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PubMed2001

Recurrent lumbosacral herpes simplex in the bedridden hospitalized patient.

A clinical variant of genital herpes simplex virus (HSV) infection, recurrent lumbosacral HSV, occurs in bedridden hospitalized patients. We want to call attention to an uncommon pattern of HSV infection in the hospitalized bedridden patient seen by the dermatology consultation service in a large university hospital. HSV is characterized by a mixture of recurrent groups of herpetic vesicles in all stages of development, with multiple, persistent hyperpigmented patches bilaterally distributed over the lumbosacral (buttocks) area.

Acyclovir↗
PubMed2004

Relationship between neutrophil-binding affinity and suitability for infection imaging: comparison of (99m)Tc-labeled NAP-2 (CXCL-7) and 3 C-terminally truncated isoforms.

UNLABELLED: The CXC chemokines are a family of closely related chemoattractant cytokines that bind to, attract, and activate neutrophils to variable degrees. In this study, the relationship between neutrophil-binding affinity and suitability for infection imaging was investigated in a selected group of CXC chemokines. Neutrophil-activating peptide-2 (NAP-2, 70 residues; also called CXCL7) binds with high affinity to the CXCR2 receptor on neutrophils. Recently, C-terminally truncated NAP-2-variants have been described that have enhanced neutrophil-binding affinity and neutrophil-stimulating capacity. Here, NAP-2 and its C-terminal shortened variants NAP-2(1-68), NAP-2(1-66), and NAP-2(1-63) were labeled with (99m)Tc via the hydrazinonicotinamide (HYNIC) chelator and their potential for imaging of infection was investigated in a rabbit model of infection. The CXC chemokine interleukin-8 (IL-8) was used for comparison. In addition, a series of (99m)Tc-labeled CXC chemokines were screened for their potential to image infection, including CTAP-III, GCP-2, ENA-78, PF-4, and IP-10. METHODS: The receptor-binding affinity of HYNIC-conjugated NAP-2 and its analogs was compared in competitive binding assays on Jurkat cells transfected with the CXCR2 receptor gene. Biodistribution of labeled NAP-2 (analogs) and other CXC chemokines in rabbits with intramuscular Escherichia coli infections was determined both by gamma-camera imaging and by counting dissected tissues at 6 h after injection. RESULTS: The CXCR2-binding affinity of the HYNIC-conjugated NAP-2 analogs relative to NAP-2 was as follows: NAP-2(1-68), 2.5-fold; NAP-2(1-66), 10-fold; and NAP-2(1-63), 3-fold. In the rabbit model, uptake in the abscess (in percentage injected dose per gram +/- SEM) was 0.084 +/- 0.015 for NAP-2, 0.098 +/- 0.010 for NAP-2(1-68), 0.189 +/- 0.044 for NAP-2(1-66), and 0.114 +/- 0.017 for NAP-2(1-63) at 6 h after injection. In comparison, higher uptake in the abscess was found for labeled IL-8, a modest uptake was found for GCP-2 and ENA-78, and a low uptake was found for CTAP-III, PF-4, and IP-10. CONCLUSION: This study showed a clear relationship between affinity to receptors on neutrophils and suitability for infection imaging. Of the NAP-2 variants, NAP-2(1-66) combined highest affinity to CXCR2 with the best characteristics for imaging. IL-8 binds to both CXCR1 and CXCR2 with high affinity and showed a superior imaging quality. The other CXC chemokines tested bind to neutrophils with lower affinity and were shown to be less suitable for infection imaging in this study.

Animals↗
PubMed1975

["Hairy cell" leukemia].

By means of individual observations the clinical, cytological and cytochemical marks of the so-called "hairy cell"leukemia are described. Peculiarities in the course of the disease and in prognosis justify this rare variant to be separated from reticular systems diseases. A diagnosis can also be made on the basis of cytomorphological characteristics.

