Heme oxygenase-1 gene promoter polymorphism and the risk of pediatric nonalcoholic fatty liver disease.

BACKGROUND AND OBJECTIVES: Oxidative stress and the insulin-resistant state are thought to be key components in the pathogenesis of pediatric nonalcoholic fatty liver disease (NAFLD). Heme oxygenase (HO) is important in the defense against oxidative stress. This study aimed to assess the association of HO-1 gene promoter polymorphism and insulin resistance with NAFLD among obese children. METHODS: A total of 101 obese children aged 6-17 years were recruited. Anthropometric, serum biochemical variables and biomarkers for glucose and insulin metabolism were measured. We screened the allelic frequencies of (GT)n repeats in the HO-1 gene promoter among these obese children. NAFLD was determined through liver ultrasonography. Because the distribution of numbers of (GT)n repeats was bimodal, we divided the alleles into two classes: class S included shorter (27) repeats, and class L included longer (⩾27) repeats. We assessed the effects of the length of (GT)n repeats in HO-1 gene promoter on pediatric NAFLD. RESULTS: Of the 101 obese subjects, 27 (26.7%) had NAFLD. The alanine aminotransferase level was higher in patients carrying L alleles (L/L and L/S) than patients with S alleles (S/S) (46.2±49.3 IU|(-1) versus 30.2±20.1 IU|(-1); P=0.027). The significant risk factors for pediatric NAFLD were patients carrying L alleles (L/L and L/S) (odds ratio (OR)=18.84; 95% confidence interval (CI): 1.45-245.22; P=0.025), homeostasis model assessment of insulin resistance (OR=1.40; 95% CI: 1.07-1.83; P=0.014) and age (OR=1.24; 95% CI: 1.03-1.50; P=0.025). CONCLUSION: In this hospital-based study, the obese children with longer GT repeats in the HO-1 gene promoter and insulin resistance were susceptible to NAFLD.

Different EEG topographic effects of painful and non-painful intramuscular stimulation in man.

To clarify the specific effects of muscle pain on electroencephalogram (EEG) activation in man, painful and non-painful sensations were produced by intramuscular injections of capsaicin and vehicle solution in the left brachioradialis muscle, with identical procedures in 15 male volunteers. Thirty-one channel EEG data acquired before, during and after the two injections were analysed and compared in respect of topography and power spectrum. Although the painful and non-painful muscular stimulations evoked similar EEG topographic patterns, statistics demonstrated that distinct EEG activation over different areas of the head were induced by the painful and non-painful stimulation compared with the baselines. The decreases in theta and alpha-1 (8-10.5 Hz) activity in central and posterior parietal parts were evoked by non-painful stimulation, but the decreases in alpha-1 and alpha-2 (11-13.5 Hz) activities in the posterior part of the head were induced by painful stimulation. The alpha-2 activity augmented during the waning pain following a decrease in the overt pain. Comparing the EEG changes between baseline, non-painful and painful stimulations as well as waning pain, we found that the increase in beta-2 activity during muscle pain was significant over the extensive areas of the head, whereas a significant increase in alpha-2 activity took place at the posterior part of the head during waning pain following a marked decrease in overt pain. These results may imply that the painful and non-painful muscular stimulations evoke distinct EEG activation in different neural networks of the human brain and the intensity of nociceptive input from muscle may encode the variety of topographic EEG changes.

Topographic effects of tonic cutaneous nociceptive stimulation on human electroencephalograph.

To examine the specific effects of cutaneous pain on electroencephalographic (EEG) activities, tonic painful and non-painful sensations in left forearm were induced by intradermal injection of capsaicin 100 microg/20microl and the same volume of vehicle, respectively, in 15 healthy males. The EEG data acquired in five experimental conditions: (i) baseline A; (ii) non-painful vehicle injection; (iii) baseline B; (iv) painful capsaicin injection and (v) waning pain, were analyzed and compared with analysis of variance. Only the painful capsaicin injection evoked significant decreases of theta, alpha-1 and alpha-2 powers over the centro-parieto-occipital regions compared with baseline B. No significant difference in EEG activation between the non-painful vehicle injection and painful capsaicin injection was found. This implicates that the observed topographic EEG activation is not specific for pain but probably related to the cutaneous stimulation.

Metabolic disorders mimicking Reye's syndrome.

