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Biomedical subjects

H Shima

Publications and source records attributed to H Shima.

At least 37 records · Page 2Linked to original sources
PubMed2000

Identification and characterization of a novel protein inhibitor of type 1 protein phosphatase.

We have isolated human cDNA for a novel type 1 protein phosphatase (PP1) inhibitory protein, named inhibitor-4 (I-4), from a cDNA library of germ cell tumors. I-4, composed of 202 amino acids, is 44% identical to a PP1 inhibitor, inhibitor-2 (I-2). I-4 conserves functionally important structure of I-2 and exhibited similar biochemical properties. I-4 inhibited activity of the catalytic subunit of PP1 (PP1C), specifically with an IC(50) of 0.2 nM, more potently than I-2 with an IC(50) of 2 nM. I-4 weakly inhibited the activity of myosin-associated phosphates (PP1M). However, the level of inhibition of PP1M was increased during preincubation of PP1M with I-4, suggesting that the inhibition is caused by interaction of I-4 with PP1C in such a manner that it competes with the M subunit of PP1M. Gel overlay experiments showed that I-4 binds PP1C directly. Three I-4 peptides containing the N-terminal residues 1-123, 1-131, and 1-142 all showed strong binding ability to PP1C but did not show PP1 inhibitory activity, whereas an I-2 peptide (residues 1-134), lacking the corresponding C-terminal residues, potently inhibited PP1C activity as previously reported. Removal of the 18 N-terminal amino acid residues from I-4 dramatically reduced the PP1 binding activity with a correlated loss of inhibitory activity, whereas removal of the 10 N-terminal residues had only a little effect. The two peptides GST-I-4(19-131) and GST-I-4(132-202) showed ability to bind to PP1C, albeit very weakly. These results strongly suggest a multiple-point interaction between I-4 and PP1C, which is thought to cause the inhibition of I-4 which is stronger than the inhibition of I-2.

Amino Acid Sequence↗
PubMed2000

Protein-tyrosine phosphatase PTPepsilon C inhibits Jak-STAT signaling and differentiation induced by interleukin-6 and leukemia inhibitory factor in M1 leukemia cells.

We engineered and expressed both a wild-type and mutant cytosolic isoform of PTPepsilon (PTPepsilonC) in murine M1 leukemic cells, which can be induced to growth arrest and monocytic differentiation by interleukin (IL)-6 and leukemia inhibitory factor (LIF). Forced expression of PTPepsilonC inhibited IL-6- and LIF-induced monocytic differentiation and apoptosis in M1 cells, whereas expression of PTPepsilonM, a transmembrane isoform of PTPepsilon, did not. PTPepsilonC expression resulted in lower levels of IL-6-induced tyrosine phosphorylation of Jak1, Tyk2, gp130, and Stat3 compared with parent cells. In M1 transfectants expressing an inactive mutant of PTPepsilonC, both tyrosine phosphorylation and apoptosis induced by IL-6 and LIF were potentiated rather than inhibited. These results suggest an important role for PTPepsilonC in negative regulation of IL-6- and LIF-induced Jak-STAT signaling.

Animals↗
PubMed2000

A sds22 homolog that is associated with the testis-specific serine/threonine protein phosphatase 1gamma2 in rat testis.

Two cDNAs sequences (1320 bp and 1180 bp) of the 55-kDa subunit associated with a testis-specific serine/threonine protein phosphatase 1gamma2 (PP1gamma2) were cloned. They were the same up to 1180 bp, suggesting that they may be generated by alternative splicing. Sequence studies showed that the 1320 bp-cDNA is a homolog of the human sds22alpha(1) (thus, named rat sds22alpha(1)). The 1180 bp-cDNA is a new splice-variant since its sequence at the 3' end has not been identified in human sds22 genes (named rat sds22alpha(3)). The 1320 bp-cDNA is ubiquitously expressed in various tissues including the immature testis. However, the expression of 1180 bp-cDNA was only observed in the testis after puberty. This expression pattern matches very well with that of PP1gamma2, suggesting that 1180 bp-cDNA may encode the 55-kDa subunit to associate with PP1gamma2 in rat testis and is involved in spermatogenesis by controlling PP1gamma2 activity.

