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Biomedical subjects

A Kahn

Publications and source records attributed to A Kahn.

At least 361 records · Page 20Linked to original sources
PubMed1987

Structure of the rat L-type pyruvate kinase gene.

The total sequence of a 13,021 base-pair (bp) genomic fragment containing the rat L-type pyruvate kinase (L-PK) gene was determined by "shot gun" sequencing. This fragment includes 8360 bp of the L-PK gene, plus 3193 bp of the 5'-flanking and 1468 bp of the 3'-flanking regions. Like the chicken PK-M1 gene, the rat L-PK gene exhibits a fully conserved exon-intron structure, with 11 exons and 10 introns. In the chicken M1 gene, the coding sequences are well conserved (about 70%), in particular at the level of the exons implicated in the formation of PK active sites, exons that are also partially homologous to the corresponding sequences of the yeast gene. Various types of repetitive sequences exist in the L-PK gene, especially two ID (identifier) sequences located in the second intron and the 11th exon. Elements very similar to the "cyclic AMP-dependent regulatory element" recently described in the phosphoenolpyruvate carboxykinase and somatostatin genes are found in the sequenced fragment, but far upstream (-2338) and downstream (+5788) from the cap site. Various sequences homologous to described regulatory elements (glucocorticoid regulatory elements, enhancers, potential Z-DNA) are also observed 5' and 3' of the cap site. A comparison of the 5'-flanking region of the L-PK gene with the same regions of liver-specific or non-specific, cyclic-AMP-responsive or non-responsive genes was also made. It revealed various potentially interesting features that will be used to guide a further functional study. The cap site was determined by primer extension and nuclease S1 mapping using either mature mRNA or precursor RNA as templates. With both templates the start site of transcription appeared to be microheterogeneous, 19 to 14 bp before the ATG translation initiation codon.

Animals↗
PubMed1987

Molecular cloning and expression of rat aldolase C messenger RNA during development and hepatocarcinogenesis.

A rat brain cDNA library was screened at low stringency with an aldolase B cDNA probe corresponding to the coding sequence of the mRNA, then at high stringency with a 3' non-coding aldolase A cDNA probe. One clone, which hybridized only under the first conditions, was further characterized and used to screen the library again. Two overlapping clones, complementary to aldolase C mRNA, were obtained. They cover the 113 carboxy-terminal coding residues and the 3' non-coding region up to the poly(A) tail. Their nucleotide sequence was determined. In the coding region the overall homology with aldolase A was 67% at the nucleotide level and 76% at the protein level. With aldolase B these values were 63% and 65% respectively. The 3' non-coding region was 380 bases long and did not exhibit any homology with the untranslated 3' extension of aldolase A and B mRNAs. Southern blot analysis indicates that probably a single aldolase C gene exists per haploid genome. Aldolase C mRNA was detected at low concentration in practically all the foetal tissues and its expression markedly and rapidly decreased after birth. In brain the concentration of aldolase C mRNA remained high and stable even after birth. Aldolase C mRNA is approximately 50-fold more abundant in brain than in foetal tissues, which are the richest in messenger RNA. In the course of azo-dye hepatocarcinogenesis the aldolase C gene is re-expressed early, with a maximum at the 4th week of carcinogenic diet, which probably corresponds to the maximal proliferation of the oval cells.

Amino Acid Sequence↗
PubMed1987

Diagnostic categories in infants referred for an acute event suggesting near-miss SIDS.

Among 857 infants admitted between 1977 and 1984 for a life-threatening apnoeic event a definite pathologic condition was found in 576 (66%). In 32 (6.5%) of the latter the polysomnogram was abnormal. The major clinical diagnostic categories were, with decreasing frequency: digestive (n = 263), vasovagal (n = 95), neurological (n = 78), respiratory obstructions (n = 33), and respiratory infections (n = 27); miscellaneous causes were found in 80 infants. No obvious cause could be traced in the remaining 281 infants. According to those caring for them the episode was severe in 77 (27%) of these infants, 57 (74%) of which had an abnormal polysomnogram, and minor in 204 (73%), 36 (18%) of which had an abnormal sleep study. Home monitoring was performed for 145 patients: all those with an abnormal polysomnogram and the 20 infants with an unexplained severe episode associated with a normal sleep study. We conclude from our experience that when an infant is referred for an acute event suggesting near-miss sudden infant death syndrome (SIDS), a large array of diagnoses can be found and that an electric monitoring device will ultimately be advocated for only 17% of all infants presented, but for all those with an unexplained severe episode, irrespective of the results of the sleep study.

