[Advances in the diagnosis of phenylketonuria with the introduction of direct detection of PAH gene mutation].

Background: Phenylketonuria is as regards the genotype a very heterogenous disease. Successful prenatal and postnatal DNA diagnosis calls for knowledge of different mutations in a given population. The objective of the investigation was to introduce direct detection of 21 mutations in the gene for phenylalanine hydroxylase and to find the distribution and frequency of these mutations in the population of northern and southern Moravia.

Regulation of the uncoupling protein gene (Ucp) by beta 1, beta 2, and beta 3-adrenergic receptor subtypes in immortalized brown adipose cell lines.

Immortalized brown adipocyte cell lines derived from a mouse hibernoma express all three beta-adrenergic receptor subtypes, including beta 3-adrenergic receptor (AR). In response to norepinephrine, cAMP production by plasma membranes from four clonal cell lines was stimulated to levels comparable with brown adipocytes isolated from interscapular brown adipose tissue (72.8-89.

Visual changes in human immuno-deficiency virus infection.

Background: Many Human Immuno-Deficiency Virus (HIV) patients develop ocular involvement during the course of the disease, including HIV retinopathy and cytomegalovirus (CMV) retinitis. It is well established that contrast sensitivity and color vision may be affected in other retinal diseases, such as diabetes, before obvious signs and symptoms. We therefore examined patients with early HIV disease for visual involvement.

Unstable triplets and their mutational mechanism: size reduction of the CGG repeat vs. germline mosaicism in the fragile X syndrome.

The mechanism responsible for the characteristic expansion of the trinucleotide repeat involved in the pathogenesis of the fragile X syndrome is still largely unclear. Slipped strand mispairing (SSM) and similar DNA replication errors could determine both increases and decreases of the unit number in simple repetitive sequences. Actually, there have been a few reports of size reduction of the (CGG)n in parent-to-child transmission of the fragile X syndrome, which may help in understanding the mutational mechanism and may have practical implications for genetic counseling.

No apparent involvement of the FMR1 gene in five patients with phenotypic manifestations of the fragile X syndrome.

Most fragile X patients have a significant increase in the number of CGG repeats in the FMR1 gene. Two patients were described with a deletion and one patient with a point mutation in the FMR1 gene. We describe 5 patients with a fragile X or Martin-Bell phenotype.

Norepinephrine-dependent selection of brown adipocyte cell lines.

A transgenic mouse carrying a simian virus-40 T-antigen gene under control of a mouse urinary protein promoter induced the formation of a brown fat tumor. In tissue culture, these tumor cells expressed the brown fat-specific mitochondrial uncoupling protein (Ucp) gene when stimulated by norepinephrine. To develop cell lines for the analysis of Ucp expression, we investigated growth conditions that would maintain expression.

An upstream enhancer regulating brown-fat-specific expression of the mitochondrial uncoupling protein gene.

Previous studies on the regulation of a Ucp minigene in transgenic mice demonstrated that the sequences necessary for brown-fat-specific expression and inducibility by norepinephrine were located in the 5' flanking region between 1 and 2.8 kb from the transcriptional start site. We have investigated this region in more detail in cultured mouse brown adipocyte tumor cells.

Development of obesity in transgenic mice after genetic ablation of brown adipose tissue.

Brown adipose tissue, because of its capacity for uncoupled mitochondrial respiration, has been implicated as an important site of facultative energy expenditure. This has led to speculation that this tissue normally functions to prevent obesity. Attempts to ablate or denervate brown adipose tissue surgically have been uninformative because it exists in diffuse depots and has substantial capacity for regeneration and hypertrophy.

Mapping of a gene for non-specific X linked mental retardation: evidence for linkage to chromosomal region Xp21.1-Xp22.3.

Linkage analysis of a non-specific form of X linked mental retardation (MRX) was performed with 16 polymorphic markers spanning the entire X chromosome in a three generation Italian family, including four male patients with moderate mental retardation. One obligate carrier woman had mild mental retardation and another two had normal intelligence. The results indicate tight linkage to DNA markers DXS84 (L754), DXS164 (pERT87-15), and DXS278 (CRI-S232).

Patterns of hospital use by patients with diagnoses related to HIV infection.

The authors analyzed the use of hospitals by patients with a diagnosis of human immunodeficiency virus (HIV) infection, using data from the National Hospital Discharge Survey. In the period 1984-90, the rates of both discharges and days of care for HIV-infected patients rose dramatically. For 1988-90, black males had the highest HIV-related discharge rate, followed by white males and black females, whose rates were similar.

The phenylketonuria G272X haplotype 7 mutation in European populations.

We have compiled data on the frequencies of the phenylketonuria G272X mutation in European populations. This mutation occurs north of the Alps. It has a particularly high frequency in the Oslo Fjord region of Norway with the adjacent Bohuslän region of Sweden.

Long-stay patients in short-stay hospitals.

