The role of the nasal region in craniofacial growth: An investigation using path analysis

This study focuses on the role of the nasal region and its interactions with adjacent facial elements during early ontogeny. A series of linear measurements, areas and volumes were extracted from a collection of 227 medical CT-scans of children from 0 to 6 years of age. These measurements describe aspects of the form of the orbit, maxilla, peri-alveolar (subnasal) region, nasal area, eye, oral region, masseter, and temporal muscles. Hypothesized interactions were then examined using path analysis. Two paths were designed: the first to investigate potential interactions in, and relative contributions of the nasal derivatives and adjacent regions to overall facial growth and development; the second path sees the addition of facial soft tissue measurements and aims to assess their effects on skeletal components, and on overall facial growth and development. The results of the first path indicate a large contribution of the nasal and subnasal regions to facial development. This indicates that the nasal septum and the developing dentition provide an important but variable contribution to facial ontogeny during early years. This result is confirmed in the second path, where the soft tissue elements were added to the diagram. Results of the second path indicate that the soft tissues contribute only locally to the development of some skeletal elements of the face. This indicates that the contribution of skeletal components has a more direct effect on facial height than soft tissue matrices, however there are complex interactions between soft tissues and skeletal elements throughout ontogeny.     

谷胱甘肽-S-转移酶M3基因-63A/C多态性与原发性高血压的相关性

目的研究谷胱甘肽-S-转移酶(glutathione S-transferase M3,GSTM3)基因-63A/C多态性在中国北方汉族中的分布及其与原发性高血压(essential hypertension,EH)的关联。方法应用聚合酶链反应-限制性片段长度多态性技术,对汉族234例EH患者及328名正常人GSTM3基因-63A/C位点多态性进行基因分型,随机选择部分基因型样品进行DNA测序验证。结果GSTM3基因-63A/C位点基因型分布在EH和对照组均符合Hardy-Weinberg遗传平衡。EH组CC基因型频率(6%)显著高于对照组(1.8%)(P<0.05),Logistic回归分析显示CC基因型是EH发生的一项独立危险因素(OR=3.447,95%CI:1.19～7.63;P=0.04)。结论GSTM3基因-63A/C多态性与EH相关,C等位基因可能是中国北方汉族人群EH的易感性标志。     

贵州三个少数民族谷胱甘肽S-转移酶M1、T1和P1基因多态性

目的研究贵州省从江县侗族、威宁县彝族、荔波县瑶族的谷胱甘肽S-转移酶基因(GSTs)多态性。方法在隔离自然人群(从江县侗族108人、威宁县彝族104人、荔波县瑶族109人)中,采用多重等位基因特异聚合酶链反应方法分析GSTM1和GSTT1基因多态性,采用聚合酶链反应及限制性片段长度多态性方法分析GSTP11578(A→G)基因多态性。结果贵州省从江县侗族、威宁县彝族、荔波县瑶族的GSTM1和GSTT1纯合缺失基因型频率分别为59.6%～71.2%、39.4%～72.5%。其GSTP11578(A→G)基因型频率分别是:AA为63.3%～75%、AG为23.2%～35.8%、GG为0～1.9%。等位基因频率:A为81.2%～86.6%,G为13.4%～18.8%。结论GSTT1基因型频率在贵州从江侗族、威宁彝族、荔波瑶族中存在差异,其分布特征可能与人群中不同种族以及同一种族不同民族相关。     

Frequencies of glutathione s-transferase (GSTM1, GSTM3 AND GSTT1) polymorphisms in a Malaysian population

Introduction

Glutathione S-transferase (GST) is a xenobiotic metabolising enzyme (XME), which may modify susceptibility in certain ethnic groups, showing ethnic dependent polymorphism. The aim of this study was to determine GSTM1, GSTM3 and GSTT1 gene polymorphisms in a Malaysian population in Kuala Lumpur.

Material and methods

Blood or buccal swab samples were collected from 137 Form II students from three schools in Wilayah Persekutuan Kuala Lumpur. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results

Glutathione-S-transferase GSTM3 gene frequencies were 89% for AA, 10% for AB and 1% for BB. The gene frequencies for deleted GSTM1 and GSTT1 were 66% and 18% respectively.

Conclusions

This study suggested that the Malay population is at risk for environmental diseases and provides the basis for gene-environment association studies to be carried out.     

