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T Kahn

Publications and source records attributed to T Kahn.

At least 37 records · Page 2Linked to original sources

A transcribed human sequence related to the mouse HC1 and the human papillomavirus type 18 E5 genes is located at chromosome 7p13-14.

The papillomavirus E5 genes play an important role in the induction of proliferation of infected cells, and these HPV genomic regions are affected by the events leading to integration of genital HPVs. Two HPV18 E5-related, transcribed mouse sequences, HC1 and Q300, have recently been described. We searched for human equivalents to these sequences, and isolated a clone with a 9.6 kb insert (633b) from a laryngeal carcinoma DNA library, that strongly cross-hybridised with both the HPV18 E5 and HC1 sequences. Restriction and Southern blot analysis showed that 633b is a single copy sequence without rearrangements and viral sequences. The E5-related region is transcribed, producing a 1.9 kb RNA band detected in the poly(A)+ RNA from different cell lines tested. Sequence alignments showed a close similarity to the HC1 and HPV18 E5 sequences, as well as to Q300 and different viral and human growth factors, allowing to fit a putative phylogenetic tree. The corresponding human gene was named PE5L. It was mapped to the short arm of chromosome 7, at 7p13-14 as determined by in situ hybridisation. A genomic region with similarities to HPV E5 sequences may constitute an HPV-DNA integration target, which is often located near chromosomal breakpoints, oncogenes, etc. We conclude that PE5L belongs to an E5-like family of cellular sequences, and that it may constitute a target for HPV recombination.

Animals

The disappearing kidney. A case of emphysematous pyelonephritis.

We describe a case of bilateral emphysematous pyelonephritis in which the left kidney could not be visualized sonographically because of multiple irregular air-fluid interfaces. This observation, which to our knowledge has been noted only once before in the literature, may be a diagnostic clue to this potentially fatal disease.

Acute Disease

Integration of human papillomavirus type 6a DNA in a tonsillar carcinoma: chromosomal localization and nucleotide sequence of the genomic target region.

Human papillomavirus type 6a (HPV 6a) DNA was detected in a tonsillar carcinoma both as integrated and episomal molecules, and one viral-cellular junction was molecularly cloned (Bercovich et al., J. Gen Virol., 72: 2569-2572, 1991). The cellular sequence was used as a probe for the isolation of a cosmid from a normal human genomic DNA library. A 2.7-kilobase subclone including the integration site was sequenced. It was shown to contain sequences with similarities to the E2 and L2 regions of human papillomaviruses, a 5' truncated long interspersed repeated DNA element type 1 retrotransposon, and a fragment of an O-repeat element. The chromosomal localization of the integration site was determined to be at region 24 of the long arm of chromosome 10 (10q24). This is the region where the fragile site is located in which HPV 18 DNA is integrated in the cell line FEP18-5. In addition it contains the site of breakpoints affecting protooncogenes Hox11 and Lyt10. Other genes related to cell division and DNA repair have also been mapped to this chromosomal band. Analysis of genomic DNA of cell lines and patients using 10q24-derived probes is presented. The integration of human papillomavirus type 6 DNA into chromosome 10q24 may have disrupted a cellular gene critical for normal cell growth, which further analysis should help to identify.

Base Sequence

Laryngeal carcinoma in a 12-year-old child. Association with human papillomavirus 18 and 33.

OBJECTIVE: A laryngeal squamous cell carcinoma was observed in a 12-year-old child. There was no history of preceding papillomatosis or radiotherapy. We searched for an association with human papillomavirus (HPV). METHODS: The resected specimens were assayed for infection with HPV types 11, 16, 18, 31, 33, 35, 39, 42 by in situ hybridization, and for HPV types 6, 16, 18, 33 by Southern blotting. In addition, cervical swabs of the mother were examined for HPV infection by filter in situ hybridization. RESULTS: Coinfection by HPV types 18 and 33 could be demonstrated by in situ hybridization, with homogeneous infection of both tumor and adjacent epithelial cells by HPV 33 and focal infection of only invasive cancer by HPV 18. Southern blot testing confirmed a high viral copy number of HPV 18 DNA. Examination of the mother at the time of tumor diagnosis revealed no evidence of HPV-related lesion in the lower genital tract. CONCLUSIONS: In this child, coinfection by at least two HPV types is the only evaluable risk factor for laryngeal carcinoma. Coinfection by two HPV types might substitute for carcinogenic cofactors normally present in adult laryngeal carcinomas.

Blotting, Southern

Anatomy of the anal sphincters. Comparison of anal endosonography to magnetic resonance imaging.

