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Biomedical subjects

W A Johnson

Publications and source records attributed to W A Johnson.

At least 19 recordsLinked to original sources
PubMed2001

Patellar tendon rupture 3 years after anterior cruciate ligament reconstruction with a central one third bone-patellar tendon-bone graft.

Use of the central one third bone-patellar tendon-bone autograft is an accepted technique for anterior cruciate ligament (ACL) reconstruction. Patellar tendon rupture following ACL reconstruction is an acknowledged, although rarely reported, complication of this procedure. Of the limited patellar tendon rupture cases reported in the literature, most are described early in the postoperative period. We present a case of late patellar tendon rupture more than 3 years after uneventful ACL reconstruction in a 32-year-old man.

Adult↗
PubMed2000

Prevalence and incidence of HIV among out-of-treatment injecting drug users, Chicago 1994-1996.

OBJECTIVES: To assess HIV prevalence, incidence, and associated risk factors among IDUs in Chicago. METHODS: Seven hundred ninety-four street-recruited IDUs ranging in age from 18 to 50 years, who were not in drug treatment at study enrollment, were interviewed and tested for HIV at baseline and at two follow-ups scheduled 6 and 12 months after baseline. Questionnaires assessed respondents' demographic characteristics, medical and drug treatment histories, drug use, and sexual practices. RESULTS: HIV seroprevalence at baseline was 18%. Logistic regression identified the following determinants of prevalent HIV infection: Puerto Rican ethnicity, homosexual or bisexual self-identification, injecting for 4 or more years, and having smoked crack cocaine in the past 6 months. Follow-up data were collected from 584 (73.6%) participants. Mean duration of follow-up was 16.5 months, indicating that most subjects had follow-up intervals longer than the scheduled 6 and 12 months. Seven HIV seroconversions were observed in 632 person years of risk, yielding an incidence rate of 1.1 per 100 person years of risk. Injection for 3 or less years was positively associated with HIV seroconversion. CONCLUSIONS: The findings provide evidence of a decline in HIV incidence among IDUs, though newer injectors remain at elevated risk for infection.

Adolescent↗
PubMed2000

Functional interactions between Drosophila bHLH/PAS, Sox, and POU transcription factors regulate CNS midline expression of the slit gene.

During Drosophila embryogenesis the CNS midline cells have organizing activities that are required for proper elaboration of the axon scaffold and differentiation of neighboring neuroectodermal and mesodermal cells. CNS midline development is dependent on Single-minded (Sim), a basic-helix-loop-helix (bHLH)-PAS transcription factor. We show here that Fish-hook (Fish), a Sox HMG domain protein, and Drifter (Dfr), a POU domain protein, act in concert with Single-minded to control midline gene expression. single-minded, fish-hook, and drifter are all expressed in developing midline cells, and both loss- and gain-of-function assays revealed genetic interactions between these genes. The corresponding proteins bind to DNA sites present in a 1 kb midline enhancer from the slit gene and regulate the activity of this enhancer in cultured Drosophila Schneider line 2 cells. Fish-hook directly associates with the PAS domain of Single-minded and the POU domain of Drifter; the three proteins can together form a ternary complex in yeast. In addition, Fish can form homodimers and also associates with other bHLH-PAS and POU proteins. These results indicate that midline gene regulation involves the coordinate functions of three distinct types of transcription factors. Functional interactions between members of these protein families may be important for numerous developmental and physiological processes.

Animals↗
PubMed2000

Regulation of central neuron synaptic targeting by the Drosophila POU protein, Acj6.

