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Biomedical subjects

A Kahn

Publications and source records attributed to A Kahn.

At least 145 records · Page 8Linked to original sources
PubMed1997

External carotid artery ligation for life-threatening hemorrhage in exsanguinating orbital facial congenital hemangiopericytoma.

A 7-week-old infant with a locally invasive, orbital, congenital hemangiopericytoma underwent emergency external carotid artery (ECA) ligation for exsanguinating hemorrhage from an intraoral biopsy site. ECA ligation was successful in controlling the life-threatening hemorrhage and in reducing tumor size and vascularity. The location and extensive nature of the tumor prevented primary excision. Preoperative adjuvant chemotherapy was unsuccessful in controlling tumor growth. After ECA ligation, with reduction in tumor bulk and blood supply, the tumor was radically excised. This technique has important implications in the management of patients with extensive hemangiopericytomas or sino-facial tumors previously regarded as unresectable and which present with life-threatening hemorrhage.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Long-term histological follow-up of genetically modified myoblasts grafted into the brain.

Although primary muscle cells have been used as intracerebral vehicles for transgene expression in the past, data concerning their long-term survival after grafting into the brain, and the reaction of the host tissue to their implantation are lacking. In order to study these aspects, we have implanted, into the brain, primary muscle cells infected ex vivo with recombinant retroviruses carrying the E. coli LacZ gene. The muscle cells were delivered stereotaxically into different areas of the brain of adult rats and the grafts were analyzed up to 105 days after implantation. Intraventricular implantations did not lead to surviving grafts. In contrast, myoblasts developed when they were grafted into gray or white matter regions. They appeared numerous during the first weeks, but decreased dramatically in number over time. Over months, the grafts appeared to fill up with collagen. Astrocytes elaborated a continuous glia limitans surrounding the implant. Blood vessels coming from the host tissue were found within the grafts. The blood-brain barrier was permanently disrupted within the transplants. beta-Galactosidase activity was abundant during the first weeks, but decreased to a very low level subsequently. This decrease paralleled that of the number of muscle cells. In conclusion, myoblasts transplanted into the adult brain survived only temporarily, which implies a transient transgene expression. In addition, before being eliminated, muscle cells were surrounded by a glia limitans, which may limit exchanges with the host tissue. Altogether, these results suggest that intracerebral transplantation of myoblasts may possibly provide a relevant vehicle only for short-term delivery of a gene product.

Animals↗
PubMed1997

Gene therapy of murine motor neuron disease using adenoviral vectors for neurotrophic factors.

Motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy cause progressive paralysis, often leading to premature death. Neurotrophic factors have been suggested as therapeutic agents for motor neuron diseases, but their clinical use as injected recombinant protein was limited by toxicity and/or poor bioavailability. We demonstrate here that adenovirus-mediated gene transfer of neurotrophin-3 (NT-3) can produce substantial therapeutic effects in the mouse mutant pmn (progressive motor neuronopathy). After intramuscular injection of the NT-3 adenoviral vector, pmn mice showed a 50% increase in life span, reduced loss of motor axons and improved neuromuscular function as assessed by electromyography. These results were further improved by coinjecting an adenoviral vector coding for ciliary neurotrophic factor. Therefore, adenovirus-mediated gene transfer of neurotrophic factors offers new prospects for the treatment of motor neuron diseases.

Adenoviridae↗
PubMed1997

An auxiliary peptide required for the function of two activation domains in upstream stimulatory factor 2 (USF2) transcription factor.

Ubiquitous upstream stimulatory factors (USF1, USF2a and USF2b) are members of the basic-helix-loop-helix-leucine-zipper family of transcription factors that have been shown to be involved in the transcriptional response of the L-type pyruvate kinase (L-PK) gene to glucose. To understand the mechanisms of action of the USF2 isoforms, we initiated a series of co-transfection assays with deletion mutants and Ga14-USF2 fusions. The transactivating efficiency of the different native and mutant factors was determined at similar DNA binding activity. We found that: (i) exons 3- and 5-encoded regions are activation domains, (ii) a modulator domain encoded by exon 4 could be necessary to their additive action, (iii) a hexapeptide encoded by the first 5' codons of exon 6 is indispensable for transmitting activation due to both exon 3- and exon 5-encoded domains to the transcriptional machinery. Therefore, USF2 presents a modular structure and mediates transcriptional activation thanks to two non-autonomous activation domains dependent on an auxiliary peptide for expressing their activating potential.

Base Sequence↗
PubMed1997

Effect of magnesium sulfate on the development of cystic periventricular leukomalacia in preterm infants.

