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Biomedical subjects

Min Wei

Publications and source records attributed to Min Wei.

At least 91 records · Page 5Linked to original sources
PubMed2003

Effects of diazepam on closed- and open-loop optokinetic nystagmus (OKN) in humans.

The effects of diazepam on optokinetic nystagmus (OKN) eye movements were studied under closed-loop and open-loop conditions in healthy humans. The open-loop condition was achieved by adding the eye-movement velocity signal of OKN to the computer-generated signal controlling the moving stimulus grating. Each of four subjects received a single oral dose of 5 mg diazepam or a placebo on two separate days in a double-blind randomized fashion. OKN eye movements were measured 90 min after administration of the treatments. As compared to placebo, diazepam significantly reduced the gain of open-loop OKN, but did not modify the gain of closed-loop OKN. The results indicate that the OKN gain under the open-loop condition is a more sensitive detector of the parameter changes of the OKN system than under the closed-loop condition. Thus, open-loop OKN gain can provide an objective, quantitative measure of benzodiazepine agonist effects.

Adult↗
PubMed2003

Liver tumorigenicity of trimethylarsine oxide in male Fischer 344 rats--association with oxidative DNA damage and enhanced cell proliferation.

Arsenic is a notorious environmental toxicant known to be carcinogenic for the skin, lung and urinary bladder in human beings. The carcinogenicity of trimethylarsine oxide (TMAO), one organic metabolite of inorganic arsenics in humans and experimental animals, was investigated here in male Fischer 344 rats in a 2-year carcinogenicity test. TMAO was administered to a total of 129 male rats ad libitum at concentrations of 0 (Control), 50 or 200 p.p.m. in the drinking water. In animals that died or were killed from the 87th week until the end of 104th week, incidences of hepatocellular adenomas were 14.3, 23.8 and 35.6% in the 0, 50 and 200 p.p.m.-treated groups, respectively; the multiplicities were 0.21, 0.33 and 0.53. Both were significantly increased in the 200 p.p.m.-treated group. While a variety of other tumors developed in various organs, they were present in all groups, including the controls, and were histologically diagnosed as those known to occur spontaneously in F344 rats. To test the contribution of reactive oxygen species (ROS) to TMAO tumorigenicity in the liver, 8-hydroxydeoxyguanosine (8-OHdG) formation was assessed by high performance liquid chromatography. The 8-OHdG values for the 200 p.p.m. TMAO group were significantly higher than those for the control group. Furthermore, as assessed by the proliferating cell nuclear antigen index, cell proliferation in the normally appearing parenchyma was elevated by the TMAO treatment. These results indicate that TMAO exerts liver tumorigenicity with possible mechanistic roles for oxidative DNA damage and enhanced cell proliferation.

Animals↗
PubMed2003

Phenobarbital at low dose exerts hormesis in rat hepatocarcinogenesis by reducing oxidative DNA damage, altering cell proliferation, apoptosis and gene expression.