BACKGROUND: Several metabolic disorders such as encephalopathy and hepatic dysfunction have been described as Reye's-like syndrome because they present with similar clinical manifestations that mimic Reye's syndrome. We performed a retrospective study to explore the underlying metabolic etiologies of Reye's-like syndrome in patients treated at National Taiwan University Hospital. METHODS: From January 1991 to June 1998, 19 children with a syndrome fitting the Reye's-like syndrome description were identified for study. Urine organic acid analysis, plasma amino acid analysis, liver pathology, and skin fibroblast enzyme assays were studied during the acute stage of illness. RESULTS: The etiologies of patients' syndromes included urea cycle disorders (n = 7), glycogen storage disease type Ia (4), primary carnitine deficiency (2), hereditary fructose intolerance (1), methylmalonic acidemia (2), and 3-hydroxy-3-methylglutaric acidemia (1). Fatty acid oxidation defects were suspected in the remaining two cases. CONCLUSIONS: A significant number of patients who present with Reye's-like syndrome have an underlying inherited metabolic disorder. In patients with Reye's-like syndrome, an accurate diagnosis is essential to ensure normal growth and development and to prevent recurrence of the condition.

Pediatric percutaneous endoscopic jejunostomy by J-tube extension through a preexisting gastrostomy site: a preliminary report.

A prematurely born 5-year-old boy with chronic lung disease, hypoxic-ischemic encephalopathy, cerebral palsy, repeated aspiration pneumonia, and stroke underwent percutaneous endoscopic jejunostomy (PEJ) to alleviate repeated aspiration pneumonia. Studies, including 24-hour esophageal pH monitoring, 99mTc gastric emptying time, upper gastroesophageal barium radiography, and endoscopic examinations showed severe gastroesophageal reflux and prolonged gastric emptying. Percutaneous endoscopic gastrostomy (PEG) was performed first, followed by placement of a polyurethane J-tube (9 French) through the preexisting gastrostomy site. We passed the style-guided J-tube through the pyloric ring endoscopically and advanced it to the jejunum. The position of the J-tube was confirmed by radiologic study. Feeding with an elemental formula, 20 mL/hour, commenced immediately after the procedure, and the rate was gradually increased to 50 mL/hour. No further episodes of aspiration pneumonia have occurred since J-tube placement. Our initial experience with jejunal feeding through a PEJ is encouraging.

Immunogenicity and safety of Haemophilus influenzae type b conjugate vaccine (HibTITER) and a combination vaccine of diphtheria, tetanus, pertussis and HibTITER (TETRAMUNE) in two-month-old infants.

A study was undertaken to evaluate the safety and immunogenicity of a combination vaccine (TETRAMUNE) of conjugate Haemophilus influenzae type b (Hib) vaccine (HibTITER) and DTP (Diphtheria, Tetanus and Pertussis) vaccine. A total of 93 healthy children were randomized to receive either TETRAMUNE (combined group), or DTP and HibTITER administered concurrently (separate group) in separate syringes at approximately 2, 4 and 6 months of age in Taiwan. Serologic responses were largely comparable between the two vaccine groups; almost all subjects were seropositive to Hib PRP (polyribosylribitol phosphate) and were protected against diphtheria and tetanus after 2 doses of vaccine and mounted prominent responses to the components of Bordetella pertussis. Subjects in the combined group did not experience more adverse reactions compared with those in the separate group. We concluded that HibTITER was highly immunogenic and safe when administered concurrently with DTP vaccine to Taiwanese children. TETRAMUNE was also safe and immunogenic and might reduce the number of injections to achieve the same protection.

Expression of a gene encoding a 16.9-kDa heat-shock protein, Oshsp16.9, in Escherichia coli enhances thermotolerance.

A gene encoding the rice 16.9-kDa class I low-molecular-mass (LMM) heat-shock protein (HSP), Oshsp16.9, was introduced into Escherichia coli using the pGEX-2T expression vector to analyze the possible function of this LMM HSP under heat stress. It is known that E. coli does not normally produce class I LMM HSPs. We compared the survivability of E. coli XL1-Blue cells transformed with a recombinant plasmid containing a glutathione S-transferase (GST)-Oshsp16.9 fusion protein (pGST-FL cells) with the control E. coli cells transformed with the pGEX-2T vector (pGST cells) under heat-shock (HS) after isopropyl beta-D-thiogalactopyranoside induction. The pGST-FL cells demonstrated thermotolerance at 47.5 degrees C, a treatment that was lethal to the pGST cells. When the cell lysates from these two E. coli transformants were heated at 55 degrees C, the amount of protein denatured in the pGST-FL cells was 50% less than that of the pGST cells. Similar results as pGST-FL cells were obtained in pGST-N78 cells (cells produced a fusion protein with only the N-terminal 78 aa in the Oshsp16.9 portion) but not in pGST-C108 cells (cells produced a fusion protein with C-terminal 108 aa in the Oshsp16.9 portion). The acquired thermotolerant pGST-FL cells synthesized three types of HSPs, including the 76-, 73-, and 64-kDa proteins according to their abundance at a lethal temperature of 47.5 degrees C. This finding indicates that a plant class I LMM HSP, when effectively expressed in transformed prokaryotic cells that do not normally synthesize this class of LMM HSPs, may directly or indirectly increase thermotolerance.

