Phenylketonuria variants in Ontario.

Since mass screening of the newborn population for phenylketonuria (PKU) by the Guthrie test was begun in Ontario in July 1965 many variants of PKU have been recognized in the 96 to 97% screened. Seventy-one cases of classic PKU were detected (four were missed). Of 48 cases of persistent hyperphenylalaninemia discovered, 18 were classified as atypical PKU and 30 as persistent benign hyperphenylalaninemia. Numerous infants with transient hyperphenylalaninemia (initial values over 10 mg/dl in 12), in many instances the result of transient neonatal tyrosinemia, were discovered. There was a slight predominance of males. Serum phenylalanine values of up to 15 mg/dl seemed to be harmless to the developing brain. A survey of 67 247 adults in the general population revealed 1 person with PKU and 1 with persistent benign hyperphenylalaninemia; both had normal intelligence quotients. Of 1548 mothers of retarded children tested, none had hyperphenylalaninemia.     

Phenylketonuria due to phenylalanine hydroxylase deficiency: an unfolding story. Medical Research Council Working Party on Phenylketonuria.

Efficient neonatal screening for phenylketonuria and the availability of complex diets for lifelong use have virtually eliminated severe mental handicap from the disease. Nevertheless, there remains a high risk of fetal damage in offspring of women with the disease, and the possibility that the diets themselves may be harmful cannot be excluded. Search for a preventive treatment for the disease has been greatly aided by advances in molecular genetics. For example, in mice modified liver cells have been implanted, which have not only corrected the phenylalanine defect but have remained healthy for the normal life span of the animal. Overall, however, prevention and treatment have not progressed as quickly as was hoped, and research and development must be pursued vigorously to take account of contemporary perceptions of the disorder.     

Renal-hepatic-pancreatic dysplasia and its variants.

A family is reported, in which two pregnancies resulted in the birth of a female fetus with multiple congenital anomalies, including renal cystic dyplasia, pancreatic fibrosis with dilated pancreatic duct, and some anomalies of the face and genitalila. The pathology of the second fetus was revealed by prenatal ultrasonographic examination. In the relevant literature 20 additional cases of renal-hepatic-pancreatic dysplasia (RHPD) could be found. It is demonstrated that cystic renal dysplasia associated with pancreatic fibrosis or cystofibrosis (with normal liver) as well as cystic renal dysplasia associated with hepatic fibrosis (with normal pancreas) should be considered as incomplete RHPD variants. In 6 cases out of 22, the infants had some features of the apolysplenia complex, including situs inversus and/or heart defects. The association of RHPD and apolysplenia has been proved to be an autosomal recessively inherited syndrome. Most probably RHPD without apolysplenia represents a separate entity with autosomal recessive mode of inheritance as well.     

Sleep and intellectual functioning in the elderly: the role of sleep quality and apnea--literature survey

In both relatively healthy and in demented elderly people mental abilities and sleep quality decrease in becoming older and nocturnal respiratory disturbance increases. Perhaps there is an association between sleep and cognition. The hypothesis that specific sleep phenomena are necessary to assure an adequate level of cognitive functioning is called the sleep cognition hypothesis. In this article the findings of research in older people are reviewed. 23 research reports were found in which sleep was measured with polysomnography. The findings in relatively healthy older people do not suggest a strong association between sleep and cognition nor a causal effect between a specific cognitive dysfunction and a specific sleep variable. The findings in demented older people concerning sleep and cognition are inconsistent. In relatively healthy older people a significant correlation between nocturnal respiratory disturbance and cognitive functioning was seldom found, whereas in demented older people a clear association was shown. Therefore, in demented older people prudence is necessary in prescribing psychopharmaca because these can enhance the appearance of sleep apneas.     

Case Finding in Phenylketonuria: II. The Guthrie Test

Experience with over 6000 Guthrie tests is presented. This test is a screening procedure for phenylketonuria using small amounts of blood spotted on a filter paper which are tested by a bacterial “inhibition assay”. Certain technical aspects of the test (e.g. relation between the concentration of phenylalanine in the blood and extent of the bacterial growth zones produced, type of filter paper, size of the blood spot on the paper) were investigated. It was shown that the Guthrie test clearly distinguishes between subjects with normal plasma phenylalanine levels and patients with untreated phenylketonuria.Applications of the Guthrie test in screening a mental hospital population, admissions to a penitentiary and newborn babies are described.     

Cytodiagnosis of classic lobular carcinoma and its variants.

The well-known cytologic features of lobular carcinoma traditionally consist of modest cellularity and small, atypical cells lying singly or in small groups. However, lobular carcinoma is a common pitfall in the cytodiagnosis of breast lesions. Knowledge of its varied histologic appearance can help to prevent diagnostic difficulties. Among 55 consecutive cases of breast needle aspirates with histologic follow-up, 9 lobular carcinomas were identified. The surgical material was examined for the following histologic variants: (1) classic, (2) solid, (3) alveolar, and (4) mixed; it was correlated with the cytologic findings. Pure, classic lesions were the most likely cause of false-negative diagnoses. Two of nine lobular carcinomas were diagnosed as benign due to scant cellularity and cell smallness. Four of nine were cytologically misclassified as ductal type due to more abundant cellularity and larger cells. This could be attributed to the predominant alveolar or solid patterns present in three cases. Only three of nine were accurately classified as lobular carcinoma, and all had a significant classic histologic element. Another important feature that is highly suggestive of lobular carcinoma is the presence of cytoplasmic vacuoles. They were overlooked in three of four cases. This study suggested that the traditional cytologic features of lobular carcinoma are present only in tumors with a predominantly classic histologic pattern. Awareness of the variant patterns and their cytologic features, including more abundant cellularity, larger cells and clusters, and cytoplasmic vacuoles, will aid in correct classification.     

