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Biomedical subjects

C Christian

Publications and source records attributed to C Christian.

At least 19 recordsLinked to original sources
PubMed2006

Expression of the coxsackievirus- and adenovirus receptor in gastrointestinal cancer correlates with tumor differentiation.

Modified adenoviruses represent a new approach to treatment of gastrointestinal cancer. However, their uptake by cells in many cases requires the major receptor for adenoviruses, the coxsackievirus and adenovirus receptor (CAR). Thus, lack of CAR expression is a potential cause of intrinsic resistance of tumor cells to this type of treatment. To evaluate this, we studied the localization of CAR protein in normal and malignant gastrointestinal tissues. In normal tissues, CAR was concentrated at sites of cell-cell interaction, in particular at the apico-lateral cellular surface. Expression was particularly strong around bile and pancreatic ducts, which is in agreement with CAR's physiological function as a tight-junction protein. In GI malignancies (esophageal, pancreatic, colorectal and liver cancer), expression of the receptor varied substantially. Loss of CAR expression at cell-cell junction was evident in many samples. A significant correlation between CAR expression and histological grade was found, with moderately to poorly differentiated tumors most frequently demonstrating loss or reduction of CAR expression. These data indicate that CAR expression is frequently altered in gastrointestinal malignancy, potentially reducing the efficacy of adenovirus-based therapies.

Adenoviridae↗
PubMed2004

Drug and alcohol use among patients admitted to a Danish trauma centre: a prospective study from a regional trauma centre in Scandinavia.

OBJECTIVES: The incidence of drug and alcohol use is unknown among Danish trauma patients, and has not been thoroughly investigated in Europe. METHODS: Patients admitted to the regional trauma centre in Aarhus, Denmark, were prospectively screened by blood and urine tests for the presence of alcohol, and legal and illicit drugs. The correlation with the Injury Severity Score, hospitalization time, and mortality after drug or alcohol intake was investigated. RESULTS: A quarter of all patients admitted in 1999 and 2000 had an alcohol level exceeding the national legal driving limit of 50 mg/dl, and one or more drugs were found in one in five patients. The presence of any drug or alcohol correlated positively with the Injury Severity Score, whereas alcohol level, hospitalization time, and mortality did not correlate. CONCLUSION: The rate of trauma patients with a blood serum level of alcohol greater than 100 mg/dl was similar to a previous European study and to US studies. The prevalence of drugs was less, and benzodiazepines were the most used group of drugs in our study. The routine screening of Danish trauma patients in order to implement preventative measures may be beneficial.

Alcohol Drinking↗
PubMed2002

Developmental regulation of SP-A receptor in fetal rat lung.

We studied the ontogeny and developmental regulation of the recently isolated SP-A receptor in fetal and postnatal rat lung. Our results show that SP-A receptor protein levels are first detectable at 16-18 days' gestation in fetal rat lung. There is a biphasic change in its levels with an initial marked increase during late gestation, a decrease in the early postnatal period (4-7 days of age), followed by another rise in levels during the second postnatal week. The results of binding isotherms show that maximal binding of monoclonal antibody to the receptor increases with differentiation of the type II cell, indicating that the increase during fetal lung development is due in part to increased numbers of receptors per cell. Bombesin (10 nM-1 microM) enhanced SP-A receptor protein levels threefold in fetal lung explants as early as 6 hours in culture. This effect of bombesin was associated with increased proliferation of type II cells as measured by levels of proliferating cell nuclear antigen (PCNA). We conclude that the increase in SP-A receptor protein level in late gestation fetal rat lung is due to increased numbers of receptors per cell and increased numbers of type II cells. Bombesin may have an important role during lung development by paracrine mechanisms that result in proliferation of lung cells.

Animals↗
PubMed2001

Orbital nodular fasciitis simulating a dermoid cyst in an 8-month-old child. Case report and review of the literature.