Our recent research indicated that phenobarbital (PB) may inhibit the development of N-diethylnitrosamine (DEN)-initiated pre-neoplastic lesions at low doses in a rat liver medium-term bioassay (Ito test), while high doses exhibit promoting activity. This raises the question of whether treatment with low doses of PB might reduce cancer risk. For clarification, male 6-week-old F344 rats were treated with PB at doses of 0, 2, 15 and 500 p.p.m. in the diet for 10 or 33 weeks after initiation of hepatocarcinogenesis with DEN. In a second, short-term experiment, animals were given PB at doses of 2, 4, 15, 60 and 500 p.p.m. for 8 days. Formation of glutathione S-transferase placental form (GST-P) positive foci and liver tumors was inhibited at 2 p.p.m. Generation of oxidative DNA damage marker, 8-hydroxy-2'-deoxyguanosine (8-OHdG), cellular proliferation within the areas of GST-P positive foci and apoptosis in background liver parenchyma were suppressed. Suppression of 8-OHdG formation by PB at low dose might be related to the enhanced mRNA expression of 8-OHdG repair enzyme, oxoguanine glycosylase 1 (Ogg1). Moreover, as detected by cDNA microarray analysis, PB treatment at low dose enhanced mRNA expression of glutamic acid decarboxylase (GAD65), an enzyme involved in the synthesis of gamma-aminobutyric acid (GABA), and suppressed MAP kinase p38 and other intracellular kinases gene expression. On the contrary, when PB was applied at a high dose, GST-P positive foci numbers and areas, tumor multiplicity, hydroxyl radicals and 8-OHdG levels were greatly elevated with the increase in CYP2B1/2 and CYP3A2 mRNA, protein, activity and gene expression of GST, nuclear tyrosine phosphatase, NADPH- cytochrome P-450 reductase and guanine nucleotide binding protein G(O) alpha subunit. These results indicate that PB exhibits hormetic effect on rat hepatocarcinogenesis initiated with DEN by differentially altering cell proliferation, apoptosis and oxidative DNA damage at high and low doses.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

[Clinical analysis of 190 cases of outbreak with atypical pneumonia in Guangzhou in spring, 2003].

OBJECTIVE: To study methods of diagnosis and treatment for atypical pneumonia (Severe Acute Respiratory Syndrome), outbreak of the illness in Guangzhou during Jan. - Mar., 2003. METHODS: 190 cases with atypical pneumonia were analyzed, and the cases were admitted in Guangzhou municipal First Hospital and Guangzhou municipal Eighth Hospital. RESULTS: Patients were infected by close quarters contacting each other. All patients manifest high fever, and accompany by dyspnea, cough, palpitate, weakness, headache and swirl. Other 46 cases were accompanied by diarrhea. Most of patients, manifestation of lungs was negative. Chest X-ray, shadow of lungs were light in beginning, and change to severity slowly or suddenly during 5 - 10 days. Of these cases, 36 cases develop to ARDS and 11 cases died with severity ARDS. Using general antibiotic was of no effect for the illness. Continual positive airway pressure (CPAP) and glucocorticoid was required that can control deprivation of the disease when toxicosis symptom of patients was severity and shadow of lungs diffuse more and more. CONCLUSION: Infectivity of the illness is evidence and spread by airway. Using general antibiotic was of no effect for the illness. Continual positive airway pressure (CPAP) and glucocorticoid are effective for control of the disease.

Adolescent↗
PubMed2003

Enhancement of lung carcinogenesis by nonylphenol and genistein in a F344 rat multiorgan carcinogenesis model.

The modifying effects of nonylphenol and genistein on cancer induction were assessed in a multi-organ carcinogenesis model in male F344 rats initially treated with five different carcinogens. In experiment 1 rats received 250 or 25 ppm nonylphenol, or 250 or 25 ppm genistein in their diet for 28 weeks. The total incidences of adenomas and carcinomas in the lungs of animals treated with nonylphenol and genistein were significantly higher than in the control group. 5-Bromo-2'-deoxyuridine labeling indices, reflecting cell proliferation, were also significantly elevated in the lungs of rats given 250 and 25 ppm nonylphenol and 250 ppm genistein. In experiment 2, rats were treated with nonylphenol or genistein at concentrations of 250 ppm after DHPN initiation. In the lung, formation of 8-hydroxy-2'-deoxyguanosine, a marker of oxygen radical-mediated DNA damage, was significantly increased. These results indicate that nonylphenol and genistein have the potential to promote rat lung carcinogenesis, possibly via a mechanism involving stimulation of cell proliferation and DNA damage caused by oxygen radicals.

Animals↗
PubMed2003

Enhancing risk of ethanol on MeIQx-induced rat hepatocarcinogenesis is accompanied with increased levels of cellular proliferation and oxidative stress.