Mutations in the Drosophila class IV POU domain gene, abnormal chemosensory jump 6 (acj6), have previously been shown to cause physiological deficits in odor sensitivity. However, loss of Acj6 function also has a severe detrimental effect upon coordinated larval and adult movement that cannot be explained by the simple loss in odorant detection. In addition to olfactory sensory neurons, Acj6 is expressed in a distinct subset of postmitotic interneurons in the central nervous system from late embryonic to adult stages. In the larval and adult brain, Acj6 is highly expressed in central brain, optic and antennal lobe neurons. Loss of Acj6 function in larval optic lobe neurons results in disorganized retinal axon targeting and synapse selection. Furthermore, the lamina neurons themselves exhibit disorganized synaptic arbors in the medulla of acj6 mutant pupal brains, suggesting that Acj6 may play a role in regulating synaptic connections or structure. To further test this hypothesis, we misexpressed two Acj6 isoforms in motor neurons where they are not normally found. The two Acj6 isoforms are produced from alternatively spliced acj6 transcripts, resulting in significant structural differences in the amino-terminal POU IV box. Acj6 misexpression caused marked alterations at the neuromuscular junction, with contrasting effects upon nerve terminal branching and synapse formation associated with specific Acj6 isoforms. Our results suggest that the class IV POU domain factor, Acj6, may play an important role in regulating synaptic target selection by central neurons and that the amino-terminal POU IV box is important for regulation of Acj6 activity.

Alternative Splicing↗
PubMed2000

Restricted patterning of vestigial expression in Drosophila wing imaginal discs requires synergistic activation by both Mad and the drifter POU domain transcription factor.

The Drosophila Vestigial protein has been shown to play an essential role in the regulation of cell proliferation and differentiation within the developing wing imaginal disc. Cell-specific expression of vg is controlled by two separate transcriptional enhancers. The boundary enhancer controls expression in cells near the dorsoventral (DV) boundary and is regulated by the Notch signal transduction pathway, while the quadrant enhancer responds to the Decapentaplegic and Wingless morphogen gradients emanating from cells near the anteroposterior (AP) and DV boundaries, respectively. MAD-dependent activation of the vestigial quadrant enhancer results in broad expression throughout the wing pouch but is excluded from cells near the DV boundary. This has previously been thought to be due to direct repression by a signal from the DV boundary; however, we show that this exclusion of quadrant enhancer-dependent expression from the DV boundary is due to the absence of an additional essential activator in those cells. The Drosophila POU domain transcriptional regulator, Drifter, is expressed in all cells within the wing pouch expressing a vgQ-lacZ transgene and is also excluded from the DV boundary. Viable drifter hypomorphic mutations cause defects in cell proliferation and wing vein patterning correlated with decreased quadrant enhancer-dependent expression. Drifter misexpression at the DV boundary using the GAL4/UAS system causes ectopic outgrowths at the distal wing tip due to induction of aberrant Vestigial expression, while a dominant-negative Drifter isoform represses expression of vgQ-lacZ and causes severe notching of the adult wing. In addition, we have identified an essential evolutionarily conserved sequence element bound by the Drifter protein with high affinity and located adjacent to the MAD binding site within the quadrant enhancer. Our results demonstrate that Drifter functions along with MAD as a direct activator of Vestigial expression in the wing pouch.

Animals↗
PubMed1999

The odor specificities of a subset of olfactory receptor neurons are governed by Acj6, a POU-domain transcription factor.

Little is known about how the odor specificities of olfactory neurons are generated, a process essential to olfactory coding. We have found that neuronal identity relies on the abnormal chemosensory jump 6 (acj6) gene, originally identified by a defect in olfactory behavior. Physiological analysis of individual olfactory neurons shows that in acj6 mutants, a subset of neurons acquires a different odorant response profile. Certain other neurons do not respond to any tested odors in acj6. Molecular analysis of acj6 shows that it encodes a POU-domain transcription factor expressed in olfactory neurons. Our data suggest that the odor response spectrum of an olfactory neuron, and perhaps the choice of receptor genes, is determined through a process requiring the action of Acj6.

Alleles↗
PubMed1998

Ripped pocket and pickpocket, novel Drosophila DEG/ENaC subunits expressed in early development and in mechanosensory neurons.

Drosophila melanogaster has proven to be a good model for understanding the physiology of ion channels. We identified two novel Drosophila DEG/ ENaC proteins, Pickpocket (PPK) and Ripped Pocket (RPK). Both appear to be ion channel subunits. Expression of RPK generated multimeric Na+ channels that were dominantly activated by a mutation associated with neurodegeneration. Amiloride and gadolinium, which block mechanosensation in vivo, inhibited RPK channels. Although PPK did not form channels on its own, it associated with and reduced the current generated by a related human brain Na+ channel. RPK transcripts were abundant in early stage embryos, suggesting a role in development. In contrast, PPK was found in sensory dendrites of a subset of peripheral neurons in late stage embryos and early larvae. In insects, such multiple dendritic neurons play key roles in touch sensation and proprioception and their morphology resembles human mechanosensory free nerve endings. These results suggest that PPK may be a channel subunit involved in mechanosensation.

