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Biomedical subjects

J M Klein

Publications and source records attributed to J M Klein.

At least 19 recordsLinked to original sources
PubMed2006

Repeat surfactant therapy for postsurfactant slump.

OBJECTIVE: To evaluate repeat surfactant therapy for the treatment of respiratory failure associated with postsurfactant slump in extremely low birth weight infants (ELBW) by characterizing the population of premature infants who develop postsurfactant slump and measuring their response to a secondary course of surfactant therapy. STUDY DESIGN: A retrospective analysis of a cohort of all patients admitted over a 3-year period with birth weights <1000 g (ELBW infants). Information was collected by chart review and the patients were categorized into three distinct groups for analysis. Initial surfactant only, patients who received surfactant replacement therapy only for respiratory distress syndrome (RDS); repeat surfactant, patients who received both initial surfactant replacement for RDS and repeat surfactant therapy for postsurfactant slump (defined as respiratory failure after 6 days of age), and no surfactant, patients in whom no surfactant was ever administered. A respiratory severity score (RSS) was used to measure the severity of lung disease and response to surfactant therapy. RESULTS: Over 3 years, there were 165 ELBW infants who could develop postsurfactant slump and be eligible for repeat surfactant therapy. There were 39 infants who never received any surfactant therapy estimated gestational age (EGA) 27.7 +/- 1.7, birth weight 856 +/- 109 g) either at birth or after 6 days of life. There were 126 patients treated for RDS with initial surfactant replacement therapy (EGA 25.6 +/- 1.9 weeks, birth weight 713 +/- 179 g). Out of these RDS patients, 101 improved with an initial course of surfactant therapy (EGA 26 +/- 1.8, birth weight 751 +/- 143 g), but 25 (20% of the patients with RDS) developed postsurfactant slump and received a repeat course of surfactant therapy (EGA 24.7 +/- 1.2, birth weight 647 +/- 120 g). The repeat surfactant group (postsurfactant slump) was significantly more premature and had significantly lower birth weights compared to both the initial surfactant only group and the no surfactant ever group. Logistic regression analysis revealed that lack of antenatal steroids, earlier gestational age, and the receiving of 2 or more doses of surfactant to treat the initial RDS were significantly associated with receiving repeat surfactant therapy for postsurfactant slump. Of the 25 patients treated with a repeat course of surfactant therapy more than 70% of patients (n = 18) had an improvement in their lung disease with a 15% reduction in their RSS. This improvement was significant at all time points evaluated (12, 24, and 48 h). CONCLUSION: We found that a repeat course of surfactant therapy, after day of life 6, led to a significant improvement in hypoxemic respiratory failure in premature infants with postsurfactant slump. Infants who received repeat surfactant therapy were born at a significantly earlier gestational age, had significantly smaller birth weight and had significantly worse lung disease. They were significantly less likely to have received antenatal steroids and were significantly more likely to have received multiple doses of surfactant to treat their initial RDS. A repeat course of surfactant therapy for patients with postsurfactant slump appeared beneficial in the short-term. These initial findings would support performing randomized control trials of repeat surfactant therapy for postsurfactant slump.

Humans↗
PubMed2000

Neuregulin-1 and human epidermal growth factor receptors 2 and 3 play a role in human lung development in vitro.

The human epidermal growth factor receptor (HER) family consists of four distinct receptors: HER1 (epidermal growth factor receptor), HER2, HER3, and HER4. Their specific activating ligands are collectively known as neuregulins (NRG). We hypothesized that one member of the NRG family, NRG-1, and the HER family would play a role in fetal lung development. To test this hypothesis, we defined NRG-1 and HER gene expression in mid-trimester human fetal lung tissue. HER2 and HER3 messenger RNA and protein were detected in the fetal lung, but HER4 expression was not detected. Immunohistochemical staining of fetal lung tissue localized HER2 and HER3 protein to the developing lung epithelium. NRG-1 expression was not found in freshly isolated human fetal lung, but it was observed in fetal lung explants after 2 d of explant culture. Immunohistochemistry of cultured human fetal lung explants revealed that NRG-1 protein was also expressed in pulmonary epithelial cells. Exposing human fetal lung to recombinant NRG-1 activated the HER receptor complex as measured by approximately 4-fold increases in receptor phosphotyrosine content. In addition, NRG-1 increased explant epithelial cell volume density approximately 2-fold (P < 0. 03); increased epithelial cell proliferation approximately 2-fold, as determined by bromodeoxyuridine labeling (P = 0.002); and reduced surfactant protein-A (SP-A) levels by 53% (P < 0.05). These data are consistent with an autocrine regulatory process mediated by NRG-1 activation of HER2/HER3 heterodimers expressed on developing human fetal lung epithelial cells. Receptor activation results in increased lung epithelial cell proliferation and volume density, and decreased SP-A production, a marker of type II pneumocyte differentiation.