We investigated promotion potential of ethanol after initiation of hepatocarcinogenesis in male, 21-day-old, F344 rats by exposure to 10 ppm 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline pellet diet for 8 weeks. The rats in group 1 were then fed on liquid control diet for 16 weeks, group 2 receiving the same diet containing 5% ethanol for 8 weeks followed by 8 weeks on the control diet, while group 3 animals were given 5% ethanol containing liquid diet for the entire16 weeks. On sacrifice at the end of week 24, glutathione S-transferase placental form positive foci, putative preneoplastic lesions in the liver, cell proliferation as indicated by proliferating cell nuclear antigen immunohistochemical staining and levels of 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage, were significantly increased in the liver of group 3 along with non significant alteration of 8-oxoguanine DNA glycosylase mRNA expression. Lack of persistent increase of above parameters was found in transient ethanol exposure group. These results suggest that chronic consumption of ethanol promotes hepatocarcinogenesis by increasing oxidative stress and cell proliferation. It is also evident that abstinence of ethanol during the second stage stops its persistent promotion effect.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

Lack of initiation activity in rat liver of low doses of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline.

It has been generally accepted that genotoxic carcinogens have no threshold in exerting their potential for cancer induction. However, the non-threshold theory can be challenged for cancer risk assessment in humans. Here we examined low dose carcinogenicity of a food-derived, genotoxic hepatocarcinogen, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), using an in vivo medium-term bioassay to detect initiating activity for rat hepatocarcinogenesis. With MeIQx initiation at various doses followed by administration of phenobarbital, a well known hepatopromoter, no induction of glutathione S-transferase placental form-positive foci, assessed as preneoplastic lesions, was noted at doses of 0.001-1 ppm. The results imply a no-observed effect level for hepatocarcinogenicity with this genotoxic agent.

Animals↗
PubMed2003

Foveal versus full-field visual stabilization strategies for translational and rotational head movements.

Because we view the world from a constantly shifting platform when our head and body move in space, vestibular and visuomotor reflexes are critical to maintain visual acuity. In contrast to the phylogenetically old rotational vestibulo-ocular reflex (RVOR), it has been proposed that the translational vestibulo-ocular reflex (TVOR) represents a newly developed vestibular-driven mechanism that is important for foveal vision and stereopsis. To investigate the hypothesis that the function of the TVOR is indeed related to foveal (as opposed to full-field) image stabilization, we compared the three-dimensional ocular kinematics during lateral translation and rotational movements with those during pursuit of a small moving target in four rhesus monkeys. Specifically, we tested whether TVOR rotation axes tilt with eye position as in visually driven systems such as pursuit, or whether they stay relatively fixed in the head as in the RVOR. We found a significant dependence of three-dimensional eye velocity on eye position that was independent of viewing distance and viewing conditions (full-field, single target, or complete darkness). The slopes for this eye-position dependence averaged 0.7 +/- 0.07 for the TVOR, compared with 0.6 +/- 0.07 for visually guided pursuit eye movements and 0.18 +/- 0.09 for the RVOR. Because the torsional tilt versus vertical gaze slopes during translation were slightly higher than those during pursuit, three-dimensional eye movements during translation could partly reflect a compromise between the two different solutions for foveal gaze control, that of Listing's law and minimum velocity strategies. These results with respect to three-dimensional kinematics provide additional support for a functional difference in the two vestibular-driven mechanisms for visual stability during rotations and translations and establish clearly the functional goal of the TVOR as that for foveal visual acuity.

Animals↗
PubMed2003

Carcinogenicity of dimethylarsinic acid in p53 heterozygous knockout and wild-type C57BL/6J mice.