IPAT及其扩展模型的应用研究进展

IPAT及其扩展模型能够定量描述人文驱动力与环境压力之间的关系,有助于理解人类和自然系统的动态耦合,是诊断因社会经济发展而产生的环境问题的有效工具.本文简要介绍了IPAT模型由来及其扩展模型的发展状况,系统总结了模型国内外应用研究进展,并对研究中的热点问题进行探讨,提出IPAT及其扩展模型的发展趋势,旨在进一步深化IPAT相关模型在环境可持续发展中的应用,为社会管理决策提供依据.     

Acetone-butanol fermentation and its variants

Recent intensive research on the acetone-butanol-ethanol and the isopropanol-butanol-ethanol fermentation has increased the basic understanding of these processes substantially. Metabolic investigations on Clostridium acetobutylicum, and Clostridium beijerinkii show that enzyme activities necessary for solvent production are induced only in solvent-producing cells. Although produced, or added, acetic and butyric acid have significant effects on the metabolic activities, the transition from acid to solvent production cannot as yet be fully explained. Based on studies in continuous cultures, the kinetics of product formation can be described. Knowledge of the mechanism of butanol toxicity is accumulating but no dramatic increase in butanol tolerance has so far been obtained. Successful results, approaching the limitations determined by biological and technological possibilities, have been obtained in batch and continuous cultures, and in continuous processes based on immobilized cells. Continuous processes are superior to batch cultures in respect of their productivity.     

Phenylketonuria mutation analysis in Northern Ireland: a rapid stepwise approach.

We present a multistep approach for the rapid analysis of phenylketonuria (PKU) mutations. In the first step, three common mutations and a polymorphic short tandem repeat (STR) system are rapidly analyzed with a fluorescent multiplex assay. In the second step, minihaplotypes combining STR and VNTR data are used to determine rare mutations likely to be present in an investigated patient, which are then confirmed by restriction enzyme analysis. The remaining mutations are analyzed with denaturant gradient-gel electrophoresis and sequencing. The first two steps together identify both mutations in 90%-95% of PKU patients, and results can be obtained within 2 d. We have investigated 121 Northern Irish families with hyperphenylalaninemia, including virtually all patients born since 1972, and have found 34 different mutations on 241 of the 242 mutant alleles. Three mutations (R408W, I65T, and F39L) account for 57.5% of mutations, while 14 mutations occur with a frequency of 1%-6%. The present analysis system is efficient and inexpensive and is particularly well suited to routine mutation analysis in a diagnostic setting.     

Ant biodiversity and its relationship to ecosystem functioning: a review

Ants are important components of ecosystems not only because they constitute a great part of the animal biomass but also because they act as ecosystem engineers. Ant biodiversity is incredibly high and these organisms are highly responsive to human impact, which obviously reduces its richness. However, it is not clear how such disturbance damages the maintenance of ant services to the ecosystem. Ants are important in below ground processes through the alteration of the physical and chemical environment and through their effects on plants, microorganisms, and other soil organisms. This review summarizes the information available on ant biodiversity patterns, how it can be quantified, and how biodiversity is affected by human impacts such as land use change, pollution, invasions, and climate change. The role of ants in ecosystems is discussed, mainly from the perspective of the effects of ground-dwelling ants on soil processes and function, emphasizing their role as ecosystem engineers. Some lines of research are suggested after demonstrating the gaps in our current information on ant-soil interactions.     

Phenylketonuria in Spain: RFLP haplotypes and linked mutations

In order to investigate the molecular basis of phenylketonuria (PKU) in Spain, we analyzed the restriction fragment length polymorphism (RFLP) haplotypes and common mutations in the phenylalanine hydroxylase (PAH) gene in 32 unrelated Spanish PKU families. The distribution of RFLP haplotypes differs from that of northern Europe. Mutant haplotypes 2 and 3 were completely absent in our sample. Approximately 65% of the mutant alleles are confined to three RFLP haplotypes, namely haplotypes 1, 6 and 9, also frequently found in other Mediterranean populations. We screened for previously described PKU mutations using the polymerase chain reaction and allele-specific oligonucleotides, and found IVS10,165T, E280K and P281L as the major mutations, representing 41% of the PKU alleles. Other mutations found were Y414C, and a new one, P244L. Mutations R408W and IVS12, prevalent in northern Europe, as well as others present in southern European populations (R252W, R261Q, L249F) were not detected in our sample. Our results reveal the genetic heterogeneity present in the Spanish PKU population, which shows similarities to others of Mediterranean origin.     

The stress reaction and its molecular events: splicing variants

The growth of cells and tissues is regulated by stress. When body is injured, it manifests a large spectrum of metabolic, endocrine, and immune alterations, which is named stress reaction. Among them, the production of growth factors may play a critical role. For osteoblasts and myoblasts, IGF-I has been shown to be involved in the process of cells in response to overloads. There are two splicing forms, one is IGF-Ea, the other is the IGF-IEb in the rodents and corresponds to IGF-IEc in humans. The latter is markedly up-regulated in response to overloads. Therefore, it has been named mechanogrowth factor. The link between the mechanical stimulus and the gene expression represents a new and important area in cell science. Understanding the process of splicing in IGF-I helps one to investigate the mechanotransduction of cells in response to mechanical stimulation at molecular level.