PURPOSE: To report a clinicopathologic correlation of orbital nodular fasciitis that simulated a dermoid cyst in an infant and to review the literature on orbital nodular fasciitis. METHOD: Case report; literature review. RESULTS: A progressively enlarging subcutaneous mass superotemporal to the right eye that clinically resembled a dermoid cyst developed in an 8-month-old boy. Magnetic resonance imaging disclosed an enhancing, circumscribed, solid, soft-tissue mass in the anterior part of the orbit superotemporally. The tumor was removed intact by a superolateral orbitotomy. Histopathologic and immunohistochemical studies revealed findings consistent with nodular fasciitis, a pseudoneoplastic lesion marked by a proliferation of myofibroblasts. CONCLUSIONS: Although nodular fasciitis in the ocular region usually occurs in adults and older children, it should also be considered in the differential diagnosis of orbital or adnexal masses in infants.

Dermoid Cyst↗
PubMed2000

Effects of salmeterol on secretion of phosphatidylcholine by alveolar type II cells.

Beta-adrenergic agents enhance secretion of phosphatidylcholine (PC) by adult and fetal type II cells. We have previously shown that terbutaline stimulates secretion of PC by fetal type II cells, but the response wanes after 30 minutes. We studied the effects of salmeterol, a highly selective, long-acting beta2-adrenergic agonist that does not cause receptor desensitization, on PC secretion by adult type II alveolar cells in primary culture. Release of lactate-dehydrogenase was < 4% and did not vary with the concentration of salmeterol. Salmeterol stimulated PC secretion in a concentration-dependent manner. The maximum effective-concentration tested was 50 nM and the EC50 was 11.40 +/- 1.14 nM. Propranolol inhibited the effect of salmeterol on release of PC, confirming that the effects of salmeterol are mediated by beta-receptors. OT50, the time for onset of action, was 32.0 +/- 1.6 minutes. RT50, the time to achieve 50% recovery from maximal stimulation was, 393.0 +/- 20.2 minutes. We conclude that salmeterol stimulates PC secretion by type II cells through activation of beta-adrenergic receptors and has a longer duration of action (>6 hours) compared to other beta2-agonists. Salmeterol may be a useful drug with which to study the role of receptor desensitization in the developmental changes in PC secretion.

Adrenergic beta-Agonists↗
PubMed1999

Bombesin inhibits apoptosis in developing fetal rat lung.

We have shown recently that apoptosis occurs during fetal and postnatal lung development. Our hypothesis that branching morphogenesis occurs through a delicate balance of cell proliferation and apoptosis predicts that substances that enhance branching of the airways would affect both cell proliferation and apoptosis in the lung. Bombesin-like peptides have a mitogenic effect on bronchial epithelium and fibroblasts, and bombesin has been shown to enhance branching morphogenesis in fetal lung. We used organ cultures of 16-day gestation fetal rat lung to study the effects of bombesin on apoptosis. Cultures were incubated in serumless medium alone or exposed to 1microM bombesin for 0-48 h. Levels of apoptosis were quantified using the TUNEL assay and expressed as percentage of apoptotic cells in paraffin sections of explants. Bombesin significantly inhibited apoptosis in fetal lung mesenchyme 48 h in culture by more than 50% (p < 0.05). The effects of bombesin on apoptosis were prevented completely if explants were exposed to the specific bombesin receptor antagonist, [D-Phe12]bombesin. To examine if the absence of serum in the media could have accounted for some of these effects, explants were cultured for 48 h in serumless medium, medium containing 10% fetal bovine serum, serumless medium with 1 microM bombesin, or medium containing both 10% fetal bovine serum and 1 microM bombesin. The addition of fetal bovine serum to the media reduced apoptosis significantly. The effect of fetal bovine serum on apoptosis was additive with bombesin. We conclude that bombesin inhibits apoptosis in developing fetal rat lung mesenchyme through its interaction with the bombesin receptor.

Animals↗
PubMed1998

Developmental regulation of the effects of surfactant protein A on phospholipid uptake by fetal rat type II pneumocytes.

