one Wilms' tumor case in remission, one hepatoblastoma case after cytotoxic therapy at disease onset and one exaggerating hemophagocytic syndrome case with suppressed natural killer cell activity. Clinical symptoms, laboratory findings and the immunologic backgrounds of these five patients were investigated. One of the patients, an 8 year old boy with hemophagocytic syndrome, died of giant cell pneumonia which was confirmed in the section of necropsy lung specimen. Two other patients who received allogeneic bone marrow transplants were not immune to measles, despite their own and their donors' immunizations. Their clinical symptoms were rather severe but both patients recovered and have remained seropositive for as long as 13 months. This fatality from measles is the first reported in a patient with hemophagocytic syndrome. Suppressed natural killer cell activity may be a poor prognostic factor. Also, secondary immunization failure for measles can occur in bone marrow transplanted patients with rather severe clinical symptoms.     

Surface marker patterns of T cells and expression of interleukin-2 receptor in measles infection

The surface marker patterns of T cells of Ghanaian children during measles infection were studied and an attempt was made to demonstrate T cell activation and viability in vitro after activation in vivo by measles virus. The frequencies of CD4⁺ and CD8⁺ naive T cells in measles patients were high while their memory T cells were remarkably reduced with no sign of proliferation even at the acute phase of the illness. The reduction of memory T cells was prolonged during the convalescent phase (2 months after onset). The anti-CD3 monoclonal antibody-induced expression of interleukin-2 receptor α chain (IL-2R/CD25) was significantly suppressed; however, the addition of phorbol 12-myristate 13-acetate or ionomycin caused a remarkable recovery of CD25 expression. On simple culture, an appreciable proportion of T cells from measles patients died rapidly in contrast with only a few T cells from healthy controls doing so. The suppression of CD25 expression was still demonstrated during the convalescent phase of the disease. Taken together these results suggest unresponsiveness and activation-induced cell death of T cells during severe measles infection in Ghanaian children. Furthermore the prolonged abnormalities of T cells (i.e. decreased memory T cells and inhibition of CD25 expression during the convalescent phase) might be related to post-measles infection immunosuppressive status.     

Sphincter-Saving Reconstruction for Radiation-Injured Rectum: A Report of Four Cases with Special Reference to the Pull-Through Procedure

Up to now sigmoid colostomy has been a widely accepted and conventionaltreatment for the radiation-injured rectum, but patients withoutresidual malignancy strongly desire to live without a colostomy.We have tried to remove the involved rectal segments by sphincter-savingprocedures. Four patients underwent these procedures, pull-throughprocedure in three and low anterior resection in one. Amongsphincter-saving procedures, the pull-through procedure wasthe most adequate. Provided the following five conditions are fulfilled, the pull-throughprocedure should be considered for the severely radiation-injuredrectum.

1. No recurrence of the initial malignancy in the pelvis.
2. Preferably,a more than 2 cm intact rectal segment above thedentate linepreserved.
3. No radiation-injured segment in the upper sigmoid.
4. No severe radiation damage in the small intestine.
5. Normalanal function.

     

Ganglion cells in Ewing's sarcoma following chemotherapy: A case report

A case of Ewing's sarcoma of the bone, arising in the right radius of a 12-year-old girl, which showed unique histologic features after pre-operative treatment, is reported. The light microscopic features of a biopsy sample were those of a small round cell tumor showing positive immunoreaction with antibodies against the product of the MIC 2 gene (O13), neuron-specific enolase, neurofilament, and synaptophysin, but no morphological differentiation. The patient received combined intensive multi drug chemotherapy and radiation before surgery. Examination of the surgical specimen showed that the tumor was less cellular than that in the biopsy specimen, and was composed mainly of loosely textured large cells mimicking ganglion cells, occasionally forming Homer-Wright rosettes. An lmmunohistochemical study revealed that neural differentiation was enhanced. Immunoreactivity for Leu-7 also became positive. Although the patient underwent postoperative chemotherapy, she died of multiple lung and bone metastases 30 months alter the diagnosis. Autopsy showed that metastatic foci were made up of densely packed small round cells like those seen In the biopsy samples, but associated with prominent Homer-Wright rosettes. To the authors' knowledge, this is the first report of a tumor being replaced almost entirely by ganglion cells after preoperative chemotherapy and radiotherapy.     