To determine if magnesium sulfate has an effect on the development of cystic periventricular leukomalacia in preterm infants, this retrospective case control study was conducted. There were 23,382 infants born at three teaching hospitals in the metropolitan New York area from January 1992 to December 1994. Four hundred ninety-two infants met our entrance criteria. Criteria included a birth weight < 1750 g, survival to at least 7 days of life and at least one cranial ultrasound after 7 days of life. Infants exposed to magnesium sulfate in utero were less likely to develop periventricular leukomalacia. Two of 18 (11%) infants with periventricular leukomalacia were exposed to magnesium sulfate in-utero compared to 14 of 36 controls (39%) (p = 0.035) (OR = 0.196, 95% CI = 0.039-0.988). Pre-eclampsia as an independent factor was not associated with a reduced risk (p = 0.251) (OR = 0.294, 95% CI = 0.033-2.65). Preterm infants exposed to antenatal magnesium sulfate were found to have a reduced risk of developing cystic periventricular leukomalacia.

Anticonvulsants↗
PubMed1997

Efficacy of a central venous access service.

A central venous access service (CVAS) was created in a 600-bed teaching hospital to do elective percutaneous central venous catheterization (PCVC) in a safe and expeditious manner. A vascular surgeon, physician assistants, and registered nurses specializing in intravenous therapy comprise the service. From November 1990 through June 1995, the CVAS was consulted for 1,008 PCVC procedures--853 primary insertion attempts and 155 guidewire exchanges. Various types of catheters were inserted for hemodialysis, fluid and medication administration, chemotherapy, and total parenteral nutrition. The primary insertion failure rate was 4% (31/853) and the major complication rate was 1% (8/853); major complications consisted of four pneumothoraces and four lymphocutaneous fistulae. Success and complication rates were superior to those previously reported for less experienced operators. The favorable results of this study support the efficacy of a CVAS.

Adolescent↗
PubMed1997

Development of cardiopulmonary integration and the role of arousability from sleep.

The recent literature on cardiopulmonary integration in infants is surveyed here, focusing on arousals from sleep. Recent studies reported that the ontogenicity of cardiopulmonary integration cannot be evaluated independently from that of sleep-wake cycles. The issue is of importance for researchers and clinicians evaluating cardiorespiratory characteristics in infants. It also has significant implications in the understanding of clinical conditions, such as parasomnias, obstructive sleep apneas, or some cases of sudden infant death syndrome. The propensity to arouse can be evaluated by exposing the sleeper to awakening challenges. Arousal thresholds are determined by measuring the intensity of the stimulus needed to induce arousals. However, these studies are complicated by factors such as the scoring of the arousal responses. Another difficulty lies in the choice and modality of the arousal stimulus. Noise, gases, light, and nociceptive, mechanical, chemical, or temperature stimuli have all been used to induce arousals. Confounding factors modify the sleeper's responses to a given stimulus. Prenatal drug, alcohol, or cigarette use and the infant's age or, previous sleep deprivation also modify thresholds. Other confounding factors include time of the night, sleep stages, the sleeper's body position, and sleeping conditions. Arousal can also occur spontaneously because of endogenous stimuli. The literature surveyed here also covers such unresolved issues as the clinical significance of aborted arousals, or the mechanisms responsible for the arousal reactions.

Age Factors↗
PubMed1997

A combination of MEF3 and NFI proteins activates transcription in a subset of fast-twitch muscles.

The human aldolase A pM promoter is active in fast-twitch muscles. To understand the role of the different transcription factors which bind to this promoter and determine which ones are responsible for its restricted pattern of expression, we analyzed several transgenic lines harboring different combinations of pM regulatory elements. We show that muscle-specific expression can be achieved without any binding sites for the myogenic factors MyoD and MEF2 and that a 64-bp fragment comprising a MEF3 motif and an NFI binding site is sufficient to drive reporter gene expression in some but, interestingly, not all fast-twitch muscles. A result related to this pattern of expression is that some isoforms of NFI proteins accumulate differentially in fast- and slow-twitch muscles and in distinct fast-twitch muscles. We propose that these isoforms of NFI proteins might provide a molecular basis for skeletal muscle diversity.

Animals↗
PubMed1997

Protein kinase A-dependent phosphorylation modulates DNA-binding activity of hepatocyte nuclear factor 4.

Hepatocyte nuclear factor 4 (HNF4), a liver-enriched transcription factor of the nuclear receptor superfamily, is critical for development and liver-specific gene expression. Here, we demonstrate that its DNA-binding activity is modulated posttranslationally by phosphorylation in vivo, ex vivo, and in vitro. In vivo, HNF4 DNA-binding activity is reduced by fasting and by inducers of intracellular cyclic AMP (cAMP) accumulation. A consensus protein kinase A (PKA) phosphorylation site located within the A box of its DNA-binding domain has been identified, and its role in phosphorylation-dependent inhibition of HNF4 DNA-binding activity has been investigated. Mutants of HNF4 in which two potentially phosphorylatable serines have been replaced by either neutral or charged amino acids were able to bind DNA in vitro with affinity similar to that of the wild-type protein. However, phosphorylation by PKA strongly repressed the binding affinity of the wild-type factor but not that of HNF4 mutants. Accordingly, in transfection assays, expression vectors for the mutated HNF4 proteins activated transcription more efficiently than that for the wild-type protein-when cotransfected with the PKA catalytic subunit expression vector. Therefore, HNF4 is a direct target of PKA which might be involved in the transcriptional inhibition of liver genes by cAMP inducers.

