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Biomedical subjects

M Barr

Publications and source records attributed to M Barr.

At least 19 recordsLinked to original sources
PubMed1999

Aphallia as part of urorectal septum malformation sequence in an infant of a diabetic mother.

A male patient with aphallia, anal stenosis, tetralogy of Fallot, multiple vertebral anomalies including sacral agenesis and central nervous system (CNS) malformations was born after a pregnancy complicated by poorly controlled maternal diabetes. Aphallia is an extremely rare abnormality and can be part of the urorectal septum malformation sequence (URSMS). While aphallia has not been reported in infants of diabetic mothers, urogenital malformations are known to occur with increased frequency. Two female products of pregnancies complicated by diabetes presented with multiple malformations including anal atresia and recto-vaginal fistula consistent with the diagnosis of URSMS. The three patients share CNS, cardiac, and vertebral anomalies, abnormalities secondary to abnormal blastogenesis and characteristic of diabetic embryopathy. URSMS is also caused by abnormal blastogenesis. Therefore, this particular malformation should be viewed in the context of the multiple blastogenetic abnormalities in the cases reported here. The overlap of findings of URSMS in our cases with other abnormalities of blastogenesis, such as VATER association or sacral agenesis is not surprising, as these associations are known to lack clear diagnostic boundaries.

Central Nervous System↗
PubMed1998

Correlates of prenatal visceromegaly.

Aside from recognized overgrowth syndromes, instances of visceromegaly are not uncommon at perinatal autopsy. The database of the University of Michigan Teratology Unit was screened for individual viscera exceeding the 90th centile for body and brain weight standards. The data were stratified for several maternal (hypertension, diabetes, obesity), gestational (chorioamnionitis, oligohydramnios, amniorrhaea, polyhydramnios), and fetal (body wall defect, cardiac malformation, renal malformation, diaphragmatic hernia, nonimmune hydrops, twin transfusion syndrome) characteristics and tested for statistically significant excessive numbers of heavy organs. The most striking associations were heavy adrenal glands and liver with chorioamnionitis, heavy heart with polyhydramnios and in the twin transfusion syndrome, and heavy heart and liver with nonimmune hydrops. Excessive brain weight for body weight had a number of correlations, each most likely reflecting growth restriction with sparing of brain growth.

Autopsy↗
PubMed1998

Renal tubular dysgenesis in twins.

In a fetal autopsy series, we have explored the occurrence of renal tubular dysgenesis in twins. Renal tubular dysgenesis was found exclusively among those monozygotic twins with evidence of twin transfusion syndrome, particularly in those donor twins with oligohydramnios and growth restriction. We infer that hypotension in the donor twin of the twin transfusion syndrome pair is responsible for the failure of proximal convoluted tubule differentiation, and the disturbance of renal function is manifested as oligohydramnios prenatally, and either oliguria or tubular dysfunction postnatally.

Anthropometry↗
PubMed1998

Neonatal thymectomy: does it affect immune function?

OBJECTIVE: The purpose of this study was to determine whether thymectomy in the newborn has a negative effect on immune function. METHODS: Twenty-five neonates (<30 days) who had thymectomy at congenital heart repair were prospectively studied to determine immune function. The percentage of T-cell subtypes including CD3 (all T cells), CD4 (helper T cells), and CD8 (suppressor T cells) was determined. In six patients, further testing of CD4 cells was done to determine whether they were newly formed, recent thymic emigrants (CD4, CD45, and RA+), or older educated lymphocytes (CD4, CD45, and RO+). Response to the mitogen phytohemagglutinin and to tetanus toxoid were determined, as were antibody titers to tetanus. Samples were drawn before the thymectomy, at approximately 3 months after immunization and at 1 year. Ten age-matched control patients were tested. At follow-up, parents were asked about infections. RESULTS: Prethymectomy T-cell subsets were all normal and comparable to controls. At 12 months, the percent of CD3 was significantly less than in the control group (48% +/- 3% versus 64% +/- 2% [mean +/- standard error of the mean]; p < 0.01) as was CD4 (31% +/- 2% versus 46% +/- 2% [mean +/- standard error of the mean]; p = < 0.01). CD8 did not drop. Surprisingly, the percent of CD4 that were recent thymic emigrants did not decrease significantly (50% +/- 8% versus 60% +/- 6% [mean +/- standard error of the mean]; p = not significant). Lymphocyte blastogenesis to phytohemagglutinin and tetanus toxoid and antibody to tetanus were all normal at 12 months. No patient required readmission for infection, and there were the expected number of minor infectious events (median 3; 95% confidence interval 1,4). CONCLUSION: Thymectomy in neonates results in a modest but significant decrease in T-lymphocyte levels, but there is no compromise in immune function.

Antigens, CD↗
PubMed1997

Pitfall: anomalous umbilical vein and absent ductus venosus in association with right congenital diaphragmatic hernia.