GSTP1在病变前列腺组织中的表达及意义

目的　探讨胎盘型谷光甘肽S 转移酶 (GSTP1)在不同病变前列腺组织中的表达情况及意义。方法　将 10 0例诊断明确的前列腺标本分为五组 ,即正常组 (NP)、良性增生组 (BPH)、高级别上皮内瘤组 (HPIN)、早期浸润癌组 (PIC)及前列腺癌组(PC) ,每组 2 0例。应用免疫组织化学SP法检测GSTP1在以上五组标本中的表达。结果　GSTP1在NP、BPH、HPIN、PIC及PC组织中的表达呈逐渐降低的趋势 ,且BPH组表达明显强于HPIN组 ,HPIN组表达也明显强于PIC组 ,差异均有显著意义 (P <0 .0 1)。结论　GSTP1可能与前列腺癌发生、发展密切相关。     

Prevalence of homozygosity for the deleted alleles of glutathione S-transferase mu (GSTMl) and theta (GSTTl) among distinct ethnic groutx from Brazil: relevance to enviromental carcinogenesis?

Arruda VR, Grignolli CE, Goncalves MS, Soares MC, Menezes R, Saad STO, Costa FF. Prevalence of homozygosity for the deleted alleles of glutathione S-transferase mu (GSTMl) and theta (GSTTl) among distinct ethnic groups from Brazil: relevance to enviromental carcinogenesis? Clin Genet 1998: 54: 210–214. 0 Munksgaard, 1998 Environmental related diseases due to occupational carcinogens and toxic substances are a serious problem particularly in developing countries. The glutathione S-transferase system is fundamental for the detoxification of numerous carcinogens and mutagens. The individual inherited susceptibility to chemical carcinogenesis due to glutathione S-transferase mu (GSTMl) and theta (GSTTl) varies significantly among distinct ethnic groups. In this study we determined the prevalence of the null genotype of the GSTMl and GSTTl genes among individuals from three distinct Brazilian racial groups using a multi-plex-PCR methodology. The results showed that the highest prevalence of the null genotype for the GSTMl occurred among Caucasians (55%, allele frequency = 0.74), followed by 33% among Brazilian Black subjects (allele frequency = 0.57). and 20% among Amazonian Indians (allele frequency = 0.45). For GSTTl a homogenous distribution of the null genotype was found among Caucasian and African descendants (18.5 and 19% homozygotes, respectively, allele. frequency = 0.43). with a lower prevalence among Amazonian Indians (11% of homozygotes, a!lele frequency = 0.34). Whether the deficiency of the GST system contributes to a predisposition to environmental related carcinogenesis in specific popuiations in Brazil remains to be determined.     

Distribution of alpha glutathione S-transferase in ovarian neoplasms: an immunohistochemical study

AIMS: Alpha glutathione S-transferase (alpha-GST) has been shown to be an immunohistochemical marker for delta(4-5) isomerase, an enzyme active in steroidogenesis. The purpose of this study was to document the distribution of alpha-GST in ovarian neoplasms in order to evaluate its usefulness as a diagnostic tool. METHODS AND RESULTS: A total of 92 tumours (25 sex cord/stromal, 53 epithelial and 14 germ cell) were subjected to immunohistochemistry using a commercially available polyclonal antibody to alpha-GST. The avidin-biotin complex was used as a detection system. Positive staining was found in luteinized stromal cells of all tumour types (58/92). This included the Leydig cells of Sertoli-Leydig cell tumours (7/7) and was particularly prominent in the stromal cells of both benign and malignant mucinous tumours (24/25). Granulosa and Sertoli cells showed weak or no intracytoplasmic staining, which is expected because they do not normally produce androstenedione. They did show some intranuclear staining. Malignant mucinous (12/25) and occasional other epithelial tumours showed focal intracytoplasmic positive staining. Yolk sac tumours showed focal positivity (7/8). CONCLUSIONS: Intracytoplasmic staining of stromal cells is considered to indicate steroidogenesis and intranuclear staining the intracytoplasmic transport function of alpha-GST. The intracytoplasmic staining of mucinous carcinomas might represent an up-regulation of some detoxification function. The findings suggest that antibody to alpha-GST has some value in the investigation of ovarian pathology and could readily be included in any panel of antibodies used to investigate ovarian neoplasms of uncertain histogenesis.     