Autocrine Communication↗
PubMed2000

Antisense inhibition of epidermal growth factor receptor decreases expression of human surfactant protein A.

Epidermal growth factor (EGF) stimulates surfactant protein A (SP-A) synthesis in fetal lung tissue through ligand binding to the EGF receptor. We hypothesized that inhibition of EGF receptor messenger RNA (mRNA) would block SP-A expression in human fetal lung tissue during alveolar type II cell differentiation in vitro. Midtrimester human fetal lung explants were maintained in serum-free Waymouth's medium for 3 to 5 d in the presence or absence of an antisense 18-mer phosphorothioate oligonucleotide (ON) complementary to the initiation codon region of EGF receptor mRNA. Sense and scrambled ONs similarly modified were used as additional controls. The concentration of EGF receptor mRNA was semiquantitatively determined by reverse transcriptase/polymerase chain reaction (RT-PCR). We found a significant 3-fold decrease in EGF receptor mRNA levels in the antisense-treated groups compared with the control group with no effect in the sense condition. Immunohistochemical staining revealed a decrease in the amount of staining for EGF receptor protein in distal pulmonary epithelial cells in the antisense-treated groups compared with either control or sense conditions. Treatment with antisense EGF receptor ON decreased both SP-A mRNA and protein compared with controls with no effect in the sense condition. The ONs did not affect tissue viability as measured by the release of lactate dehydrogenase. We conclude that selective degradation of EGF receptor mRNA with antisense ON treatment results in a decrease in SP-A expression in human fetal lung. These findings support the critical importance of the EGF receptor for the regulation of SP-A gene expression during human alveolar type II cell differentiation.

Blotting, Northern↗
PubMed1998

Transient surfactant protein B deficiency in a term infant with severe respiratory failure.

A 38-day-old male infant with persistent pulmonary hypertension and respiratory failure since birth was found to have a complete absence of surfactant protein B (SP-B) along with an aberrant form of SP-C in his tracheal aspirate fluid, findings consistent with the diagnosis of hereditary SP-B deficiency. Surprisingly, SP-B and SP-B messenger ribonucleic acid were present in lung biopsy tissue. However, DNA sequence analysis demonstrated a point mutation in exon 5 of one of the SP-B gene alleles. The infant's mother was found to be a carrier of this mutation. The infant's other SP-B allele did not differ from the published DNA sequence for the SP-B gene. We conclude that this patient had a transient deficiency of SP-B, in contrast to that of previously described infants with irreversible respiratory failure caused by hereditary SP-B deficiency. We recommend that infants with suspected SP-B deficiency have serial analysis of tracheal fluid samples for both SP-B and SP-C before lung biopsy, along with genetic analysis for the known SP-B mutations. We speculate that the new mutation found in one of this patient's SP-B genes was in part responsible for the transient deficiency of SP-B.

Exudates and Transudates↗
PubMed1998

Syllabic effects in word processing: evidence from the structural induction paradigm.

Spoken words have a rich structural organization in memory, consisting of syllabic and subsyllabic representations. A phoneme monitoring paradigm, in which the target phoneme occurs more frequently in one syllabic position than another (e.g., onset of the 2nd syllable vs. the coda of the 1st syllable: neu-tral vs. nut-meg; C. Pallier, N. Sebastian-Galles, T. Felguera, A. Christophe, & J. Mehler, 1993) was used to explore the formation of syllabic structure during word processing. Experiment 2 investigated how a recognition system that uses syllabic structure processes words with unclear syllable boundaries (e.g., pa-lace or pal-ace?). Two methodological issues were explored: The importance of a baseline condition for measuring effects of induction (Experiment 1) and the form of the representation used in the induction paradigm (Experiment 3). Findings suggest that syllabic structure begins to form early in word processing, and they demonstrate the adequacy of the induction procedure for measuring such processes.

Brain↗
PubMed1998

Effect of tyrosine kinase inhibition on surfactant protein A gene expression during human lung development.

Epidermal growth factor (EGF) stimulates surfactant protein (SP) A synthesis in human fetal lung explants. Ligand binding to the EGF receptor stimulates an intrinsic receptor tyrosine kinase with subsequent activation of second messengers. We hypothesized that inhibition of EGF-receptor tyrosine kinase activity would block SP-A expression in spontaneously differentiating cultured human fetal lung tissue. Midtrimester fetal lung explants were exposed for 4 days to genistein (a broad-range inhibitor of tyrosine kinases) and tyrphostin AG-1478 (a specific inhibitor of EGF-receptor tyrosine kinase). Genistein significantly decreased SP-A and SP-A mRNA levels without affecting either tissue viability or the morphological differentiation of alveolar type II cells. Tyrphostin AG-1478 also decreased SP-A content and SP-A mRNA levels in cultured fetal lung explants. Treatment with EGF could not overcome the inhibitory effects of either genistein or tyrphostin on SP-A; however, only tyrphostin inhibited EGF-receptor tyrosine phosphorylation. We conclude that specific inhibition of EGF-receptor tyrosine kinase with tyrphostin AG-1478 blocks the expression of SP-A during spontaneous differentiation of cultured human fetal lung tissue. Furthermore, exposure to genistein also decreases SP-A expression and blocks the effects of EGF in human fetal lung tissue without inhibiting EGF-receptor tyrosine phosphorylation. These findings support the importance of tyrosine kinase-dependent signal transduction pathways in the regulation of SP-A during human fetal lung development.

