Biomedical subjects

J D Murray

Publications and source records attributed to J D Murray.

At least 19 recordsLinked to original sources

PubMed1999

A minimal mechanism for bacterial pattern formation.

Colonies of Escherichia coli or Salmonella typhimurium form geometrically complex patterns when exposed to, or feeding on, intermediates of the tricarboxylic acid (TCA) cycle. In response to the TCA cycle intermediate, the bacteria secrete aspartate, a potent chemo-attractant. As a result, the cells form high-density aggregates arranged in striking regular patterns. The simplest are temporary spots formed in a liquid medium by both E. coli and S. typhimurium. In semi-solid medium S. typhimurium forms concentric rings arising from a low-density bacterial lawn, which are either continuous or spotted, whereas E. coli forms complex patterns arising from a dense swarm ring, including interdigitated spots (also called sunflower spirals), radial spots, radial stripes and chevrons. We present a mathematical model that captures all three of the pattern-forming processes experimentally observed in both E. coli and S. typhimurium, using a minimum of assumptions.

Bacterial Adhesion↗

PubMed1999

Comparative mapping of 18 equine type I genes assigned by somatic cell hybrid analysis.

Polymerase chain reaction primers designed from horse cDNA sequences and from consensus sequences highly conserved in mammalian species were used to amplify markers for synteny mapping 18 equine type I genes. These markers were used to screen a horse-mouse somatic cell hybrid panel (UCDavis SCH). Fourteen primer sets amplified horse-specific fragments, while restriction enzyme digests of PCR products were used to distinguish the fragments amplified from horse and mouse with four primer sets. Synteny assignments were made based on correlation values between each marker tested and other markers in the UCDavis SCH panel database. The 18 horse genes were assigned to previously established synteny groups. Synteny mapping of two genes previously mapped in the horse by FISH was used to anchor two UCD synteny groups to horse chromosomes. Previous chromosome assignments of three equine loci by FISH were confirmed. Comparative mapping analysis based on published human-horse Zoo-FISH data and the synteny mapping of 14 horse genes confirmed the physical assignment of 12 synteny groups to the respective horse chromosomes and was used to infer the physical location of one synteny group.

Animals↗

PubMed1999

Fiber type composition of four hindlimb muscles of adult Fisher 344 rats.

The limb and trunk muscles of adult rats express four myosin heavy chain (MHC) isoforms, one slow (MHCI) and three fast (MHCIIa, MHCIId, and MHCIIb). The distribution of these isoforms correlates with fiber types delineated using myofibrillar actomyosin adenosine triphosphatase (mATPase) histochemistry. For example, type I fibers express MHCI and fiber types IIA, IID, and IIB express MHCIIa, MHCIId, and MHC-IIb, respectively. Fibers containing only one MHC isoform have been termed "pure" fibers. Recent evidence suggests that a population of "hybrid" fibers exist in rat skeletal muscle which contain two MHC isoforms. The purpose of the present investigation was to document the entire range of histochemically defined "pure" and "hybrid" fiber types in untreated muscles of the young adult Fisher 344 rat hindlimb. The selected hindlimb muscles (soleus, tibialis anterior, extensor digitorum longus, and gastrocnemius muscles) were removed from 12 male rats and analyzed for muscle fiber type distribution, cross-sectional area, and MHC content. Care was taken to delineate eight fiber types (I, IC, IIC, IIA, IIAD, IID, IIDB, and IIB) using refined histochemical techniques. Hybrid fibers were found to make up a considerable portion of the muscles examined (a range of 8.8-17.8% of the total). The deep red portion of the gastrocnemius muscle contained the largest number of hybrid fibers, most of which were the fast types IIAD (8.5+/-2.8%) and IIDB (5.2+/-2.3%). In conclusion, hybrid fibers make up a considerable portion of normal rat limb musculature and are an important population that should not be ignored.

Animals↗

PubMed1999

A synteny map of the horse genome comprised of 240 microsatellite and RAPD markers.