An analysis of orthodontically induced changes in craniofacial form

Traditional cephalometric analyses facilitate only cursory craniofacial evaluation. When a more rigorous geometric technique, in the form of finite element analysis, was applied to a retrospective series of lateral cephalographs taken before and after the completion of the orthodontic therapy, however, complex craniofacial size and shape changes were apparent. Such complexities could not have been detected from conventional cephalographic appraisal.     

An analysis of craniofacial form in cleft palate patients

Lateral cephalometric form was compared between age-sex matched cleft palate and normocephalic (control) samples aged 6-12 years. Analogous arrays of 3 cephalometric datum points were subjected to finite element analysis, a rigorous geometric technique. The results showed that normocephalic craniofacial size changes were greater than those of the cleft palate sample, although the degree of contrast varied depending upon the particular finite element included in the analysis. More complex lateral cephalometric shape changes were denoted by this technique, however, again depending upon the specific finite element included in the analysis. These data therefore suggested that the differences in craniofacial size and shape changes between normocephalic and cleft palate patients were far more complex than traditionally envisaged.     

乳腺癌中胎盘型谷胱甘肽S－转移酶基因的扩增与异常表达

在国内首次制备并用光敏生物素方法标记胎盘型谷胱甘肽Ｓ－转移酶（ＧＳＴ－π）ｃＤＮＡ探针，应用斑点杂交技术检测２４例乳腺癌ＧＳＴ－π基因ＤＮＡ扩增与ｍＲＮＡ异常表达。结果发现，２４例乳腺癌中，３例（１２．５％）存在ＤＮＡ扩增，７例（２９．２％）存在ｍＲＮＡ异常表达，ＤＮＡ扩增和ｍＲＮＡ表达之间存在正相关性，二者均与患者年龄、肿瘤大小、淋巴结转移无明显相关，但ｍＲＮＡ异常表达与乳腺癌ＥＲ表达呈现负相关性。结果证实人乳腺癌中既存在ＧＳＴ－π基因ＤＮＡ扩增，又存在ｍＲＮＡ异常表达，提示ＧＳＴ－π与乳腺癌有密切关系。     

Effect of long-term cold exposure on activities of cytochrome P450-containing monooxygenases and glutathione S-transferase in rat liver microsomes

Long-term cold exposure (5°C) was followed by induction of rat liver monooxygenases. We revealed an increase in activity of NADPH-cytochrome C reductase, total content of cytochrome P450 (CYP), and activities of its molecular forms CYP1A1, 1A2, 2B1/B2, 2E1, and 3A1/A2 in microsomes. These indexes reached maximum by the 10th day, but decreased with lengthening of cold exposure. Glutathione S-transferase activity decreased under these conditions. Changes in enzyme activity could be related to the increase in blood corticosterone concentration.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 9, pp. 268–271, September, 2004     

Effect of long-term cold exposure on activities of cytochrome P450-containing monooxygenases and glutathione S-transferase in rat liver microsomes

Long-term cold exposure (5°C) was followed by induction of rat liver monooxygenases. We revealed an increase in activity of NADPH-cytochrome C reductase, total content of cytochrome P450 (CYP), and activities of its molecular forms CYP1A1, 1A2, 2B1/B2, 2E1, and 3A1/A2 in microsomes. These indexes reached maximum by the 10th day, but decreased with lengthening of cold exposure. Glutathione S-transferase activity decreased under these conditions. Changes in enzyme activity could be related to the increase in blood corticosterone concentration. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 9, pp. 268–271, September, 2004     

Cytogenetic monitoring of occupational exposure to pesticides: Characterization of GSTM1, GSTT1, and NAT2 genotypes

Occupational exposure of floriculturists is characterized by alternating periods of intense pesticide spraying and reduced or no activity. Induction of sister chromatid exchanges (SCE), structural chromosome aberrations (CA) and micronuclei (MN) was investigated in peripheral lymphocytes of a group of 23 Italian floriculturists and 22 matched controls. Blood sampling was performed during and one month after the end of intensive pesticide treatments, in order to cover a period of high and low exposure, respectively. Each donor was genotyped for glutathione S-transferase M1 (GSTM1), T1 (GSTT1), and N-acetyltransferase 2 (NAT2), three polymorphic genes involved in xenobiotic metabolism, to assess their potential role in individual genotoxic response to the pesticide exposure. No effect of the pesticide exposure on the cytogenetic parameters were detected. Smoking, however, was found to increase SCE levels. The only significant influence of phenotype composition on cytogenetic response was an increase in SCE levels in the GSTT1 positive individuals compared with the GSTT1 nulls (P = 0.02). This finding was, however, based on only four GSTT1 null donors (n = 41 for GSTT1 positive donors). In addition, a possible interaction was observed between smoking and GSTM1 genotype in the CA assay, GSTM1 null smokers, earlier reported to have an elevated risk for lung cancer, showing higher CA frequencies than GSTM1 positive smokers. © 1996 Wiley-Liss, Inc.     

