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PubMed1995

[Synthesis and antigenic activity of peptides from the ORF3 protein sequence of hepatitis E virus].

The hepatitis E virus (HEV) is an infection agent (detected recently) responsible for an enterically transmitted non-A, non-B hepatitis [1,2]. Hepatitis E is a big problem in many developing countries, including the Central Asian areas of the former Soviet Union [2]. By cloning followed by sequence analysis of the HEV genome, three open reading frames (ORF) have been identified, among them ORF3 encoding a protein containing 123 amino acid residues, the function of this protein being unknown. Recently [3], one of the immunodominant regions of ORF3 protein was revealed between the 91st and 123rd amino acid residue. The purpose of the present study was a more precise localization of epitopes in the C-terminal portion of HEV ORF3 protein by using synthetic peptides.

Amino Acid Sequence↗
PubMed2000

Big mitogen-activated kinase regulates multiple members of the MEF2 protein family.

Big mitogen-activated protein (MAP) kinase (BMK1), a member of the mammalian MAP kinase family, is activated by growth factors. The activation of BMK1 is required for growth factor-induced cell proliferation and cell cycle progression. We have previously shown that BMK1 regulates c-jun gene expression through direct phosphorylation and activation of transcription factor MEF2C. MEF2C belongs to the myocyte enhancer factor 2 (MEF2) protein family, a four-membered family of transcription factors denoted MEF2A, -2B, -2C, and -2D. Here, we demonstrate that, in addition to MEF2C, BMK1 phosphorylates and activates MEF2A and MEF2D but not MEF2B. The blocking of BMK1 signaling inhibits the epidermal growth factor-dependent activation of these three MEF2 transcription factors. The sites phosphorylated by activated BMK1 were mapped to Ser-355, Thr-312, and Thr-319 of MEF2A and Ser-179 of MEF2D both in vitro and in vivo. Site-directed mutagenesis reveals that the phosphorylation of these sites in MEF2A and MEF2D are necessary for the induction of MEF2A and 2D transactivating activity by either BMK1 or by epidermal growth factor. Taken together, these data demonstrate that, upon growth factor induction, BMK1 directly phosphorylates and activates three members of the MEF2 family of transcription factors thereby inducing MEF2-dependent gene expression.

Amino Acid Sequence↗
PubMed1993

Expression of the three endothelin genes and plasma levels of endothelin in pre-eclamptic and normal gestations.

1. Maternal vasoconstriction and fetal growth retardation are part of the syndrome of pre-eclampsia and are thought to be related to placental insufficiency. There is evidence to suggest that the powerfully vasoactive endothelin peptides might be involved in the pathogenesis. 2. The production of endothelins appears to be regulated mainly by modulation of mRNA levels, and they are thought to exert their effects locally, rather than systemically. Hence, the measurement of endothelin mRNA levels in tissues would be expected to reflect the activity of the endothelin systems. 3. RNAase protection assays, using specific antisense probes capable of distinguishing between the endothelin mRNA isoforms, have been used to examine the expression of the three endothelin genes in placental villous tissue, amniotic membrane and myometrium. Samples were taken from 15 pre-eclamptic women and from 14 women with normal gestations. Myometrium was taken at hysterectomy from five non-pregnant women as an additional control. Plasma concentrations of immunoreactive endothelin [endothelin-1, endothelin-2 and big endothelin (not distinguished)] were measured in samples taken concurrently from uterine vein and peripheral blood during surgery in ten patients. 4. The level of endothelin-1 mRNA in placental villous tissue was significantly higher in pre-eclamptic women (32 weeks gestation) than in control subjects (38 weeks gestation) (1.85 +/- 0.26 versus 0.52 +/- 0.09 arbitrary units, means +/- SEM, P < 0.001) and in gravid than in non-gravid myometrium (P < 0.001). Endothelin-2 was not expressed in villous tissue, but was expressed in amniotic membrane and myometrium, with relatively little difference between pre-eclamptic and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

Prediction of lipid posttranslational modifications and localization signals from protein sequences: big-Pi, NMT and PTS1.