There is abundant epidemiological evidence that arsenic is an environmental carcinogen related to human cancers of the skin, lung, liver and urinary bladder, in particular. Dimethylarsinic acid (DMA) has also been reported to act as a carcinogen/or a promoter in rat models. To elucidate molecular mechanisms, we conducted an 18 month carcinogenicity study of DMA in p53 heterozygous (+/-) knockout mice, which are susceptible to early spontaneous development of various types of tumors, and wild-type (+/+) C57BL/6J mice. Totals of 88-90 males, 7-8 weeks of age, were divided into three groups each administered 0, 50 or 200 p.p.m. DMA in their drinking water for 18 months. Mice that were found moribund or died before the end of the study were autopsied to evaluate the tumor induction levels, as well as those killed at the end. Both p53(+/-) knockout and wild-type mice demonstrated spontaneous tumor development, but lesions were more prevalent in the knockout case. Carcinogenic effect of DMA was evident by significant early induction of tumors in both treated p53(+/-) knockout and wild-type mice, significant increase of the tumor multiplicity in 200 p.p.m.-treated p53(+/-) knockout mice, and by significant increase in the incidence and multiplicity of tumors (malignant lymphomas) in the treated wild-type mice. By the end of 80 weeks, tumor induction, particularly malignant lymphomas and sarcomas, were similar in treated and control p53(+/-) knockout mice. No evidence for organ-tumor specificity of DMA was obtained. Molecular analysis using PCR-SSCP techniques revealed no p53 mutations in lymphomas from either p53(+/-) knockout or wild-type mice. In conclusion, DMA primarily exerted its carcinogenic effect on spontaneous development of tumors with both of the animal genotypes investigated here.

Animals↗
PubMed2003

Significance of overexpression of metallothionein in mouse urinary bladder focal lesions induced by treatment with N-butyl-N-(4-hydroxybutyl)-nitrosamine.

Metallothionein (MT) is expressed in various types of human tumors, including transitional cell carcinomas of the urinary bladder, but its biological significance remains unclear. In the present study, the role of MT in urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) treatment was investigated using C57BL/6 mice. One hundred 5-week-old male C57BL/6 mice were divided into two groups, which were given drinking water with or without 0.05% BBN throughout the experimental period. Subgroups of ten animals from each group were sacrificed at weeks 5, 10, 15, 20 and 25, and urinary bladder samples were examined immunohistochemically for MT, proliferating cell nuclear antigen (PCNA) and apoptosis. MT was found to be abundant in normal-looking mucosa, but decreased with progression from precancerous lesions to invasive carcinoma in the urinary bladder obtained from BBN-treated mice. Lesions could be divided into MT-positive and negative. There was a tendency for greater MT expression in PCNA-positive lesions, while apoptosis was rather associated with MT-negativity. These data suggest that the overexpression of MT may play a role in mouse urinary bladder carcinogenesis.

Animals↗
PubMed2003

Urinary bladder lesions induced by persistent chronic low-dose ionizing radiation.

The incidence of urinary bladder cancer in the Ukraine increased from 26.2 to 43.3 per 100,000 population between 1986 and 2001 after the Chernobyl accident. The present study was conducted to evaluate the development of radiation-dependent lesions in the urinary bladders of people living in cesium 137 ((137)Cs) radio-contaminated areas of the Ukraine. Bladder urothelial biopsies from 159 male and 5 female patients were subjected to histological examination and immunohistochemical study of p38 mitogen-activated protein kinase (MAPK), as well as the p50 and p65 subunits of nuclear factor kappa B (NF-kappa B). A pattern of chronic proliferative atypical cystitis accompanied with large areas of sclerosis of connective tissue in the lamina propria was commonly observed in all cases. Interestingly, these lesions were associated with a dramatic increase in the incidences of dysplasia/carcinoma in situ, and, moreover, small urothelial carcinomas were incidentally detected. We defined the overall condition as "Chernobyl cystitis." Greatly elevated levels of p38, p65 and p50 expression in the urothelium were evident and the patients showed increased (137)Cs in urine. The data support conclusions from our previous studies of a critical role for increased oxidative stress in generation of urinary bladder urothelial lesions in individuals chronically exposed to low-dose (137)Cs radiation. Alterations in the p38 MAPK cascade and accumulation of NF-kappa B subunits could be crucial early molecular events in the pathogenesis of Chernobyl cystitis.

