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Biomedical subjects

T Kahn

Publications and source records attributed to T Kahn.

At least 73 records · Page 4Linked to original sources
PubMed1996

Promoter activity of sequences located upstream of the human papillomavirus types of 16 and 18 late regions.

The regulation of human papillomavirus (HPV) late gene expression is difficult to analyse because the late proteins L1 and L2 are only produced in the upper layers of terminally differentiated keratinocytes. However, for the minor capsid protein L2 of HPV types 1, 6, 11 and 16, rare mRNAs or cDNAs starting 3' of the E5 open reading frame (ORF) were previously described. In order to analyse whether the DNA region preceding the late ORFs (late upstream region, LUR) of HPV-16 and HPV-18 has promoter activity, transient transfection assays employing luciferase reporter constructs were performed. The results show that the LUR of HPV-16 and HPV-18 exhibits an orientation-dependent promoter activity in different cells. By analysing 3'-deletion mutants of the HPV-16 LUR, we identified 78 bp within the sequence between the E5 and L2 ORFs to be critical for the promoter activity. Furthermore, the analysis of a 5'-deletion mutant revealed a negative cis-regulatory element located within the E2 ORF. The HPV-16 early poly(A) signal is located downstream of the critical promoter region. Inactivation of this element by site-directed mutagenesis strongly enhanced luciferase activity. However, mutation of two potential TATA-binding protein (TBP) sites located within the critical promoter region did not abolish the activity. Altogether, these data indicate the possibility of a TATA-less promoter in the HPV-16 and HPV-18 LURs. Together with the early poly(A) signal, this potential promoter might be involved in the differentiation-dependent regulation of late gene expression.

Animals↗
PubMed1996

Fetal CNS damage after exposure to maternal trauma during pregnancy.

Nine case reports are presented to indicate the possible effects of maternal trauma on surviving fetuses. Previous reports have only addressed fatal consequences. Traumata occurred between gestational weeks 23 and 37. Seven mothers had motor-vehicle accidents (MVA), two had blunt abdominal traumata. Four mothers suffered severe injuries, such as cerebral contusion, fractures or placental abruption leading to emergency Cesarean section. Premature uterine contractions were observed in five mothers and hemorrhage in two. The nine children were born after 30 to 40 weeks of gestation. Seven had normal postpartal vital signs, one required resuscitation and one premature needed assisted ventilation. Clinical symptoms were variable: movement disorders (n = 3), hydrocephalus (n = 2), convulsions (n = 1), cerebral palsy (n = 1), and normal (n = 3). Follow-up ranged from 7 months to 5 years. Neuroimaging revealed periventricular leukomalacia (n = 2), localized vascular infarctions (n = 2), hemorrhage (n = 1), hydrocephalus (n = 2) and global damage (n = 1). The causative role of maternal accidents was extremely likely in one patient, and probable but unproved in the remaining cases.

Accidents, Traffic↗
PubMed1996

Mapping of the cortical motor hand area with functional MR imaging and MR imaging-guided laser-induced interstitial thermotherapy of brain tumors. Work in progress.

PURPOSE: To localize the cortical motor hand area with functional magnetic resonance (MR) imaging before and after MR imaging--guided laser-induced interstitial thermotherapy of tumors in the precentral brain region to control energy delivery and to improve safety. MATERIALS AND METHODS: Functional MR images were obtained in eight patients (five men, three women; aged 27-63 years) while they flexed their fingers. MR imaging--guided laser-induced interstitial thermotherapy was terminated when there was less than 8-12 mm between the border of the laser-induced lesion and the motor hand area anterior aspect. RESULTS: Seven patients had a statistically significant localized change in signal intensity in the central region of the contralateral hemisphere. This area was a spotlike circumscribed focus in three patients and scattered over a larger zone in four patients. Persistent deficits did not occur after thermotherapy in any patient. In three patients, onset of reversible perifocal edema in the motor hand area coincided with the development of hemiparesis, which completely resolved. No patient had activity within the tumor on functional MR images. CONCLUSION: Functional MR imaging findings can be used to prevent neurologic damage during MR imaging--guided laser-induced interstitial thermotherapy.