Humans↗
PubMed1987

Impact of home monitoring for sudden infant death syndrome on family life. A controlled study.

As home monitoring has been advocated for the prevention of sudden infant death (SIDS) we investigated the influence of such a monitoring programme on family life. Twenty European middle and lower-class families with a child monitored at home after a near miss for SIDS event were investigated. Some psychological and social findings were compared with a group of 20 matched control families. It appears that home monitoring induces severe stress, mainly in the mothers. Fathers and siblings also manifested significant emotional stress. Poor schooling of the parents and previous marital discord seem to be predictors of bad adaptation to home monitoring.

Female↗
PubMed1987

Transferrin gene expression in choroid plexus of the adult rat brain.

Transferrin immunoreactivity and transferrin messenger RNA (mRNA) were recently found to be present in oligodendrocytes of the adult rat brain by using immunohistochemistry and in situ hybridization procedure. The present study demonstrates, in the same way, that epithelial cells of the choroid plexus also contain transferrin together with transferrin mRNA. Choroid plexus of the lateral and the third ventricle are rich in transferrin mRNA, while choroid plexus of the fourth ventricle contain few if any transferrin mRNA. These results demonstrate that epithelial cells of the choroid plexus as well as oligodendrocytes express the transferrin gene in the adult rat brain.

Animals↗
PubMed1987

Characterization of proopiomelanocortin transcripts in human nonpituitary tissues.

Proopiomelanocortin (POMC), the precursor to adrenocorticotropic hormone and other related peptides, was originally identified in the corticotropic cell. Recent evidence shows that POMC products are also normally present in a variety of nonpituitary tissues. To investigate this phenomenon in humans we looked for the presence and characteristics of POMC transcripts in various adult tissues. Blot hybridization analysis of normal adrenal, thymus, and testis RNAs revealed a small RNA species approximately 400 nucleotides shorter than the 1200-nucleotide pituitary species. Primer extension and S1 nuclease mapping studies showed that this small RNA lacked exon 1 and exon 2 of the gene, and it corresponded to a set of at least six molecules starting 41 to 162 nucleotides downstream from the 5' end of exon 3. These RNAs appear to result from heterogeneous transcription initiation sites presumably under the control of "GC box" promoter sequences located in the 3' end of intron 2. They cannot encode a complete POMC molecule, and the only truncated POMC molecules that could be translated would lack a signal peptide necessary for membrane translocation and precursor processing. The use of highly sensitive S1 nuclease mapping techniques with uniformly labeled single-stranded DNA probes allowed the detection of a small but definite amount of the "normal," 1200-nucleotide, mRNA species. It is suggested that it is this POMC mRNA that is responsible for the local production of all the POMC peptides.

Adrenal Glands↗
PubMed1987

Transepidermal water loss during sleep in infants.

Transepidermal water evaporation rate (ER) was measured in 207 infants with a mean postnatal age of 12.7 +/- 10.6 weeks. Measurements were made from the forehead with the use of an Evaporimeter during polygraphic sleep recordings performed under standard conditions. ER values were computed in g/m2 X h. Evaporation rates were significantly lower during rapid eye movement (REM) sleep (8.5 +/- 4.4 g/m2 X h), compared to values measured during quiet wakefulness (11.6 +/- 7.4) or non-REM (NREM) sleep (11.2 +/- 7.6). The differences were not related to age, sex, weight, or rectal temperature, as shown by a covariance analysis. These data, recorded in normal infants, indicate the need to consider the state of sleep or wakefulness of the subjects when comparing results of water evaporation studies.

Humans↗
PubMed1987

Difficulty in initiating and maintaining sleep associated with cow's milk allergy in infants.

To confirm that sleeplessness in infants can be related to an undiagnosed allergy to cow's milk proteins, 71 infants were studied. Group I consisted of 20 infants referred for chronic insomnia that had appeared in the early days of life. Group II was made up of 31 infants admitted for skin or digestive symptoms attributed to cow's milk intolerance; 13 of these infants were shown to sleep as poorly as the infants of group I. Group III consisted of 20 infants with no history of sleep disturbance or milk allergy. The three groups of infants were comparable for sex and age. Laboratory tests revealed immunologic reactions to milk in all the infants in groups I and II. The sleep of the insomniac infants (group I, and the 13 "poor sleepers" in group II) became normal after cow's milk was eliminated from the diet. Insomnia reappeared when the infants in group I were challenged with milk. We conclude that infants with clinically evident milk allergy may suffer from sleeplessness and that when no evident cause for a chronic insomnia can be found in an infant the possibility of milk allergy should be given serious consideration.