Many posttranslational modifications (N-myristoylation or glycosylphosphatidylinositol (GPI) lipid anchoring) and localization signals (the peroxisomal targeting signal PTS1) are encoded in short, partly compositionally biased regions at the N- or C-terminus of the protein sequence. These sequence signals are not well defined in terms of amino acid type preferences but they have significant interpositional correlations. Although the number of verified protein examples is small, the quantification of several physical conditions necessary for productive protein binding with the enzyme complexes executing the respective transformations can lead to predictors that recognize the signals from the amino acid sequence of queries alone. Taxon-specific prediction functions are required due to the divergent evolution of the active complexes. The big-Pi tool for the prediction of the C-terminal signal for GPI lipid anchor attachment is available for metazoan, protozoan and plant sequences. The myristoyl transferase (NMT) predictor recognizes glycine N-myristoylation sites (at the N-terminus and for fragments after processing) of higher eukaryotes (including their viruses) and fungi. The PTS1 signal predictor finds proteins with a C-terminus appropriate for peroxisomal import (for metazoa and fungi). Guidelines for application of the three WWW-based predictors (http://mendel.imp.univie.ac.at/) and for the interpretation of their output are described.

Acyltransferases↗
PubMed1988

Isolation and characterization of a corticotropin-releasing hormone-like peptide from human placenta.

Immunoreactive CRH was detected in extracts of human term placentae [5.2 +/- 0.8 (+/- SE) pmol/g wet wt; n = 9]. Molecular sieve chromatography revealed three size classes of immunoreactive CRH. The major species eluted with the Kav of synthetic rat CRH; the minor species had apparent mol wt (MW) of 18,000 and 8,000. A placental CRH-(1-41)-sized peptide was isolated by fractional acetone precipitation, molecular sieve chromatography, and sequential reverse phase high performance liquid chromatography steps. This peptide had the same chromatographic behavior as did rat CRH in all high performance liquid chromatographic isolation steps as well as the same UV absorbance to immunoreactive CRH ratio after the final purification step. Purified placental CRH stimulated ACTH release from anterior pituitary tissue in a dose-dependent manner and was equipotent with synthetic rat CRH. Partial sequencing indicated that 32 amino acids of this peptide are identical to those of rat and human CRH (sequence deduced from genomic sequence), and comparative peptide mapping with rat CRH provided further evidence that the placental CRH-like peptide is very homologous if not identical to CRH. The high mol wt placental CRH fractions also were partially purified by acetone precipitation, immune affinity chromatography, and gel filtration. Neither of these materials [big form (MW, 18,000) or intermediate form (MWr, 8,000)] stimulated ACTH release from rat pituitary tissue in vitro. Limited trypsin digestion of the highest MW CRH, followed by gel filtration analysis, resulted in conversion to the smaller [8,000 MW-sized and CRH-(1-41)-sized] forms. The detection of a CRH-like peptide in placenta together with our previous demonstration of plasma immunoreactive CRH in pregnant women suggest that the placenta synthesizes and secretes CRH into the maternal circulation.

Amino Acid Sequence↗
PubMed2006

Monthly number of newborns and environmental physical activity.

UNLABELLED: In the last decades many studies have demonstrated the cosmophysical influences on human homeostasis. The aim of the study was to explore links between environmental physical activity--solar, geomagnetic, cosmic ray--and monthly number of newborns in general and, separately, for each gender. MATERIAL AND METHODS: The distribution of newborns' number (n=286,963) over 96 months in the Republic of Lithuania from 1995 to 2002 was compared with the monthly cosmophysical indices nine months before the month of delivery. For the comparison of gender ratio, other 52,289 newborns at the same time were studied in a big Israeli hospital. Pearson's correlation coefficients and their probabilities between the newborns' number and cosmophysical indices were established. RESULTS: A strong and significant inverse correlation of monthly newborns' number with monthly solar activity indices (r=-0.72, p<0.0001) and similar, but positive, with cosmic ray activity was shown (r=0.67, p<0.0001). CONCLUSIONS: The monthly number of newborns of both genders is strongly and significantly related to the level of monthly cosmic ray and, inverse, to solar activity indices nine months before the month of delivery. Geomagnetic activity was not significantly related to the monthly number of newborns. The subject and mechanism of these relationships needs further investigation.