PURPOSE: A recent application of endosonography in the evaluation of anal sphincter morphology has led to controversy about the possibility of precisely assessing the diameter of external and internal anal sphincter muscles. On the other hand, magnetic resonance imaging (MRI) has been proposed to allow a more detailed view of the anatomy of the pelvic floor. However, both techniques have not yet been compared directly. METHODS: Eight healthy volunteers (age range, 25-40 years; 5:3, male:female) participated. Anal ultrasound was performed using a 7.5-MHz rectal transducer which produced a transversal panorama display of 360 degrees, allowing an image perpendicular to the anal canal. Imaging of the diameter of the internal and external anal sphincter muscles was performed with the transducer placed in the midanal canal, and measurement was always performed by the same investigator in dorsal projection. MRI was performed using a 1.5 Tesla Magnetom (Siemens, Erlangen, Germany) to obtain sagittal and angled axial (perpendicular to the anal canal) planes for consecutive 3-mm slices which were evaluated by four independent raters. RESULTS: Muscle thickness of the sphincter muscles in dorsal projection was 1.96 +/- 0.61 mm for the internal sphincter and 6.35 +/- 1.07 mm for the external sphincter using ultrasound. It was 1.72 +/- 0.13 mm and 3.99 +/- 0.99 mm, respectively, using MRI. When both measures were compared, only the internal sphincter data correlated significantly (r = 0.818, P = 0.0023) between both measures. Sagittal resonance imaging of the anal canal did not allow for differentiation of both muscles at all. Differentiation among mucosa, submucosa, and internal anal sphincter is not possible with MRI but may well be performed with high-resolution ultrasound. CONCLUSION: Anal ultrasound carries the potential of becoming a routine clinical procedure for evaluation of the anal anatomy and morphology in defecation disorders, but current MRI assessment of the anal anatomy is elaborate, costly, and does not provide any further insights.

Adult

[Infratentorial brain tumors in childhood and adolescence--value of MRT in initial and recurrence diagnosis].

MRI is the current method of choice for the diagnosis of infratentorial tumors in children and adolescents. The present article discusses the individual tumor entities on the basis of their magnetic resonance imaging characteristics in the patient pool of 1991/1992. New magnetic resonance imaging procedures are considered for infratentorial vascular anomalies. In addition to its use in the primary diagnosis, the significance of MRI for the detection of recurrences is discussed. Problems arising after prior surgery and irradiation as well as metastasization through CSF pathways are also mentioned.

Adolescent

[The selective arterial and venous MR angiography of intracranial arteriovenous malformations].

This study evaluates the usefulness of MR angiography (MRA) in analysing cerebral arterial blood supply and venous drainage in patients with intracranial arteriovenous malformations (AVM). Selective MRA of the carotid, middle cerebral or vertebrobasilar territories was performed by means of presaturation of up to three of the brain-supplying arteries at the level of the middle or lower neck (angled presaturation slabs). Results obtained with selective, non-selective arterial, as well as venous MRA in 13 consecutive patients were compared with the findings at intraarterial angiography, the latter serving as the "gold standard". Sensitivity in identifying major feeding arteries was 100%. Determination of the absolute and relative AVM sizes at selective MRA corresponded with IAA. The mean difference was 17.6 and 3.9% respectively. Both display of superficial and deep venous drainage was provided by 2-dimensional venous MRA. The authors conclude that selective MRA of cerebral arteries as used here is a powerful non-invasive method to demonstrate blood supply by single feeding vessels in intracranial malformations. 2D venous MRA permits an accurate evaluation of the venous drainage pattern.

Adult

[Quantification of extracranial carotid stenosis. Magnetic resonance angiography and Doppler sonography versus intra-arterial angiography].

UNLABELLED: To assess various non-invasive techniques for quantifying internal carotid artery CA stenosis, per cent luminal diameter reduction on intraarterial angiograms (IAA) was measured in 63 patients with ICA stenosis or occlusion. These data were compared with independent measurements based on MR-angiography, continuous-wave (cw) Doppler ultrasonography, systolic peak flow velocity and colour Doppler assisted duplex imaging. Correlations with IAA were equally strong for MR angiography, cw Doppler and colour Doppler analysis (0.95; 0.92; 0.92). Positive predictive values for > or = 70% ICA stenosis were lower and negative predictive values were higher for cw Doppler (0.85; 0.92) and colour duplex analysis (0.81; 0.94) than for MR angiography (0.86; 0.88). Statistical analysis showed non-linear correlations between percentage of lumen diameter narrowing and the length of the zone of signal intensity loss (0.72) and maximum systolic peak flow velocity (0.77). CONCLUSION: Several non-invasive methods do compare with IAA in identifying and quantifying high-grade ICA stenosis and may suffice for decisions on treatment.

