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Biomedical subjects

K Montgomery

Publications and source records attributed to K Montgomery.

At least 19 recordsLinked to original sources
PubMed2006

Upregulation of histidine decarboxylase expression in superficial cortical nephrons during pregnancy in mice and women.

Mechanisms regulating pregnancy-induced changes in renal function are incompletely understood. Few candidate genes have been identified and data suggest that alternate mechanisms remain to be elucidated. Our objective was to screen thousands of genes expressed in kidneys from mice throughout gestation to identify possible key regulators of renal function during pregnancy. Mouse complementary DNA microarrays were used to screen for differences in expression during pregnancy in C57BL/6 mice. Interesting candidate genes whose expression varied with pregnancy were further analyzed by reverse transcription-PCR and Northern blot. Expression was localized by in situ hybridization and immunohistochemistry. Follow-up immunohistochemical analyses in archival human kidney sections from the fetus, non-pregnant, and pregnant women were also performed. Histidine decarboxylase (HDC), the enzyme that synthesizes histamine, was markedly upregulated in the mouse kidney during pregnancy. HDC expression localized to proximal tubule cells of fetal and adult mice. Females showed strong expression in the juxtamedullary zone before pregnancy and upregulation in the superficial cortical zone (SCZ) by mid-gestation. Histamine colocalized with HDC. Male mice showed only low HDC expression. Similar expression patterns were observed in human kidneys. Our results show that HDC expression and histamine production are increased in the SCZ during pregnancy. If histamine acts as a vasodilator, we speculate that increasing production in the SCZ may increase renal blood flow to this zone and recruit superficial cortical nephrons during pregnancy.

Adolescent↗
PubMed2006

'Right' way to 'do' illness? Thinking critically about positive thinking.

Exhortations to 'be positive' accompany many situations in life, either as a general injunction or in difficult situations where people are facing pressure or adversity. It is particularly evident in health care, where positive thinking has become an aspect of the way people are expected to 'do' illness in developed society. Positive thinking is framed both as a moral injunction and as a central belief system. It is thought to help patients cope emotionally with illness and to provide a biological benefit. Yet, the meanings, expectations and outcomes of positive thinking are infrequently questioned and the risks of positive thinking are rarely examined. We outline some of the latter and suggest that health professionals should exercise caution in both 'prescribing' positive thinking and in responding to patients and carers whose belief systems and feelings of obligation rest on it.

Expressed Emotion↗
PubMed2003

Minimal residual disease detection in childhood precursor-B-cell acute lymphoblastic leukemia: relation to other risk factors. A Children's Oncology Group study.

Minimal residual disease (MRD) can be detected in the marrows of children undergoing chemotherapy either by flow cytometry or polymerase chain reaction. In this study, we used four-color flow cytometry to detect MRD in 1016 children undergoing therapy on Children's Oncology Group therapeutic protocols for precursor-B-cell ALL. Compliance was excellent, with follow-up samples received at the end of induction on nearly 95% of cases; sensitivity of detection at this time point was at least 1/10,000 in more than 90% of cases. Overall, 28.6% of patients had detectable MRD at the end of induction. Patients with M3 marrows at day 8 were much more likely to be MRD positive (MRD+) than those with M2 or M1 marrows. Different genetically defined groups of patients varied in their prevalence of MRD. Specifically, almost all patients with BCR-ABL had high levels of end-of-induction MRD. Only 8.4% of patients with TEL-AML1 were MRD+>0.01% compared with 20.3% of patients with trisomies of chromosomes 4 and 10. Our results show that MRD correlates with conventional measures of slow early response. However, the high frequency of MRD positivity in favorable trisomy patients suggests that the clinical significance of MRD positivity at the end of induction may not be the same in all patient groups.

Adolescent↗
PubMed2001

Ethical thinking and stakeholders.

Modern medical practice increasingly requires us to think beyond the confines of the doctor-patient relationship to other stakeholders. Problems and issues that can be identified as being of interest to a number of people are defined as "focal entities". Stakeholders are those with an interest in the outcome of the problem or issue. The salience of stakeholders is defined by their power, legitimacy and urgency. The process of thinking about stakeholders can help to clarify our ethical thinking about matters of importance to people beyond the doctor-patient relationship.

Attitude to Health↗
PubMed2001

Analysis of MUM1/IRF4 protein expression using tissue microarrays and immunohistochemistry.