Congenital abnormalities of the umbilical venous system are rare. A case of fatal right congenital diaphragmatic hernia (CDH) in association with an anomalous umbilical vein bypassing the liver and directly entering the right atrium is presented. The ductus venosus was absent. Although much of the liver was within the right hemithorax, radiographs showed an apparently normal umbilical venous catheter (UVC) course, suggesting a normally positioned liver and mitigating against the diagnosis of CDH. Aberrant umbilical drainage, yielding a falsely normal appearing UVC course, may delay the diagnosis of CDH.

Adult↗
PubMed1997

Multiple regulatory domains on the Byr2 protein kinase.

Byr2 protein kinase, a homolog of mammalian mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEKK) and Saccharomyces cerevisiae STE11, is required for pheromone-induced sexual differentiation in the fission yeast Schizosaccharomyces pombe. Byr2 functions downstream of Ste4, Ras1, and the membrane-associated receptor-coupled heterotrimeric G-protein alpha subunit, Gpa1. Byr2 has a distinctive N-terminal kinase regulatory domain and a characteristic C-terminal kinase catalytic domain. Ste4 and Ras1 interact with the regulatory domain of Byr2 directly. Here, we define the domains of Byr2 that bind Ste4 and Ras1 and show that the Byr2 regulatory domain binds to the catalytic domain in the two-hybrid system. Using Byr2 mutants, we demonstrate that these direct physical interactions are all required for proper signaling. In particular, the physical association between Byr2 regulatory and catalytic domains appears to result in autoinhibition, the loss of which results in kinase activation. Furthermore, we provide evidence that Shk1, the S. pombe homolog of the STE20 protein kinase, can directly antagonize the Byr2 intramolecular interaction, possibly by phosphorylating Byr2.

Cloning, Molecular↗
PubMed1996

Long-term acute care: meeting the strategic needs for outcomes information.

Nursing home quality improvement has historically relied on annual surveys conducted by state agencies for its impetus. Such reviews play an important role for assuring that minimum standards are met. However, we need to search for incentives that will make it in the best interest of nursing homes to improve beyond the minimum. This article explores incentives that may play that role.

Cost-Benefit Analysis↗
PubMed1996

Persistence of partial molar placenta and severe preeclampsia after selective termination in a twin pregnancy.

BACKGROUND: Triploid molar pregnancies are usually managed by evacuation of the uterine contents. CASE: A 25-year-old woman had a clomiphene citrate-induced twin pregnancy. Ultrasound scan at 13 weeks revealed one anomalous twin. Cytogenetic analysis revealed a karyotype of 69, XXY and a normal other twin. In an attempt to salvage the normal fetus, selective termination was successfully performed at 15 weeks by intracardiac potassium chloride injection. However, the placenta continued to grow and severe preeclampsia developed at 19 weeks, requiring pregnancy termination. CONCLUSION: Selective termination of a triploid twin does not guarantee resolution of molar growth and sequelae of the mole; severe preeclampsia can still develop.

Adult↗
PubMed1995

Craniomicromelic syndrome: a newly recognized lethal condition with craniosynostosis, distinct facial anomalies, short limbs, and intrauterine growth retardation.

We report on two sisters with an unusual form of craniosynostosis, protruding nasal spine, micrognathia, short limbs, lung hypoplasia, absent or hypoplastic gallbladder, short intestine with ileal distention, hypoplastic uterus, and intrauterine growth retardation. This combination of defects appears to be a newly recognized and probably autosomal recessive disorder.

Abnormalities, Multiple↗
PubMed1995

Combining humerus and femur length for improved ultrasonographic identification of pregnancies at increased risk for trisomy 21.

OBJECTIVE: Our purpose was to evaluate the value of the combination of femur and humerus length measurements in ultrasonographic screening for trisomy 21. STUDY DESIGN: Direct necropsy measurements were analyzed on 703 midgestational fetuses (641 normal, 62 with trisomy 21). The (leg+arm length)/foot length ratio was found to be significantly shortened for fetuses with trisomy 21. On the basis of necropsy data 576 midgestational pregnancies were evaluated ultrasonographically for (femur+humerus length)/foot length ratio to identify fetuses at increased risk for trisomy 21. RESULTS: An ultrasonographic (femur+humerus length)/foot length ratio < or = 1.75 gave a 15.3 odds ratio risk for trisomy 21 in our high-risk population and correctly identified 53% of fetuses with trisomy 21, with a false-positive rate of 7%. In addition, the use of this ratio eliminates the need for gestational age-corrected nomograms and complicated calculations in ultrasonographic screening. CONCLUSION: The (femur+humerus length)/foot length ratio may be an additional effective ultrasonographic marker for identification of fetuses at increased risk for trisomy 21.

Anthropometry↗
PubMed1995

Log-linear allometry of fetal craniofacial growth in Down's syndrome.