Embryonic and Fetal Development↗
PubMed1997

Inhibition of tyrosine kinase activity decreases expression of surfactant protein A in a human lung adenocarcinoma cell line independent of epidermal growth factor receptor.

Epidermal growth factor (EGF) enhances fetal lung development in vivo and in vitro. Ligand binding to the EGF receptor stimulates an intrinsic receptor tyrosine kinase initiating a signal transduction cascade. We hypothesized that blocking EGF receptor function with tyrosine kinase inhibitors would decrease the expression of surfactant protein A in human pulmonary epithelial cells. Human pulmonary adenocarcinoma cells (NCI-H441) were exposed to genistein (a broad range inhibitor of tyrosine kinases) and tyrphostin AG1478 (a specific inhibitor of EGF receptor tyrosine kinase). Genistein significantly decreased surfactant protein A (SP-A) and SP-A mRNA levels in H441 cells without affecting cell viability. The inhibitory effect of genistein on SP-A content was reversible. In contrast, tyrphostin AG1478 had no effect on SP-A levels despite a greater inhibitory effect than genistein on EGF receptor tyrosine autophosphorylation. Furthermore, treatment of H441 cells with exogenous EGF did not increase SP-A content or mRNA levels beyond baseline. We conclude that inhibition of tyrosine kinase activity other than the EGF receptor decreases the expression of surfactant protein A at a pretranslational level in human pulmonary adenocarcinoma cells. These results suggest the importance of tyrosine kinases in modulating human SP-A synthesis.

Benzylidene Compounds↗
PubMed1996

Effects of attentional set and rhythmic complexity on attending.

In a target detection task involving sustained attentional monitoring, rhythmic properties of tone sequences were found to affect detection performance (area under receiver-operating characteristic curves) and reaction times. Alternating tone frequencies (high, low) formed three different recurrent rhythms (binary, trinary, mixed) which varied in complexity. Attentional set was also manipulated so that participants attended either to tones of both frequencies (divided) or to only the higher of the two tones (selective). The most interesting finding involved an interaction between attention set and rhythm, indicating that selective attending is enhanced by the most complex (mixed) rhythm, whereas divided attending tends to be best with the simplest rhythm (binary). Results are discussed in terms of a theory of dynamic attending, in which it is assumed that listeners actively use attending oscillators to direct attending.

Attention↗
PubMed1995

A highly conserved red pigment-concentrating hormone precursor in the blue crab Callinectes sapidus.

A cDNA library was established from the eyestalk ganglia of the blue crab Callinectes sapidus. One clone was isolated (644 bp excluding the poly(A) tail) which encodes the red pigment-concentrating hormone (RPCH)-precursor, consisting of the 25 amino acid residue signal peptide, the RPCH, and a 73 amino acid residue RPCH-precursor related peptide. This clone displays high sequence similarity with a clone isolated from an eyestalk cDNA library of the shore crab Carcinus maenas, in accordance with the close phylogenetic relationship between these species. Northern blot experiments indicated the presence of two different mRNA transcripts which hybridized with a specific RPCH-cDNA probe pointing to the possibility of multiple RPCH isoforms in the blue crab. Although crustacean RPCH and the insect adipokinetic hormones (AKH) are structurally related, their precursors show little similarity.

Amino Acid Sequence↗
PubMed1995

Outcome of infants with birth weights less than 1000 g with respiratory distress syndrome treated with high-frequency ventilation and surfactant replacement therapy.