Adult↗
PubMed2003

[Analysis of gene expression patterns of leukemia K562 cells after cytochalasin B treatment].

BACKGROUND & OBJECTIVE: The advanced technique of DNA microarray makes it possible to monitor the expression of thousands of genes simultaneously in one hybridization experiment. This technique accelerates demonstration of anti-tumor drug mechanisms and discovery of new drug targets. This study was designed to investigate the differential gene expression of K562 cells after cytochalasin B treatment using cDNA microarray. METHODS: Restriction display polymerase chain reaction (RD-PCR) products of 277 human genes were spotted on a glass slide in microarray. K562 cells grew in RPMI 1640 medium with 10 microg/ml cytochalasin B. After 24 hours, the total RNA was isolated from K562 cells, and mRNA was purified. Both mRNA from the treated K562 cells and the controlled K562 cells were reversely transcribed into cDNA and labeled with two different fluorescence dyes: Cy5 or Cy3, using a method of restriction digestion and PCR labeling (RD-PCR). The probes were hybridized to the cDNA microarrays. After high-stringent washing,the cDNA microarray was scanned for the fluorescent signals and showed difference between the two cells. RESULTS: Among the 277 target genes, 18 down-regulated genes were identified after cytochalasin B treatment. CONCLUSION: There is a consistent tendency toward lower-expressed genes in partial K562 cells after cytochalasin B treatment. Most down-regulated genes were correlated with cell proliferation, signal transduction, and transcription factor.

Cytochalasin B↗
PubMed2003

[The effect of insulin-like growth factor 1 on the fusion of cranial suture].

OBJECTIVE: To evaluate the effect of insulin-like growth factor 1 for the bone induction and the regulation for the fusion of the sagittal cranial sutures. METHODS: The cells, derived from cranial sutures in the newborn SD rats and the sagittal suture from the mice, were cultured with a serum-free medium and treated with and without insulin-like growth factor 1. The osteoblast phetotypes (osteocalcin, alkaline, osteoponcin and type-1 collagen) were measured with the RT-PCR and ELISA, and the explanted sagittal sutures were then evaluated under light microscopy. RESULTS: The cells, treated with the insulin-like growth factor 1, significantly produced more osteocalcin, alkaline, osteoponcin and type-1 collagen than those without insulin-like growth factor 1. The fusion of the sagittal suture explants will delay till to 30 days when it was not treated with IGF1. However, in the group with IGF1 the fusion was observed to start in 8 days, and a small amount of the sagittal suture fusion was found at the 20th day while a large amount was at the 30th day. CONCLUSION: The IGF1 has a direct effect on the fusion of cranial suture due to enhancing bone induction of cranial suture cell.

Animals↗
PubMed2003

[Variation of CO2 concentration in solar greenhouse in Northern China].

