A specific COX-2 inhibitor attenuates cell infiltration but does not prolong graft survival in murine cardiac transplantation.

COX-2 is a key factor in the progression of inflammation, the effects of a specific COX-2 inhibitor in cardiac transplantation have not yet been elucidated. To test the hypothesis that a COX-2 inhibitor can alter cardiac rejection, we analyzed graft survival using totally allomismatched grafts. Although the COX-2 inhibitor attenuated myocardial cell infiltration, the inhibitor did not prolong survival. We conclude that the COX-2 inhibition may have potential for the suppression of inflammation in cardiac allografts.

Cutaneous Destombes-Rosai-Dorfman disease: absence of detection of HHV-6 and HHV-8 in skin.

BACKGROUND: We report three new cases of cutaneous Destombes-Rosai-Dorfman disease (DRDD). Two were skin-limited, and one was associated with systemic involvement. In all cases typical large S100 positive macrophages with emperipolesis were present, but different patterns were seen. A viral etiology has long been suspected in DRDD. METHODS: Thus, all cases were investigated for presence of HHV-6 major capsid protein gene by polymerase chain reaction (PCR), and for presence of HHV-8 latency-associated nuclear antigen 1 by immunohistochemistry. RESULTS: All results were negative. HHV-6 antibody tests were positive for IgG but not for IgM in one case. With regard to HHV-6, previous studies supplied inconclusive results while, to our knowledge, HHV-8 has never been investigated in DRDD. CONCLUSION: This study suggests that HHV-8 is not involved in the pathogenesis of cutaneous DRDD. However, this should be confirmed by further studies. We can postulate three hypotheses in regard to HHV-6 role in DRDD pathogenesis: 1) its presence in lesionnal tissues is fortuitous, 2) HHV-6 plays a role in promoting more aggressive diseases and 3) various causes, including HHV-6, are implicated in the pathogenesis of DRDD.

Left ventricular apical aneurysm in cardiac sarcoidosis.

A 53-year-old woman was hospitalized for general fatigue and palpitations. An electrocardiogram showed ST elevation and T wave inversion in leads II, III, aVF, and V4-6. Cardiac catheterization was performed since the echocardiogram demonstrated the existence of a left ventricular apical aneurysm. Left ventriculography showed an aneurysm of the apex. An endomyocardial biopsy specimen from the left ventricular apical wall demonstrated typical noncaseating granulomas with giant cells. The patient was diagnosed as having cardiac sarcoidosis. There was no evidence suggesting involvement of other systemic organs. Cardiac sarcoidosis should be considered within a spectrum of diseases that cause left ventricular aneurysm.

Epidemiological study of human herpesvirus-6 and human herpesvirus-7 in pityriasis rosea.

BACKGROUND: Pityriasis rosea (PR) is a common papulosquamous skin disorder that is suspected to have an infectious aetiology. OBJECTIVES: We aimed to study the role of human herpesvirus (HHV)-7 and HHV-6 in the pathogenesis of PR. METHODS: We performed seroepidemiological studies (indirect immunofluorescence test) and polymerase chain reaction (PCR) analysis for HHV-6 and HHV-7 in patients with PR. Seventy-two serum samples and 37 samples of peripheral blood mononuclear cells (PBMC) from 44 patients with PR were obtained. Twenty-five patients with other skin disorders such as drug eruption, urticaria or herpes zoster were studied as controls in the PCR analysis. RESULTS: HHV-7 DNA was detected in 13 of 30 (43%) samples of PBMC of the patients with PR and 14 of 25 (56%) samples of PBMC of controls. HHV-6 DNA was detected in six of 29 (21%) patients with PR and nine of 23 (39%) controls. Thus there was no difference in the prevalence of HHV-6 or HHV-7 in PBMC between patients with PR and those with other skin disorders. In the seroepidemiological study, two cases of at least a fourfold rise in titre and five cases of a fourfold decrease in titre to HHV-7 antibody, and two cases of a fourfold rise in titre and two cases of a fourfold decrease in titre to HHV-6 antibody, were observed in 24 patients with PR. This seroepidemiological study revealed antibody responses consistent with active infection in several PR patients, but the greater proportion of the patients had no definite increase in the antibody titres. CONCLUSIONS: We conclude that HHV-7 and HHV-6 may play a part in some patients with PR, but that other causative agents may exist. Further analyses are needed to determine the causative agents of PR.