Retroperitoneal cystic lymphangioma: report of one case.

Cystic lymphangioma is a developmental malformation of the lymphatic system. It is extremely rare for this type of tumor to arise from retroperitoneum in newborns. We present a male mature newborn infant with a retroperitoneal cystic lymphangioma proven by autopsy. The clinical manifestation of chylous ascites may mimic retroperitoneal cystic lymphangioma. The finding in supine abdomen X ray and abdominal sonography may help us to make some differential diagnosis.

Immunogenicity of Haemophilus influenzae b conjugate vaccine (HibTITER) and safety of HibTITER and a combination vaccine of diphtheria, tetanus, pertussis and HibTITER in infants two months of age: a preliminary report.

A study was undertaken to evaluate the safety and immunongenicity of a conjugate Haemophilus influenzae type b (Hib) vaccine (HibTITER) when administered concurrently with DTP (diphteria, tetanus and pertussis) vaccine in separate syringes. A total of 90 healthy children (45 per group) were randomized to receive either TETRAMUNE, a vaccine combining HibTITER with whole-cell DTP (group A), or DTP and HibTITER administered concurrently (group B) in separate syringes at approximately 2, 4 and 6 months of age in Taiwan. All children in group B achieved anti-Hib PRP (polyribosylribitol phosphate) antibody titers above 0.15 microgram/ml and 91% developed antibody titers above 1.0 microgram/ml following the third immunization. Incidences of adverse reactions were comparable between groups A and B. Besides, the incidences of adverse reactions were not significantly more frequent compared with DTP vaccination alone. We concluded that HibTITER was highly immunogenic and safe when administered concurrently with DTP vaccine to Taiwanese children. TETRAMUNE was also safe and the number of injections may be reduced in the future.

Lipoblastomatosis in a newborn: case report.

A male newborn had a well-circumscribed, solid mass on the right anterior chest wall at birth. Computed tomography disclosed an infiltrating soft-tissue mass over the right 6th to 9th ribs near the costochondral junction. Surgical excision was done at the age of 5 days. Pathologic examination showed lipoblastomatosis.

Intradural extramedullary epidermoid cyst of the spinal canal: report of one case.

A 9-year-old girl developed a progressive unsteady gait for one month. Hyperactive reflexes of the four extremities and a spasticity of the lower extremities were found. Bilateral Babinski responses were elicited. An intradural extramedullary mass of upper thoracic spinal cord was demonstrated using magnetic resonance imaging and was confirmed as an intradural extramedullary epidermoid cyst at surgery. This epidermoid cyst was from congenital origin. No congenital anomalies such as spina bifida or dermal sinus were associated. The epidemiology, clinical features, radiology, surgical treatment and pathology of this benign tumor are discussed.

Cloning and characterization of a cDNA encoding an 18.0-kDa class-I low-molecular-weight heat-shock protein from rice.

A novel cDNA clone, Oshp18.0 cDNA, encoding a rice (Oryza sativa L. cv. Tainong 67) 18.0-kDa heat-shock protein (HSP), was isolated from a cDNA library of heat-shocked rice seedlings by use of the rice HSP cDNA, Oshsp17.3 cDNA, as a probe. The sequence showed that Oshsp18.0 cDNA contains a 749-bp insert encoding an ORF of 160 amino acids, with a predicted molecular mass of 18.0 kDa and a pI of 7.3. Sequence comparison reveals that Oshsp18.0 cDNA is highly homologous to other low-molecular-weight (LMW) HSP cDNAs. Also, the results of hybrid-selected in vitro translation clearly establish that Oshsp18.0 cDNA is the rice 18.0-kDa LMW HSP-encoding cDNA clone. The recombinant Oshsp18.0 fusion protein produced in Escherichia coli was of the size predicted, and was recognized by the class-I rice 16.9-kDa HSP antiserum. The results suggest that Oshsp18.0 cDNA is an 18.0-kDa class-I LMW HSP- encoding cDNA clone from rice.

A recombinant rice 16.9-kDa heat shock protein can provide thermoprotection in vitro.

It is difficult to obtain large amounts of purified low-molecular-mass heat shock proteins (LMM HSPs), which are unique to plants, for biochemical and physiological studies. Therefore, an attempt was made to produce such a HSP by applying recombinant DNA technology. We fused the cDNA for a rice class I 16.9-kDa HSP, pTS1, to the gene for glutathione S-transferase (GST) of Schistosoma japonicum and we obtained large amounts of the fusion protein from transformed Escherichia coli cells. In addition, we found that the 16.9-kDa HSP obtained by cleavage of the recombinant protein could also form a protein complex of approximately 310 kDa under nondenaturing conditions as can the small, native, class I HSPs from heat-shocked rice seedlings. An assay in vitro to examine the thermoprotection of rice soluble proteins from heat denaturation revealed the strong stabilizing effect of the recombinant HSP.

