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Biomedical subjects

A Kahn

Publications and source records attributed to A Kahn.

At least 379 records · Page 21Linked to original sources

Tyrosine kinases in normal human blood cells. Platelet but not erythrocyte band 3 tyrosine kinase is p60c-src.

The major tyrosine kinase from platelets was purified as a 51 kDa active enzyme which was shown to be a degradation product of the protooncogene product p60c-src. Immuno-depletion experiments using a monoclonal antibody recognizing p60c-src failed to remove band 3 phosphorylating activity from red blood cell membranes. The erythrocyte tyrosine kinase was not at all immunoprecipitated by this antibody under conditions where the platelet enzyme was immunoprecipitated.

Anion Exchange Protein 1, Erythrocyte↗

In vivo developmental modifications of the expression of genes encoding muscle-specific enzymes in rat.

cDNA clones for rat muscle-type creatine kinase and glycogen phosphorylase and aldolase A were isolated from a rat muscle cDNA library. An additional clone recognizing an unidentified 2.7-kilobase pair mRNA species was also isolated. These cDNA clones were used as probes to investigate the expression of the corresponding mRNAs during muscle development. Two aldolase A mRNA species were detected, one of 1650 bases expressed in non-muscle tissues, fetal muscle, and adult slow-twitch muscle, the other of 1550 bases was highly specific of adult fast-twitch skeletal muscle differentiation. These aldolase A mRNAs were shown by primer extension to differ by their 5' ends. The accumulation of muscle-type phosphorylase and creatine kinase and muscle-specific aldolase A mRNA accumulation during muscle development seems to be a coordinate process occurring progressively from the 17th day of intrauterine life up to the 30th day after birth. In contrast, the 2.7-kilobase pair RNA species is maximally expressed at the 1st week after birth as is the neonatal form of myosin heavy chain mRNA.

Aging↗

Tissue-specific heterogeneity of the 3'-untranslated region of L-type pyruvate kinase mRNAs.

A single L-type pyruvate kinase (PK) gene seems to exist per haploid genome. It is expressed in the liver, kidney and small intestine in the form of three mRNA species of 2, 2.2 and 3.2 X 10(3) bases (kb). All three species are polyadenylated and translatable into the same L-type subunit. Primer extension experiments demonstrate that all three PK mRNAs have the same 5' ends. Nuclease S1 protection experiments with various cDNA and 3' genomic probes indicate that the different mRNA species only differ by the length of their 3' noncoding region. The mechanism responsible for the production of the three transcripts seems to be the use of alternative unusual polyadenylation sites. Run-on assays with specific probes recognizing only the 3.2-kb or all three mRNA species show that the transcription proceeds across the gene with similar rate. This means that the process involved in generation of the three transcripts is a posttranscriptional event, probably due to different sites of endonucleolytic cleavage of primary transcripts extending 3' from the gene region encoding the mature mRNAs. The ratio between the different PK mRNA species is, to a certain extent, tissue-specific and changes with development. The role of an 'identifier sequence' located in the 3' noncoding sequence of the 3.2-kb species in such a tissue-specific use of alternative polyadenylation sites is discussed.

Animals↗

Transcriptional and post-transcriptional regulation of L-type pyruvate kinase gene expression in rat liver.

The effects of starvation, refeeding a diet high in carbohydrate, administration of glucagon and cyclic AMP, thyroidectomy, and adrenalectomy on transcription of the gene for liver L-type pyruvate kinase and on the accumulation of cytoplasmic mRNA for L-type pyruvate kinase were investigated in rat. Transcription of the gene was undetectable in either fasted or protein-fed rats. Refeeding fasted rats a carbohydrate-rich diet stimulated an increase in L-type pyruvate kinase mRNA, preceded by an increase in the gene transcription. Transcription was maximal at 12 h of refeeding, decreasing to 10% of maximum at 72 h. The level of L-type pyruvate kinase mRNA remained constant at 50% of maximum for at least 120 h. Neither thyroidectomy nor adrenalectomy affected gene transcription in fasted rats refed the carbohydrate-rich diet, despite a decrease in mRNA abundance to 40 and 20%, respectively, of controls fed a normal diet. Glucagon or cyclic AMP totally blocked the increase in transcription of the L-type pyruvate kinase gene caused by feeding a carbohydrate-rich diet to previously fasted rats. Nevertheless, the level of L-type pyruvate kinase mRNA remained high for 3 h after glucagon administration. After 3 h, the mRNA decreased rapidly with a half-life less than 1 h. Thus, expression of the gene for L-type pyruvate kinase is regulated at both transcriptional and post-transcriptional levels. The transcription is regulated by two major effectors, one positive, namely carbohydrates, and one negative, namely glucagon (via cyclic AMP). Both agents probably act at the level of the mRNA stability as well. Glucocorticoids and thyroid hormones do not regulate transcription of the gene for L-type pyruvate kinase but do appear to be required for a normal accumulation of the transcripts in the cytoplasm.