Animals↗
PubMed1987

Continuous transepidermal water loss measurement in sleeping infants.

Transepidermal water evaporation rate was measured continuously in 8 infants with the use of an evaporimeter during one night of polygraphic sleep recording. Evaporation rates were significantly lower during REM than during NREM sleep. In both sleep stages it decreased during the night with the lowest values between 02.00 and 04.00 h. Evaporation values showed cyclic changes which were studied by measuring minute-by-minute differences between the maximum and the minimum values (the "amplitude variability") and the number of evaporation peaks per minute (the "peak density"). Both the "amplitude variability" and the "peak density" were smaller in REM than in NREM sleep. The "amplitude variability" decreased during the night with lowest values seen between 02.00 and 04.00 h. These changes in evaporation rates could reflect autonomic nervous system activity as well as basal metabolic activity and should be taken into account whenever such measurements are performed in sleeping infants.

Female↗
PubMed1987

Molecular mechanisms of McArdle's disease (muscle glycogen phosphorylase deficiency). RNA and DNA analysis.

Lack of muscle glycogen phosphorylase activity leads to McArdle's disease, a rare metabolic myopathy. To investigate its molecular basis at the nucleic acid level, we isolated muscle phosphorylase cDNA clones from a human cDNA library in Escherichia coli plasmid pBR 322. Subcloning of one insertion of M13 bacteriophage permitted its definite identification by sequencing. Northern blot experiments revealed one specific messenger RNA of 3.4 kilobases found uniquely in tissues expressing muscle phosphorylase. We show that McArdle's disease exhibits a molecular heterogeneity at the messenger RNA level. In eight unrelated cases of McArdle's disease in which no inactive proteins had been detected, we assayed muscle biopsies for phosphorylase mRNA by Northern blotting. In five cases, no muscle phosphorylase mRNA could be detected, while in three other cases, normal length mRNA was present in lower amounts. Moreover, Southern blot analysis of DNA isolated from white blood cells in four McArdle patients revealed no major deletion or rearrangements of the phosphorylase gene as compared with controls.

Base Sequence↗
PubMed1987

Detection of mRNAs present at low concentrations in rat liver by in situ hybridization: application to the study of metabolic regulation and azo dye hepatocarcinogenesis.

In situ hybridization on tissue sections was used to detect mRNAs present at low concentrations during metabolic adaptation and azo dye carcinogenesis in rat liver. The method consisted of hybridizing the slices at relatively high stringency with [35S]-labeled single-stranded probes derived from cDNA insert clones into the M13 phage. L-pyruvate kinase mRNA was proved to be present at very low concentrations in hepatocytes of fasted rats and to be relatively abundant in all hepatocytes after 18 hr of refeeding on a carbohydrate-rich diet. Aldolase A mRNA concentrations have been previously shown to increase markedly in liver of 3'-methyl DAB-fed rats, with a maximum at the fourth week. We demonstrate here, using our in situ hybridization technique, that this phenomenon is not due to re-expression of this "fetal marker" in hepatocytes but to its abundancy in proliferating small cells (i.e., so-called oval and transitional cells). Small amounts were also detected in sinusoidal cells. In normal liver, aldolase A mRNAs were detected only in some sinusoidal cells.

Animals↗
PubMed1987

Binding of tumor necrosis factor alpha (TNF-alpha) to high-affinity receptors on polymorphonuclear cells.

The effects of tumor necrosis factor alpha (TNF-alpha) on human polymorphonuclear (PMN) cells were investigated. We found that 125I-TNF-alpha bound specifically to high-affinity receptors on PMN cells. At 4 degrees C, the binding occurred rapidly and reached steady state after 20 min. The Scatchard plot showed a single class of high-affinity receptors with approximately 2200 receptors/cell and a dissociation constant of 2 x 10(-10) M. There was a linear relationship between TNF-alpha binding and TNF-alpha-induced PMN cell adherence. The concentration of TNF-alpha required to achieve approximately 50% of maximum binding was also approximately the concentration required to reach 50% cell adherence. Auranofin was shown to inhibit TNF-alpha-induced PMN cell adherence at a dose of 5-10 micrograms/ml. This inhibitory effect was not due to the inhibition of TNF-alpha binding to PMN cells by the drug. These observations may have clinical implications.