Adult↗
PubMed1993

Prophylaxis against a Melanesian variant of human T-lymphotropic virus type I (HTLV-I) in rabbits using HTLV-I immune globulin from asymptomatically infected Japanese carriers.

Molecular variants of human T-lymphotropic virus type I (HTLV-I), which diverge significantly from the so-called cosmopolitan prototypes, have been discovered in Melanesia. In this study, HTLV-I IgG (I-IgG) prepared from seropositive healthy Japanese carriers was evaluated for its protective effect against a Melanesian isolate, HTLV-IMEL5, in rabbits. Normal IgG (N-IgG) prepared from seronegative healthy Japanese was used as control. Both preparations contained 50 mg/mL of IgG and I-IgG had a high neutralizing antibody titer, as determined by vesicular stomatitis virus--HTLV-I pseudotype assay. Of four experimental groups (A, B, C, and D), each with three rabbits, groups A and B were infused with 10 mL of N-IgG and I-IgG, respectively, and animals were challenged immediately by transfusion of 5 mL of blood from a rabbit infected with HTLV-IMEL5. Animals in groups C and D were immunized with 10 mL of I-IgG 24 and 48 hours, respectively, after being transfused with 5 mL of blood from the virus-infected rabbit. HTLV-I infection, as determined by seroconversion and verified by polymerase chain reaction, occurred in all rabbits in groups A and D after 2 to 6 weeks, but in none of the animals in groups B and C. These data indicate that I-IgG is protective against HTLV-IMEL5 infection when administered before or within 24 hours of transfusion with virus-contaminated blood. Moreover, our study shows that the neutralizing domains of the so-called cosmopolitan and Melanesian strains of HTLV-I are functionally indistinguishable.

Animals↗
PubMed2004

Eosinophilic dysplasia of the cervix: a newly recognized variant of cervical squamous intraepithelial neoplasia.

A proportion of cervical squamous intraepithelial lesions encountered in surgical pathology practice contain both metaplastic features and some degree of atypia [so-called eosinophilic dysplasia (ED)] that defy classification according to established criteria. To elucidate the nature of these lesions, we compared 44 cases of ED to 20 classic high-grade squamous intraepithelial lesions (HSILs) and 10 squamous metaplasias using a panel of biomarkers and human papillomavirus (HPV) testing. EDs were defined as 1) lack of normal maturation; 2) relatively abundant eosinophilic cytoplasm and distinct cell borders compared with conventional HSIL; 3) mildly to moderately increased nuclear to cytoplasmic ratio; and 4) focal dysplastic nuclei showing nuclear enlargement, hyperchromasia, variable nuclear membrane irregularities, and appreciable nucleoli. Expression of p16 (p16), MIB-1 (Ki-67) labeling index, and HPV DNA detection and typing were performed on each case. The majority of EDs showed more than three atypical cells in an entire lesion but lack of apparent features of HSIL. It was common to find neighboring cervical squamous metaplasia and/or conventional SILs (either HSIL or low-grade squamous intraepithelial lesion [LSIL]). Among the 44 cases, 18 (45%) ED lesions were found to be associated with HSIL, 15 (34%) with LSIL or condylomatous lesions, and 13 (30%) EDs were seen without any SILs in the entire specimens. Area of benign squamous metaplasia was found in all ED cases. High levels of p16 and MIB-1 expression were seen in 41 (93%) of 44 ED cases with degrees of immunoreactivity closely resembling those seen with HSIL. Of 16 EDs tested, 13 (81%) were positive for HPV DNAs. Among 10 HPV-positive cases subtyped, 9 (90%) cases contained intermediate- and/or high-risk HPVs and 1 case contained a novel HPV. In the follow-up of pure ED cases, the majority showed presence of dysplastic lesions of either HSIL or LSIL on either loop electric excision procedures or Papanicolaou test samples after a 6- to 10-week period. Therefore, ED represents an unrecognized and potentially clinically significant subgroup of cervical intraepithelial lesions. Based on the unique histologic appearance of ED, its association in some cases with HSIL, the overall immunohistochemical findings, frequent association of ED with intermediate- and/or high-risk HPV infection, and limited follow-up data, we believe that ED represents a variant of HSIL (CIN 2). Since ED possesses histologic features of both dysplasia and metaplasia, we speculate that it may arise from metaplastic cervical squamous epithelium that has subsequently become infected with intermediate- or high-risk HPV.

