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Biomedical subjects

R L Johnson

Publications and source records attributed to R L Johnson.

At least 73 records · Page 4Linked to original sources
PubMed1998

Control of dorsoventral somite patterning by Wnt-1 and beta-catenin.

In vertebrates, the dorsoventral patterning of somitic mesoderm is controlled by factors expressed in adjacent tissues. The ventral neural tube and the notochord function to promote the formation of the sclerotome, a ventral somite derivative, while the dorsal neural tube and the surface ectoderm have been shown to direct somite cells to a dorsal dermomyotomal fate. A number of signaling molecules are expressed in these inducing tissues during times of active cell fate specification, including members of the Hedgehog, Wnt, and BMP families. However, with the exception of the ventral determinant Sonic hedgehog (Shh), the functions of these signaling molecules with respect to dorsoventral somite patterning have not been determined. Here we investigate the role of Wnt-1, a candidate dorsalizing factor, in the regulation of sclerotome and dermomyotome formation. When ectopically expressed in the presomitic mesoderm of chick embryos in ovo, Wnt-1 differentially affects the expression of dorsal and ventral markers. Specifically, ectopic Wnt-1 is able to completely repress ventral (sclerotomal) markers and to enhance and expand the expression of dorsal (dermomyotomal) markers. However, Wnt-1 appears to be unable to convert all somitic mesoderm to a dermomyotomal fate. Delivery of an activated form of beta-catenin to somitic mesoderm mimics the effects of Wnt-1, demonstrating that Wnt-1 likely acts directly on somitic mesoderm, and not through adjacent tissues via an indirect signal relay mechanism. Taken together, our results support a model for somite patterning where sclerotome formation is controlled by the antagonistic activities of Shh and Wnt signaling pathways.

Animals↗
PubMed1998

On the quantification of suckling intensity in primates.

The inhibitory effect that suckling has on the reproductive function of primate mothers varies as a function of the intensity with which they are suckled. Here we present an easily computed index of one parameter of suckling intensity, namely the temporal patterning of suckling bouts. High intensity suckling is characterized by frequent nursing bouts demarcated by short interbout intervals. Therefore, our suckling index is based on the brevity of observed interbout intervals, more specifically the proportion of such intervals that fail to exceed a criterion length. The index is an appropriate means of making interspecific comparisons of the development of infant suckling and is well suited for application to field data that include interbout intervals that were not observed in their entirety. To demonstrate its utility, we apply the index to field data collected on the suckling behavior of free-ranging rhesus monkey (Macaca mulatta) infants in India. In this context, we demonstrate that, in rhesus, between-infant differences in suckling intensity manifest themselves early in the postpartum period and contribute to between-female differences in the timing of first mating postpartum.

Animals↗
PubMed1998

Multiple calvarial defects in lmx1b mutant mice.

The vertebrate cranial vault, or calvaria, forms during embryonic development from cranial mesenchyme of multiple embryonic origins. Inductive interactions are thought to specify the number and location of the calvarial bones, including interactions between the neuroepithelium and cranial mesenchyme. An important feature of calvarial development is the local inhibition of osteogenic potential which occurs between specific bones and results in the formation of the cranial sutures. These sutures allow for postnatal growth of the skull to accommodate postnatal increase in brain size. The molecular genetic mechanisms responsible for the patterning of individual calvarial bones and for the specification of the number and location of sutures are poorly understood at the molecular genetic level. Here we report on the function and expression pattern of the LIM-homeodomain gene, lmx1b, during calvarial development. Lmx1b is expressed in the neuroepithelium underlying portions of the developing skull and in cranial mesenchyme which contributes to portions of the cranial vault. Lmx1b is essential for proper patterning and morphogenesis of the calvaria since the supraoccipital and interparietal bones of lmx1b mutant mice are either missing or severely reduced. Moreover, lmx1b mutant mice have severely abnormal sutures between the frontal, parietal, and interparietal bones. Our results indicate that lmx1b is required for multiple events in calvarial development and suggest possible genetic interaction with other genes known to regulate skull development and suture formation.

Animals↗
PubMed1998

A survey of lead-based paint abatement projects performed in public buildings in Erie and Crawford Counties, Pennsylvania, during the time period 1995-1997.