Adrenalectomy↗

Expression of aldolase A messenger RNAs in human adult and foetal tissues and in hepatoma.

3 specific cDNA clones for human aldolase A were isolated from a human muscle library. One of them was subcloned in M 13 phage, then used as a probe to investigate the patterns and the levels of aldolase A mRNA in various human tissues. Two mRNA species differing in length were observed. The lighter one -1550 bases- was found specific to skeletal muscle; its amount increased during muscle development. The heavier aldolase A mRNA -1650 bases- accounted for foetal and ubiquitous presence of aldolase A isozyme. The resurgence of aldolase A in hepatomas occurred through this latter mRNA species.

Animals↗

Sequences complementary to the brain-specific "identifier" sequences exist in L-type pyruvate kinase mRNA (a liver-specific messenger) and in transcripts especially abundant in muscle.

A sequence complementary to the brain-specific identifier sequence has been found in the 3' untranslated extension of the heavy 3.2-kilobase (kb) long liver L-type pyruvate kinase mRNA while it is absent in the other two 2- and 2.2-kb long pyruvate kinase mRNA species. A 53-base fragment corresponding to this identifier sequence was subcloned in both orientations in the single-stranded bacteriophage M13, both strands being used as probes to detect homologous sequence in different tissues. Both strands are transcribed in various tissues and are detected in heterogeneous high molecular weight RNA species which are especially abundant in the adult muscle. In addition, the probe identical to the identifier sequence recognized a discrete 0.6-kb RNA species in the muscle and the probe complementary to the identifier-sequence recognized the expected two small brain-specific identifier BC-1 and BC-2 RNAs described by Sutcliffe et al. (Sutcliffe, J. G., Milner, R. J., Bloom, F. E., and Lerner, R. A. (1982) Proc. Natl. Acad. Sci. U. S. A. 79, 4942-4946; Sutcliffe, J. G., Milner, R. J., Gottesfeld, J. M., and Lerner, R. A. (1984) Nature 308, 237-241; Milner, R. J., Bloom, F. E., Lai, C., Lerner, R. A., and Sutcliffe, J. G. (1984) Proc. Natl. Acad. Sci. U. S. A. 81, 713-717; Sutcliffe, J. G., Milner, R. J., Gottesfeld, J. M., and Reynolds, W. (1984) Science 225, 1308-1314).

Animals↗

Complete nucleotide and deduced amino acid sequences of rat L-type pyruvate kinase.

Four overlapping cDNA clones for L-type pyruvate kinase (PK-L) were isolated from carbohydrate-induced rat liver cDNA libraries. They contained all the coding sequence of the enzyme from the 7th codon and the entire 3'-untranslated extension up to the poly(A) tail. The sequence of the first 7 codons and that of the 5'-untranslated region were determined by primer extension. The analyzed PK-L mRNA has 19 5'-untranslated bases, 1629 coding bases and 1281 3'-untranslated bases without the poly(A) tail; it corresponds to the heavier, 3.2 kb species of the L-type mRNAs. The codons for the phosphorylatable site are located at the 5'-end of the messenger. The unusually long 3'-untranslated extension contains a repetitive element complementary to the 'brain-specific' identifier sequence described by Sutcliffe et al. [(1982) Proc. Natl. Acad. Sci. USA 79, 4942-4946].

Amino Acid Sequence↗

Polysomnographic studies and home monitoring of siblings of SIDS victims and of infants with no family history of sudden infant death.