OBJECTIVE: To compare outcomes in premature infants with respiratory distress syndrome who received surfactant replacement therapy and were treated with either high-frequency or conventional mechanical ventilation. DESIGN: Retrospective chart review of patient series. SETTING: Tertiary academic medical center. PATIENTS: One hundred fourteen extremely low-birth-weight infants (< 1000 g) with respiratory distress syndrome treated with surfactant replacement therapy, consecutively admitted to the neonatal intensive care unit between September 1989 and August 1992. INTERVENTIONS: Treatment with either high-frequency ventilation (n = 46) or conventional mechanical ventilation (n = 68) after surfactant replacement therapy. MAIN OUTCOME MEASURES: Intraventricular hemorrhage and neurodevelopmental status. RESULTS: Infants who received high-frequency ventilation had significantly lower birth weights and were more premature than infants receiving conventional mechanical ventilation. Despite this, patients ventilated with high frequency had similar incidences of intraventricular hemorrhage and impaired neurodevelopmental outcomes when compared with the conventionally ventilated patients. As expected, the smaller and more premature infants receiving high-frequency ventilation required a longer duration of respiratory support (mechanical ventilation and nasopharyngeal continuous positive airway pressure). Additionally, multiple logistic regression analysis to control for differences in birth weight and gestational age between the two groups revealed a significant association between the combined use of high-frequency ventilation and antenatal corticosteroids and the absence of either intraventricular hemorrhage or pneumothorax. CONCLUSION: We conclude that high-frequency ventilation combined with surfactant therapy is as safe as conventional mechanical ventilation combined with surfactant therapy for treating respiratory distress syndrome in extremely low-birth-weight infants (< 1000 g) and does not increase the risk of either intraventricular hemorrhage or abnormal neurodevelopmental outcome.

Biological Products↗
PubMed1995

Treatment of respiratory failure in an infant with bronchopulmonary dysplasia infected with respiratory syncytial virus using inhaled nitric oxide and high frequency ventilation.

A 2-month-old, former 28-week premature infant with bronchopulmonary dysplasia infected with respiratory syncytial virus was treated with nitric oxide and high frequency oscillatory ventilation after conventional therapy failed. Nitric oxide and high frequency oscillatory ventilation rapidly improved oxygenation allowing recovery without the need for extracorporeal membrane oxygenation. This treatment regimen should be considered as an option in high-risk infants with respiratory syncytial virus infection who meet extracorporeal membrane oxygenation criteria.

Administration, Inhalation↗
PubMed1994

Molecular cloning of two pigment-dispersing hormone (PDH) precursors in the blue crab Callinectes sapidus reveals a novel member of the PDH neuropeptide family.

A cDNA library was established from the eyestalk ganglia of the blue crab Callinectes sapidus. Screening resulted in the isolation of a clone (497 bp excluding poly(A) tail) which encodes a beta-PDH previously found in several crustacean species. It displays high sequence similarity with a clone isolated from an eyestalk cDNA library of the shore crab Carcinus maenas, indicating the close phylogenetic relationship of both species. A second clone (414 bp exclusive of the poly(A) tail) encodes a novel beta-PDH analog which displays 400-fold less potency in crab bioassays. Both cDNAs encode open reading frames of 234 bp for the prepropeptides, consisting of signal peptides, PDH-precursor-related peptides, and PDH sequences.

Amino Acid Sequence↗
PubMed1994

Low incidence of rheumatoid arthritis in France.

The incidence of rheumatoid arthritis (RA) was estimated in the Lorraine district, eastern France, over the period 1986-1989. Cases were identified from in- and outpatients at the district Rheumatology Hospital Centre, private rheumatologists, general practitioners and by regional media announcements. Supplementary cases resident in the area were sought by extending the procedure to adjacent districts. The population count was obtained from the national Census. An overall age-adjusted incidence rate of 8.8/100,000 was found using the 1987 ACR criteria (12.7/100,000 in females, 4.7/100,000 in males; sex ratio = 2.65) and 9.5/100,000 using the 1958 ARA criteria (definite and classic RA). These rates were compared, using the same standard population, with the age-adjusted incidence rates in other incidence studies mainly conducted in Caucasian populations. The RA incidence rates appeared lower in France than in any other country in Europe, USA and Japan.

Adult↗
PubMed1993

Molecular cloning of crustacean putative molt-inhibiting hormone (MIH) precursor.

A cDNA encoding the complete precursor of the putative molt-inhibiting hormone (MIH) of the shore crab, Carcinus maenas, was isolated and sequenced. The precursor consists of a putative 35 amino acid signal peptide and the 78 amino acid mature MIH. The deduced MIH amino acid sequence is in complete agreement with the sequence previously determined by Edman degradation. In situ hybridization revealed MIH-expression in a subpopulation of large neurosecretory perikarya of the medulla terminalis X-organ in the eyestalk.

Amino Acid Sequence↗
PubMed1993

Molecular cloning of crustacean red pigment concentrating hormone precursor.

A cDNA encoding the precursor of the red pigment concentrating hormone (RPCH) of the shore crab, Carcinus maenas, was isolated and sequenced. The predicted preprohormone sequence consists of a putative 25 amino acid signal peptide, the eight amino acid RPCH sequence followed by a Gly as amide donor, a dibasic processing site and a 74 residue peptide of unknown function, referred to as RPCH-precursor-related peptide (RPRP). In in situ hybridisation experiments, the RPCH gene transcript could be localised in two clusters of neurons in the medulla terminalis of the eyestalk.

Amino Acid Sequence↗