Aging↗
PubMed2000

Development of an assay method for activities of serine/threonine protein phosphatase type 2B (calcineurin) in crude extracts.

Despite the physiological importance of serine/threonine protein phosphatase type 2B (PP2B/calcineurin), an accurate assay method of PP2B in crude tissue extracts has not been established. By using recombinant protein phosphatase inhibitor-1 as a substrate and ascorbic acid as an antioxidant, we developed an improved assay method for PP2B activity in crude extracts from mouse tissues and investigated tissue distribution of its activity. Under the assay conditions, the PP2B activities were stable for at least 30 min with more than 100-fold higher sensitivity than those previously reported. The specific activities of PP2B were 22.3, 0.85, 2.9, 0.36, and 1.5 mU/mg protein in mouse brain, heart, spleen, liver, and testis, respectively, and furthermore in each region of the brain they were 26.1, 13.7, 42.8, 40.5, 15.1, and 8.6 mU/mg protein in cerebrum, midbrain plus interbrain, striatum, hippocampus, cerebellum, and brain stem, respectively. This is the first paper to demonstrate a close correlation between tissue distributions and content of PP2B. These results showed that the present assay method is extremely powerful for precise measurement of a wide range of PP2B activities including not only high PP2B activity in the brain but also low PP2B activities in other tissues.

Animals↗
PubMed2000

Effect of hyperoxia on surfactant protein gene expression in hypoplastic lung in nitrofen-induced diaphragmatic hernia in rats.

The hypoplastic lung in congenital diaphragmatic hernia (CDH) has both a quantitative and qualitative reduction in surfactant. Recently, the role of oxygen (O2) as a regulator of pulmonary surfactant-associated protein (SP) gene expression has been reported. The mRNA level of SP has been demonstrated to be increased in the lungs of animals exposed to hyperoxia. The aim of this study was to investigate SP mRNA expression in hypoplastic CDH lung in rats during mechanical ventilation in order to determine the effect of O2 on SP synthesis in CDH. A CDH model was induced in pregnant rats following administration of nitrofen. The newborn rats with CDH and controls were intubated and ventilated. Ventilation was continued for 6 h under 100% oxygen. Reverse-transcription polymerase chain reaction (RT-PCR) was performed to evaluate the relative amounts of mRNA expression of SP-A, SP-B, SP-C, and SP-D. Relative amounts of SP-A, SP-B, and SP-D mRNA expression in CDH lung were significantly decreased compared to controls at birth and 6 h after ventilation. There was no significant difference in SP-C mRNA expression between CDH animals and controls. Upregulated mRNA expression of SP-A, SP-B, and SP-D in lungs of control animals at 6 h after ventilation suggests that oxygenation accelerates postnatal SP synthesis in normal lungs. The inability of O2 to increase SP mRNA expression in hypoplastic CDH lung suggests that the hypoplastic lung is not responsive to increased oxygenation for the synthesis of SP.

Abnormalities, Drug-Induced↗
PubMed2000

The hypoplastic heart in congenital diaphragmatic hernia: reduced expression of basic fibroblast growth factor and platelet-derived growth factor.