Adult

[The hemodynamics and anatomy of the circle of Willis. The technic and clinical value of selective MR angiography].

This study evaluates the usefulness of MR angiography in analysing the individual collateral flow dynamics and anatomy of the circle of Willis in 56 patients with high-grade extracranial carotid stenosis or occlusion. Selective MRA of the carotid or vertebrobasilar area was performed by means of presaturation up to the brain-supplying arteries at the level of the middle neck (angled presaturation slabs). Results obtained with selective and non-selective MRA in 56 consecutive patients were compared with the findings at transcranial Doppler ultrasonography and arterial angiography. Ischaemic cerebral infarctions were classified by computerized tomography and correlated with the results of collateral flow analysis: Sensitivity of selective MRA in detecting intracranial collateral flow via anterior or posterior communicating artery was 96 and 97%, respectively; sensitivity in depicting extracranial transorbital flow was lower (71%). Non-selective MRA was 100% sensitive in detecting a non-filling of the horizontal (A1) segment of the anterior cerebral artery and in identifying an origin of the posterior cerebral artery from the intracranial carotid artery. Slow flow infarctions occurred more frequently in patients with transorbital and posterior-to-anterior collateral flow than in patients with collateral flow via anterior communicating artery.

Angiography

The genetic drift of human papillomavirus type 16 is a means of reconstructing prehistoric viral spread and the movement of ancient human populations.

We have investigated the diversity of a hypervariable segment of the human papillomavirus type 16 (HPV-16) genome among 301 virus isolates that were collected from 25 different ethnic groups and geographic locations. Altogether, we distinguished 48 different variants that had diversified from one another along five phylogenetic branches. Variants from two of these branches were nearly completely confined to Africa. Variants from a third branch were the only variants identified in Europeans but occurred at lower frequency in all other ethnic groups. A fourth branch was specific for Japanese and Chinese isolates. A small fraction of all isolates from Asia and from indigenous as well as immigrant populations in the Americas formed a fifth branch. Important patterns of HPV-16 phylogeny suggested coevolution of the virus with people of the three major human races, namely, Africans, Caucasians, and East Asians. But several minor patterns are indicative of smaller bottlenecks of viral evolution and spread, which may correlate with the migration of ethnic groups in prehistoric times. The colonization of the Americas by Europeans and Africans is reflected in the composition of their HPV-16 variants. We discuss arguments that today's HPV-16 genomes represent a degree of diversity that evolved over a large time span, probably exceeding 200,000 years, from a precursor genome that may have originated in Africa. The identification of molecular variants is a powerful epidemiological and phylogenetic tool for revealing the ancient spread of papillomaviruses, whose trace through the world has not yet been completely lost.

Africa

Between-method correlation in quantifying internal carotid stenosis.

BACKGROUND AND PURPOSE: The degree of internal carotid stenosis has emerged as the most important predictor of ischemic stroke in extracranial carotid artery disease. The purpose of this study was to assess the validity of the noninvasive techniques for quantifying internal carotid stenosis with respect to the accepted standard of intra-arterial angiography. METHODS: We measured the maximum percentage reduction in luminal diameter on the intra-arterial digital subtraction angiograms of 56 symptomatic patients with extracranial internal carotid stenosis (n = 77) or occlusion (n = 20). These data were compared with independent measurements based on continuous-wave Doppler ultrasonography, pulsed-wave Doppler spectrum analysis, color Doppler-assisted duplex imaging, and magnetic resonance angiography. RESULTS: Correlations with intra-arterial angiography were equally strong (r > .90) for magnetic resonance angiography, continuous-wave Doppler, and color duplex analysis. Positive and negative predictive values for (therapeutically relevant) 70% to 99% stenosis were higher for continuous-wave Doppler (.82, .97) and color duplex (.84, .98) than for magnetic resonance angiography (.79, .81). Also, accuracy in quantifying high-grade stenosis was better for both of these ultrasonographic techniques, mainly due to the frequent occurrence of a "flow gap" on the magnetic resonance angiograms. Continuous-wave Doppler and magnetic resonance angiography, but not color duplex, failed to detect slow residual arterial flow in one and two cases of symptomatic "pseudo-occlusion" of the internal carotid, respectively. CONCLUSIONS: (1) Several noninvasive methods compare well with intra-arterial angiography in identifying and quantifying high-grade internal carotid stenosis; (2) the use of these noninvasive methods may suffice for treatment decisions; and (3) because residual between-method disagreement is partly explained by principles of physics, the validity of continuous-wave Doppler and color duplex in quantifying 60% to 99% stenosis is likely to be underestimated by correlation with intra-arterial angiography.