In 1980 and 1990, only 4-5 percent of patients in short-stay hospitals were hospitalized for more than 3 weeks. The number of discharges and days of care for these long-stay patients were lower in 1990 as compared with 1980, but they continued to use more than a quarter of all hospital days in 1990. Long-stay patients were more likely than all patients to be 65 years of age and over and have Medicare as their expected principal source of payment.

Haplotype distribution at the phenylalanine hydroxylase locus in PKU families from the Moravian area of Czechoslovakia.

The analysis of 21 families affected with classical phenylketonuria (PKU) from the Moravian area of Czechoslovakia has revealed 12 different RFLP haplotypes. Nine and eight haplotypes were associated with the normal and with the mutant alleles, respectively. Most normal alleles are associated with haplotype 1 (42.

Adrenergic regulation of the mitochondrial uncoupling protein gene in brown fat tumor cells.

A tumor appeared on the back of a transgenic mouse carrying the SV40 T-antigen under control of a mouse major urinary protein promoter. High levels of mRNA for the mitochondrial uncoupling protein (UCP) indicated that the tumor was a hibernoma. The tumor has been established as a transplantable tumor line in nude (nu/nu) mice and used as a source of cells to develop a tissue culture system for analyzing brown fat development and differentiation.

Estimates from two survey designs: national hospital discharge survey.

The methodology for the National Hospital Discharge Survey (NHDS) has been revised in several ways. These revisions, which were implemented for the 1988 NHDS, included adoption of a different hospital sampling frame, changes in the sampling design (in particular the implementation of a three-stage design), increased use of data purchased from abstracting service organizations, and adjustments to the estimation procedures used to derive the national estimates. To investigate the effects of these revisions on the estimates of hospital use from the NHDS, data were collected from January through March of 1988 using both the old and the new survey methods.

[Screening for alpha 1-antitrypsin deficiency in neonates].

In a two-year investigation 113,274 children were screened for alpha-1-antitrypsin deficiency. An original and cheap method was used. In children with an alpha-1-antitrypsin values lower than 1.

National Hospital Discharge Survey.

This report presents statistics on the utilization of non-Federal short-stay hospitals based on data collected through the National Hospital Discharge Survey from a national sample of hospital records of discharged inpatients. Estimates are provided by the demographic characteristics of patients discharged, geographic region of hospitals, conditions diagnosed, and surgical and nonsurgical procedures performed. Measurements of hospital use include frequency, rate, percent of discharges and days of care, and average length of stay.

Abnormal brown and white fat development in transgenic mice overexpressing glycerol 3-phosphate dehydrogenase.

Mice carrying approximately 25 copies of a transgene encoding glycerol 3-phosphate dehydrogenase expressed from 50 to 200 times the level of enzyme produced by a single copy of the normal endogenous gene. The enzyme constituted greater than 50% of the cytoplasmic protein in the brown fat of a transgenic mouse. Young transgenic mice (10 days to 8 weeks of age) appeared physically and reproductively normal; however, at the earliest times analyzed, the amount of brown fat of transgenic mice was greater than that of nontransgenic littermate controls.

Genetic hypothyroid mice: normal cerebellar morphology but altered glycerol-3-phosphate dehydrogenase in Bergmann glia.

The present study was undertaken to investigate the effects of thyroid deficiency on cerebellar development with mouse endocrine genetic models. Four types of mutant mice, the growth hormone- and thyroid hormone-deficient Snell dwarf mouse (dw/dw), the growth hormone-deficient little mouse (lit/lit), the primary hypothyroid mouse (hyt/hyt), and the congenital genital goiter mouse (cog/cog) were analyzed for expression of the glial enzyme marker glycerol-3-phosphate dehydrogenase (GPDH) and several other marker proteins. GPDH expression, as determined by enzyme activity and Northern blot analysis, was reduced by about 50% in the cerebellum and brainstem of the three hypothyroid mutant mice.

The mitochondrial uncoupling protein gene in brown fat: correlation between DNase I hypersensitivity and expression in transgenic mice.

The mitochondrial uncoupling protein gene is rapidly induced in mouse brown fat following cold exposure. To identify cis-regulatory elements, approximately 50 kb of chromatin surrounding the uncoupling protein gene was examined for its hypersensitivity to DNase I. Seven DNase I-hypersensitive sites were identified in the 5'-flanking DNA, and one site was identified in the 3'-flanking DNA.

Hospital use by adolescents and young adults.

This article provides a descriptive profile of hospital use by adolescents (10-14 and 15-18 years of age) and young adults (19-24 years) based on the 1987 National Hospital Discharge Survey. During 1987, nearly 5 million adolescents and young adult patients were discharged from short-stay hospitals. The discharge rate for adolescents was 56.

Surgical and nonsurgical procedures associated with hospital delivery in the United States: 1980-1987.

Data from the National Hospital Discharge Survey were used to examine changes in the rates of procedures performed on women hospitalized for delivery from 1980 to 1987 in the United States. The rate of procedures reported per 100 deliveries increased 42 percent. Much of this increase was reported from 1984 to 1987, when there may have been more complete recording of secondary procedures due to the implementation of prospective payment systems.