The gene encoding MUM1 was characterized as a possible translocation partner in chromosomal abnormalities involving a significant number of multiple myelomas. The overexpression of the MUM1 protein as a result of translocation t(6;14) (p25;q32) identified MUM1 as a putative regulatory molecule involved in B-cell differentiation and tumorigenesis. The expression of MUM1 protein in multiple myelomas supports this hypothesis. In the current study, using tissue microarray technology, we have tested the expression of the MUM1 protein in 1335 human malignancies and normal tissues. Our data show that the MUM1 protein is expressed in a wide spectrum of hematolymphoid neoplasms and in malignant melanomas but is absent in other human tumors. In addition, in tissue microarrays as well as in conventional paraffin sections, MUM1 staining was found to lack specificity in detecting plasmacytic differentiation as compared with two markers, CD138/Syndecan and VS38, commonly used in paraffin immunohistochemistry for detection of plasma cells.

Antibodies, Monoclonal↗
PubMed2001

Wireless vital sign telemetry to hand held computers.

Most physicians and other health care providers share/access patient information via hard copy chart records, telephone conversations, or through hospital computer networks. These modalities are cumbersome when physicians are away from the hospital and ground wiring infrastructure is not readily available. In a prior study, we used wireless in-flight telephony and the Internet to transmit vital signs from an airborne Boeing 757 to three remote locations on the ground. However, because all recipient stations relied on an institutional network to receive the information, it was not possible to transfer data to a given location beyond the hospital campus. We now propose an innovative system capable of transmitting telemetry information from any location in the globe to a single portable computer using Wireless Application Protocol (WAP) technology for the Internet. Medical data including blood pressure, pulse, respiratory rate, end tidal CO2, oxygen saturation and EKG tracings were transferred from a G2 (digital cellular) phone linked to a hand held computer to a remote hand held device and were viewed in real time using customized software. Cellular Digital Packet Protocols (CDPD) enabled data transfer speeds up to 19,200 bps. Advances including the Internet and wireless computer technology may revolutionize the way medical information is shared, making it possible for physicians and health allies to directly access patient data from anywhere at any time.

Humans↗
PubMed2001

Virtual reality based surgical assistance and training system for long duration space missions.

Access to medical care during long duration space missions is extremely important. Numerous unanticipated medical problems will need to be addressed promptly and efficiently. Although telemedicine provides a convenient tool for remote diagnosis and treatment, it is impractical due to the long delay between data transmission and reception to Earth. While a well-trained surgeon-internist-astronaut would be an essential addition to the crew, the vast number of potential medical problems necessitate instant access to computerized, skill-enhancing and diagnostic tools. A functional prototype of a virtual reality based surgical training and assistance tool was created at our center, using low-power, small, lightweight components that would be easy to transport on a space mission. The system consists of a tracked, head-mounted display, a computer system, and a number of tracked surgical instruments. The software provides a real-time surgical simulation system with integrated monitoring and information retrieval and a voice input/output subsystem. Initial medical content for the system has been created, comprising craniofacial, hand, inner ear, and general anatomy, as well as information on a number of surgical procedures and techniques. One surgical specialty in particular, microsurgery, was provided as a full simulation due to its long training requirements, significant impact on result due to experience, and likelihood for need. However, the system is easily adapted to realistically simulate a large number of other surgical procedures. By providing a general system for surgical simulation and assistance, the astronaut-surgeon can maintain their skills, acquire new specialty skills, and use tools for computer-based surgical planning and assistance to minimize overall crew and mission risk.

Aerospace Medicine↗
PubMed2001

A virtual environment for simulated rat dissection.

Animal dissection for the scientific examination of organ subsystems is a delicate procedure. Performing this procedure under the complex environment of microgravity presents additional challenges because of the limited training opportunities available that can recreate the altered gravity environment. Traditional crew training often occurs several months in advance of experimentation, provides limited realism, and involves complicated logistics. We have developed an interactive virtual environment that can simulate several common tasks performed during animal dissection. In this paper, we describe the imaging modality used to reconstruct the rat in virtual space, provide an overview of the simulation environment and briefly discuss some of the techniques used to manipulate the virtual rat.

Animals↗
PubMed2000

A sequence-ready physical map of the region containing the human natural killer gene complex on chromosome 12p12.3-p13.2.