To generate a domestic horse genome map we integrated synteny information for markers screened on a somatic cell hybrid (SCH) panel with published information for markers physically assigned to chromosomes. The mouse-horse SCH panel was established by fusing pSV2neo transformed primary horse fibroblasts to either RAG or LMTk mouse cells, followed by G418 antibiotic selection. For each of the 108 cell lines of the panel, we defined the presence or absence of 240 genetic markers by PCR, including 58 random amplified polymorphic DNA (RAPD) markers and 182 microsatellites. Thirty-three syntenic groups were defined, comprised of two to 26 markers with correlation coefficient (r) values ranging from 0.70 to 1.0. Based on significant correlation values with physically mapped microsatellite (type II) or gene (type I) markers, 22 syntenic groups were assigned to horse chromosomes (1, 2, 3, 4, 6, 9, 10, 11, 12, 13, 15, 18, 19, 20, 21, 22, 23, 24, 26, 30, X and Y). The other 11 syntenic groups were provisionally assigned to the remaining chromosomes based on information provided by heterologous species painting probes and work in progress with type I markers.

Animals↗

PubMed1998

Comparison of soleus muscles from rats exposed to microgravity for 10 versus 14 days.

The effects of two different duration space-flights on the extent of atrophy, fiber type composition, and myosin heavy chain (MHC) content of rat soleus muscles were compared. Adult male Fisher rats (n=12) were aboard flight STS-57 and exposed to 10 days of microgravity and adult ovariectomized female Spraque-Dawley rats (n=12) were aboard flight STS-62 for 14 days. Soleus muscles were bilaterally removed from the flight and control animals and frozen for subsequent analyses. Muscle wet weights, fiber types (I, IC, IIC, and IIA), cross-sectional area, and MHC content were determined. Although a significant difference was found between the soleus wet weights of the two ground-based control groups, they were similar with regard to MHC content (ca 90% MHCI and ca 10% MHCIIa) and fiber type composition. Unloading of the muscles caused slow-to-fast transformations which included a decrease in the percentage of type I fibers and MHCI, an increase in fibers classified as type IC, and the expression of two fast myosin heavy chains not found in the control rat soleus muscles (MHCIId and MHCIIb). Although the amount of atrophy (ca 26%) and the extent of slow-to-fast transformation (decrease in the percentage of MHCI from 90% to 82.5%) in the soleus muscles were similar between the two spaceflights, the percentages of the fast MHCs differed. After 14 days of spaceflight, the percentage of MHCIIa was significantly lower and the percentages of MHCIId and MHCIIb were significantly higher than the corresponding MHC content of the soleus muscles from the 10-day animals. Indeed, MHCIId became the predominant fast MHC after 14 days in space. These data suggest fast-to-faster transformations continued during the longer spaceflight.

Animals↗

PubMed1998

Regulation of CAT protein by ribozyme and antisense mRNA in transgenic mice.

Transgenic mouse lines were engineered to express stably antisense mRNA or antisense mRNA containing catalytic ribozyme (rbz) structures complementary to bacterial chloramphenicol acetyltransferase (CAT) gene transcripts. One transgenic line expressed antisense mRNA that specifically targeted full-length CAT coding sequences (ACAT). Another transgenic line expressed full-length antisense CAT mRNA which was modified by mutagensis to include four rbz cassettes (rbz-ACAT) in order to compare antisense versus antisense-rbz function in vivo. Preliminary data were also collected from a transgenic mouse line expressing antisense mRNA targeting 72% of the 5' region of CAT coding sequences (5' ACAT). All constructs contained similar control elements in their design. Promoter elements were derived from the bovine alpha s1-casein gene, while the small t intron and 3' control sequences were derived from SV40. The ability of these various constructs to down-regulate CAT protein levels was compared by analysis of CAT protein production in lactating double-hemizygous transgenic female mice. Every double-hemizygous mouse analysed expressed mRNA from the alpha s1-casein-CAT construct (Clarke et al., 1994) and equivalent levels of mRNA from one of the three antisense constructs. Transgenic mouse lines expressing both ACAT and CAT mRNA down-regulated CAT protein levels by 90% of that found in the CAT only transgenic population. Similarly, double-hemizygous transgenic lines expressing both rbz-ACAT and CAT mRNA regulated CAT protein levels by 87%. Preliminary data suggests that expression of mRNA from 5' ACAT/CAT double-hemizygote mice allowed approximately 67% down-regulation of normal CAT protein levels. We conclude that incorporation of multiple ribozymes within the full-length antisense CAT construct does not enhance the effectiveness of antisense mRNA in the down-regulation of CAT protein production in our system.