HHV-6, 7 and their related diseases.

Human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) are relatively recently discovered beta-herpesvirus. They are prevalent in the human population. Primary infection of HHV-6 has been associated with exanthem subitum and febrile illness. Little information is known about the clinical characteristics of primary infection with HHV-7, although some cases of exanthem subitum have been linked to it. HHV-6 has been recently recognized as an opportunistic pathogen in patients with HIV infection and in transplant recipients. The techniques now available to detect these two viruses remain limited, though putative roles for HHV-6 and HHV-7 in several diseases linked to viral infection have been reported. This report reviews the current knowledge of HHV-6 and HHV-7 biology and their pathogenesis.

Comparison of the complete DNA sequences of human herpesvirus 6 variants A and B.

Human herpesvirus 6 (HHV-6), which belongs to the betaherpesvirus subfamily and infects mainly T cells in vitro, causes acute and latent infections. Two variants of HHV-6 have been distinguished on the basis of differences in several properties. We have determined the complete DNA sequence of HHV-6 variant B (HHV-6B) strain HST, the causative agent of exanthem subitum, and compared the sequence with that of variant A strain U1102. A total of 115 potential open reading frames (ORFs) were identified within the 161,573-bp contiguous sequence of the entire HHV-6 genome, including some genes with remarkable differences in amino acid identity. All genes with <70% identity between the two variants were found to contain deleted regions when ORFs that could not be expressed were excluded from the comparison. Except in the case of U47, these differences were found in immediate-early/regulatory genes, DR2, DR7, U86/90, U89/90, and U95, which may represent characteristic differences of variants A and B. Also, we have successfully typed 14 different strains belonging to variant A or B by PCR using variant-specific primers; the results suggest that the remarkable differences observed were conserved evolutionarily as variant-specific divergence.

Aggressive B-cell lymphoma induced by Epstein-Barr virus infection in erythrodermic cutaneous T-cell lymphoma.

The coexistence of two cutaneous non-Hodgkin's lymphomas of different lineage is rare. We report a patient with an indolent erythrodermic cutaneous T-cell lymphoma followed by an aggressive B-cell lymphoma. To our best knowledge, this is the first report describing Epstein-Barr virus-associated B-cell lymphoma in a patient with cutaneous T-cell lymphoma. We suggest that the long-standing cutaneous T-cell lymphoma, as well as the long-term chemotherapy, suppressed host immunity and caused reactivation of latent Epstein-Barr virus.

Nucleotide sequence analysis of a 30-kilobase-pair region of human herpesvirus-6B (HHV-6B) genome and strain-specific variations in major immediate-early genes.

Human herpesvirus 6 (HHV-6) is now classified into two distinct variants such as HHV-6 variant A(HHV-6A) and B(HHV-6B) (Ablashi et al., Arch. Virol. 129, 1993, 1-4) and the DNA of HHV-6A strain U1102 was completely sequenced (Gompels et al., Virology 209, 1995, 29-51). We have sequenced a 30-kilobase pair (kbp) (genomic positions around 111-141 kb) of HHV-6B strain HST, and a sequence of this region was compared with that of HHV-6A strain U1102. Dodecameric repeats, G/T and Kpn repeat elements, putative major immediate early 1 (MIE1) and major immediate early 2 (MIE2) genes were found in this region. The DNA sequences of HHV-6A (U1102) and HHV-6B (HSI) were markedly different in the MIE1 region, Kpn repeat elements and the putative MIE2 region. Dodecameric repeat element was located in the putative MIE2 locus of HHV-6. When primers covering dodecameric repeat region were used to amplify HHV-6 DNA of clinical isolates from patients with exanthem subitum (ES) by polymerase chain reaction (PCR), variations in size of PCR products in each isolate were found, indicating strain-specific features. Furthermore, the results of molecular biological analysis by PCR using DNA samples in a family suggest that HHV-6 infects within a family.

Kaposi's sarcoma-associated herpesvirus (KSHV) sequences in premalignant and malignant skin tumors.