The variation of CO2 concentration in winter-spring cultivated solar greenhouse in northern China was studied. The diurnal change of CO2 concentration showed an irregular 'U' shape in most case, the maximum value appeared prior to unveiling straw mat in the morning, and the minimum between 12:00 and 14:00 PM. Sometimes, an irregular 'W' shape curve with two valleys was also observed, with the first one appeared prior to the ventilation at noon, and the second occurred between 15:00-16:30 PM. During the period of winter-spring cultivation, the daily maximum concentration of CO2 in solar greenhouse decreased gradually, while the daily minimum concentration and daytime average concentration dropped first, then went up. At the same time, the time of CO2 depletion lasted longer and longer. In December, CO2 depletion happened 2.1-3.1 hours after morning unveiling. In the next March, however, it moved up to 0.6-1.1 hours after unveiling in the morning. At daytime, both during and after ventilation, solar greenhouse often showed CO2 depletion. The period of CO2 depletion extended from 4-5.8 hours per day in December to 8-8.5 hours per day in March of next year. The spacial distribution of CO2 concentrations within the greenhouse showed that in the morning and in the evening, the order was the front > the middle > the back, and the ground > the canopy > the upper, and at midday, the order was the front < the middle < the back, and the ground > the upper > the canopy. Photon flux density was the most important environmental factor affecting CO2 concentration in greenhouse. Ventilation did not avoided CO2 depletion. Canopy photosynthetic rate and soil respiratory rate were measured at different growth stages of tomato. At seedling stage, CO2 concentration in greenhouse was higher than that outside, due to the vigorous soil respiration and lower canopy photosynthetic rate. But at fruiting stage, severe CO2 depletion occurred because of stronger canopy photosynthesis and weak soil respiration.

Carbon Dioxide↗
PubMed2003

[Sequence variation in the env V3-V4 region of HIV type 1 predominant subtype B and C strains circulating in China].

OBJECTIVE: To identify genetic variation of HIV-1 predominant subtype B and C strains in China during rapid horizontal transmission and to elucidate the potential relationship between genetic variation and selective pressure. METHODS: After the fragments of HIV-1 env gene were amplified by nested-PCR from the whole blood of 258 HIV-1 infected individuals, PCR products were directly sequenced using ABI 377 DNA sequencer. The sequences covering env V3-V4 region of 72 HIV-1 subtype B(n=37) and C(n=35) strains were selected for phylogenetic analysis. In addition, the ratios of synonymous (Ks) substitutions per nonsynonymous (Ka) substitutions were calculated using DIVERGE. RESULTS: The genetic distances of the V3-V4 region of subtype B strains were higher than that of subtype C strains. Furthermore, sequence analysis revealed that the V4 region was more variable than the V3 region for both subtype B and C strains. What's more, the V3 loop was less variable compared with the V3 upstream region and C3 region for subtype C Ks/Ka ratios of the entire aligned sequence of the two subtypes were below 1 0, with the lowest values found in the V3 region of subtype B strain and the V4 region of subtype C strain. CONCLUSIONS: The majority of variation in both subtypes B and C strains occurred in the V4 rather than the V3 region. It is important that our study found for the first time the V3 loop was more conservative than the V3 upstream region and C3 region for subtype C. Calculations of the Ks/Ka ratios throughout the V3-V4 region demonstrate that significant selective pressures experienced during the rapid horizontal spread of the virus in the Chinese HIV-1 infected population may have directed change in the V3 loop for the subtype B strain and the V4 loop for the subtype C strain. These results will contribute to the policy of AIDS prevention and control and the ongoing development vaccine.

Amino Acid Sequence↗
PubMed2003

[Study on the evolutionary pressure on the env gene of the human immunodeficiency virus type 1 CRF01-AE strains circulating in China].