Animals↗

PubMed1998

Overexpression of growth hormone affects alternatively spliced IGF-I mRNA expression in oMt1a-oGH transgenic mice.

Restorative growth hormone (GH) treatment of hypophysectomized rats differentially enhances the transcription of alternative IGF-I mRNA classes in liver. The goal of the present study was to determine the effects of GH overexpression on various classes of hepatic IGF-I mRNA in GH transgenic mice. Unstimulated oMt1a-oGH transgenic mice had low levels of transgene expression, and therefore were used to determine the effects of long-term, slightly elevated GH levels on the abundance on each alternative IGF-I mRNA class. The acute effects of high GH levels on the expression of alternative IGF-I mRNA were studied by gavaging transgenic mice with 25 mM zinc sulfate to activate oMt1a-oGH transgene expression. Long-term, low levels of oGH transgene expression in unstimulated transgenic mice resulted in a 73% down regulation of IGF-I 2Ea mRNA but not 1Ea and 2Eb mRNA. Acute stimulation of transgene expression triggered a rapid, 240% increase in 1Ea mRNA levels within 4 hours of transgene expression while 2Ea mRNA was down regulated to nearly non-detectable levels by 6 hours. IGF-I 2Eb mRNA was not affected by the short-term GH elevation. Our results showed that IGF-I 1Ea and 2Ea mRNA were differentially regulated by chronic low or acute high levels of GH. These results suggest that the regulation of IGF-I 1Ea and 2Ea mRNA transcription involve different postreceptor molecules and/or feedback mechanisms.

Alternative Splicing↗

PubMed1998

Antimicrobial properties of human lysozyme transgenic mouse milk.

The antimicrobial properties of standard human lysozyme and the milk of transgenic mice expressing human lysozyme were investigated using bacterial strains important to the dairy industry. Standard human lysozyme was found to be effective at significantly slowing the growth of the milk cold-spoilage organism Pseudomonas fragi (P < 0.001), of a clinical isolate of the mastitis-causing organism Staphylococcus aureus (P < 0.005), and a nonpathogenic strain of E. coli (P < 0.05). Milk from transgenic mice secreting human lysozyme in their milk at an average concentration of 0.3 mg/ml was found to be bacteriostatic against the cold-spoilage organisms Pseudomonas fragi and Lactobacillus viscous and a mastitis-causing strain of Staphylococcus aureus, but not against a pathogenic strain of E. coli. These results demonstrate that transgenic animals producing human lysozyme in their milk can affect the microbial nature of milk.

Animals↗

PubMed1998

Mesenchymal hamartoma of the liver.

Mesenchymal hamartomas of the liver are the second most common benign liver tumor of childhood. The experience with this tumor at Egleston's Children Hospital at Emory University from 1989 to 1994 is reviewed. Eight patients presented with abdominal distention or an upper abdominal mass. Six patients presented at a mean age of 8 months, and two patients presented at 17 and 23 years of age, respectively. Four patients displayed normal alpha-fetoprotein levels, whereas one patient had an elevated level. Liver function studies were normal in all patients. Abdominal ultrasonography and CT scans revealed a cystic, septated mass within the liver or on a pedicle in all patients. Five patients had simple excision of the tumor, and two had major hepatic resections. The cysts were multiloculated and lined with cuboidal bile duct epithelium surrounded by stroma containing proliferating bile ducts, blood vessels, and compressed liver tissue with no calcifications. In one patient, some pathologists favored the diagnosis of malignant myxoid fibrous histiocytoma because of similar-appearing stroma. Follow-up (mean, 35 months) revealed one symptomatic recurrence after initial resection was incomplete. There were no other recurrences and no malignant transformations. A septated, noncalcified, cystic hepatic mass in an infant with normal liver function studies and characteristic ultrasound or CT is likely a benign mesenchymal hamartoma that can be cured by total local excision.