Effects of Social Isolation on Neuromuscular Excitability and Aggressive Behaviors in Drosophila: Altered Responses by Hk and gsts1, Two Mutations Implicated in Redox Regulation

Social deprivation is known to trigger a variety of behavioral and physiological modifications in animal species, but the underlying genetic and cellular mechanisms are not fully understood. As we described previously, adult female flies reared in isolation show increased frequency of aggressive behaviors than those reared in a group. Here, we report that isolated rearing also caused significantly altered nerve and muscle excitability and enhanced synaptic transmission at larval neuromuscular junctions (NMJs). We found that mutations of two genes, Hyperkinetic (Hk) and glutathione S-transferase-S1 (gsts1), alter the response to social isolation in Drosophila. Hk and gsts1 mutations increased adult female aggression and larval neuromuscular hyperexcitability, even when reared in a group. Unlike wild type, these behavioral and electrophysiological phenotypes were not further enhanced in these mutants by isolated rearing. Products of these two genes have been implicated in reactive oxygen species (ROS) metabolism. We previously reported in these mutants increased signals from an ROS probe at larval NMJs, and this study revealed distinct effects of isolation rearing on these mutants, compared to the control larvae in ROS-probe signals. Our data further demonstrated modified nerve and muscle excitability by a reducing agent, dithiothreitol. Our results suggest that altered cellular ROS regulation can exert pleiotropic effects on nerve, synapse, and muscle functions and may involve different redox mechanisms in different cell types to modify behavioral expressions. Therefore, ROS regulation may take part in the cellular responses to social isolation stress, underlying an important form of neural and behavioral plasticity.     

Combined analysis of EPHX1, GSTP1, GSTM1 and GSTT1 gene polymorphisms in relation to chronic obstructive pulmonary disease risk and lung function impairment

Smoking is considered as the major causal factor of chronic obstructive pulmonary disease (COPD). Nevertheless, a minority of chronic heavy cigarette smokers develops COPD. This suggests important contribution of other factors such as genetic predisposing. Our objective was to investigate combined role of EPHX1, GSTP1, M1 and T1 gene polymorphisms in COPD risk, its phenotypes and lung function impairment. Prevalence of EPHX1, GSTP1, M1 and T1 gene polymorphisms were assessed in 234 COPD patients and 182 healthy controls from Tunisia. Genotypes of EPHX1 (Tyr113His; His139Arg) and GSTP1 (Ile105Val; Ala114Val) polymorphisms were performed by PCR-RFLP, while the deletion in GSTM1 and GSTT1 genes was determined using multiplex PCR. Analysis of combinations showed a significant association of 113His/His EPHX1/null-GSTM1 (OR=4.07) and null-GSTM1/105Val/Val GSTP1 (OR =3.56) genotypes with increased risk of COPD (respectively P=0.0094 and P=0.0153). The null-GSTM1/ null-GSTT1, 105Val/Val GSTP1/null GSTT1, 113His/His EPHX1/null-GSTM1 and null-GSTM1/105Val/Val GSTP1 genotypes were related to emphysema (respectively P=0.01; P=0.009; P=0.008 and P=0.001). Combination of 113His/His EPHX1/null-GSTM1 genotypes showed a significant association with the decrease of Δ FEV1 in patients (P =0.028).In conclusion, our results suggest combined EPHX1, GSTP1, GSTM1 and GSTT1 genetic polymorphisms may play a significant role in the development of COPD, emphysema and decline of the lung function.     