Surfactant protein A (SP-A) enhances the uptake of phospholipid by type II cells derived from adult and late gestation fetal rat lung. The present study was performed to examine more fully the developmental biology of the effects of SP-A on phosphatidylcholine (PC) uptake, to determine the effect of SP-A on the cellular location of bound and internalized phospholipid and on the metabolism of internalized phospholipid by morphologically undifferentiated (18-day) and morphologically differentiated (19-day) fetal type II cells. SP-A enhanced uptake almost two-fold in a dose-dependent manner in 19-day fetal cells, but it had no effect on uptake by 18-day fetal cells at any concentration. Stimulation of uptake by 19-day fetal cells was saturable at concentrations above 1 microgram/ml SP-A. Maximal uptake was 1.12 nmol of PC/mg of protein, and the effective concentration that yields 50% maximal response, K phi, was 58.9 ng/ml (84.1 pM). The effect of SP-A on uptake by 19-day fetal cells was detectable as early as 1 min of exposure. Uptake correlated significantly with time both in the absence (r = 0.98, p < 0.001) and presence of 5 micrograms/ml SP-A (r = 0.979, p < 0.001). The rate of uptake in the presence of SP-A (0.019 +/- 0.002 nmol of PC/mg of protein/min) was twice the rate of uptake in controls (0.009 +/- 0.001 nmol of PC/mg of protein/min). SP-A had no effect on binding to plasma membranes and uptake of phospholipid into lamellar bodies by 18-day fetal cells. On the other hand, SP-A significantly enhanced binding of dipalmitoyl phosphatidylcholine to plasma membranes (two- to threefold) and uptake into lamellar bodies (threefold) of 19-day fetal cells. SP-A caused a significant reduction in the degradation of internalized phospholipid by differentiated fetal type II cells. Based on the lack of effect of exogenous SP-A on 18-day fetal cells, we conclude that the response to SP-A is under developmental control. SP-A enhances the initial binding to the plasma membranes of fetal type II cells and subsequent internalization into the lamellar bodies. This effect is associated with a protection of internalized phospholipid from metabolic degradation. Both of these processes are developmentally regulated during the transition from the canalicular to the saccular phase of lung development.

Animals↗
PubMed1998

Isolation and partial characterization of a receptor to surfactant protein A expressed by rat type II pneumocytes.

Surfactant protein A (SP-A), the most abundant protein component in pulmonary surfactant, has been shown to enhance surfactant phospholipid uptake by the type II alveolar epithelial cell. Recent evidence has shown that this process may be receptor-mediated. We undertook this study to isolate the putative receptor from type II cell membranes. We isolated two specific SP-A binding proteins from type II cells with apparent molecular weights (Mr) of 86 and > 200 kD under nonreducing conditions. Under reducing conditions, the higher-Mr protein was not present, but three proteins with apparent Mr of 65, 55, and 50 kD were visible, in addition to the 86-kD protein, indicating that the higher-Mr protein was composed of the smaller peptides which form disulfide bonds. The 86-kD protein is a glycoprotein with approximately 30% of its mass as carbohydrate. The 50-kD protein is also a glycoprotein (approximately 30% of its mass as carbohydrate), and SP-A binds to the protein core. Polyclonal and monoclonal antibodies to these peptides saturably bind to the surface of type II cells but not other lung cells, as shown by immunohistochemistry. SP-A competitively inhibits binding of one monoclonal antibody to type II cells, and the monoclonal antibody was able to block the effect of SP-A on phospholipid uptake by type II cells, indicating that this complex is a receptor to SP-A which is expressed on type II cells. This novel receptor is fundamental to the biology of surfactant metabolism in the lung.

Animals↗
PubMed1998

Private psychotherapy patients of psychiatrist psychoanalysts.

OBJECTIVE: The characteristics of private psychotherapy patients of medical psychoanalysts are described. METHOD: A structured interview was administered to 51 medical psychoanalysts. Patients' demographic characteristics, historical features, and other clinically relevant aspects of behavior were assessed. RESULTS: Of 575 patients, 88% had at least one axis I disorder and 46% had at least one axis I and one axis II disorder. Treatment duration varied from less than 6 months to more than 6 years. Forty-three percent of the patients were also treated with psychotropic drugs. CONCLUSIONS: The patients in this cohort met the criteria for DSM-IV psychiatric disorders, had lifetime histories of major psychiatric disturbances, and were not the "worried well."

Age Factors↗
PubMed1998

Ontogeny of apoptosis during lung development.