Adult↗
PubMed1996

Production of fruits and vegetables at the homestead is an important source of vitamin A among women in rural Bangladesh.

BACKGROUND: Vitamin A deficiency is considered to be an important public health problem in Bangladesh. A universal biannual distribution of high-dose vitamin A capsules has been in place for over the past two decades. This supplementation has been beneficial for preschool children. Bangladesh has been exploring more sustainable approaches for all segments of the population. To support this initiative, Helen Keller International has implemented a homegardening promotion project since 1993. This project is executed on a large scale and currently reaches an estimated 244,000 families. METHODS: This paper presents data from 7341 women of reproductive age which were collected as part of the baseline census of a community monitoring system whose objective is to track progress and measure the impact of home-gardening activities. RESULTS: Vitamin A intake in this population derived almost entirely from the consumption of fruits and vegetables. Logistic regression analyses showed that maternal vitamin A intake was determined by qualitative indicators of homestead gardens (type of home garden, the total quantity of provitamin A-rich food produced and the number of fruits and vegetables varieties grown in the garden) after adjusting for socio-economic status. CONCLUSIONS: These results indicate that traditional production of provitamin A-rich fruits and vegetables in the homestead may provide a valuable contribution to vitamin A intake in communities where alternative dietary sources of vitamin A are scarce.

Agriculture↗
PubMed1995

[Arachnoid cyst as the differential diagnosis of ischemic optic neuropathy in type-II diabetes].

HISTORY AND CLINICAL FINDINGS: A 71-year-old woman, a diabetic (type IIb) for 27 years, developed bilateral hemianopsia over a period of about 2 years. A few weeks before hospital admission the defect in her visual fields increased more rapidly and double vision occurred intermittently. The hemianopsia was demonstrated by finger perimetry. There was no evidence of heart failure or peripheral vascular disease. Muscle reflexes were normal, but there was a decrease in vibratory sensation in both feet. The cause of the visual disturbance was at first thought to be an ischaemic optic neuropathy. INVESTIGATIONS: Biochemical tests showed an HbA1 of 12.8%, blood sugar levels were between 230 and 359 mg/dl, and there was increased intravascular platelet activation. Ophthalmological examination confirmed bitemporal hemianopsia and early retinopathy. Magnetic resonance imaging of the skull revealed an intra- and suprasellar cystic space-occupying lesion extending to the right optic chiasma. These findings, taken together, indicated an arachnoidal cyst. TREATMENT AND COURSE: After the diabetic metabolic state had been normalized with insulin treatment (average of 30 IU of an intermediary insulin) and dietary measures, the cyst was evacuated stereotactically. The hemianopsia quickly improved markedly and the patient was discharged 4 days after the operation with her vision nearly fully restored.

Aged↗
PubMed1995

Magnetic resonance imaging of microwave induced tissue heating.

MR-guided interstitial thermotherapy offers a minimally invasive treatment for localized tumors and tissue structures exhibiting functional abnormalities. In this study, microwaves (2.45 GHz) were used for tissue irradiation to overcome some limitations of the heating sources used so far. To this end, a microwave antenna was positioned in a specimen of porcine myocardium and irradiated for 10 min under MRI control using a T1-weighted FLASH sequence. The heating procedure resulted in a spherical tissue lesion of 26 mm in diameter. Thus, we could demonstrate the feasibility to monitor the microwave-induced coagulation process by MR-imaging in vitro.

Animals↗
PubMed1995

Focal brain lesions in patients with AIDS: aetiologies and corresponding radiological patterns in a prospective study.