An analysis of craniofacial form; the need for new analytic techniques

This study was based on lateral cephalographs of 443 patients aged 7--18 years to determine the effects of age and occlusal (Angle) relationships on craniofacial form. From 33 datum points, 56 linear and angular dimensions were subjected to the multivariate statistical technique termed principal component analysis. This technique not only enabled a number of parameters to be combined together but also computed a series of orthogonal variates (components) accounting for over 90 percent of the total variance. The subsequent analysis of the component scores revealed marked contrasts in craniofacial form not only between age groups but also between different occlusal categories. The interpretation of such data remains controversial, since not only do traditional craniofacial parameters combine both size and shape together, but they are based upon datum points of unknown degrees of homology. This study therefore confirmed the complexity of craniofacial form and demonstrated the need to develop more appropriate analytic techniques with the specific objective of defining shape and shape change.     

A cross-sectional study of human craniofacial growth

It is generally accepted that different cranial regions do not follow the same growth pattern. In this study, size changes of the functional cranial components (FCCs) in 228 human skulls of age at death between 0 and 20 years were evaluated. The skull is considered as divided into anteroneural, midneural, posteroneural, otic, optic, respiratory, masticatory and alveolar FCCs. Age-related changes of FCCs were assessed by fitting curves with the smoothing spline method, and quantifying the proportional increments at different stages. All FCCs show a high growth rate in the first 3–5 years of life. Two groups of growth trajectories can be distinguished. The anteroneural, midneural, posteroneural and optic FCCs are more advanced at all stages; they show a high growth rate before 3–5-years-old and a low rate later. This difference is less pronounced in the group comprising the respiratory, masticatory and otic FCCs. The alveolar FCC shows an independent pattern. The similarities among FCCs of the two groups are best explained by their common embryological origin. In contrast, the participation in a common function cannot be associated with the co-ordinated variation, given that the masticatory and alveolar FCCs show independent trajectories.     

HLA polymorphisms in Italian bone marrow donors: a regional analysis

Abstract: The aim of this study was to analyse the genetic structure of the Italian bone marrow donor population on the basis of HLA polymorphisms. Maximum likelihood estimates of gene and haplotype frequencies, goodness of fit to Hardy-Weinberg predictions and heterozygosity were calculated for 18 Italian administrative regions. Moreover, the phenotypic peculiarity of the regional populations was assessed by analysing the number of "typical phenotypes" found in each region. Multivariate analyses carried out on HLA-A and HLA-B gene frequencies gave a genetic pattern of the donor pools that reflects the structure of the Italian population determined in previous population genetic studies. Sardinia shows a very large genetic difference with respect to the other regions; of these, the central-southern regions are well-differentiated from the central-northern. Southern regions present higher genetic heterogeneity and a higher probability of providing donors with phenotypes not already present in the Italian bone marrow registry. The large sample size of the bone marrow donor registry allowed us to estimate gene and haplotype frequencies with greater accuracy than in previous studies. Our results may be of use in determining strategies for donor recruitment and selecting unrelated donors for patients requiring bone marrow grafting, as well as for anthropological, epidemiological and population genetics studies.     

Different carcinogenic process in cholangiocarcinoma cases epidemically developing among workers of a printing company in Japan

Recently, cholangiocarcinoma has epidemically developed among young adult workers of a printing company in Japan. Exposure to organic solvents including 1,2-dichloropropane and/or dichloromethane is supposed to be associated with the carcinoma development. The metabolism of dichloromethane proceeds through a Theta-class glutathione S-transferase (GST) T1-1-catalyzed pathway, where its reactive intermediates have been implicated in genotoxicity and carcinogenicity. This study examined features of the carcinogenic process of the cholangiocarcinoma developed in the printing company. Surgically resected specimens of the cholangiocarcinoma cases were analyzed, where all cases were associated with precursor lesions such as biliary intraepithelial neoplasia (BilIN) and/or intraductal papillary neoplasm of the bile duct (IPNB). Immunohistochemical analysis confirmed constitutional expression of GST T1-1 in normal hepatobiliary tract. Immunostaining of γ-H2AX, a marker of DNA double strand break, showed that its expression was significantly increased in foci of BilIN, IPNB and invasive carcinoma as well as in non-neoplastic biliary epithelial cells of the printing company cases when compared to that of control groups. In the printing company cases, immunohistochemical expression of p53 was observed in non-neoplastic biliary epithelial cells and BilIN-1. Mutations of KRAS and GNAS were detected in foci of BilIN in one out of 3 cases of the printing company. These results revealed different carcinogenic process of the printing company cases, suggesting that the exposed organic solvents might act as a carcinogen for biliary epithelial cells by causing DNA damage, thereby contributing to the carcinoma development.