Apoptosis has been shown to be involved in several processes during embryogenesis, but the ontogeny of apoptosis during lung development ahs not been studied. The goals of the current study were to determine if apoptosis occurs during lung development, and to determine the ontogeny of the changes in apoptosis that occur. We studied the ontogeny of apoptosis in vivo using lungs from 14-18-d gestation fetal rats, newborn rats, and 1-d-, 2-d-, 5-d-, and 10-d-old rat pups. Apoptosis was assessed by electron microscopy and the terminal deoxyribonucleotidyl transferase dUTP nick end-labeling assay. We compared the in vivo results with explants of 14-d gestation fetal rat lung placed in culture for 1-4 d because the biochemical development of the lung in organ culture has been shown to closely parallel the development of the lung in vivo. We found apoptosis of mesenchymal cells at the periphery of distal lung buds in early fetal lung (14-16-d gestation). Apoptosis of both mesenchyme and epithelium was present in later fetal lung (18-d gestation). There were no qualitative differences in apoptosis between in vivo fetal lung and explant cultures of fetal lung. There was a 14-fold increase in apoptosis at birth and in the first postnatal day of life (9-12% of cells) compared with fetal lung (0.6-1% of cells). This was followed by a rapid decline in the percentage of apoptotic cells to fetal levels at postnatal d 2-10. We conclude that apoptosis occurs in a spatially, temporally, and cell-specific manner during lung development. The number of cells undergoing apoptosis increases dramatically in the first day after birth.

Animals↗
PubMed1997

Hyperoxia inhibits fetal rat lung fibroblast proliferation and expression of procollagens.

The direct effects of hyperoxia on collagen production by fetal lung fibroblasts are unknown and would be important to the understanding of the molecular mechanisms involved in bronchopulmonary dysplasia in premature infants. We studied the effect of hyperoxia on 1) proliferation, 2) mRNA levels for type I and III procollagens, and 3) net collagen production in primary cultures of fetal rat lung fibroblasts. Fibroblasts from 19-day-old rat fetuses (term is 22 days) were obtained. Test plates were incubated in hyperoxia and controls in room air for varying time periods. Cell viability in both conditions was >97% as determined by trypan blue exclusion. Fibroblast proliferation in nonconfluent cultures was found to be significantly reduced with exposure to hyperoxia (P < 0.001). Steady-state levels of type I and III procollagen mRNAs, analyzed on Northern blots hybridized to [32P]cDNA probes, were significantly decreased in hyperoxia (P < 0.01). This effect was noted as early as 4 h of exposure to hyperoxia and persisted for 5 days. There was a significant inverse correlation between duration of exposure to O2 and steady-state levels of mRNA for alpha1(I)-procollagen (r = -0.904) and alpha1(III)-procollagen (r = -0.971). There were no significant changes in steady-state levels of beta-actin mRNA. We also found a significant decrease in collagen synthesis in hyperoxia-exposed fibroblasts (P < 0.05). We conclude that hyperoxia directly effects a reduction in fetal lung fibroblast proliferation and net collagen production at a pretranslational level.

Animals↗
PubMed1997

Early specification and autonomous development of cortical fields in the mouse hippocampus.

Studies of the specification of distinct areas in the developing cerebral cortex have until now focused mainly on neocortex. We demonstrate that the hippocampus, an archicortical structure, offers an elegant, alternative system in which to explore cortical area specification. Individual hippocampal areas, called CA fields, display striking molecular differences in maturity. We use these distinct patterns of gene expression as markers of CA field identity, and show that the two major hippocampal fields, CA1 and CA3, are specified early in hippocampal development, during the period of neurogenesis. Two field-specific markers display consistent patterns of expression from the embryo to the adult. Presumptive CA1 and CA3 fields (Pca1, Pca3) can therefore be identified between embryonic days 14.5 and 15.5 in the mouse, a week before the fields are morphologically distinct. No other individual cortical areas have been detected by gene expression as early in development. Indeed, other features that distinguish between the CA fields appear after birth, indicating that mature CA field identity is acquired over at least 3 weeks. To determine if Pca1 and Pca3 are already specified to acquire mature CA field identities, the embryonic fields were isolated from further potential specification cues by maintaining them in slice culture. CA field development proceeds in slices of the entire embryonic hippocampus. More strikingly, slices restricted to Pca1 or Pca3 alone also develop appropriate mature features of CA1 or CA3. Pca1 and Pca3 are therefore able to develop complex characteristics of mature CA field identity autonomously, that is, without contact or innervation from other fields or other parts of the brain. Because Pca1 and Pca3 can be identified before major afferents grow into the hippocampus, innervation may also be unnecessary for the initial division of the hippocampus into separate fields. Providing a clue to the source of the true specifying signals, the earliest field markers appear first at the poles of the hippocampus, then progress inwards. General hippocampal development does not follow this pronounced pattern. We suggest that the sources of signals that specify hippocampal field identity lie close to the hippocampal poles, and that the signals operate first on cells at the poles, then move inwards.