Adolescent↗

PubMed1998

Consequences of limited exposure to elevated growth hormone in the mature oMt1a-oGH transgenic mouse.

Male and female transgenic mice carrying the regulatable ovine metallothionein-ovine growth hormone (oMt1a-oGH) transgene were exogenously induced to express elevated GH at maturity. Male transgenics responded to continuously elevated GH with smaller white adipose tissue depots (WAT); cessation of transgene stimulation with restoration of basal circulating GH ablated the improvement in WAT. Transgenic males in which the transgene was never exogenously activated expressed low levels of oGH (60.2 ng/ml) and this low, chronic level resulted in 30-50% larger (p < 0.05) gonadal, inguinal, and mesenteric WAT relative to all wildtype controls, transgenics actively expressing the transgene, or transgenics exposed to elevated GH for a limited time. Mature females continued to accrue body mass proportional to circulating GH. Similar to that observed in the males, transgenic females in which the transgene was never exogenously activated exhibited enlarged WAT that were 20-40% larger than the same depots in wildtype control females. However, in contrast to the data for the males, transgenic females that had experienced a four week exposure to elevated GH followed by a return to basal conditions tended to have the greatest WAT depots (p < 0.10). This would indicate that female adipocytes are still capable of responding to elevated GH with proliferation/differentiation at maturity. These data support the hypothesis that the generalized sexual dimorphic pattern of lipid deposition may be attributed to the sexually dimorphic pattern of GH experienced by the two sexes.

Animals↗

PubMed1997

Myonuclear loss in atrophied soleus muscle fibers.

BACKGROUND: A skeletal muscle fiber consists of many successive "territories," each controlled by the nucleus residing in that territory. Because nuclei appear to control a specific amount of territory (nuclear domain), nuclei must be added to accommodate an increase in fiber size. Because growth and hypertrophy require the addition of nuclei to fibers, it is of interest to determine whether atrophy causes a decrease in myonuclear number. This study compared the myonuclear population in the soleus muscles of rats that had undergone atrophy due to 10 days of spaceflight in the space shuttle, Endeavour, with muscles of ground-based control animals (10 rats each). METHODS: Myofibrillar ATPase activity was used to determine the major skeletal muscle fiber types in control rats and those having spent 10 days in space, and dystrophin antibodies were used to label the sarcolemma to identify underlying myonuclei. RESULTS: Type I and II fibers were atrophied after the flight, but type I fibers were atrophied twice as much as type II. Myonuclei were counted in identified and measured fibers, and the distribution normalized to number per millimeter of fiber circumference; this was significantly greater in type II than in type I fibers in both groups of rats. However, although the muscle fibers from flight animals were significantly atrophied, the normalized number of nuclei were identical between control and flight animals, indicating that nuclei decreased in numbers as the fibers atrophied. CONCLUSION: The nuclear domain is under strict control, and a decrease in the domain, as induced by atrophy, will cause nuclear degeneration and loss, which maintains a relatively constant size of the nuclear domain.

Adenosine Triphosphatases↗

PubMed1997

Early transcription of the SRY gene by bovine preimplantation embryos.