Auranofin↗
PubMed1987

Expression of c-myc is under dietary control in rat liver.

Expression of c-myc has often been related to the control of growth and differentiation of a variety of cell types. However, in some cases, such a relation has not been found. The rate of cell division is very low in liver, but c-myc expression is yet easily detected. We show here that a short-time physiological fasting results in a dramatic decrease of c-myc expression in rat liver. This effect does not seem to be dependent on glucagon, since administration of glucagon leads to an increase in c-myc mRNA. This is to our knowledge, the first evidence of a physiological variation of proto-oncogene expression linked to food intake, and we suggest that this variation could play a role in liver cell growth control.

Animals↗
PubMed1987

Transepidermal water loss during sleep in infants at risk for sudden death.

To search for excessive sweating during sleep in infants considered at risk for sudden infant death syndrome (SIDS), we studied 258 infants during one night. There were 134 normal infants (controls), 85 siblings of SIDS victims (siblings), and 39 infants who survived an apparent life-threatening event (ALTE) with no cause found for the incident. Mean postnatal ages were between 10 and 16 weeks. Transepidermal water evaporation rate was measured from the forehead using an evaporimeter during one night's polygraphic sleep recording. Measurements were made before feedings, during the first part of the night, and evaporation rate values were expressed as grams per square meter of body surface area per hour. In the three groups of patients evaporation rates were significantly lower during rapid eye movement (REM) sleep, compared with values measured during quiet wakefulness or nonrapid eye movement (NREM) sleep. Infants with an ALTE had significantly higher evaporation rate values during NREM sleep than the two other groups (20.1 +/- 1.93, 11.3 +/- 0.68, and 11.5 +/- 0.98 for the ALTE, control, and sibling infants, respectively). The differences were not related to age, sex, weight, or rectal temperature. During NREM sleep, evaporation rate values greater than 25 mg/m2/h were seen in 10/190 (5.3%) of the asymptomatic infants and in 11/36 (30.6%) of the infants with an ALTE. The results are in agreement with reports in the literature of repeated night sweating in infants who eventually died of SIDS. Although we are unable to conclude why evaporation rate values are higher in the ALTE group than in the two other groups, we cannot exclude that it reflects differences in autonomous system activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1987

Reduction of adverse drug reactions by computerized drug interaction screening.

Computerized drug-interaction screening systems (CDISS) have been developed as a tool to help decrease the enormous morbidity and expense related to adverse drug interactions. In previous studies the CDISS was used primarily by pharmacists in hospital settings to screen for interactions after the prescription had been written. This study tests the feasibility of family physicians using CDISS before writing the prescription to allow for changes in the prescription while the patient is still in the office. In a 30-day period, 103 patients were screened by family physicians for potential drug-drug, drug-alcohol, and drug-food interactions. Potential drug interactions of varying clinical significance were detected for 71 patients (68.9 percent). The prescription plan was changed for 16 patients (15.5 percent) as a result of using the CDISS. Participating physicians reported that they gained new information in 45.8 percent of the patient encounters, that their awareness of the potential for drug interactions was heightened by participation in this study, and that their exposure to the CDISS was worthwhile as an educational tool. While a few problems, mainly logistic, were noted with the CDISS as used in this study, the authors conclude that with modifications a CDISS can be of great educational and clinical value to the family physician and his or her patients.

Computer Systems↗
PubMed1986

Early modifications of gene expression induced in liver by azo-dye diet.

The expression and regulation of the phosphoenolpyruvate carboxykinase gene were not grossly modified by feeding rats a 3'-methyl-4-(dimethylamino)azobenzene-containing diet despite maximum expression of the L-type pyruvate kinase gene being dramatically reduced as early as the 24th hour of the carcinogenic diet. Inhibition of aldolase B mRNA synthesis occurred more slowly, being maximum at the 3rd day. After stopping administration of the carcinogen, a very rapid, but transient increase of the L-type pyruvate kinase mRNA was observed at the 24th hour, whereas aldolase B mRNA increased only slowly. The amount of aldolase A mRNA fell quickly after termination of carcinogen administration, levels being normal at the 2nd-3rd day. At this time, the histological structure of the liver was indistinguishable from that of animals still receiving the azo-dye diet. It appears, therefore, that in the rat both administration and withdrawal of the azo-dye carcinogen induce rapid modifications of the expression of some genes, before any cellular modification is distinguishable.

Animals↗