Amino Acid Sequence↗
PubMed1997

Dominant X linked subcortical laminar heterotopia and lissencephaly syndrome (XSCLH/LIS): evidence for the occurrence of mutation in males and mapping of a potential locus in Xq22.

X linked subcortical laminar heterotopia and lissencephaly syndrome (XSCLH/ LIS) is an intriguing disorder of cortical development, which causes classical lissencephaly with severe mental retardation and epilepsy in hemizygous males, and subcortical laminar heterotopia (SCLH) associated with milder mental retardation and epilepsy in heterozygous females. Here we report an exclusion mapping study carried out in three unrelated previously described families in which males are affected with lissencephaly and females with SCLH, using 38 microsatellite markers evenly distributed on the X chromosome. Most of the X chromosome was excluded and potential intervals of assignment in Xq22.3-q23 or in Xq27 are reported. Although the number of informative meioses did not allow a decision between these two loci, it is worth noting that the former interval is compatible with the mapping of a breakpoint involved in a de novo X;autosomal balanced translocation 46,XX,t(X;2)(q22;p25) previously described in a female with classical lissencephaly. In addition, haplotype inheritance in two families showed a grandpaternal origin of the mutation and suggested in one family the presence of mosaicism in germline cells of normal transmitting males.

Adult↗
PubMed1997

A gene for dominant nonspecific X-linked mental retardation is located in Xq28.

A large family (MRX48) with a nonspecific X-linked mental retardation condition is described. An X-linked semidominant inheritance is suggested by the segregation in three generations of a moderate to severe mental retardation in seven males and by a milder intellectual impairment in two females, without any specific clinical, radiological, or biological feature. Two-point linkage analysis demonstrated significant linkage between the disorder and several markers in Xq28 (maximum LOD score [Zmax] = 2.71 at recombination fraction [theta] = 0); multipoint linkage analyses confirmed the significant linkage with a Zmax of 3.3 at theta = 0, at DXS1684. A recombination event observed with the flanking marker DXS8011 delineates a locus between this marker and the telomere. The approximate length of this locus is 8-9 cM, corresponding to 5.5-6 Mb. In an attempt to explain the variable intellectual impairment in females, we examined X-chromosome inactivation in all females of the family. Inactivation patterns in lymphocytes were random or moderately skewed, and no correlation between the phenotypic status and a specific inactivation pattern was observed. The interval of assignment noted in this family overlaps with five MRX loci previously reported in Xq28.

Adult↗
PubMed1997

Morphometric determination of AgNORs in breast carcinoma. Correlation with flow cytometry and proliferating cell nuclear antigen.

OBJECTIVE: To determine the relationship between argyrophilic nucleolar organizer regions (AgNORs), ploidy and proliferative activity in breast carcinomas. STUDY DESIGN: AgNOR staining was performed in 25 cases of infiltrating ductal carcinoma of the breast, and several features were quantified by image analysis: nuclear area, mean value of the number of AgNORs (M_N_Ag), area of AgNORs (A_Ag), area of AgNOR per nucleus (A_Ag/N), A_Ag variance (A_Ag_V) and coefficient of variation of AgNOR area per nucleus (CV_A_Ag/N). These findings were correlated with ploidy and proliferative activity obtained by flow cytometry, also quantifying the latter with proliferating cell nuclear antigen (PCNA). Comparison of AgNORs with size of the tumor and lymph node status was also made RESULTS: We observed a good correlation between M_N_Ag and A_Ag with ploidy (P < .001), M_N_Ag and A_Ag with S-phase fraction (SPF) (P < .001), A_Ag with S+G2M (P < .02) and PCNA with M_N_Ag (P < .05). The mean value of A_Ag allowed division of the cases into two groups: diploid (D) and near diploid (ND) with low SPF (A_Ag < or = 2.50 microns2), and D and ND with high SPF and aneuploidy (A) (A_Ag > 2.50 microns2) (P < .05). There was a statistically significant correlation between M_N_Ag and A_Ag and between tumor size and lymph node metastases (P < .05). CONCLUSION: AgNORs correlate with various cell cycle and clinicopathologic features and will be used eventually as prognostic markers in breast cancer.

Breast Neoplasms↗