Birth Rate↗
PubMedDate not supplied

A fluorogenic assay for endothelin-converting enzyme.

The potent vasoconstrictor peptide endothelin-1 is proposed to arise via proteolysis of a precursor molecule, "big endothelin," at a unique cleavage site. To aid in the identification of a putative endothelin-converting enzyme, we have developed an assay that mimics the relevant cleavage reaction. The assay takes advantage of the intramolecular fluorescence energy transfer between the scissile-site tryptophan and a dansyl moiety present in the same synthetic substrate. Cleavage of the peptide chain separates the fluorophore and quencher, resulting in an increase in fluorescence. The assay has been validated using chymotrypsin as a model protease and has been employed in the identification of novel endothelin-converting enzyme activities.

Amino Acid Sequence↗
PubMed2004

Susceptibility of rats to mammary gland carcinogenesis by the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) varies with age and is associated with the induction of differential gene expression.

2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine found in cooked meat, induces mammary gland cancer when administered to adolescent female rats (43-day-old). In contrast, mature virgin rats (150-day-old) were resistant to mammary carcinogenesis by PhIP. To explore the possible mechanisms for the age-related differences in susceptibility, PhIP-DNA adduct levels, mutations, and gene expression were examined in glands from 43-day and 150-day-old PhIP-treated rats. In rats of different ages, PhIP-DNA adduct levels detected by the (32)P-post-labeling assay and mutant frequency measured in the lacI reporter gene of Big Blue rats were not statistically different. PhIP-DNA adduct levels, adduct removal, and mutation burden did not appear to account for the variation in carcinogen susceptibility with age. However, cDNA microarray analysis indicated that PhIP treatment differentially altered the profile of gene expression in glands from 43-day-old and 150-day-old rats. In 150-day-old rats, PhIP enhanced the expression of genes associated with differentiation (eg, beta-casein, kappa-casein, whey acidic protein) and induced morphological differentiation. In contrast, in 43-day-old rats, PhIP inhibited the expression of differentiation genes and enhanced cellular proliferation. From 3 hours to 6 weeks after PhIP dosing, the number of clones showing altered expression declined more than 50% in 150-day-old rats but increased fourfold in 43-day-old rats (29 clones versus 194, respectively) suggesting that PhIP induced a cascade of gene expression alterations only in susceptible rats. Genes showing altered expression specifically in 43-day-old rats included the Ras superfamily genes and genes associated with protein synthesis/degradation (lysosomal proteins, heat shock proteins, and proteasomes). The microarray data support the notion that the mechanism of age-dependent susceptibility to mammary gland cancer is largely associated with differential responses in expression of genes involved in cellular differentiation, proliferation, and protein homeostasis.

Aging↗
PubMed2003

Too small for a seatbelt: predictors of booster seat use by child passengers.