Newborn infants with congenital diaphragmatic hernia (CDH) still have high mortality. Recently, the possible role of a cardiac maldevelopment in the high mortality has been suggested. Human and animal studies have demonstrated that heart weight is significantly reduced in the presence of CDH. Basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) are pleiotropic regulatory peptides that are expressed in myocardium in precise developmental and spatial programs. PDGF and bFGF both stimulate cardiac growth by inducing cell proliferation and stimulating the synthesis of extracellular matrix. The aim of this study was to investigate the presence of heart hypoplasia in nitrofen-induced CDH in rats and the role of specific tissue growth factors (bFGF and PDGF) in its genesis. CDH was induced in pregnant rats following administration of 100 mg nitrofen on day 9.5 of gestation (term 22 days). In control animals the same dose of olive oil was given without nitrofen. Cesarean section was performed on day 21 of gestation. The fetuses were divided in two groups: normal controls (n = 8) and nitrofen-induced CDH (n = 8). Total RNA, DNA, and soluble proteins were extracted from the heart in each group and measured. mRNA was extracted from total RNA and a reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate mRNA expression of bFGF and PDGF. The heart/body weight ratio (HBWR) and DNA content were significantly decreased (P < 0.01) in CDH animals compared to controls. RNA and protein content were also reduced in CDH. The expression of bFGF and PDGF mRNA was significantly reduced in the CDH group compared to controls (P < 0.01). The decreased HBWR, DNA, RNA, and protein content in the CDH heart indicates that the heart is hypoplastic in nitrofen-induced left CDH. The downregulation of bFGF and PDGF gene expression in the CDH heart suggests that these regulating peptides may play an important role in the genesis of cardiac hypoplasia in CDH.

Actins↗
PubMed2000

Antenatal dexamethasone improves atrial natriuretic peptide receptors in hypoplastic lung in nitrofen-induced diaphragmatic hernia in rats.

Atrial natriuretic peptide (ANP) plays a major role in electrolyte and volume homeostasis through potent biological effects including vasorelaxation, bronchorelaxation, lung permeability, and clearance. There are two distinct biochemical and functional classes of ANP receptors, guanylate cyclase receptor (GC-R) and clearance receptors (clearance-R). Two subtypes of GC-R have been described, GCA-R and GCB-R. Antenatal glucocorticoid therapy (AGT) has been demonstrated to improve pulmonary immaturity and abnormal structure of pulmonary arteries in animal models of congenital diaphragmatic hernia (CDH). The aim of this study was to investigate the effect of antenatal glucocorticoid administration on the ANP system in nitrofen-induced CDH hypoplastic lung in rats. A CDH model was induced in pregnant rats following administration of nitrofen on day 9.5 of gestation. Dexamethasone (Dex) was given intraperitoneally on days 18.5 and 19.5; cesarean section was performed on day 21. Reverse transcription polymerase chain reaction was performed to evaluate the relative amounts of GCA-R, GCB-R and clearance-R mRNA expression. The mRNA expression of GCA-R, GCB-R, and clearance-R was significantly increased in CDH compared to control lung. ANP receptor mRNA expression was significantly decreased in CDH lung with compared to without Dex treatment. Our finding of increased ANP receptor mRNA expression in CDH lung suggests that the hypoplastic lung has high sensitivity for ANP. Decreased mRNA expression of ANP receptors in CDH lung after Dex treatment suggests that AGT may improve pulmonary physiological function of ANP in hypoplastic CDH lung.

Animals↗
PubMed2000

Muscarinic acetylcholine receptor expression in aganglionic bowel.