Animals↗
PubMed1996

Long-term outcome in infants with the shaking-impact syndrome.

Nonaccidental injury accounts for nearly one quarter of all hospital admissions for head injury in infancy, and is associated with significant morbidity and mortality. Long-term outcome in survivors, however, has been incompletely studied. In this series, 84 infants 2 years of age and younger with the shaking-impact syndrome consecutively admitted to a single hospital between 1978 and 1988 were identified. A questionnaire detailing current medical, developmental, and behavioral status was developed, and attempts were made to locate the 62 children surviving the acute injury. Family instability and strict confidentiality restrictions precluded locating the majority of children, but 14 children with demographic and injury characteristics similar to those of the overall group were contacted at an average of 9 years after injury. Seven children were severely disabled or vegetative, 2 were moderately disabled, and 5 had a good outcome. Of the latter group, 3 had repeated grades and/or required tutoring. Acute factors associated with poor outcome included unresponsiveness on admission, need for intubation, age less than 6 months, and bilateral or unilateral diffuse hypodensity on CT scan. All children with bilateral diffuse hypodensity and loss of gray-white differentiation on CT scan remained blind, retarded, nonverbal, and nonambulatory in spite of aggressive medical and surgical management. This study suggests that the majority of children surviving the shaking-impact syndrome suffer major permanent morbidity, and that acute factors predicting long-term outcome may help guide aggressiveness of care.

Adolescent↗
PubMed1996

Disappearing subdural hematomas in children.

Subdural hematomas in infants and young children are uncommon, usually occurring from nonaccidental trauma in infants or from trauma associated with motor vehicles. We report 4 children with apparent unilateral convexity subdural hematomas, 3 of which occurred from household falls and 1 occurring from a fall out of a window. These injuries were characterized by clinical symptoms consistent with the apparent forces involved, which were relatively minor in the first three instances. The clots resolved spontaneously within the first 1-2 days after injury. Such collections are likely located at least partly within the subarachnoid space, but may mimic more clinically significant subdural hematomas. Their recognition may influence decisions regarding both surgical evacuation and the likelihood of nonaccidental injury. Clinical and radiographic features distinguishing these 'disappearing subdurals' from more typical subdural hematomas are discussed.

Accidental Falls↗
PubMed1994

Steel factor affects SCL expression during normal erythroid differentiation.

Steel factor is one of the growth factors that controls the proliferation and differentiation of hematopoietic cells and SCL, also known as Tcl-5 or Tal-1, is a transcription factor involved in erythropoiesis. In this report, we studied the role of SCL in the proliferation of human peripheral blood burst-forming unit-erythroid (BFU-E) and the effects of Steel factor on SCL expression in proliferating erythroid cells. BFU-E-derived colonies increase progressively in size, as determined by cell number, from day 7 to day 14 of culture, with the greatest increase in colony size (10-fold expansion) occurring between day 7 and day 10. SCL protein levels in BFU-E-derived cells were highest in day 7 cells and decreased progressively from day 7 to day 14 of culture, suggesting an association of SCL with erythroid proliferation. In contrast, SCL mRNA levels did not decrease significantly between day 7 and day 14 cells, suggesting that posttranscriptional mechanisms are largely responsible for the decrease in SCL protein observed. The role of SCL in Steel factor-induced erythroid proliferation was then examined. In BFU-E-derived colonies cultured with Steel factor, colony size was significantly increased compared to control. In day 7 and day 10 erythroid precursors cultured with Steel factor, SCL protein was increased significantly compared to control. The increase in SCL protein levels in early erythroid precursors stimulated with Steel factor suggests one mechanism through which Steel factor may enhance normal erythroid proliferation. SCL mRNA levels assessed by Northern blot in day 7 cells did not increase significantly in response to Steel factor stimulation, suggesting that posttranscriptional mechanisms may also be important in the increase in SCL protein observed in response to Steel.

Base Sequence↗