OBJECTIVES: Motor vehicle injury is the leading cause of injury death for children 4 to 8 years of age. Although booster seat use in this age group substantially reduces the risk of injury, most children are currently restrained by seatbelts designed for adults. The objective of this study was to measure booster seat use directly, determine factors predictive of proper child restraint, and assess parental reasons for booster use and nonuse. METHODS: We conducted a cross-sectional, observational study in Seattle, Washington, Spokane, Washington, and Portland, Oregon, from February to April 2000. Drivers were surveyed in their vehicles after picking up children from schools and child care centers. Trained observers recorded child age, weight, and height and directly observed restraint use. Observed restraint use was compared with the recommended restraint method based on the child's weight and age. Data were analyzed using multivariate logistic regression, adjusted for clustering by car and site. RESULTS: We observed 2880 children traveling in cars, 1539 of whom were eligible for booster seat use. Eighty-eight percent of drivers agreed to respond to our survey. Only 16.5% of children for whom a booster seat was recommended were properly restrained, compared with 80% of younger children for whom a child safety seat was recommended and 55% of children for whom an adult seatbelt was recommended. Relative to a 4-year-old booster-eligible child, a 6-year-old was only half as likely to use a booster seat (odds ratio [OR]: 0.47; 95% confidence interval [CI]: 0.31-0.71) and an 8-year-old almost never used a booster seat (OR: 0.04; 95% CI: 0.01-0.19). Booster use was more common when the driver wore a seatbelt (OR: 3.1; 95% CI: 1.8-5.4). Parents whose children were using booster seat cited "safety" (61%) and "child comfort and visibility" (12%) as their primary concerns. When a child was not using a booster seat, parents most often believed that their child was "too big for a car seat" (56%), reported that the seat was in another vehicle (9%), or stated that they "had not heard" of booster seats (8%). CONCLUSIONS: Many parents still incorrectly believe that children are safe in a seatbelt and have outgrown the need for a car seat. These results demonstrate the need for public education campaigns to educate parents about booster seat use.

Automobile Driving↗
PubMed2003

PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease.

Peptidylarginine deiminase (PAD, EC 3.5.3.15) enzymes catalyze the conversion of protein-bound arginine to citrulline. This post-translational modification may have a big impact on the structure and function of the target protein. In this review, we will discuss the effects of citrullination and its involvement in several human diseases, including rheumatoid arthritis and multiple sclerosis. So far, four isotypes of PAD have been described in mammals. We describe the existence of PAD in non-mammalian vertebrates and the existence of a fifth mammalian PAD. In addition, tissue-specific expression, genomic organization and evolutionary conservation of the different PAD isotypes will be discussed in detail. This article contains supplementary material which may be viewed at the BioEssays website at http://www.interscience.wiley.com/jpages/0265-9247/suppmat/2003/25/v25.1106.html.

Amino Acid Sequence↗
PubMed2005

Allergenic proteins in soybean: processing and reduction of P34 allergenicity.

Soybean ranks among the "big 8" of the most allergenic foods, and with increasing consumption of soybean products, the incidence of soy-caused allergies is expected to escalate. Soybean and its derivatives have become ubiquitous in vegetarian and many meat-based food products, and as a result, dietary avoidance has become difficult. However, soybeans can be manipulated in a variety of ways to alter their allergenicity. Several studies have focused on reducing the allergenicity of soybeans by changing the structure of the immunodominant allergen P34 using food processing, agronomic, or genetic manipulation techniques. A review of the literature pertaining to these studies is presented here.

Allergens↗
PubMed2001

[Character of the big-city municipal waste water bacterial contamination and assessment of its elimination degree as a result of biological treatment process].

The highest possible effectiveness of sewage treatment is of particular significance when the sewage is discharged into surface waters used for recreational purposes. The Gulf of Gdańsk, with its much frequented beaches along the shore, is the disposal reservoir for the wastewater from two large biological treatment plants collecting the sewage from Gdańsk and Gdynia. The purpose of this work was to perform bacteriological examination of the communal sewage from these two large agglomerations before and after their biological treatment. On that basis the degree of reduction of bacteriological contamination of sewage as a result of biological treatment was determined. The examination included determining of coliform and faecal coliform bacteria MPN (Most Probably Number), faecal streptococci index as well as Salmonella sp. and coagulase positive staphylococci. An extremely high level of bacterial contamination of raw sewage was found amounting from 9.3 x 10(18) (Gdańsk) to 1.8 x 10(20) (Gdynia) faecal coliform bacteria in 100 cm3 of sewage and respectively from 5.6 x 10(5) to 1.8 x 10(6) faecal streptococci in 100 cm3 of sewage on average. It was also observed that the effectiveness of the sewage treatment plants is so high that it assures the level of reduction of bacterial contamination within the limits of 92% for staphylococci and streptococci to 99.999% for coliform bacteria. It was also pointed out that despite a very effective work of sewage treatment stations the level of contamination of treated sewage discharged into the surface waters is often high. Hence the necessity of verification of data concerning level of sewage contamination which are usually assumed in the project documentation.