We developed a sequence-ready physical map of a part of human chromosome 12p12.3-p13.2 where the natural killer gene complex (NKC) is located. The NKC includes a cluster of genes with structure similar to that of the Ca(2+)-dependent lectin superfamily of glycoproteins that are expressed on the surface of most natural killer (NK) cells and a subset of T cells. These killer cell lectin-like receptors (KLR) are involved in NK target cell recognition, leading to activation or inhibition of NK cell function. We used a number of sequence-tagged site (STS) markers from this region to screen two large insert bacterial artificial chromosome (BAC) libraries and a bacteriophage P1-derived (PAC) chromosome library. The clones were assembled into contiguous sets by STS content analysis. The 72-BAC and 11-PAC contig covers nearly 2 Mb of DNA and provides an average marker resolution of 26 kb. We have precisely localized 17 genes, 5 expressed sequence tags, and 49 STSs within this contig. Of this total number of STS, 30 are newly developed by clone-end sequencing. We established the order of the genes as tel-M6PR-MAFAL (HGMW-approved symbol KLRG1)-A2M-PZP-A2MP-NKRP1A (HGMW-approved symbol KLRB1)-CD69-AICL (HGMW-approved symbol CLECSF2)-KLRF1-OLR1-CD94 (HGMW-approved symbol KLRD1)-NKG2D (HGMW-approved symbol D12S2489E)-PGFL-NKG2F (HGMW-approved symbol KLRC4)-NKG2E (HGMW-approved symbol KLRC3)-NKG2A (HGMW-approved symbol KLRC1)-LY49L (HGMW-approved symbol KLRA1)-cen. This map would facilitate the cloning of new KLR genes and the complete sequencing of this region.

Antigens, CD↗
PubMed2000

Development and application of a virtual environment for reconstructive surgery.

OBJECTIVE: This paper details the development and application of a Virtual Environment for Reconstructive Surgery (VERS). It addresses the technical and user-interface challenges in developing such a system, and the lessons learned during application of the system in the case of a 17-year-old boy with a severe facial defect arising from the removal of a soft-tissue sarcoma. MATERIALS AND METHODS: Computed tomography (CT) scans were segmented into bone and soft-tissue classifications using traditional and novel algorithms, a surface mesh was generated, and imaging artifacts were removed, yielding a mesh suitable for visualization. This patient-specific mesh was then used in a virtual environment by the surgeons for preoperative visualization of the defect, planning of the surgery, and production of a custom surgical template to aid in repairing the defect. RESULTS: This system was successfully used to plan the surgery of the patient and to produce a custom, patient-specific template that was used to harvest bone from a donor site in order to reconstruct the defect. CONCLUSION: Despite technical challenges, virtual-environment surgical planning is useful as a clinical tool for preoperative visualization, cephalometric analysis, and surgical intervention. It can provide a more precise surgical result than would otherwise be realized using traditional methods.

Adolescent↗
PubMed2000

Genetic analysis of the APAF1 gene in male germ cell tumors.

Cytogenetic and molecular analyses have shown that the chromosome band 12q22 is recurrently deleted in male germ cell tumors (GCTs), indicating the presence of a candidate tumor suppressor gene (TSG) in this region. To identify the TSG, we mapped the APAF1 gene, a proapoptotic mammalian homologue of ced-4, to chromosomal band 12q22, that suggested that this might be the candidate deleted gene in GCTs. We further localized the gene between the polymorphic markers D12S1671 and D12S1082 at 12q22 to determine the role of APAF1 in the pathogenesis of GCT, and we characterized its normal genomic structure and analyzed its alterations in GCTs. The APAF1 gene comprises 27 exons, with the coding region spanning 26. The region containing APAF1 was found to be deleted in GCT by fluorescence in situ hybridization analysis, but without evidence of coding sequence alterations. RT-PCR and Western blot analysis showed APAF1 gene expression at detectable levels in all GCT cell lines analyzed. An aberrant-sized APAF1 protein was seen in one cell line. This and 2 other cell lines carrying APAF1 deletions also exhibited defects in dATP-mediated caspase-3 activation. Caspase-3 activity was effectively restored by addition of recombinant caspase-9 and APAF1 proteins, and to a lesser extent by caspase-9 alone, but not by APAF1 alone. These data do not support a TSG role for APAF1, but defects in other components of the apoptotic pathway that may be related to 12q22 deletion cannot be ruled out. Genes Chromosomes Cancer 28:258-268, 2000.

Apoptosis↗
PubMed2000

Human KLRF1, a novel member of the killer cell lectin-like receptor gene family: molecular characterization, genomic structure, physical mapping to the NK gene complex and expression analysis.

The human NK gene complex localized on chromosome 12p12.3 - p13.2 codes for several lectin-like receptor genes expressed by NK cells as well as by other hematopoietic cells. In this study, by using the expressed sequence tag database we identified a novel receptor gene, designated as killer cell lectin-like receptor, subfamily F, member 1 (KLRF1), encoding a putative type II transmembrane glycoprotein. The KLRF1 gene has been localized on the high-resolution physical map of chromosome 12p. The genomic structure of the KLRF1 gene and the existence of one spliced variant are also described. KLRF1 was expressed at the mRNA level in peripheral blood leukocytes, activated NK cells, monocytes and NK and myeloid cell lines. The presence of two immunoreceptor tyrosine-based inhibitory-like motifs within the cytoplasmic tail of KLRF1 suggests an inhibitory role in NK cell and monocyte activity.