Adolescent↗
PubMed1983

Gene activation and re-expression of a Trypanosoma brucei variant surface glycoprotein.

The expression of the Trypanosoma brucei variant surface glycoprotein AnTat 1.1 proceeds by a mechanism that transfers a duplicated gene copy into a new genomic environment, the so-called expression site, where it will be expressed. We have isolated a genomic fragment containing the region spanning the expression site-transposon junction, and the 5' half of the coding sequence. Comparing this DNA segment with its template copy (basic copy) allowed us to identify the exact breaking point and indicated a base sequence which could be involved in initiating the transposition event. Sequencing data also indicated that the co-transposed segment 5' to the coding sequence is 430 bp in length. The extreme 5' end of the mRNA is derived from a region in the expression site not immediately adjacent to the transposed DNA segment. This particular sequence exists in multiple copies in the genome and is common to the mRNA of all variant surface glycoproteins so far analysed.

Animals↗
PubMed1997

Analysis of the mitochondrial DNA from patients with Wolfram (DIDMOAD) syndrome.

Wolfram or DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness) syndrome, which has long been known as an autosomal-recessive disorder, has recently been proposed to be a mitochondrial-mediated disease with either a nuclear or a mitochondrial genetic background. The phenotypic characteristics of the syndrome resemble those found in other mitochondrial (mt)DNA mediated disorders such as Leber's hereditary optic neuropathy (LHON) or maternally inherited diabetes and deafness (MIDD). Therefore, we looked for respective mtDNA alterations in blood samples from 7 patients with DIDMOAD syndrome using SSCP-analysis of PCR-amplified fragments, encompassing all mitochondrial ND and tRNA genes, followed by direct sequencing. Subsequently, we compared mtDNA variants identified in this disease group with those detected in a group of LHON patients (n = 17) and in a group of 69 healthy controls. We found that 4/7 (57%) DIDMOAD patients harbored a specific set of point mutations in tRNA and ND genes including the so-called class II or secondary LHON mutations at nucleotide positions (nps) 4216 and 4917 (haplogroup B). In contrast, LHON-patients were frequently (10/17, 59%) found in association with another cluster of mtDNA variants including the secondary LHON mutations at nps 4216 and 13708 and further mtDNA polymorphisms in ND genes (haplogroup A), overlapping with haplogroup B only by variants at nps 4216 and 11251. The frequencies of both haplogroups were significantly lower in the control group versus the respective disease groups. We propose that haplogroup B represents a susceptibility factor for DIDMOAD which, by interaction with further exogeneous or genetic factors, might increase the risk for disease.

DNA, Mitochondrial↗
PubMed1998

Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes.

Some viruses, including human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in humans, and lymphocytic choriomeningitis virus (LCMV) in mice, are initially controlled by cytotoxic T lymphocytes (CTLs), but may subsequently escape through mutation of the relevant T-cell epitope. Some of these mutations preserve the normal binding to major histocompatibility complex class I molecules, but present an altered surface to the T-cell antigen receptor. The exact role of these so-called altered peptide ligands in vivo is not clear. Here we report that mice primed with LCMV-WE strain respond to a subsequent infection by WE-derived CTL epitope variants with a CTL response directed against the initial epitope rather than against the new variant epitope. This phenomenon of 'original antigenic sin' was initially described in influenza and is an asymmetric pattern of protective antibody crossreactivity determined by exposure to previously existing strains, which may therefore extend to some CTL responses. Original antigenic sin by CTL leads to impaired clearance of variant viruses infecting the same individual and so may enhance the immune escape of mutant viruses evolving in an individual host.