In Hirschsprung's disease (HD) there exists an overabundance of acetylcholine (ACh), which in turn stimulates excessive production of the enzyme acetylcholinesterase. Muscarinic ACh receptors (mAChRs) play an important role in smooth-muscle contraction. Recent studies have indicated five different subtypes of mAChRs encoded by five different genes, ml to m5. The purpose of this study was to investigate the expression of each mAChR subtype in aganglionic (AG) colon to further understand the pathophysiology of HD. Entire colon resected at the time of pull-through operation for HD was obtained from 14 patients. Specimens obtained at autopsy from 8 age-matched patients without gastrointestinal disease acted as controls. Frozen sections were used for indirect immunohistochemistry as well as in-situ hybridization. Immunohistochemistry was performed using specific antiserum against each mAChR subtype and in-situ hybridization was performed using specific oligonucleotide probes against ml to m5 subtypes. Messenger RNA (mRNA) was extracted from normoganglionic (NG) and AG bowel of HD patients and normal control bowel. Reverse transcription-polymerase chain reaction was performed to evaluate mRNA levels of each mAChR subtype. To adjust the levels of mRNA expression, a housekeeping gene G3PDH, known to be expressed normally, was used as an internal control. Strong m2 and m3 immunoreactivity was observed in the mucosal layer, smooth-muscle layers, and myenteric plexus of NG bowel, whereas ml immunoreactivity was only detected in the mucosal layer. The most striking finding was the abundance of m3-immunoreactive fibers in muscle layers of NG bowel while there was a total lack of m3 fibers in smooth-muscle of AG bowel. Intense mRNA signals encoding m2 and m3 and to a lesser degree ml were detected in NG bowel, and these signals were weak in AG bowel. Immunoreactivity and mRNA expression of m4 and m5 was not detected in NG or AG bowel. The lack of m3-immunoreactive fibers in the smooth-muscle layers of AG bowel and decreased m2 and m3 mRNA expression in AG bowel may be responsible for the motility dysfunction in the aganglionic segment.

Child↗
PubMed2000

Structural immaturity of the pylorus muscle in infantile hypertrophic pyloric stenosis.

Recent reports indicate that extracellular matrix and cytoskeleton plasmalemmal elements are altered in infantile hypertrophic pyloric stenosis (IHPS). Desmin is a cytoskeletal protein that is important for the organization and function of muscular fibers. It has been found to be increased in the smooth muscle in chronic intestinal pseudo-obstruction and in skeletal muscle in some forms of myopathies as well as in unexplained hypertrophic cardiomyopathies. The aim of this study was to analyze the expression of desmin in IHPS. Full-thickness muscle-biopsy specimens were obtained from 8 IHPS patients (age range 23 to 41 days) at pyloromyotomy, from 8 age-matched controls without evidence of gastrointestinal (GI) disease at autopsy, and from 2 stillborns who died at 27 and 30 weeks of gestation without evidence of GI disease. Indirect immunohistochemistry was performed using the avidin-biotin-peroxidase complex method with anti-desmin and visualized by development with 3-diaminobenzidine tetrahydrochloride. Pyloric muscle in IHPS demonstrated strong desmin immunoreactivity. The expression of desmin was also strong in the muscular layers of fetal pylorus. In the age-matched controls absent or weak desmin immunoreactivity was seen in the pyloric muscle layer. The increased amount of desmin in hypertrophied pyloric muscle in IHPS may result in inco-ordination of contraction and relaxation of the pylorus, thus causing motility dysfunction. The similar pattern of desmin expression in IHPS and fetal pylorus suggests that the organization of intermediate filaments in IHPS is in a fetal stage of development.

Desmin↗
PubMed2000

Increased expression of fibroblast growth factors in segmental renal dysplasia.

Renal dysplasia (RD) is a disorganized development of renal parenchyma that results in a deficit of functional renal tissue. Dysplastic renal tissue is characterized by primitive tubular epithelium associated with increased mesenchyme. Several polypeptide growth factors (GF), which interact with target cells through a cell-surface membrane receptor, have been reported to be involved in the regulation of urothelial cell growth in normal and neoplastic states. Recent reports have demonstrated that basic fibroblast GF (bFGF, FGF-2) is a mitogen for renal proximal-tubule epithelial cells. Keratinocyte GF (KGF, FGF-7), which belongs to the FGF family, is believed to be a paracrine mediator of epithelial-cell proliferation. The aim of this study was to investigate the immunoactivity of bFGF and KGF and their receptors in the dysplastic kidney in order to further understand the pathogenesis of RD. Specimens of dysplastic upper poles of duplex kidneys were surgically resected from ten patients. Age-matched control material included six kidney specimens taken at autopsy from patients without evidence of urologic disease. Indirect immunohistochemistry was performed using the Strept-ABC method with four antibodies: bFGF, KGF, FGF receptor (flg), and KGF receptor (bek). There was absent or weak bFGF, KGF, flg, and bek immunoreactivity in normal kidneys. In the dysplastic kidneys, there was strong immunoreactivity of bFGF and KGF and their receptors in the epithelium of primitive tubules. Increased local expression of bFGF and KGF and their receptors in primitive tubules suggests that bFGF and KGF may play an important role in the development of RD.