A survey of lead-based paint abatement projects in public buildings of Crawford and Erie Counties, Pennsylvania, was conducted during the time period January 1995 to March 1997. These survey results suggest that few lead abatement projects were performed during this time period. Projects that were performed commonly did not employ proper lead abatement practices as described by the U.S. Occupational Safety and Health Administration, U.S. Environmental Protection Agency, and U.S. Department of Housing and Urban Development. These data suggest that most contractors and public officials have misunderstandings of both environmental regulations and required procedures for safe and effective lead-based paint abatement.

Air Pollution, Indoor↗
PubMed1998

Acute functional consequences of left ventriculotomy.

BACKGROUND: Left ventriculotomies are sometimes used during intracardiac congenital defect repair. Acute changes in left ventricular function after longitudinal or apical ventriculotomy were assessed using dynamic pressure-dimensional data. METHODS: Ultrasonic dimension transducers along the major, minor, and septal free wall axes and micromanometers were placed in 24 piglets. Pressure-volume data were collected during caval occlusions at baseline and 60 minutes after warm cardiopulmonary bypass alone or with longitudinal ventriculotomy or apical left ventriculotomy. Hemodynamics, contractility, and contraction geometry were analyzed. RESULTS: Cardipulmonary bypass caused decreased compliance in all groups, with equally decreased preload and cardiac output. Heart rate increased, but ventriculotomy led to a significantly greater increase. Longitudinal ventriculotomy produced a greater loss of stroke volume and ejection fraction than apical ventriculotomy. Contractility assessed by the preload recruitable stroke work relationship showed no difference between groups; however, all groups showed a slight increase in unit myocardial power at 60 minutes. Axis fractional shortening revealed that the septal freewall is responsible for 50% of stroke volume and that this axis is significantly impaired after longitudinal ventriculotomy. CONCLUSION: Apical left ventriculotomy impairs the less important major axis only and is predicted to be better tolerated.

Animals↗
PubMed1998

Protection against MPTP treatment by an analog of Pro-Leu-Gly-NH2 (PLG, MIF-1)

3(R)-[(2(S)-Pyrrolidinyl-carbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA) is a peptidomimetic analog of Pro-Leu-Gly-NH2 (PLG or MIF-1) that has previously been demonstrated to be more potent and efficacious that MIF-1 in enhancing dopamine receptor activity. Given the ability of MIF-1 to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioning in C57 BL/6 mice, the present study was undertaken to evaluate the neuroprotective effect of PAOPA in this model. PAOPA was found to be more potent and efficacious that MIF-1 in sparing dopamine and its metabolite levels following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. Whether the enhanced neuroprotective effect of PAOPA is due to dopamine receptor stimulation, or a result of reduced oxidative stress through normalization of dopamine turnover, remains to be determined.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1998

Development of a short version of the Barriers Questionnaire.

Among the reasons that cancer pain is not controlled adequately are patient-related barriers. Patient beliefs that may contribute to poor outcome have been measured in previous research with the Barriers Questionnaire (BQ). The purpose of this study was to examine the internal consistency of a shortened version of the BQ. A sample of 217 outpatients with cancer completed a 17-item version of the scale. Factor analysis suggested two subscales, one reflecting beliefs about communication about pain and the other reflecting beliefs about the use of analgesics. Both subscales demonstrated adequate internal consistency. Beliefs did not differ between patients who had and those who had not experienced pain within the previous two weeks. Findings suggest the shortened BQ provides an internally consistent measure of two broad patient barriers to pain management.

Adolescent↗
PubMed1998

New players and puzzles in the Hedgehog signaling pathway.

Members of the Hedgehog (Hh) family of signaling proteins control cell fates and proliferation during animal development in part by regulating the transcription of specific genes. Depending on the tissue, Hh can act over long or short distances, to signal directly or by inducing secondary signals. Recent discoveries include new components of the pathway as well as novel regulatory mechanisms involving cholesterol, proteolysis, and the cytoskeleton. The role of Hh in carcinogenesis is underscored by the identification of mutations in several pathway components in skin and brain tumors.

Animals↗
PubMed1998

Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome.

The LIM-homeodomain protein Lmx1b plays a central role in dorso-ventral patterning of the vertebrate limb. Targeted disruption of Lmx1b results in skeletal defects including hypoplastic nails, absent patellae and a unique form of renal dysplasia (see accompanying manuscript by H. Chen et al.; ref. 2). These features are reminiscent of the dominantly inherited skeletal malformation nail patella syndrome (NPS). We show that LMX1B maps to the NPS locus and that three independent NPS patients carry de novo heterozygous mutations in this gene. Functional studies show that one of these mutations disrupts sequence-specific DNA binding, while the other two mutations result in premature termination of translation. These data demonstrate a unique role for LMX1B in renal development and in patterning of the skeletal system, and suggest that alteration of Lmx1b/LMX1B function in mice and humans results in similar phenotypes. Furthermore, we provide evidence for the first described mutations in a LIM-homeodomain protein which account for an inherited form of abnormal skeletal patterning and renal failure.