Animals↗
PubMed1984

Dynamic heterogeneity and metastasis.

Parallel clonal populations grown to small defined sizes were used to quantitate rates of generation of metastatic cells. In murine KHT fibrosarcoma and B16 melanoma lines, metastatic cells are generated at effective rates of 10(-5) per cell per generation, or greater. These variant cells are unstable, and are apparently lost at very high rates. It thus appears that metastases could arise from unstable variants, and that rapid rates of change in some phenotypes may be an important feature of malignant progression. We have called such rapid variations dynamic heterogeneity. This may be a useful concept for further investigating aspects of tumor heterogeneity.

Animals↗
PubMed2001

Expression of Xist RNA is sufficient to initiate macrochromatin body formation.

MacroH2A1 is a histone variant that is found as a component of the inactive X chromosome where it is detected as a dense accumulation called a macrochromatin body (MCB). Macrochromatin bodies co-localize with Xist RNA, which is an untranslated RNA that is expressed exclusively from the inactive X chromosome of placental mammals. However, no studies to date have investigated whether Xist RNA expression is necessary or sufficient to cause the formation of MCBs. Here we show that expression of Xist RNA is sufficient to cause the formation of MCBs even when Xist is expressed from an inducible transgene at ectopic autosomal sites. Macrochromatin bodies form at sites of transgenic Xist expression in differentiating mouse ES cell lines and transgenic fibroblasts, but MCBs cannot form in undifferentiated ES cells even after prolonged Xist expression. The kinetics of MCB formation revealed that Xist expression precedes MCB formation and that differentiating ES cells undergo a rapid and synchronous transition that renders them competent to form MCBs. Once MCBs have formed, continued expression of Xist is required for their maintenance. These results show that Xist RNA and macroH2A1 function in a common pathway. Expression of Xist in a permissive nuclear environment is sufficient to initiate a chromatin-remodeling event culminating in the incorporation of macroH2A1. The results also strongly suggest the existence of additional regulatory factors for X inactivation that are regulated developmentally. In addition, we present evidence that macroH2A1 density is not simply a measure of the general degree of DNA compaction.

Animals↗
PubMed2006

Lock and roll: single-molecule genotyping in situ using padlock probes and rolling-circle amplification.

In this review I will describe the development of a technique that enables genotyping of individual DNA molecules in the context of morphologically preserved fixed cells, from the fundamental concept published in 1994 to the present status. The review describes enzyme-assisted histochemistry approaches to achieve highly specific molecular identification reactions coupled to efficient signal amplification. The primary molecular identification is accomplished through circularization of oligonucleotide probes, called padlock probes. The circularization reaction is catalyzed by a DNA ligase, which provides robust distinction between single-nucleotide variants under standard reaction conditions. To generate a detectable signal from individual circularized probe molecules, a DNA polymerase is added that replicates probe circles, generating a long tandem-repeated DNA product, easily visualized using a standard epi-fluorescence microscope. Individual signals are recorded as bright dots, providing digital information about the abundance of specific sequences and opportunities for simultaneous detection of several targets using spectral multiplexing. The importance of strictly target-dependent signal amplification will be discussed.

Animals↗
PubMed2003

RELP, a novel human REG-like protein with up-regulated expression in inflammatory and metaplastic gastrointestinal mucosa.

We screened expressed sequence tag databases for genes with up-regulated expression in inflammatory bowel diseases. A gene encoding a regenerating protein (REG)-like protein called RELP was identified and characterized. The relp gene encodes a major transcript of 1518 nucleotides, and two truncated splice variants. Unlike the reg genes, which form a cluster in chromosome 2, relp maps to chromosome 1p12-13.1. The predicted translation product is a 158-amino acid preprotein, showing 43% to 47% similarity to the REG proteins. It contains a 22-amino acid signal peptide, and a conserved calcium-dependent carbohydrate-recognition domain. Complementary DNA for the orthologous mouse gene was also cloned. The RELP protein is constitutively expressed in epithelial neuroendocrine cells of the small intestine and in parietal cells of the gastric mucosa. An up-regulated expression of RELP was seen in epithelial cells of inflammatory mucosa in ulcerative colitis and Crohn's disease, in regenerating epithelial borders of gastric ulcers, and in metaplastic epithelium in the antrum and the esophagus. Our findings suggest that RELP might be involved in inflammatory and metaplastic responses of the gastrointestinal epithelium.