Child↗
PubMed2000

Antenatal dexamethasone administration inhibits smooth-muscle-cell DNA synthesis in pulmonary-arterial media in nitrofen-induced congenital diaphragmatic hernia in rats.

The aim of this study was to investigate the effect of antenatal glucocorticoid therapy on smooth-muscle-cell (SMC) DNA synthesis in the pulmonary arteries (PA) in a nitrofen-induced congenital diaphragmatic hernia (CDH) rat model following nitrofen administration on day 9.5 of gestation. Antenatal dexamethasone (DEX) was given intraperitoneally on days 18.5 and 19.5 of gestation. Bromodeoxyuridine (BrdU) was injected via a jugular vein into the dam 1 h before the fetuses were killed by cesarean section at term. The fetuses were divided into three groups: group I (n = 10): normal controls; group II (n = 10): nitrofen-induced CDH; group III (n = 10): nitrofen-induced CDH with antenatal DEX treatment. Immunostaining of the lungs with anti-BrdU antibody was obtained by a standard avidin-biotin complex method. The number of immunopositive cells in the PA media and adventitia were counted using an image analyzer and analyzed statistically. The number of BrdU-immunopositive cells in the media was significantly increased in group II (16.83 +/- 3.01) compared to groups I (9.16 +/- 2.20) and III (6.83 +/- 1.70) (P < 0.01). There was no significant difference between groups I and III. The number of BrdU-immunopositive cells in the adventitia was not significantly different between the three groups. Antenatal DEX treatment inhibits SMC DNA synthesis in PA media in CDH lungs. This may be a possible mechanism by which antenatal DEX prevents structural PA changes in nitrofen-induced CDH in rats.

Animals↗
PubMed2000

Molecular analysis of familial androgen insensitivity syndrome due to replacement of glutamic acid 802 by lysine.

We studied a Japanese family presenting at least two cases of complete androgen insensitivity syndrome (CAIS) and negative androgen receptor binding. The index subject showed a 46, XY karyotype and a complete female phenotype. For the purpose of further diagnosis and genetic counseling, molecular analysis of the androgen receptor (AR) gene was performed. Direct sequencing of the AR gene identified a mutation at nucleotide 2935 (A-->G). This replacement was a novel missense mutation, resulting in the substitution of glutamic acid 802 by lysine which deleted a recognition site for EcoRI in exon 6 of the AR gene. We identified another affected individual, using chromosome and molecular analysis of the AR gene at exon 6. Furthermore, although heterozygote carriers could not be identified on clinical grounds, molecular identification of healthy individuals and heterozygote carriers in the family members provided definitive information for genetic counseling. We believe that the molecular analysis of familial CAIS is very informative for both the affected individuals and other family members.

Adolescent↗
PubMed2000

Administration of antenatal glucocorticoids upregulates peptide growth factor gene expression in nitrofen-induced congenital diaphragmatic hernia in rats.