Trisomy 21 develops as a result of nondisjunction of two homologous chromosomes during either the first or second meiotic division. One of the more important consequences of these genetic alterations is the predictable, although variable disturbance in the architecture of the craniofacial region [1]. Postnatal craniofacial morphology has been extensively studied in Down's syndrome (DS). However, little information is available on human prenatal development of the head and face in such patients. The time at which changes in craniofacial phenotype first emerge in Down's syndrome fetuses and at which physical growth begins to diverge from normal is unknown. To explore these questions, we compared prenatal craniofacial growth in 50 Down's syndrome fetuses with that of 555 fetuses judged to be "typical for body weight and age" using the method of log-linear allometry [2].

Cephalometry↗
PubMed1995

Log-linear allometry of normal fetal craniofacial growth.

Normative data on human craniofacial growth during the fetal period and important to provide a broader perspective on normal morphogenesis as well as to serve as reference for analyzing craniofacial syndromes in which growth has gone awry. Over a 19-year period, the Teratology Unit at the University of Michigan Medical Center has collected data on 2,568 legally donated fetuses that have undergone necropsy examination at various gestational ages. From previous analyses, 609 of the total fetal population (25%) were designated as typical for age or body weight on the basis of normal morphology, absence of maceration, and general growth symmetry. Of the 609 fetuses reviewed, 54 were excluded secondary to incomplete data. The remaining 555 constitute the basis of this study. Seven craniofacial measurements were recorded, including head circumference (HC), brain weight, inner canthal and outer canthal distances, and distances from nasion to menton, outer canthus to tragus and auditory meatus to vertex. Statistical analysis was carried out using the single-factor allometric model of Sewall Wright. Size was estimated as the first unstandardized principal component of the logarithms of lengths and of cube roots of weights, and then allometry was expressed in the regressions of each log variable on size. Significant allometry was found as were significant differences in errors about the allometric relation, but no evidence for more than a single factor or of "nonlinearity" in the regression curves was noted. Although there were differences of specific allometric coefficients between the various measurements (i.e., the slope of the curve for IC was significantly smaller than the slope of the curve generated for HC), these specific growth rates remain in relatively strict proportion to one another from early in gestation (body weight, 54.2 gm) to later in gestation (body weight, 1,000 gm).

Cephalometry↗
PubMed1994

Cooperative interaction of S. pombe proteins required for mating and morphogenesis.

We isolated two S. pombe genes, scd1 and scd2, that are required for normal morphology and mating. scd1 and scd2 are homologous to CDC24 and BEM1, respectively, of S. cerevisiae. Epistasis analyses indicate that scd2 and ras1 converge upon scd1, which, in turn, interacts with cdc42sp, a RHO-like GTPase. Studies with the yeast two-hybrid system indicate that scd2 forms complexes with both scd1 and cdc42sp. Furthermore, biochemical studies indicate that the interaction between scd1 and scd2 is direct. The yeast two-hybrid data further suggest that scd1, scd2, cdc42sp, and ras1, in its GTP-bound state, act cooperatively to form a protein complex.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Complexes between STE5 and components of the pheromone-responsive mitogen-activated protein kinase module.

We present genetic evidence for complex formation of STE5 and the STE11, STE7, and FUS3 protein kinases, the pheromone-responsive mitogen-activated protein kinase module of Saccharomyces cerevisiae. Interaction between STE5 and STE11 is not dependent on STE7, and interaction between STE5 and STE7 does not require STE11. The N-terminal regulatory domain of STE11 is both necessary and sufficient for interaction with STE5. Interaction between STE7 and STE11 is bridged by STE5, suggesting the formation of a multiprotein complex. We also demonstrate biochemical interaction between STE5 and STE11 by using a combination of bacterially expressed fusion proteins and extracts prepared from yeast. Our results suggest that STE5 is a scaffolding protein that facilitates interactions between components of the pheromone-responsive mitogen-activated protein kinase module. We further propose that such scaffolding proteins serve to inhibit cross-talk between functionally unrelated mitogen-activated protein kinase modules within the same cell.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Human fetal somatic and visceral morphometrics.

Because of the increasing prenatal use of high-resolution ultrasonography to assess fetal growth and because growth aberration is one of the principal manifestations of abnormal intrauterine development, a more precise definition of normal growth is desirable. Our data set from autopsies of fetuses/neonates (50-4,000 g), collected with systematic attention to precision of measurement, is analyzed and presented. Previous computations of fetal growth curves appear to overstate the variation about the mean. Through the identification and exclusion of outliers and the use of appropriate curve fitting techniques, the problem of overestimation of variation about the mean has been largely eliminated. The new growth standards we present can be used to assess aberration from proportional growth and correlate it with gestational circumstances and particular morphological features of the fetus.

Congenital Abnormalities↗