We have examined mRNA expression of two genes located on the Y chromosome, the sex-determining region Y gene (SRY) and the linked zinc finger gene (ZFY), using in vitro fertilized-in vitro cultured bovine embryos. Expression of the SRY gene, implicated in sex determination in mammals, has been reported to occur both for a short time at the sex-determining stage of development around the period of the primitive undifferentiated gonad and in the adult testis. In this study, using a sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) assay, we detected SRY but not ZFY mRNA expression as early as the 4- to 8-cell stage and through to the blastocyst stage in bovine embryos. The expression of SRY at these early stages and the previous observation that in vitro-produced male bovine embryos develop faster in culture than female embryos suggest that sex differences are evident prior to gonadal differentiation and that preimplantation bovine embryos have sexually dimorphic gene expression at least with respect to SRY transcripts.

Animals↗

PubMed1997

Tumor angiogenesis as a prognostic factor in laryngeal cancer.

BACKGROUND: Lymph node metastasis is the single greatest predictor of recurrence in laryngeal cancer. Prognostic factors are needed to target patients who may benefit from adjuvant therapy. Tumor angiogenesis correlates with metastasis in breast, bladder, and oral cavity cancer and may have prognostic value in other tumors. METHODS: In order to examine the relationship of tumor angiogenesis to recurrence, 51 patients with squamous cell carcinoma of the larynx were reviewed. In a blinded design, previously sectioned slides were chosen for advanced tumor and highest vessel concentration. Samples were cut and immunocytochemically stained for CD-31 (an endothelial marker). A computer image analyzer quantitated the percent area of staining. Variables were statistically examined against recurrence. RESULTS: Patients were stratified by percent tumor staining. Nodal involvement was seen in 9 (36%) patients with tumor staining < or = 20% and in 20 (77%) with tumor staining > 20% (P = 0.003). Patients with < or = 20% staining and without metastasis had a 13% rate of recurrence whereas patients with > 20% staining and without metastasis had a 67% rate of recurrence (P = 0.025). CONCLUSIONS: Though nodal status was suggestive of predictability, only angiogenesis is a statistically significant predictor of recurrence in node negative patients (P = 0.025). Angiogenesis shows strong correlation with regional recurrence and may be used as an independent prognostic indicator to determine clinically node negative patients who may be at higher risk for metastasis and require adjuvant therapy.

Carcinoma, Squamous Cell↗

PubMed1997

What should be the focus of emotion regulation in children? A nonlinear dynamic mathematical model of children's peer interaction in groups.

This paper questions the assumption that children's social and emotional competence be placed within the developing child, rather than in the interaction of the child with the range of peer social ecologies in which the children might function. This paper presents a new nonstatistical mathematical approach to modeling children's peer social interaction in small groups using nonlinear difference equations in which both an uninfluenced and an influenced regulatory set point of positive minus negative interaction can be separately estimated. Using this model and the estimation procedure, it is possible to estimate what a focal child and the group initially brings to the group interaction and also how these regulatory set points are influenced by the interaction to determine two influenced regulatory set points. Six-person mainstreamed and specialized groups were established involving three types of unacquainted preschool boys: children with and without developmental delays and a language disordered but intellectually normally functioning group, using a methodology that ensured appropriate matching of child and family characteristics. For each 2-week play group, the social interactions of each child were observed during a designated free play period. Handicapped children were observed in either a specialized or mainstreamed setting. The application made of this modeling process in this paper is generating theory to attempt to understand influence processes. Parameters are introduced that reflect uninfluenced target child and group set points, emotional inertia, and influence functions.

Child, Preschool↗

PubMed1997

The response of transgenic mice to beta-adrenergic agonist administration is different from that of normal mice.