Bacteria↗
PubMed2004

Possible contributions of reactive oxygen species and mitogen-activated protein kinase to renal injury in aldosterone/salt-induced hypertensive rats.

Studies were performed to test the hypothesis that reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) contribute to the pathogenesis of aldosterone/salt-induced renal injury. Rats were given 1% NaCl to drink and were treated with one of the following combinations for 6 weeks: vehicle (0.5% ethanol, SC, n=6); aldosterone (0.75 microg/H, SC, n=8); aldosterone plus a selective mineralocorticoid receptor antagonist; eplerenone (0.125% in chow, n=8); aldosterone plus an antioxidant; and tempol (3 mmol/L in drinking solution, n=8). The activities of MAPKs, including extracellular signal-regulated kinases (ERK)1/2, c-Jun-NH2-terminal kinases (JNK), p38MAPK, and big-MAPK-1 (BMK1) in renal cortical tissues were measured by Western blot analysis. Aldosterone-infused rats showed higher systolic blood pressure (165+/-5 mm Hg) and urinary excretion of protein (106+/-24 mg/d) than vehicle-infused rats (118+/-3 mm Hg and 10+/-3 mg/d). Renal cortical mRNA expression of p22phox, Nox-4, and gp91phox, measured by real-time polymerase chain reaction, was increased in aldosterone-infused rats by 2.3, 4.3, and 3.0-fold, respectively. Thiobarbituric acid-reactive substances (TBARS) content in renal cortex was also higher in aldosterone (0.23+/-0.02) than vehicle-infused rats (0.09+/-0.01 nmol/mg protein). ERK1/2, JNK, and BMK1 activities were significantly elevated in aldosterone-infused rats by 3.3, 2.3, and 3.0-fold, respectively, whereas p38MAPK activity was not changed. Concurrent administration of eplerenone or tempol to aldosterone-infused rats prevented the development of hypertension (127+/-2 and 125+/-5 mm Hg), and the elevations of urinary excretion of protein (10+/-2 and 9+/-2 mg/day) or TBARS contents (0.08+/-0.01 and 0.11+/-0.01 nmol/mg protein). Furthermore, eplerenone and tempol treatments normalized the activities of ERK1/2, JNK, and BMK1. These data suggest that ROS and MAPK play a role in the progression of renal injury induced by chronic elevations in aldosterone.

Aldosterone↗
PubMed2005

Development and validation of a simple and direct ELISA method for the determination of conjugated (glucuronide) and non-conjugated testosterone excretion in urine.

BACKGROUND: Several methods are now available to estimate urinary testosterone levels that can only be performed in established big laboratories using GC/MS techniques. In clinical practice or for research projects, an inexpensive method that does not require skilled technicians would be useful. A simple, rapid and accurate ELISA method has been developed and applied in our laboratory to measure urinary non-conjugated and total testosterone. METHODS: High affinity anti-testosterone antibody and HRP-Donkey anti-sheep IgG (Horse Radish Peroxidase) as enzyme tracer were used to develop the ELISA method. The assay was evaluated for specificity, sensitivity, parallelism, accuracy and imprecision by the established methods on samples obtained from healthy volunteers. The results from the direct ELISA were compared to those after enzyme hydrolysis plus solvent extraction and HPLC or commercial kits. RESULTS: A satisfactory standard curve for the direct testosterone ELISA has been developed with good sensitivity. Cross-reactivity values of anti-testosterone antibody with major interfering steroids were minimal except for testosterone-3-glucuronide (58.8%). The validity of urinary testosterone assay was confirmed by the good correlation between the results obtained by the direct ELISA and those after enzyme hydrolysis and solvent extraction (Y = 0.987X + 0.398, R2 = 0.97). Accuracy studies, parallelism and imprecision data were determined and all found to be satisfactory. Urinary testosterone excretion values obtained by our direct ELISA from healthy volunteers were generally in agreement with those published by other workers. Male urinary total testosterone excretion (non-conjugated and testosterone glucuronide) ranged from 177.9 to 865.3 nmol/day, which was about 3-6 times more than the range for women urinary testosterone excretion (34.5-308.8 nmol/day). CONCLUSION: A direct, reliable, easy to perform, sensitive and highly specific ELISA type assay for the measurement of total testosterone in urine samples (conjugated and non-conjugated) has been developed. The novel features of the assay are that it does not require an initial extraction step or involve time consuming procedures such as chromatography. A simple method has also been developed to measure non-conjugated urinary testosterone excretion after solvent extraction alone.