Amiloride↗
PubMed1998

Nutritional supplements: fact vs. fiction.

An athlete may think that if a small amount of a chemical helps his or her performance, more will work better. The most appealing supplements are those that claim to help build muscle, improve endurance, and reduce body fat. Widespread acceptance of herbal of "natural" alternatives to mainstream medicine (especially nutritional supplements) is increasing, and the market is largely unregulated. The authors summarize the facts and fiction surrounding the use of popular products that may be found at the pharmacy and health food store that are being used in the locker rooms of high schools, colleges, and gyms in the U.S. They urge clinicians to stress the value of a well balanced diet to their active adolescent patients and not to encourage supplement use.

Adolescent↗
PubMed1997

Genetic evidence that heparin-like glycosaminoglycans are involved in wingless signaling.

We have identified the Drosophila UDP-glucose dehydrogenase gene as being involved in wingless signaling. Mutations in this gene, called kiwi, generate a phenotype identical to that of wingless. UDP-glucose dehydrogenase is required for the biosynthesis of UDP-glucuronate, which in turn is utilized in the biosynthesis of glycosaminoglycans. By rescuing the kiwi phenotype with both UDP-glucuronate and the glycosaminoglycan heparan sulfate, we show that kiwi function in the embryo is crucial for the production of heparan sulfate in the extracellular matrix. Further, injection of heparin degrading enzyme, heparinase (and not chondroitin, dermatan or hyaluronic acid degrading enzyme) into wild-type embryos leads to the degradation of heparin-like glycosaminoglycans and a 'wingless-like' cuticular phenotype. Our study thus provides the first genetic evidence for the involvement of heparin-like glycosaminoglycans in signal transduction.

Amino Acid Sequence↗
PubMed1996

Longevity and the genetic determination of collagen glycoxidation kinetics in mammalian senescence.

A fundamental question in the basic biology of aging is whether there is a universal aging process. If indeed such a process exists, one would expect that it develops at a higher rate in short- versus long-lived species. We have quantitated pentosidine, a marker of glycoxidative stress in skin collagen from eight mammalian species as a function of age. A curvilinear increase was modeled for all species, and the rate of increase correlated inversely with maximum life-span. Dietary restriction, a potent intervention associated with increased life-span, markedly inhibited glycoxidation rate in the rodent. On the assumption that collagen turnover rate is primarily influenced by the crosslinking due to glycoxidation, these results suggest that there is a progressive age-related deterioration of the process that controls the collagen glycoxidation rate. Thus, the ability to withstand damage due to glycoxidation and the Maillard reaction may be under genetic control.

Aging↗
PubMed1996

Disruption of mesectodermal lineages by temporal misexpression of the Drosophila POU-domain transcription factor, drifter.

Among the first cells to differentiate in the Drosophila ventral nerve cord, the mesectodermal (midline) lineage gives rise to a discrete set of neurons and glia previously demonstrated to play an important role in the organization of the developing nervous system. The relative simplicity of the midline has allowed the elucidation of many aspects of initial lineage commitment and subsequent differentiation. Based upon its mesectodermal expression pattern and loss-of-function phenotype, we have proposed a key role for the Drosophila POU-domain transcription factor, drifter (dfr), in mesectodermal lineage development. In this study, we have examined the developmental consequences of dfr misexpression using transgenic lines expressing wild-type Drifter protein under control of the heat-inducible hsp70 promoter. Induction of ubiquitous DFR protein during a restricted period of embryogenesis causes a defective axonal phenotype characterized by failure of commissure formation. Based on examination of cell-specific markers for mesectodermal cells, these defects appear to be the result of a suppression of single-minded expression resulting in the disruption of mesectodermal lineage designation and differentiation. The observed temporally restricted sensitivity to DFR expression suggests possible interactions between DFR protein and other stage-specific mesectodermal regulatory factors present before or after a defined mesectodermal developmental event.