Amino Acid Sequence↗
PubMed2000

Youth and digital media: a policy research agenda.

At a time when researchers are still sorting out the complex relationship between adolescents and the mass media, the entire nature of the media system is undergoing dramatic change. The explosive growth of the Internet is ushering in a new digital media culture. Youth are embracing the new technologies much more rapidly than adults. In addition, because of their increased spending power, youth have become a valuable target market for advertisers. These trends have spurred the proliferation of Web sites and other forms of new-media content specifically designed for teens and children. The burgeoning digital marketplace has spawned a new generation of market research companies, and market research on children and youth is outpacing academic research on youth and the newer media. The emergence of this new media culture holds both promise and peril for youth. Whether the positive or negative vision of the digital future prevails will be determined, in large part, by decisions being made now and in the next few years in the halls of government and in corporate boardrooms. Research has contributed to the resolutions of several recent legislative and policy decisions in areas including television violence and the V-chip, children's educational television programming, and privacy and marketing to children on the Web. Future research needs to be designed with the public policy agenda in mind. The academic community has much to contribute to the debates over new developments in the digital age.

Adolescent↗
PubMed2000

High-resolution transcript map of the region spanning D12S1629 and D12S312 at chromosome 12q13: triple A syndrome-linked region.

For those searching for human disease-causing genes, information on the position of genes with respect to genetic markers is essential. The physical map composed of ESTs and genetic markers provides the positional information of these markers as well as the starting point of gene identification in the form of genomic clones containing exons. To facilitate the effort of identification of genes in the region spanning D12S1629 and D12S312, we constructed a high-resolution transcript map with PAC/BAC/cosmid clones. The strategy for the construction of such a map involved utilization of STSs for the screening of the large insert bacterial chromosome libraries and a chromosome 12-specific cosmid library by hybridization. The contig was constructed based on the STS contents of the clones. The resulting high-resolution transcript map of the region between P273P14/SP6 and D12S312 spans 4.4 cM from 66.8 to 71.2 cM of the Généthon genetic map and represents approximately 2.4 Mb. It was composed of 81 BAC, 45 PAC, and 91 cosmid clones with a minimal tiling path consisting of 16 BAC and 4 PAC clones. These clones are being used to sequence this part of chromosome 12. We determined the order of 135 STSs including 74 genes and ESTs in the map. Among these, 115 STSs were unambiguously ordered, resulting in one ordered marker per 21 kb. The order of keratin type II locus genes was determined. This map would greatly enhance the positional cloning effort of the responsible genes for those diseases that are linked to this region, including male germ cell tumor as well as palmoplantar keratoderma, Bothnian-type, and triple A syndrome. This transcript map was localized at human chromosome 12q13.

Addison Disease↗
PubMed2000

Mutations in the protein kinase A R1alpha regulatory subunit cause familial cardiac myxomas and Carney complex.

Cardiac myxomas are benign mesenchymal tumors that can present as components of the human autosomal dominant disorder Carney complex. Syndromic cardiac myxomas are associated with spotty pigmentation of the skin and endocrinopathy. Our linkage analysis mapped a Carney complex gene defect to chromosome 17q24. We now demonstrate that the PRKAR1alpha gene encoding the R1alpha regulatory subunit of cAMP-dependent protein kinase A (PKA) maps to this chromosome 17q24 locus. Furthermore, we show that PRKAR1alpha frameshift mutations in three unrelated families result in haploinsufficiency of R1alpha and cause Carney complex. We did not detect any truncated R1alpha protein encoded by mutant PRKAR1alpha. Although cardiac tumorigenesis may require a second somatic mutation, DNA and protein analyses of an atrial myxoma resected from a Carney complex patient with a PRKAR1alpha deletion revealed that the myxoma cells retain both the wild-type and the mutant PRKAR1alpha alleles and that wild-type R1alpha protein is stably expressed. However, in this atrial myxoma, we did observe a reversal of the ratio of R1alpha to R2beta regulatory subunit protein, which may contribute to tumorigenesis. Further investigation will elucidate the cell-specific effects of PRKAR1alpha haploinsufficiency on PKA activity and the role of PKA in cardiac growth and differentiation.

Abnormalities, Multiple↗