Adult↗
PubMed1998

Parent personality traits and psychopathology associated with antisocial behaviors in childhood attention-deficit hyperactivity disorder.

Although a role for family and parent factors in the development of behavioral problems in childhood is often acknowledged, the roles of specific parental characteristics in relation to specific child actions need further elucidation. We studied parental "Big Five" personality traits and psychiatric diagnoses in relation to their children's antisocial diagnoses and naturalistically observed antisocial behaviors, in boys with and without the diagnosis of Attention-Deficit Hyperactivity Disorder (ADHD). First, regardless of comorbid antisocial diagnosis, boys with ADHD, more often than comparison boys, had mothers with a major depressive episode and/or marked anxiety symptoms in the past year, and fathers with a childhood history of ADHD. Second, compared to the nondiagnosed group, boys with comorbid ADHD + Oppositional Defiant or Conduct Disorder (ODD/CD) had fathers with lower Agreeableness, higher Neuroticism, and more likelihood of having Generalized Anxiety Disorder. Third, regarding linkages between parental characteristics and child externalizing behaviors, higher rates of child overt antisocial behaviors observed in a naturalistic summer program were associated primarily with maternal characteristics, including higher Neuroticism, lower Conscientiousness, presence of Major Depression, and absence of Generalized Anxiety Disorder. The association of maternal Neuroticism with child aggression was larger in the ADHD than in the comparison group. In contrast, higher rates of observed child covert antisocial behaviors were associated solely with paternal characteristics, including history of substance abuse and higher Openness. Results provide external validation in parent data for a distinction between overt and covert antisocial behaviors and support inclusion of parent personality traits in family studies. The interaction of maternal Neuroticism and child ADHD in predicting child aggression is interpreted in regard to a conceptualization of child by parent "fit."

Adult↗
PubMed2006

Monitoring water quality and quantity of national watersheds in Turkey.

National data from the hydrological network for 38 rivers out of 25 watersheds were used to detect spatial and temporal trends in water quality and quantity characteristics between 1995 and 2002. Assessment of water quality and quantity included flow rate, water temperature, pH, electrical conductivity, sodium adsorption rate, Na, K, Ca+Mg, CO(3), HCO(3), Cl, SO(4), and boron. Among the major ions assessed on a watershed basis, Turkish river waters are relatively high in Ca+Mg, Na and HCO(3), and low in K and CO(3). The watersheds in Turkey experienced a general trend of 16% decrease in flow rates between 1995 and 2002 at a mean annual rate of about 4 m(3) s(-1), with a considerable spatial variation. Similarly, there appeared to be an increasing trend in river water temperature, at a mean annual rate of about 0.2 degrees C. A substantial proportion of watersheds experienced an increase in pH, in particular, after 1997, with a maximum increase from 8.1 to 8.4 observed in Euphrates (P < 0.01). Kendall's tau test revealed increasing trends of EC and SAR concentrations that exceeded existing standards, particularly, in the Meriç, Kizilirmak and Big Menderes watersheds where intensive agricultural activities take place. Such continued levels may threaten biotic integrity and both drinking and irrigation water quality of rivers. Best multiple linear regression (MLR) models constructed both annually and monthly differed in R (2) values in accounting for variations of pH and water temperature only. The findings of the study can provide a useful assessment of controls over water quality and quantity and assist in devising integrated and sustainable management practices for watersheds at the regional scale in Turkey.