Animals↗
PubMed1996

Transformational leadership of clinical nutrition managers.

OBJECTIVE: To identify leadership qualities of clinical nutrition managers and associate these leadership qualities with selected demographic variables (eg, training/degree, length of time in management, number of people supervised, income, and participation in advanced practice activities). DESIGN: The theory of transformational leadership, that is, leadership that incorporates specific interpersonal behaviors of the leader and his or her actions within the organization, provided the framework for the study. Specific transformational leadership qualities--leader behavior, leader personal characteristics, and the effect of the leader on organizational functioning and culture--were measured using the Leadership Behavior Questionnaire (LBQ). The reliability and validity of the LBQ have been reported previously. Other data were obtained using two demographic surveys. SAMPLE: Demographic surveys were mailed to 1,599 members of the Clinical Nutrition Management dietetic practice group. From the 951 (59.8%) respondents, a study sample of 150 clinical nutrition managers and their subordinates was selected to receive the LBQ; 116 (77.3%) instrument sets were used for analysis. STATISTICAL ANALYSIS: Descriptive statistics were used to analyze the demographic surveys. A specified mixed linear model repeated measures Statistical Analysis System procedure was used to compare the clinical manager and subordinate LBQ scores. Association of the selected demographic variables with leadership qualities was measured by lambda, a predictive value measure, using the BMDP 4F program. RESULTS: Clinical nutrition managers exhibited transformational leadership qualities as rated by the LBQ, rating lowest on the communication leadership score and highest on the respectful leadership score. Most of the clinical nutrition manager self LBQ scores were significantly higher than the clinical nutrition manager LBQ scores rated by subordinates. The selected demographic variables appeared to have the strongest predictive effect for the visionary culture building subscore of the LBQ. The visionary culture building subscore is a measure of how well the leader interacts with and affects the functioning of an organization. APPLICATIONS/CONCLUSIONS: More research is needed to define leadership in dietetics: this study can serve as a possible model. One way clinical nutrition managers may be able to enhance their leadership behaviors is to strengthen their skills in communicating their vision. Programs are needed to help clinical nutrition managers shape their organizations to foster leadership development in their subordinates.

Dietetics↗
PubMed1996

Vitamin E levels and susceptibility to lipid peroxidation increase with aging in heart plasma membrane from miniature swine.

Age-related changes in heart plasma membrane fatty acid composition, vitamin E content, membrane fluidity, susceptibility to lipid peroxidation, and the subcellular distribution of vitamin E were observed in male and female Hormel-Hanford miniswine over a wide range of ages: prepubertal, < 0.5 years; young, 0.5-2.5 years; middle-aged, 5.9-10 years; and old, 11.5-13.9 years. Pigs were continuously fed the same low-fat, cholesterol-free, vitamin E-adequate stock diet at restricted maintenance levels. Membrane lipid peroxidation tended to increase in middle-aged and elderly pigs, but not significantly, perhaps being somewhat ameliorated by the significantly increased membrane vitamin E in middle-aged and old pigs. Mid-bilayer membrane fluidity was significantly increased in old pigs, but fluidity of the polar headgroup domains decreased with age. Thus, lipid peroxidation tended to increase over the long life span of miniswine even when they are food restricted.

Aging↗
PubMed1996

Distinct variant DNA-binding sites determine cell-specific autoregulated expression of the Drosophila POU domain transcription factor drifter in midline glia or trachea.