Amino Acid Sequence↗
PubMed1998

Limb and kidney defects in Lmx1b mutant mice suggest an involvement of LMX1B in human nail patella syndrome.

Dorsal-ventral limb patterning in vertebrates is thought to be controlled by the LIM-homeodomain protein Lmx1b which is expressed in a spatially and temporally restricted manner along the dorsal-ventral limb axis. Here we describe the phenotype resulting from targeted disruption of Lmx1b. Our results demonstrate that Lmx1b is essential for the specification of dorsal limb fates at both the zeugopodal and autopodal level with prominent phenotypes including an absence of nails and patellae. These features are similar to those present in a dominantly inherited human condition called nail patella syndrome (NPS), which also has renal involvement. Mouse Lmx1b maps to a region syntenic to that of the NPS gene, and kidneys of Lmx1b mutant mice exhibit pathological changes similar to that observed in NPS (refs 5,6). Our results demonstrate an essential function for Lmx1b in mouse limb and kidney development and suggest that NPS might result from mutations in the human LMX1B gene.

Animals↗
PubMed1998

Secondary conditions following spinal cord injury in a population-based sample.

This prospective study investigates the frequency of both medical and non-medical complications reported by the population based cohort of SCI survivors reported to the Colorado Spinal Cord Injury Early Notification System (ENS). Persons reported to the ENS between January 1 1986 and December 31 1993, representing the broad spectrum of all severities of spinal cord injury and potential complications, were solicited to participate in comprehensive follow-up interviews at their first, third and fifth year post injury. Hospitalizations of a week or longer were experienced by more than 10% of the participants at each of the three interview years. Similarly, the medical complications of spasticity or pain were reported by more than 25% of the participants, and pressure sores were reported by more than 10% at all three time periods. The chief non-medical complications (conditions) were financial concerns and transportation problems. Although these reported medical and non-medical complications present significant obstacles to be overcome, less than three percent of those surveyed at any of the time periods reported experiencing depression; and only 14% rated their quality of life as being poor.

Adolescent↗
PubMed1998

Identification of mutations in the human PATCHED gene in sporadic basal cell carcinomas and in patients with the basal cell nevus syndrome.

Mutations in PATCHED (PTC), the human homolog of the Drosophila patched gene, have been identified in most exons of the gene in patients with the basal cell nevus syndrome and in sporadic basal cell carcinomas. We have screened the 23 PTC exons for mutations using single strand conformation polymorphism analysis of DNA from 86 basal cell nevus syndrome probands, 26 sporadic basal cell carcinomas, and seven basal cell nevus syndrome-associated basal cell carcinomas. This screen identified mutations located in eight exons in 13 of the basal cell nevus syndrome patients and in three of the tumors. The most common mutations were frameshifts resulting in premature chain termination. These results provide further evidence for the crucial role of PTC as a tumor suppressor in human keratinocytes.

Amino Acid Substitution↗
PubMed1998

Carcinosarcoma of the parotid gland: report of a case with cytohistologic and immunohistochemical findings.

True malignant mixed tumors (carcinosarcomas) of salivary gland origin are exceedingly rare and demonstrate malignant epithelial and stromal components. We report a case of parotid gland carcinosarcoma that showed squamous cell carcinoma and malignant fibrous hystiocytoma without clinical or histologic evidence of a preexisting pleomorphic adenoma. This tumor consisted of 2 histologically different populations of cells without evidence of a common origin from the myoepithelial cell, which is the putative precursor cell of pleomorphic adenoma and its derived carcinosarcoma. In addition to supplementing the literature, this case report includes cytohistologic and immunohistochemical analyses that provide further insights into the variable histogenesis of this neoplasm and the distinction between de novo carcinosarcoma and carcinosarcoma originating from pleomorphic adenoma.

Aged↗
PubMed1997

Design, synthesis, and dopamine receptor modulating activity of diketopiperazine peptidomimetics of L-prolyl-L-leucylglycinamide.