OBJECTIVE: To identify variations in the env gene of human immunodeficiency virus type 1 (HIV-1) subtype CRF01-AE strains circulating in China and to elucidate the potential relationship between genetic variation and evolutionary pressure. METHODS: Fragments of the HIV-1 env gene were amplified by nested-polymerase chain reaction (n-PCR) from the whole blood of HIV-1 infected individuals from four provinces in Southeast China (Guangdong, Hunan, Jiangsu and Jiangxi). The PCR products were then directly sequenced by ABI 377 DNA sequencers. The sequences covering the env V3-V4 region of 34 HIV-1 subtype CRF01-AE strains were selected to analyse phylogenetic trees and amino acid mutations. The accumulation of synonymous (Ks) and antonymous (Ka) substitutions as well as Ks/Ka ratios were calculated using DIVERGE. RESULTS: Phylogenetic trees showed that the 34 HIV-1 subtype CRF01-AE strains from China clustered with the Chinese AE reference strain (AE.97CNGX2F), as well as with the reference strains from Thailand (AE.CM240 and AE.93TH253). The amino acid sequences of the env V4 and C3 regions in the samples were highly variable, compared with those of V3 and V3-downstream regions. The V3 loop central motif in the majority (87.5%) of the strains was GPGQ. The majority of strains did not contain positively charged amino acids at positions 306 and 320 in V3 loop. The N-linked glycosylation sites in the V3-V4 region and flanking regions in these strains were relatively conserved. Analysis of the entire region showed that the mean Ks values were significantly higher than that of the Ka values (P < 0.001), with the Ks/Ka significantly higher than 1.0 (P < 0.001). In contrast, the Ks/Ka ratio in the V4 region was significantly lower than 1.0 (P < 0.01). CONCLUSIONS: Our study indicated that the majority of HIV-1 subtype CRF01-AE strains circulating in China were highly homogeneous. The amino acid sequences of the V4 and C3 regions were significantly more variable than those of the V3 loop. Our analysis also suggested that the phenotype of nearly all strains was likely to be non-syncytium inducing (NSI). Finally, the variation found in the V3-V4 sequence was significantly influenced by functional constraints as opposed to positive selective pressure, while the variability of the lone V4 region was strongly related to positive selective pressure.

Adult↗
PubMed2003

[Heterogeneous phenotypes in Chinese glycogen storage disease type Ia patients with homozygous G727T mutation].

UNLABELLED: Glycogen storage disease (GSD) type Ia is an autosomal recessive disorder caused by a deficiency of glucose-6-phosphatase (G6Pase). The gene that encodes G6Pase was mapped to 17q21. The molecular genetic basis of GSD type Ia in the mainland Chinese population has not been explored. OBJECTIVE: To analyze the G6Pase gene mutations, and to compare the phenotypic features and the response to the corn starch treatment among patients who share the same mutation. METHODS: With the consent of the parents and their children, the authors studied 18 families with clinically diagnosed GSD type Ia from our long time follow-up groups. Direct DNA sequencing of all 5 exons and the exon-intron boundaries of G6Pase gene were done on the blood specimens. Seven of the 18 patients, male 2 and female 5, aged 1.5 to 16 years, were homozygous for same mutation. The clinical symptoms, signs and the serum biochemical values before and after treatment were compared in these 7 patients. RESULTS: The 7 patients were homozygous of G-->T transversion at the nucleotide 727 in exon 5 (G727T), which has previously been reported to cause abnormal splicing. The parents were heterozygous of the G727T mutation. All the patients exhibited typical features of GSD type Ia with variable severity, including hypoglycemia, hepatomegaly, kidney enlargement, growth retardation, bleeding diathesis, lactic acidemia, hyperlipidemia, and hyperuricemia. Two of the patients had repeated hypoglycemic seizures before the age of 2 years. One had moderate splenomegaly when he came to our clinic at the age of 16, the spleen size was reduced to 2 cm below the left costal margin after 5-year treatment. His sister, homozygous of G727T, did not show splenomegaly. One had multiple hepatic adenoma since the age of 5 years. Four had 5-year-delayed bone age when they started treatment at the age of 9 to 16 years, the bone age reached normal after 2 - 3 years treatment. No matter when they started corn starch treatment, the height increase in the first year was most obvious with an average of 10 cm. All the patients had abnormal liver function before treatment, 5 had constant slightly elevated liver enzymes with the treatment. All had normal urinalysis test, but the urine beta(2)- microglobulin was elevated. CONCLUSIONS: G727T mutation may be the major cause of GSD type Ia in China. Patients with the same mutation could have variable phenotypic characteristics, and the response to the corn starch treatment was different. The diagnosis of GSD type Ia can be based on clinical and biochemical abnormalities combined with mutation analysis instead of enzyme assays on liver biopsy.

Adolescent↗