BACKGROUND/PURPOSE: There is increasing evidence to suggest that various growth factors play a crucial role in fetal lung growth and morphogenesis. An array of peptide growth factors regulate cell proliferation, differentiation, and various other cell functions in the developing lung. The aim of this study was to investigate the effect of antenatal glucocorticoids administration on gene expression of basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-beta1 in nitrofen-induced congenital diaphragmatic hernia (CDH) in rats. METHODS: A CDH model was induced in pregnant rats after administration of nitrofen. Dexamethasone (Dex; 0.25 mg/kg) was given intraperitoneally on day 18.5 and 19.5 of gestation (term, day 22). Cesarean section was performed on day 21 of gestation. mRNA was extracted from left lung and reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate mRNA expression of each growth factors. Relative levels of mRNA were expressed as a ratio of the band density divided by that of beta-actin, a housekeeping gene known to be expressed at a constant level. RESULTS: Relative mRNA levels of bFGF and TGF-beta1 were decreased significantly in CDH lung compared with controls. Antenatal Dex treatment up-regulated gene expression of bFGF, PDGF, and TGF-beta1 in the hypoplastic CDH lung. CONCLUSIONS: The authors' findings suggest that decreased gene expression of bFGF, PDGF, and TGF-beta1 in the CDH lung may suppress lung growth and development. Increased gene expression of bFGF, PDGF, and TGF-beta1 in Dex-treated lung suggests that antenatal glucocorticoid administration may accelerate fetal lung growth by up-regulating these growth factors.

Animals↗
PubMed2000

Antenatal dexamethasone enhances endothelin receptorB expression in hypoplastic lung in nitrofen-induced diaphragmatic hernia in rats.

BACKGROUND/PURPOSE: The hypoplastic lung and persistent pulmonary hypertension (PPH) are the principle causes of high mortality and morbidity in infants with congenital diaphragmatic hernia (CDH). Endothelin-1 (ET-1), which is produced by vascular endothelial cells and some leukocytes, plays a key role in modulating pulmonary vascular tone in PPH. Two different receptors (ET(A) and ET(B)) for ET-1 have been characterized. Binding of ET-1 to ET(A), which is present on smooth muscle cells in fetal lung, results in vasoconstriction. However, binding of ET-1 to ET(B), which is present on endothelial cells results in vasodilation mediated by endogenous nitric oxide. Antenatal glucocorticoid therapy has been shown to prevent abnormal pulmonary arterial structural changes in animal model with CDH. The aim of this study was to investigate the effect of antenatal glucocorticoid administration on ET-1 system in nitrofen-induced CDH hypoplastic lung in rats. METHODS: A CDH model was induced in pregnant rats after administration of nitrofen on day 9.5 of gestation. Dexamethasone (Dex) was given intraperitoneally on days 18.5 and 19.5 of gestation. Cesarean section was performed on day 21 of gestation. Rat ET-1 protein expression was measured in solubilized lung tissue extracts, by sandwich type enzyme-linked immunosorbent assay (ELISA) analysis. Reverse transcription polymerase chain reaction was performed to evaluate the relative amount of ET-1, ET(A), and ET(B) mRNA expression. RESULTS: The ET-1 protein and mRNA expression of ET-1 and both receptors were increased significantly in CDH lung compared with controls. Although there was no significant difference in ET(A) mRNA expression between CDH lung with Dex treatment and without Dex treatment, ET(B) mRNA expression was elevated significantly in CDH lung with Dex treatment compared with CDH lung without Dex treatment. CONCLUSION: These findings suggest that antenatal glucocorticoid therapy may modulate pulmonary vascular tone in CDH hypoplastic lung by selectively upregulating local expression of ET(B).

Animals↗
PubMed2000

Antenatal dexamethasone enhances surfactant protein synthesis in the hypoplastic lung of nitrofen-induced diaphragmatic hernia in rats.