The diketopiperazine "C5" conformational mimic has been incorporated into the L-prolyl-L-leucylglycinamide (PLG, 1) structure and into the bicyclic lactam PLG peptidomimetic structure 3 to give compounds 5 and 6, respectively. These analogues were designed to explore the idea that the N-terminal "C5" conformation, which was found in the crystal structure of 2 and which was mimicked in 4 by the diketopiperazine function, was a factor in the high potency of these two agents. Through the use of the [3H]spiroperidol/N-propylnorapomorphine (NPA) D2 receptor competitive binding assay, both 5 and 6 were found to increase the affinity of the dopamine receptor for agonists and both were found to increase the percentage of D2 receptors which existed in the high-affinity state. These effects were observed when Gpp(NH)p was either absent or present, and they were analogous to the effects observed previously for PLG and the PLG peptidomimetics 2 and 4. However, the potency seen with 5 and 6 was less than that seen for 2 and 4, suggesting that while the N-terminal "C5" conformation may play a role in the potency of the gamma-lactam peptidomimetics of PLG, it does not appear to be the primary factor. In the 6-hydroxydopamine-lesioned animal model of Parkinson's disease, 5 altered apomorphine-induced rotational behavior in a dose-dependent manner. The maximum effect occurred at a dose of 0.01 mg/kg i.p. and resulted in a 52.27 +/- 13.96% (p < 0.001, n = 7) increase in rotations compared to apomorphine administered alone.

Animals↗
PubMed1997

Evaluating sources of traumatic spinal cord injury surveillance data in Colorado.

The purpose of this study is to evaluate the sources reporting hospitalized spinal cord injury cases to the statewide, population-based surveillance system in Colorado for the year 1994. Three reporting sources were evaluated: clinical contact persons, medical records departments, and a centralized statewide hospital discharge database. Two evaluation strategies were utilized; these include both measures of accuracy and estimates of missed cases. For the latter, capture-recapture techniques were used to estimate the number of hospitalized spinal cord injury cases missed by all three reporting sources. The clinical contact persons reported 84 confirmed cases, missed 80 confirmed cases, and reported 10 cases that were later determined not to have spinal cord injuries, resulting in a sensitivity of 0.51. Medical records departments and the discharge database reported 143 and 147 cases, respectively, missed 21 and 17 confirmed cases, and reported 118 and 69 cases that were later determined not to be cases of hospitalized injuries of the spinal cord, resulting in sensitivities of 0.87 and 0.90. Capture-recapture results indicate all three sources combined missed an estimated 1-5 cases, yielding a total annual incidence rate for hospitalized spinal cord injury ranging from 45.1 to 46.3 per million population.

Colorado↗
PubMed1997

Mutations of the PATCHED gene in several types of sporadic extracutaneous tumors.

Patients with basal cell nevus syndrome have a high incidence of multiple basal cell carcinomas, medulloblastomas, and meningiomas. Because somatic PATCHED (PTCH) mutations have been found in sporadic basal cell carcinomas, we have screened for PTCH mutations in several types of sporadic extracutaneous tumors. We found that 2 of 14 sporadic medulloblastomas bear somatic nonsense mutations in one copy of the gene and also deletion of the other copy. In addition, we identified missense mutations in PTCH in two of seven breast carcinomas, one of nine meningiomas, and one colon cancer cell line. No PTCH gene mutations were detected in 10 primary colon carcinomas and eighteen bladder carcinomas.

Amino Acid Sequence↗
PubMed1997

Modulation of dopamine receptor agonist-induced rotational behavior in 6-OHDA-lesioned rats by a peptidomimetic analogue of Pro-Leu-Gly-NH2 (PLG).

The present study was undertaken to determine if the previously reported in vitro interactions of the Pro-Leu-Gly-NH2 (PLG) peptidomimetic analogue 3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacet amide (PAOPA) with the dopaminergic system could be exhibited in an in vivo animal model using 6-hydroxydopamine (6-OHDA)-lesioned rats. In this model, PAOPA was found to potentiate the contralateral rotational behavior induced by either apomorphine or L-DOPA. PAOPA was 100-fold more potent than PLG, and produced a fourfold greater response than PLG when administered i.p. PAOPA also potentiated contralateral rotations induced by SKF-38393 and quinpirole. In summary, the results of this study indicate that PAOPA, a conformationally constrained peptidomimetic analogue of PLG, can modulate dopaminergic activity in vivo with higher potency and efficacy than PLG.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