Animals↗
PubMed2001

A genomic island in Pseudomonas aeruginosa carries the determinants of flagellin glycosylation.

Protein glycosylation has been long recognized as an important posttranslational modification process in eukaryotic cells. Glycoproteins, predominantly secreted or surface localized, have also been identified in bacteria. We have identified a cluster of 14 genes, encoding the determinants of the flagellin glycosylation machinery in Pseudomonas aeruginosa PAK, which we called the flagellin glycosylation island. Flagellin glycosylation can be detected only in bacteria expressing the a-type flagellin sequence variants, and the survey of 30 P. aeruginosa isolates revealed coinheritance of the a-type flagellin genes with at least one of the flagellin glycosylation island genes. Expression of the b-type flagellin in PAK, an a-type strain carrying the glycosylation island, did not lead to glycosylation of the b-type flagellin of PAO1, suggesting that flagellins expressed by b-type bacteria not only lack the glycosylation island, they cannot serve as substrates for glycosylation. Providing the entire glycosylation island of PAK, including its a-type flagellin in a flagellin mutant of a b-type strain, results in glycosylation of the heterologous flagellin. These results suggest that some or all of the 14 genes on the glycosylation island are the genes that are missing from strain PAO1 to allow glycosylation of an appropriate flagellin. Inactivation of either one of the two flanking genes present on this island abolished flagellin glycosylation. Based on the limited homologies of these gene products with enzymes involved in glycosylation, we propose that the island encodes similar proteins involved in synthesis, activation, or polymerization of sugars that are necessary for flagellin glycosylation.

Chromosomes, Bacterial↗
PubMed2002

Median and ulnar nerve compression at the wrist caused by anomalous muscles.

Compression of the median and ulnar nerves at the wrist is frequently encountered. Carpal tunnel syndrome usually occurs without any obvious extrinsic cause; several cases have however been reported caused by anomalous or hypertrophic muscles. A survey of the literature shows that compression neuropathy of the median nerve has been reported in relation with anomalies affecting three muscles: the first (or second) lumbrical, the palmaris longus and its anatomic variants and the superficial flexor of the index finger. In the ulnar tunnel the situation is thoroughly different: so-called idiopathic ulnar tunnel syndrome is rare and an extrinsic compressing structure can usually be disclosed. Anomalous muscles belong to the palmaris longus/abductor digiti minimi group; the flexor carpi ulnaris is sometimes involved. One can suspect the presence of such an anomalous muscle when the compression syndrome concerns a patient who is not within the "usual" age group with symptoms initiated or aggravated by physical exercise.

Hand↗
PubMed1992

Correction of sulfatide metabolism after transfer of prosaposin cDNA to cultured cells from a patient with SAP-1 deficiency.

The lysosomal removal of the sulfate moiety from sulfatide requires the action of two proteins, arylsulfatase A and sphingolipid activator protein-1 (SAP-1). Recently, patients have been identified who have a variant form of metachromatic leukodystrophy which is characterized by mutations in the gene coding for SAP-1, which is also called "prosaposin." All of the mutations characterized in these patients result in (a) deficient mature SAP-1, as determined by immunoblotting after SDS-PAGE of tissue and cell extracts, and (b) decreased ability of cultured skin fibroblasts to metabolize endocytosed [14C]-sulfatide. We now report the insertion of the full-length prosaposin cDNA into the Moloney murine leukemia virus-derived retroviral vector, pLJ, and the infection of cultured skin fibroblasts from a newly diagnosed and molecularly characterized patient with SAP-1 deficiency. The cultured cells infected with the prosaposin cDNA construct now show both production of normal levels of mature SAP-1 and completely normal metabolism of endocytosed [14C]-sulfatide. These studies demonstrate that the virally transferred prosaposin cDNA is processed normally and is localized within lysosomes, where it is needed for interaction between sulfatide and arylsulfatase A. In addition, normal as well as mutant sequences can now be found by allele-specific oligonucleotide hybridization of PCR-amplified genomic DNA by using exonic sequences as primers.