BACKGROUND/PURPOSE: Pulmonary hypoplasia is one of the main causes for the high mortality rate in patients with congenital diaphragmatic hernia (CDH). The expression of surfactant protein A in the hypoplastic CDH lung is reduced, and its concentration is decreased in the amniotic fluid of pregnancies complicated by CDH. In a CDH experimental model, prenatal glucocorticoid treatment has proved its efficacy in correcting the parameters of pulmonary biochemical and morphologic immaturity. The aim of this study was to investigate whether maternal administration of dexamethasone has any effect on the expression of surfactant protein A and surfactant protein B in nitrofen-induced experimental CDH rat model. METHODS: CDH was induced in pregnant rats after administration of 100 mg of nitrofen on day 9.5 of gestation (term, 22 days). Dexamethasone (Dex, 0.25 mg/kg) was given by intraperitoneal injection on days 18.5 and 19.5 of gestation. Cesarean section was performed on day 21 of gestation. The fetuses were divided into 3 groups: group I, control (n = 16); group II, nitrofen-induced CDH (n = 16); group III, nitrofen-induced CDH with antenatal Dex treatment (n = 16). Indirect immunohistochemistry was performed using alkaline-phosphatase-coagulated streptavidin using anti-SP-A and anti-SP-B polyclonal antibodies. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate relative amount of SP-A and SP-B mRNA expression. RESULTS: In the CDH lung (group II) we observed a markedly reduced number of type II pneumocytes positive for SP-A, and SP-B was increased to a level close to that of the control group. The relative amount of SP-A and SP-B was reduced significantly in group II compared with controls (P < .05) and significantly increased in group III compared with group II animals (P < .01). CONCLUSION: These results suggest that antenatal glucocorticoid treatment increases the production of surfactant proteins in the CDH hypoplastic lung.

Animals↗
PubMed2000

Glial-derived growth factor signaling pathway in infantile hypertrophic pyloric stenosis.

BACKGROUND/PURPOSE: Glial-derived growth factor (GDNF), which is the ligand of RET is reported to be essential for the development of enteric nervous system. A GDNF knockout mouse model has shown that the gastric region is a critical passing site between GDNF-RET-independent neuroblasts (colonizing the esophagus) and GDNF-RET-dependent neuroblasts (colonizing the small and large bowel). The earliest GDNF site of production is the mesenchyme and the outer smooth muscle cell (SMC) layer of the developing bowel. In the mature gastrointestinal tract the presence of GDNF is restricted to enteric glial cells. The aim of this study was to investigate the expression of GDNF and RET in infantile hypertrophic pyloric stenosis (IHPS). METHODS: Full-thickness muscle biopsy specimens were obtained from 8 IHPS patients at pyloromyotomy and from 8 age-matched controls without gastrointestinal disease. Indirect immunohistochemistry was performed using avidin-biotin-peroxidase complex method with anti-GDNF and anti-RET antibodies. Quantitative analysis was performed using sandwich-type enzyme-linked immunosorbent assay (ELISA) for GDNF. RESULTS: GDNF- and RET-positive nerve fibers were absent or markedly reduced in IHPS compared with controls. GDNF was expressed strongly by smooth muscle cells of both muscular layers in IHPS, whereas no GDNF expression was detected in pyloric muscle of controls. The quantity of total GDNF in IHPS was significantly higher than in controls (P < .01). CONCLUSIONS: The lack or markedly decreased number of GDNF-positive nerve fibers in IHPS supports the hypothesis of a selective immaturity of the enteric glia in the muscular layers in IHPS. The strong expression of GDNF in smooth muscle cells in IHPS and the increased levels of GDNF in IHPS suggest a compensatory mechanism by which the smooth muscle cells continue to produce GDNF until maturation of the enteric glial cells occurs.

Drosophila Proteins↗
PubMed2000

Abnormal pulmonary accumulation of indium-111 chloride in pneumocystis carinii pneumonia as detected by bone marrow scintigraphy.

PURPOSE: Unusual pulmonary uptake of In-111 chloride in a patient with Pneumocystis carinii pneumonia and autoimmune hepatitis is described. METHOD: In-111 chloride bone marrow scintigraphy was performed to evaluate the bone marrow activity associated with pancytopenia in a 56-year-old woman with autoimmune hepatitis. RESULTS: An In-111 chloride bone marrow scan showed increased pulmonary uptake predominantly in both upper lung fields. P. carinii pneumonia was seen to be developing as an immunocompromised complication after treatment for autoimmune hepatitis. CONCLUSION: When In-111 chloride bone marrow scintigraphy shows increased uptake in the lungs of immunocompromised patients, a combined opportunistic inflammatory disease such as P. carinii pneumonia should be considered in the diagnosis.

Bone Marrow↗