Hepatitis B precore mutant in children with chronic hepatitis B virus infection

BACKGROUND: In adults, hepatitis B virus (HBV) with a G to A point mutation at nucleotide 83 in the precore region (mutant HBV 83), is commonly found in HB e antibody positive HBV carriers. It has been reported that this mutant is not able to produce HB e antigen. The exact prevalence of mutant HBV 83 in patients with chronic HBV infection is not fully understood, especially in children. METHODS: To investigate the role of mutant HBV 83 in children with chronic HBV infection, sera were tested for the presence of mutant HBV 83 using a mutation site-specific assay. RESULTS: Mutant HBV 83 was detected in 15 of 22 children (68%). Seven children were followed longitudinally, of which three were asymptomatic carriers and the other four had chronic hepatitis B on entry. There was no clear relationship between the disease activity and the presence of mutant HBV 83. CONCLUSIONS: It was concluded that mutant HBV 83 is commonly present in children with chronic HBV infection and this mutant is not necessarily associated with activation of hepatitis.     

p53 GENE ALTERATIONS AND p53 PROTEIN IN ORAL EPITHELIAL DYSPLASIA AND SQUAMOUS CELL CARCINOMA

To examine the expression of p53 protein and gene alterations in oral epithelial lesions including epithelial dysplasias and primary squamous cell carcinomas, immunohistochemical and temperature gradient gel electrophoresis (TGGE) methods were applied to formalin-fixed and paraffin-embedded tissues. Morphologically normal mucosal epithelium stained negatively for p53 protein. Three out of 11 (27·3 per cent) epithelial dysplasias and 19 out of 57 (33·3 per cent) primary squamous cell carcinomas stained positively for p53 protein. Although more than half of the cases were positive for p53 protein in stage I, the positive cancer cases were found at other stages with variable frequency. Immunoreactive products were localized in the nucleus, especially in the basal and suprabasal layers. The analysis by TGGE revealed gene alterations in exons 5–8 in 3 out of 3 epithelial dysplasias and 17 out of 19 (89·5 per cent) primary squamous cell carcinomas which were immunohistochemically positive for p53 protein. These results suggest that p53 gene mutation may be involved in carcinogenesis in the oral squamous epithelium even in the early stage of the dysplasia–carcinoma sequence.     

EXPRESSION OF NUCLEOPHOSMIN/B23 IN NORMAL AND NEOPLASTIC COLORECTAL MUCOSA

Nucleophosmin/B23 is a 38 kD molecular phosphoprotein involved in ribosome assembly and transport. In view of the fact that nucleophosmin/B23 appears to be more abundant in tumour cells than in normal cells, the mRNA expression and immunohistochemical localization of nucleophosmin/B23 were investigated in 19 samples of non-neoplastic mucosa, six adenomas, and 16 adenocarcinomas of the colorectum. Northern blot analysis revealed that nucleophosmin/B23 mRNA is expressed at a higher level in adenomas and carcinomas than in non-neoplastic mucosa of the colorectum. Immunohistochemical staining of formalin-fixed, paraffin-embedded tissue sections after microwave antigen retrieval, using a nucleophosmin/B23-specific monoclonal antibody, showed almost exclusively diffuse nuclear reactivity of a majority of the epithelial cells in non-neoplastic mucosa: in adenomas, reactivity was almost exclusively nucleolar and in carcinomas, nuclear as well as nucleolar staining was observed. During mitosis, the immunoreactivity of nucleophosmin/B23 appears in the cytoplasm. The results indicate that the expression of nucleophosmin/B23 is higher in neoplastic than in non-neoplastic colorectal mucosa. Furthermore, the pattern of nucleophosmin/B23 expression shifts from nuclear to nucleolar early in the adenoma–carcinoma sequence. The exact function of nucleophosmin/B23 in colorectal carcinogenesis remains to be determined.