Transcriptional regulators utilizing the POU domain DNA-binding motif have been shown to form multi-protein complexes dependent on the POU domain itself and its flexible recognition of various octamer sequence elements. We have identified two variant POU domain recognition elements DFRE1 and DFRE2, which are found within a 514-bp autoregulatory enhancer of the Drosophila melanogaster POU domain gene drifter (dfr). Both elements are capable of binding bacterially produced full-length DFR protein with high affinity, although they differ in the 5'-to-3' orientation of POU-specific and POU homeodomain subelements. When placed in dfr loss-of-function genetic backgrounds, all expression of dfr-lacZ fusion genes under control of the autoregulatory enhancer is dependent on DFR activity levels. However, the complete enhancer sequence directs beta-galactosidase expression in only a subset of cells which normally express the endogenous DFR protein, including the middle pair of midline glias of the ventral nerve cord, the oenocyte clusters, and all tracheal cells. In addition, DFRE1 and DFRE2 exhibit separable tissue-specific functions when independently disrupted or deleted. Disruption of DFRE1 function specifically abolishes beta-galactosidase expression in the middle pair of midline glias. Deletion of DFRE causes a specific loss of tracheal expression, leaving oenocyte and midline glia expression intact. These results suggest that dfr cell-specific autoregulation is determined by the context of DFR POU domain binding within the enhancer, which is possibly mediated by the formation of recognition element-specific heteromultimeric complexes containing additional tissue-specific factors.

Animals↗
PubMed1996

Function of the Drosophila POU domain transcription factor drifter as an upstream regulator of breathless receptor tyrosine kinase expression in developing trachea.

Organogenesis of the Drosophila tracheal system involves extensive directed cell migrations leading to a stereotypic series of interconnected tubules. Although numerous gene products have been shown to be essential for tracheal morphogenesis, direct functional relationships between participants have not been previously established. Both the breathless gene, encoding a Drosophila fibroblast growth factor receptor tyrosine kinase homologue, and the POU-domain transcription factor gene, drifter, are expressed in all tracheal cells and are essential for directed cell migrations. We demonstrate here that ubiquitously expressed Breathless protein under control of a heterologous heat-shock promoter is able to rescue the severely disrupted tracheal phenotype associated with drifter loss-of-function mutations. In the absence of Drifter function, breathless expression is initiated normally but transcript levels fall drastically to undetectable levels as tracheal differentiation proceeds. In addition, breathless regulatory DNA contains seven high affinity Drifter binding sites similar to previously identified Drifter recognition elements. These results suggest that the Drifter protein, which maintains its own expression through a tracheal-specific autoregulatory enhancer, is not necessary for initiation of breathless expression but functions as a direct transcriptional regulator necessary for maintenance of breathless transcripts at high levels during tracheal cell migration. This example of a mechanism for maintenance of a committed cell fate offers a model for understanding how essential gene activities can be maintained throughout organogenesis.

Animals↗
PubMed1995

drifter, a Drosophila POU-domain transcription factor, is required for correct differentiation and migration of tracheal cells and midline glia.

The Drosophila drifter (dfr) gene, previously referred to as Cf1a, encodes a POU-domain DNA-binding protein implicated as a neuron-specific regulator in the developing central nervous system (CNS). We have isolated full-length dfr cDNA clones that encode a 46-kD protein containing the conserved POU-domain DNA-binding domain. The use of alternate polyadenylation sites produces two dfr mRNA transcripts that are first expressed in stage 10 embryos at 5- to 6-hr of development. A specific anti-dfr polyclonal antiserum generated against a dfr-glutathione S-transferase fusion protein recognizes a 46-kD protein on Western blots and has been used to analyze the cell-specific distribution of dfr protein during embryonic development. dfr protein is distributed in a complex expression pattern including the tracheal system, the middle pair of midline glia, and selected CNS neurons. We have carried out a genetic characterization of the dfr locus, previously localized to region 65D of the third chromosome, by generating a series of overlapping deficiencies between 65A and 65E1 that were used to isolate dfrE82, an EMS-induced lethal allele. Analysis of dfrE82 mutant embryos shows a disruption of the developing tracheal tree as well as commissural defects in the developing CNS. Based on an examination of a cell-specific marker for tracheal cells and midline glia, these defects appear to be caused by a failure of these cells to follow their characteristic routes of migration. The dfrE82 tracheal phenotype is rescued by a dfr minigene present as a P-element transposon expressing wild-type dfr protein in tracheal cells. These results suggest that the dfr protein plays a fundamental role in the differentiation of tracheal cells and midline glia possibly by regulating the expression of essential cell-surface proteins required for cell-cell interactions involved in directed cell migrations.

Animals↗