A NaCl-regulated plant gene encoding a brain protein homology that activates ADP ribosyltransferase and inhibits protein kinase C.

A cDNA clone pCZ1, with a 1.1 kb insert, was isolated from a NaCl-adapted tobacco cell cDNA library that encodes an apparently full-length 29 kDa protein (251 amino acids) with a calculated pI of 5.7. The encoded peptide had a high amino acid sequence identity with bovine 14-3-3 protein which was originally found as an abundant protein in the animal central nervous system. Recently, proteins with sequence identity to 14-3-3 protein have also been found in plants, insects and yeast, and appear to have diverse physiological functions. Similar to the bovine brain 14-3-3 protein, the recombinant pCZ1 protein stimulated ADP-ribosylation of protein substrate by ADP-ribosyltransferase from the plant and animal pathogenic bacterium Pseudomonas aeruginosa. This recombinant protein also inhibited protein kinase C activity in vitro. Southern blot analyses indicated that most likely five genes encoding 14-3-3-like proteins are present in tobacco. The pCZ1 cDNA insert hybridized to a single mRNA of 1.1 kb from cultured tobacco cells. The level of this mRNA transcript in tobacco cells was downregulated upon adaptation to NaCl but was unaffected by short-term treatment with NaCl, ABA or ethylene. In tobacco plants, expression of transcript that hybridized to pCZ1 was tissue specific, and was most abundant in roots and flower parts. Monoclonal antibody raised against GF14 protein, a maize protein with substantial sequence identity with 14-3-3 protein detected two bands on SDS-PAGE of total proteins from unadapted tobacco cells and only a single band from cells adapted to NaCl. The GF14 antibody was also used to illustrate that the G-box element of a salt-induced gene is associated with a 14-3-3-type protein.

The potential use of catalytic RNAs in therapy of HIV infection and other diseases.

This article describes the applications (both real and potential) of a new antiviral strategy, based on the use of antisense, catalytic RNAs (ribozymes) as therapeutic agents. An understanding of both antisense inhibition of gene expression and RNA autocleavage reactions are essential to the use of this technology. In addition, for the successful application of this technology in clinical settings, an interdisciplinary approach involving clinicians, molecular and cellular biologists, will be necessary. The following treatise will highlight several salient features of ribozyme technology, emphasizing its application as an antiviral as well as discuss some problems and potential solutions pertinent to the clinical application of this technology.

[Parental attitude and adjustment to childhood epilepsy].

Parental attitude and adjustment were examined in 20 epileptic children (ages 6.8-16.6 yrs), using semi-structured interview. The results indicated that parental understandings of epilepsy were generally poor and incorrect. Fifteen (75%) of 20 parents had their own interpretations of causality and 19 (95%) had unrealistic hope for early and complete cure. Parents tended to overprotect and overrestrict their children. Sixteen (80%) concealed the illness for fear of social prejudice, therefore the social support systems were generally poorly utilized. As in other chronic diseases, all parents went through feelings of shock, denial, anger, guilt, fear, anxiety and depression. Family relationships were not affected much, however, poor communications were commonly found between parents and children. Thirteen (65%) parents never talked to their children about epilepsy. We concluded that parents of epileptic children showed negative attitudes toward their children and had difficulties in their psychosocial adjustment probably related to social stigmata and misunderstanding of the illness. Therefore, communication between physician and parents in both medical and psychosocial aspects should be encouraged.

Mutagenicity of the C-nitroso analog of fenitrothion.

The chemicals fenitrothion, nitroso fenitrothion, amino fenitrothion and 3-methyl-4-nitrophenol were tested for mutagenicity to Salmonella typhimurium strains TA98 and TA100, both in the presence and absence of rat liver S-9 mix. The strong mutagenicity of nitroso fenitrothion to both strains either in the presence or absence of S-9 mix contrasted with the observation that fenitrothion displayed no mutagenicity in these tester strains. The results suggest that the normal nitroreductases present in TA98 and TA100 cannot metabolize fenitrothion to a mutagenic metabolite. This inability of the tester strains to effect partial nitroreduction results in the failure of this screening system to predict the potential genotoxicity of this pesticide.

A comparative study of laboratory utilization behavior of "on-service" and "off-service" housestaff physicians.

Highly specialized housestaff programs often call for training in another specialty area, especially internal medicine. Because of differences in training background and experience with internal medicine, laboratory utilization patterns might differ. Hence, laboratory test comparisons between medical ("on-service") and nonmedical ("off-service") housestaff were carried out on the general medicine service. On-service and off-service housestaff were found to have similarly ill patients and similar workloads. Off-service housestaff generally used less laboratory services than on-service housestaff, although both groups used large numbers of tests. Despite differences in experience and training, off-service housestaff appeared to deliver less costly and apparently equal quality medical care, compared with on-service housestaff.