Blood Flow Velocity

[DNA identification of human papillomavirus in anogenital condyloma of a male population].

Human Papillomaviruses (HPV) are the cause of benign human anogenital lesions where HPV 6 and HPV 11 are most commonly found. Conversely, HPV 16, 18, 31 and 33 are frequently detected in genital carcinomas and are thus considered as oncogenic types. In order to analyze the prevalence of specific HPV types in an Argentine male population, 43 anogenital lesions from different patients with diagnosis of condyloma acuminata were analyzed. These lesions were localized in different regions of the male genitalia comprising the corona glandis, urethral meatus, skin of the penis, scrotum and anus. The biopsies were screened for the presence of HPV 6, 11, 16, 18, 30, 31 and 33 by Southern blot at different stringent conditions of hybridization (Tm -48 degrees C and Tm -20 degrees C). HPV DNA was found in 41 examined cases (95.3%) with a clear prevalence of HPV 6 and HPV 11 types (51.2% and 23.3% respectively). Six samples (14.0%) were positive only under nonstringent conditions of hybridization. Mixed infections between HPV 16, 18, 30, 31, 33 or a HPV 30 related type with HPV 6 or HPV 11 were detected in 8 specimens (18.6%). Only one case was between HPV 16 and HPV 30. Two additional samples were only positive for HPV 30. Experiments in progress about the prevalence of HPV types in female lesions as well as in normal subjects will contribute to complete the description of the epidemiology of these infections in Argentina.

Adult

Molecular cloning, analysis, and chromosomal localization of a mouse genomic sequence related to the human papillomavirus type 18 E5 region.

The E5 open reading frame (ORF) from bovine papillomavirus type 1 (BPV 1) as well as the E5 ORFs from human papillomaviruses (HPV) type 6 and type 16 have been reported to transform immortalized rodent cells. In an analysis of murine and human tumors for the presence of putative papillomavirus-related sequences, we cloned amplified cellular sequences from the mouse cell line Eb that cross-hybridized with the E5 ORF of HPV 18. A 2.1-kb fragment termed HC1 was sequenced. In normal murine cells, it was present as a single-copy genomic sequence located on chromosome 8. A region of 213 nucleotides corresponded to the E5 gene (HC1 E5), based on the best alignments and on the presence of direct and inverted repeats bearing a central sequence motif. These structural elements are also present in the HPV 18 E5 ORF. HC1 E5 contained an ORF that was transcribed bidirectionally. The transcription in the E5 direction was enhanced in RNA obtained from organs and tumors from carcinogen-treated animals and C127 cells. The polypeptide deduced from the sequence was related to E5 proteins from genital papillomaviruses, to the putative product of the Q300 mouse gene, and to several viral and human growth factors. The data suggest that there may be several cellular counterparts to the viral E5 proteins.

Amino Acid Sequence

Sudden loss of hearing and vestibular function, muscular weakness, and multiple white matter lesions in preschool children.

Sudden cochlear hearing loss, occurring successively or simultaneously in both ears, was observed in four unrelated preschool children. Vestibular testing could be carried out in three patients and showed complete bilateral loss of function. All patients had a mildly retarded motor development due to nonprogressive muscular weakness. On MR imaging all patients showed multiple periventricular and subcortical white matter lesions. These lesions were not clearly progressive in one patient examined repeatedly over 6 years. Virological, bacteriological, immunological, and metabolic examinations were normal in all patients. Muscle biopsy showed morphologically abnormal mitochondria in two and lipid storage in one patient. No indications have been found for a disturbed functioning of the muscle mitochondria. The identical pattern and course of the disease in these patients suggests a new nosological entity, the aetiology of which can only speculatively be attributed to a vascular process associated with a mitochondriopathy.

Biopsy

Seroprevalence of antibodies to the human immunodeficiency virus in dialysis workers: results of a multi-center study.

The Center for Devices and Radiological Health, in collaboration with the Department of Veterans Affairs Medical Center, Brooklyn, N.Y., conducted a multi-center, multi-institutional study of the seroprevalence of antibodies to the human immunodeficiency virus (HIV) among dialysis workers. Seven dialysis units and 112 dialysis workers participated in the study over a period of 2 years. Participation was limited to dialysis workers who, by questionnaire, denied non-occupational risk factors for HIV infection. The vast majority of the study participants were drawn from areas where the prevalence of HIV infection and AIDS cases are substantially greater than the national average. Study participants received the ELISA test for HIV antibodies. All 112 of the participants tested negative for HIV antibodies. These results are encouraging, as they failed to reveal unrecognized occupational transmission of HIV infection among dialysis workers.

HIV