We report preliminary results of a prospective study conducted to prevent sudden death in asymptomatic infants. From 1977-1984, 3658 infants were studied polygraphically. There were 923 siblings of SIDS victims and 2735 infants with no personal of family history of SIDS. The infants were studied at 8 weeks of age. Polygraphic "risk factors" were defined by central apnoeas longer than 15 s; periodic breathing above 5% sleep time; or obstructive apnoeas above 3 s. In 937 infants "risk factors" were seen and a second study was requested 4 weeks later. Out of 891 infants re-studied at 12 weeks, 153 still presented some "risk factors" and were selected for a home monitoring programme; 150 families agreed to monitor their infants at home with a cardiorespiratory monitor with the alarms set at 20 s apnoea, and 50 beats per min bradycardia. Repeated alarms were reported for 97/150 (65%) infants; 48/150 (32%) infants were stimulated and 8/150 (5.3%) were resuscitated on at least one occasion. No death occurred during monitoring, which could be interrupted before the end of the first year of life in all infants. In the group of 3459 infants with normal results and not monitored, three siblings (0.35%) and one infant without history (0.04%) died of SIDS. Of the infants with abnormal polygraphic results, one sibling not returned for the second recording, and two out of three infants for whom the parents refused monitoring, died of SIDS. It is concluded that the programme, may prevent the death of some infants, but that the outcome of a child with normal results cannot be foreseen.

Arrhythmias, Cardiac↗

Cloning and expression of cDNA for anti-müllerian hormone.

Messenger RNA, prepared from fetal bovine testicular tissue, was used to construct a cDNA library in lambda gt11 phage. The library was screened with an antibody probe directed against bovine anti-Müllerian hormone and three positive clones were isolated. Cross-hybridizing cDNA inserts carried by clones 4 and 5 (1.2 and 0.08 kilobases long, respectively) code for a fragment of authentic anti-Müllerian hormone, as shown by the ability of the anti-epitope antibodies eluted from fusion protein 4 to bind strongly to anti-Müllerian hormone on immunoblots and by the capacity of anti-epitope antibodies 4 and 5 to precipitate radioiodinated bovine anti-Müllerian hormone. A probe prepared from insert 4 hybridizes with an mRNA present only in tissues that are known producers of anti-Müllerian hormone, such as the fetal testis and adult ovarian follicles. The amount of specific mRNA in tissues of males and females is related to the rate of their anti-Müllerian hormone production. The 2.1-kilobase size of this mRNA species is large enough to code for the Mr 62,000 anti-Müllerian hormone polypeptide chain. Insert 4 also hybridizes with an mRNA of similar size in human and rat fetal testicular tissue. The third isolated clone, clone 8, which does not cross-hybridize with the others, carries a cDNA insert coding for a ubiquitous protein, smaller than anti-Müllerian hormone, with which it apparently shares an epitope.

Animals↗

Auditory arousal thresholds of normal and near-miss SIDS infants.

The sleep characteristics and auditory arousal thresholds of 20 near-miss sudden infant death syndrome (SIDS) infants and 97 age- and sex-matched normal infants were studied. It was observed that spontaneous arousals occurred significantly less frequently in the near-miss SIDS infants. In both groups, induced arousals occurred at comparable stimulation intensities, and arousal thresholds decreased significantly from the 44th to the 52nd postconceptional week. This supports the notion that both groups present a similar maturational process within the auditory pathways and brainstem, and that arousal is not related to differences in behavioural response to ambient noise during sleep.

Acoustic Stimulation↗

Sudden infant death syndrome in a twin: a comparison of sibling histories.

To determine possible characteristics of infant victims of sudden death, we examined 114 items related to the pre- and postnatal histories of 42 pairs of twins one of whom died of sudden infant death syndrome (SIDS) leaving a surviving sibling. Interviews with the parents were conducted after the occurrence of SIDS, and the data were checked with records held by gynecologists and pediatricians. To evaluate the specificity of any factors, we studied a control group of 42 age- and sex-matched pairs of twins, both of whom survived the first year of life. Only 11 of 114 characteristics were significantly related to SIDS: future victims had a smaller weight and height at birth, stayed longer in the nursery, and followed a moving object with their eyes, had head control, and smiled at a later age than their surviving siblings. They also fatigued more often during feeding (11/42) and had reduced arm and neck tonus (9/42). They were described as longer sleepers than their surviving siblings. During sleep, some SIDS twins, but no surviving twin, were found to be cyanotic at least once or pale (4/42) and were repeatedly covered with abundant sweat (8/42). In the control group of normal twins, the occurrence of most of these characteristics was found with a frequency comparable to that seen in the SIDS infants; the specificity of these characteristics is thus considered doubtful. The mean birth weight and height were significantly greater in the control group, and no control infant had an episode of cyanosis or pallor or repeated episodes of profuse sweating observed during their sleep.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