Seasons↗
PubMed1997

Comparative assessment of peripheral sympathetic function by postural vasoconstriction arteriolar reflex and sympathetic skin response in NIDDM patients.

PURPOSE: The aim of the study was to compare peripheral sympathetic adrenergic and cholinergic nerve function in NIDDM (non-insulin-dependent diabetes mellitus) patients with various degrees of diabetic neuropathy and neuropathic foot ulceration. The parameters used were postural vasoconstriction arteriolar reflex (VAR) and sympathetic skin response (SSR), respectively. PATIENTS AND METHODS: Forty-seven NIDDM patients were studied. No patients had clinically significant peripheral vascular disease. They were divided according to peripheral somatic neuropathy, assessed by clinical score and vibration perception threshold (VPT). Twenty-two patients showed no significant evidence of peripheral neuropathy and normal VPT (DN-); 15 had signs and symptoms of neuropathy and VPT alteration (DN+); 10 had diabetic neuropathy and foot ulceration (DNU). Twenty-two normal subjects were also examined as a control group. Resting arteriovenous shunt skin blood flow, measured using laser-Doppler flowmetry, and the VAR of the big toe on lowering the foot were studied. Sympathetic skin response was assessed by an EMG apparatus. Autonomic function was also investigated by using standard cardiovascular reflex tests. RESULTS: Resting blood flow values were similar in the three NIDDM groups and in the control group. VAR to foot lowering was significantly impaired in all NIDDM groups by comparison with controls (72.8 +/- 2.1%, mean +/- SEM), this impairment being progressively more pronounced in DN- (58.8 +/- 2.3%, P < 0.001), DN+ (33.3 +/- 3.0%, P < 0.001 versus DN-) and DNU (8.6 +/- 2.7%, P < 0.001 versus DN+). Sympathetic skin response was assessed in 28 patients and was significantly impaired in DN-compared with the control group (2.53 +/- 0.04 versus 2.71 +/- 0.04 log mcV, P < 0.01). This impairment was severe in the DNU compared with the DN+ group (1.36 +/- 0.05 versus 2.26 +/- 0.04 log mcV, P < 0.005). A positive correlation was found between VAR values and SSR (P < 0.001), and these measurements were also closely correlated with several parameters of central autonomic and somatic neuropathy. CONCLUSION: These results indicate that peripheral sympathetic adrenergic and cholinergic fibers simultaneously undergo early alterations in diabetic patients, even when there is no clinical neuropathy. Our data also show almost complete abolition of peripheral sympathetic activity in NIDDM patients with foot ulceration.

Blood Flow Velocity↗
PubMed1996

Mutations in the founder of the MIP gene family underlie cataract development in the mouse.

The major intrinsic protein (MIP) of the vertebrate eye lens is the first identified member of a sequence-related family of cell-membrane proteins that appears to have evolved by gene duplication. Several members of the MIP family transport water (aquaporins), glycerol and other small molecules in microbial, plant and animal cells. Mutations in two aquaporin homologues of MIP underlie an autosomal recessive form of nephrogenic diabetes insipidus and absence of the Colton blood group antigens in humans, whereas, mutation of a third MIP-like gene underlies 'big brain' development in Drosophila. Here we show that distinct mutations in the murine Mip gene underlie one form of autosomal dominant cataract in the mouse. The cataract Fraser mutation is a transposon-induced splicing error that substitutes a long terminal repeat sequence for the carboxy-terminus of MIP. The lens opacity mutation is an amino-acid substitution that inhibits targeting of MIP to the cell-membrane. These allelic cataract mutations provide the first direct evidence that MIP plays a crucial role in the development of a transparent eye lens.

Amino Acid Sequence↗