The novel herpesvirus-like DNA sequences, which were identified in AIDS-related Kaposi's sarcoma (KS) and designated KS associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8), have been reported to be associated with various forms of KS. Here, we searched for the presence of KSHV sequences in various other skin lesions including premalignant or malignant skin tumors of a total of 69 clinical cases without immunodeficiency due to AIDS or following organ transplantation. Strikingly high rates of detection were obtained for premalignant Bowen's disease and malignant squamous cell carcinoma, accounting for 71.4% and 50%, respectively. A less frequent but as yet high incidence (33.3%) was scored for actinic keratosis, a premalignant epidermal disorder. In contrast, the frequency remained low (16.7%) for another type of proliferative skin lesions of extramammary Paget's disease and non-proliferative skin lesions (dermatitis, morphea, epidermal cyst and scar). These results suggest a close association of KSHV with at least some non-KS malignant and premalignant skin lesions in non-immunocompromised patients.

[The accuracy of computed tomography and magnetic resonance imaging in evaluating the extent of endometrial carcinoma].

The present study was designed to determine the accuracy of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) in evaluating the extent of the tumor in 36 patients with endometrial carcinoma. The CT and MRI findings were compared with the microscopic pathologic characteristics in all cases. Linear regression analysis for measurements of residual normal myometrium revealed significant positive correlations (p < 0.001) between MRI (r = 0.861) and CT (r = 0.826) findings and pathologic evaluation. Thirty-six patients were divided into two groups according to our previous CT and MRI criteria: the superficial myometrial invasion group and advanced tumor group. In MRI findings, higher incidences of deep (> or = 1/2) myometrial invasion (p < 0.001), vessel permeation (p < 0.05) and cervical involvement (p < 0.05) were observed in the advanced group. In CT findings, deep myometrial invasion (p < 0.001) was observed in the advanced group. The incidence of extrauterine extension of the tumor did not differ significantly between CT and MRI findings. The accuracy figures for cervical involvement evaluated by CT and MRI were 83% and 86%, respectively. In four of 6 patients, in whom an intact Junctional zone (j-zone) was detected by MRI, the tumor was localized in the endometrium. The remaining 2 patients had only superficial myometrial invasion histologically. In all 16 patients, in whom the j-zone was interrupted in MRI findings, myometrial invasion was confirmed pathologically.(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular epidemiological studies of human herpesvirus 6 in families.

The mode of transmission of human herpesvirus 6 (HHV-6) was investigated by molecular epidemiological techniques in four families. HHV-6 was isolated from the peripheral blood of seven infants with exanthem subitum, including siblings, and from the saliva of two mothers. These isolates were examined for genetic relatedness by means of restriction enzymes analysis of purified DNA. While the profiles of the digestion patterns differed among families, they were very similar in a particular family. These results may suggest that HHV-6 is transmitted primarily from mother to child.

Radioimmunoassay of human pancreatic amylase with monoclonal antibody.

A monoclonal antibody (E-21) was obtained that specifically binds to human pancreatic amylase and shows negligible cross-reaction with human salivary amylase. Using this antibody a radioimmunoassay was developed for pancreatic amylase in human serum. The assay was shown to be sensitive (detectable up to 7 mg/L), reproducible, and specific for pancreatic amylase. In normal subjects, the mean concentration of serum pancreatic amylase determined by this method was 36.3 mg/L with a 95% confidence range of 16.5 to 79.2 mg/L. A good correlation was observed between the concentrations of immunoreactive pancreatic amylase (IR-PA) and enzymatic activities in 20 serum samples (r = 0.97). The concentration of serum IR-PA was below the detectable limit in pancreatectomised patients, and was greatly increased in patients with acute pancreatitis; the latter was accompanied by parallel changes in total enzymic activity. In patients with mumps, the serum IR-PA level was within the normal range whereas the total enzymic activity was elevated.

Enzyme immunoassay of cyclazocine using peroxidase as label.

A sensitive enzyme immunoassay for the determination of serum or urinary cyclazocine was developed. Horseradish peroxidase was used as the labelling enzyme; it was conjugated with cyclazocine derivatives by the mixed anhydride method. After the immune reaction, bound and free fractions were separated by a double-antibody solid-phase method, using Sepharose 4B gel coupled with purified IgG from goat anti-rabbit IgG serum. The enzyme activity was measured fluorophotometrically, with p-hydroxyphenyl propionic acid and hydrogen peroxide as substrates. The correlation coefficients verified that there was excellent agreement between the results obtained by the new enzyme immunoassay and those of radioimmunoassay (r=0.92) and gas chromatography-mas spectrometry (r=0.94).