Antisense Elements (Genetics)↗
PubMed1989

[Value of echocardiography and amplified atrial vectorcardiography for selecting the methods of therapy and prevention of paroxysmal atrial fibrillation].

Atrial and left-ventricular myocardial activity was assessed in 85 coronary patients with paroxysmal atrial fibrillation. Their age varied between 43 and 88 years. The methods used included ECG, amplified atrial vectorcardiography after I. T. Akulinichev's schedule (amplification: 1 mv = 100 mm) and M-scan echocardiography. The comparison of these methods has substantiated criteria for the selection of differential treatment and preventive measures in these patients, on the basis of the prevailing type of atrial myocardial changes ("arrhythmic", "hemodynamic" or "combined" ones). A supportive treatment with cardiotonic agents is advisable in cases of the "hemodynamic" type with apparent signs of the overstrain (dilation) of the left atrium or both atria. In the "arrhythmic" variant, where conductivity, automatism and excitation disorders are predominant, antiarrhythmic agents (cordaron, quinidine, adrenoblockers) are indicated while the "combined" type calls for combined treatment with cardiotonic and antiarrhythmic agents.

Adult↗
PubMed1993

[Rounded atelectasis with emphasis on its wide spectrum].

While rounded atelectasis (RA) is considered to be rather common in the United States and Europe, the total number of RA cases reported from Japan still remains approximately 30. We have long been aware that there are many variations in the radiographic appearance of so-called RA and that RA has never been clearly defined. We retrospectively reviewed 22 cases collected as RA and its variants from several institutions. We defined RA as "peripheral atelectasis mimicking tumor secondary to shrinkage or bending of the pleura of various degrees, and accompanied by lung distortion." The diagnostic criteria of typical RA include (1) peripheral tumoral shadow in contact with pleural effusion or thickened pleura, (2) acute angle between the pleura and the shadow, (3) convergence of the pulmonary vessels and bronchi and (4) volume loss of the affected lobe. However, there are cases which lack some of these criteria but are considered to be included in the broad category of RA. We propose that RA should be considered to be an entity having a wide spectrum. Typical lesions showing "cranial tilting" of Hanke are on one side of the spectrum and small linear or strand shadows extending from the thickened pleura are on the other.

Adult↗
PubMedDate not supplied

[Suitability of SSCP-PCR analysis for molecular detection of quinolone resistance in Campylobacter jejuni].

Foodborne infections with Campylobacter spp. are increasing, especially antibiotic resistant strains are emerging. Quinolone resistant isolates can cause failure of therapy in severe clinical infections. Molecular characterisation is needed for the detection of resistant variants of C. jejuni. Therefore 23 isolates from poultry and human medicine as well as three control strains were tested for their minimal inhibitory concentration, their Single-Strand-Conformation-Polymorphism (SSCP)-PCR pattern (a method for the detection of resistance determining point mutations), and their sequence of the quinolone resistance determining region (QRDR). Six different SSCP types could be identified: two types for quinolone resistant isolates and other types containing so called silent mutations without influence on the resistance. A genotypic monitoring of the quinolone resistance in C. jejuni can be useful for the early detection of new resistance variants. As a screening method for detection of point mutations in the QRDR the SSCP-PCR can be applied. Compared to other genotypic methods the SSCP-PCR is less time and cost consuming and needs only standard technical equipment.

Animals↗