Eighteen transgenic mice carrying an ovine metallothionein la-ovine growth hormone (oMTla-oGH) transgene and 18 littermate normal mice were used to investigate the effects of transgene expression and clenbuterol administration on growth performance and skeletal muscle characteristics. The oGH transgene was activated from 21 d of age, and half of the mice were fed 15 ppm clenbuterol from 42 to 70 d of age. All mice were killed at 70 d of age after 4 wk of treatment, and organs and muscles were dissected, weighted, and analyzed. Transgenic mice (TM) gained 2.6 times more than normal mice (NM). However, TM had a significantly lower (-20%, P < .01) proportion of muscle, expressed as percentages of body weights, and a higher percentage of heart (+10%), liver (+26%, P < .01) and spleen (+64%, P < .01) than NM. Clenbuterol improved the weight gain of TM by 20%, compared with 10% for NM. The growth-promoting effect of clenbuterol was almost exclusively confined to skeletal muscle (24% increase) in NM, in contrast to a more generalized growth increase in all tissues including skeletal muscle (11% increase) in TM. The skeletal muscles of TM were longer but smaller in diameter due to 30% smaller muscle fiber cross-sectional area. Clenbuterol increased the muscle fiber size of all fiber types by 60% in NM, compared to 30% in TM. Muscle DNA concentrations and content were higher (P < .05) in TM than in NM, and clenbuterol administration decreased DNA concentrations but not total DNA content for both genotypes. Cathepsin B, C, and H activities were higher (P < .01) in TM muscle, but the significance is not clear at the present time, although it points to a potential for greater protein degradation and(or) turnover rates as suggested by smaller muscle weights.

Adrenergic beta-Agonists↗

PubMed1997

Connectives and narrative text: the role of continuity.

Connectives are text devices that signal the relation between adjacent sentences. Recently there has been a surge of research interest in the role played by connectives in on-line processing. The present research tested the hypothesis that connectives will impact on-line processing to the extent that they signal a text event that represents a departure from the continuity of the events stated in the text. In Experiment 1, participants generated sentences to follow a stimulus sentence. An additive, causal, or adversative connective (or no connective) was provided to serve as the first word of the participants' sentence. Results showed that sentences generated in response to additive or causal connectives depicted text events that were continuous with the stimulus text. In contrast, sentences generated in response to adversative connectives depicted discontinuous text events. In Experiments 2 and 3, participants read coherent sentence pairs containing inappropriately placed additive, causal, or adversative connectives. Support for the continuity hypothesis was found when it was shown that adversative connectives led to the greatest amount of processing disruption, as measured by longer reading time on the postconnective sentence (Experiment 2) and lower ratings of coherence (Experiment 3). Future research in this area is discussed.

Analysis of Variance↗

PubMed1997

The interaction of growth rates and diffusion coefficients in a three-dimensional mathematical model of gliomas.

This paper is a natural three-dimensional extension of a simple two-dimensional mathematical model of glioma growth and diffusion. The model was originally constructed to simulate a case of recurrent anaplastic astrocytoma treated with chemotherapy, and then modified to allow estimation of the effects of the extent of surgical resection and of variations in growth and diffusion to cover the whole range of glioma behavior. Growth is considered to be constant and exponential (analogous to continuously compounding interest) and is expressed as a decimal fraction per day; the diffusion coefficient is expressed as cm2 per day. Model predictions suggest that diffusion, practically ignored until the present, is a more important component of glioma growth than the growth rate. Even with very early diagnosis, only those tumors with a low diffusion coefficient and a rapid growth rate benefit from a wide resection. Surgical resections generally fail, just as dropping fire-fighters into the burned out center of a forest fire fails, the action being on the periphery as the tumor cells or fires spread out from the center.

Astrocytoma↗

PubMed1997

Mental health service delivery in rural areas: organizational and clinical issues.

The mental health funding cuts and the block grant shift of the last decade have placed an increased emphasis on fee-generating services. In already underserved rural areas, this has generated immense challenges for mental health professionals on how to provide services to persons other than those with chronic mental illness. This chapter has discussed alternatives and innovations that have proven successful. Linkages with primary care physicians and indigenous residents who have been trained to provide basic mental health services under the supervision of mental health professionals are just two of the ways in which mental health professionals have risen to meet the challenges placed before them. A review of the literature produced few articles about rural programs addressing the issues of substance abuse, services to women, children, the elderly, those with severe mental illness or developmental disability, and the homeless, or crisis intervention programs. Much work needs to be done to provide adequate services to these special rural populations. It is hoped that the renewed interest in rural areas generated by the farm crisis will produce additional programs addressing the needs of these often underserved populations.

Humans↗