We report the results of a hospital-based study of 188 consecutive patients seropositive for the human immune deficiency virus type 1 (HIV-1) who presented in a 4-year period (1988-1991) with possible signs or symptoms of first-ever central nervous system disease. Confirmed diagnoses were cerebral toxoplasmosis in 47 patients (25.0%), HIV-1 encephalopathy in 19 (10.1%), progressive multifocal leucoencephalopathy (PML) in 9 (4.8%), cerebral lymphoma in 1 (0.5%), and other conditions in 9 patients (4.8%). Seventy-three subjects (38.8%) showed focal brain lesions on initial computed tomography or magnetic resonance imaging, which were assessed prospectively. Positive predictivity for toxoplasmosis was 100% if multiple lesions occurred in combination with mass effect or contrast enhancement (23 patients), or if at least one space-occupying or enhancing lesion was located in the basal ganglia or the thalamus (26 patients). Solitary lesions with mass effect or contrast enhancement were seen in 26 patients and were caused by cerebral toxoplasmosis in 22 (84.6%). Eight of the 9 PML patients presented with one or more non-enhancing, non-mass lesions, although the predictive value of this pattern was low (47.1% for PML). Thus, in our epidemiological context, certain imaging findings in HIV-1-seropositive patients were highly predictive of cerebral toxoplasmosis. This may differ from findings from other parts of the world where cerebral toxoplasmosis may be less prevalent among HIV-1-infected individuals.

AIDS Dementia Complex↗
PubMed1995

[Magnetic resonance tomography and localized proton spectroscopy in 2 siblings with Canavan's disease].

We present the findings of magnetic resonance imaging (MRI) and localised 1H magnetic resonance spectroscopy (MRS) in two brothers with Canavan's disease, a rare autosomal recessive leukodystrophy. Urine specimens of one child were evaluated by MRS. All examinations were performed in the same whole body 1.5 T superconducting magnet. MRI revealed the typical pattern of leukodystrophy including a more severe demyelination in the older child. The younger brother showed additional high signal lesions in the globi pallidi on T2-weighted images. MRS of the brain had an elevated ratio of N-acetyl-aspartate (NAA)/phosphocreatin + creatin (Cr) while the ratio of Cholin/Cr was reduced. in urine spectroscopy the concentration of NAA was markedly increased. The ratio of NAA/creatin + creatinin was 880 +/- 10% mmol/mol (normal: 5-21 mmol/mol). Diagnosis of Canavan's disease was supported by gas chromatographic urine examination with an 80-100 fold elevation of NAA concentration. Hence, the diagnosis of Canavan's disease could be established by increased ratio of NAA/Cr and decreased ratio of Cho/Cr relation in brain spectroscopy and high NAA concentration in urine spectroscopy.

Aspartic Acid↗
PubMed1995

Preserved merosin M-chain (or laminin-alpha 2) expression in skeletal muscle distinguishes Walker-Warburg syndrome from Fukuyama muscular dystrophy and merosin-deficient congenital muscular dystrophy.

The merosin M-chain (or laminin-alpha 2) is one of three subunits of laminin-2 which is highly expressed in striated muscle and peripheral nerve. Complete lack of laminin-alpha 2 expression in skeletal muscle is the hallmark of one form of congenital muscular dystrophy which is characterized by dysmyelination of the central nervous system (CNS), links to chromosome 6q2 and is common among Caucasians. Laminin-alpha 2 expression was also found to be significantly reduced in Fukuyama congenital muscular dystrophy which links to chromosome 9q3. We report consistently preserved laminin-2 expression, including laminin-alpha 2, as detected by immunofluorescence in skeletal muscle from five patients with Walker-Warburg syndrome which is characterized by congenital muscular dystrophy and, in addition, type II lissencephaly or pachygyria, defective CNS myelination, and ocular dysgenesis. These findings show that in spite of partial phenotypic overlap between Fukuyama CMD and Walker-Warburg syndrome the two disorders are nosologically separate disease entities. They also exclude that Walker-Warburg syndrome is allelic to the common form of congenital muscular dystrophy with laminin-alpha 2 deficiency.

Antibodies↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