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Biomedical subjects

K Wallace

Publications and source records attributed to K Wallace.

At least 19 recordsLinked to original sources

Gastric nematodes of nile crocodiles, Crocodylus niloticus Laurenti, 1768, in the Okavango River, Botswana.

The ascaridoid nematodes Dujardinascaris madagascariensis Chabaud & Caballero, 1966, Dujardinascaris dujardini (Travassos, 1920), Gedoelstascaris vandenbrandeni (Baylis, 1929) Sprent, 1978 and Multicaecum agile (Wedl, 1861) Baylis, 1923 were recovered from the stomach contents of Crocodylus niloticus Laurenti, 1768 from the Okavango River, Botswana, together with Eustrongylides sp., a dioctophymatoid nematode usually parasitizing piscivorous birds. Dujardinascaris madagascariensis was present in most of the infected hosts, while the remaining species were mostly represented in single collections in one to three hosts. All four ascaridoid nematodes represent new geographic records.

Alligators and Crocodiles↗

Identification of a high affinity nucleocapsid protein binding element within the Moloney murine leukemia virus Psi-RNA packaging signal: implications for genome recognition.

Murine leukemia virus (MLV) is currently the most widely used gene delivery system in gene therapy trials. The simple retrovirus packages two copies of its RNA genome by a mechanism that involves interactions between the nucleocapsid (NC) domain of a virally-encoded Gag polyprotein and a segment of the RNA genome located just upstream of the Gag initiation codon, known as the Psi-site. Previous studies indicated that the MLV Psi-site contains three stem loops (SLB-SLD), and that stem loops SLC and SLD play prominent roles in packaging. We have developed a method for the preparation and purification of large quantities of recombinant Moloney MLV NC protein, and have studied its interactions with a series of oligoribonucleotides that contain one or more of the Psi-RNA stem loops. At RNA concentrations above approximately 0.3 mM, isolated stem loop SLB forms a duplex and stem loops SL-C and SL-D form kissing complexes, as expected from previous studies. However, neither the monomeric nor the dimeric forms of these isolated stem loops binds NC with significant affinity. Longer constructs containing two stem loops (SL-BC and SL-CD) also exhibit low affinities for NC. However, NC binds with high affinity and stoichiometrically to both the monomeric and dimeric forms of an RNA construct that contains all three stem loops (SL-BCD; K(d)=132(+/-55) nM). Titration of SL-BCD with NC also shifts monomer-dimer equilibrium toward the dimer. Mutagenesis experiments demonstrate that the conserved GACG tetraloops of stem loops C and D do not influence the monomer-dimer equilibrium of SL-BCD, that the tetraloop of stem loop B does not participate directly in NC binding, and that the tetraloops of stem loops C and D probably also do not bind to NC. These surprising results differ considerably from those observed for HIV-1, where NC binds to individual stem loops with high affinity via interactions with exposed residues of the tetraloops. The present results indicate that MLV NC binds to a pocket or surface that only exists in the presence of all three stem loops.

Amino Acid Sequence↗

Deep and stable interferometric nulling of broadband light with implications for observing planets around nearby stars

The number of indirectly detected planetary systems around nearby stars has grown tremendously since their initial discovery five years ago. But the direct observation of light reflected from these systems remains a formidable task, because of the high contrast ratios between them and their parent stars, and because of the tiny angular separations. Theoretically, these difficulties can be overcome by using a dual-aperture stellar interferometer in which the starlight is cancelled, or 'nulled' by broadband destructive interference, leaving the planet's light visible. Although the basic requirement of equal and oppositely directed electric fields is easy to state, an experimental demonstration of deep broadband nulling has been lacking, owing to difficulties engendered by the needs for extreme symmetry and stability, and low dispersion in the optical system. Here we report the deep (10(-4)) and stable nulling of broadband (18% bandwidth) thermal light. These results validate the physical principles underlying future planet-searching interferometers, and our laboratory instrument will serve as a prototype for the nulling instrument to be implemented on the Keck interferometer in 2001.

Journal Article↗

The pan-neural bHLH proteins DEADPAN and ASENSE regulate mitotic activity and cdk inhibitor dacapo expression in the Drosophila larval optic lobes.

Developmental regulators and cell cycle regulators have to interface in order to ensure appropriate cell proliferation during organogenesis. Our analysis of the roles of the pan-neural genes deadpan and asense defines critical roles for these genes in regulation of mitotic activities in the larval optic lobes. Loss of deadpan results in reduced cell proliferation, while ectopic deadpan expression causes over-proliferation. In contrast, loss of asense results in increased proliferation, while ectopic asense expression causes reduced proliferation. Consistent with these observations endogenous Deadpan is expressed in mitotic areas of the optic lobes, and endogenous Asense is expressed in cells that will become quiescent. Altered Deadpan or Asense expression results in altered expression of the cyclin dependent kinase inhibitor gene dacapo. Thus, regulation of mitotic activity during optic lobe development may, at least in part, involve deadpan and asense mediated regulation of the cyclin dependent kinase inhibitor gene dacapo. genesis 26:77-85, 2000.

Animals↗

The incidence of ventilator-associated pneumonia and success in nutrient delivery with gastric versus small intestinal feeding: a randomized clinical trial.

BACKGROUND: Enteral feeding provides nutrients for patients who require endotracheal tubes and mechanical ventilation. There is a presumed increase in the risk of ventilator-associated pneumonia (VAP) with tube feeding. This has stimulated the development of procedures for duodenal intubation and small intestinal (SI) feeding as primary prophylaxes to prevent VAP. OBJECTIVE: To investigate the rate of VAP and adequacy of nutrient delivery with gastric (G) vs. SI feeding. DESIGN: A prospective, randomized, controlled trial. SETTING: A medical intensive care unit of a county hospital. PATIENTS: A total of 44 endotracheally intubated, mechanically ventilated patients requiring enteral nutrition. INTERVENTION: Subjects were randomized to receive enteral nutrition via G or SI feeding. Protocols directed the placement of the feeding tube and the infusion of enteral nutrition and defined the radiographic and clinical criteria for a diagnosis of VAP. MEASUREMENTS AND OUTCOMES: The incidence of VAP and the adequacy of nutritional supplementation were prospectively followed. The relative risk of VAP with SI was 1.1 (95% confidence interval 0.96-2.44) compared with G. The SI group received a greater percentage of their caloric requirements (SI 69 +/- 7% vs. G 47 +/- 7%, mean +/- SEM, p < .05). Mortality did not differ between G (26 +/- 9%) and SI (24 +/- 10, p = .86). CONCLUSIONS: There is no clear difference in the incidence of VAP in SI compared with G enteral nutrition. Patients given feeding into the SI do receive higher calorie and protein intakes.

Enteral Nutrition↗

Phase I study of docetaxel dose escalation in combination with fixed weekly gemcitabine in patients with advanced malignancies.

PURPOSE: To determine the maximum-tolerated dose of monthly docetaxel combined with fixed-dose weekly gemcitabine and describe the dose-limiting toxicities (DLTs) of the combination. PATIENTS AND METHODS: Patients with refractory solid tumors were treated with gemcitabine days 1, 8, and 15 every 4 weeks at a fixed dose of 800 mg/m2. Two docetaxel administration schedules were studied, with the drug administered either day 1 or day 15 at doses of 45, 60, 75, and 100 mg/m2 per cycle. RESULTS: Forty patients received 132 cycles of chemotherapy. On the day-1 schedule, the maximum-tolerated docetaxel dose was the highest planned dose of 100 mg/m2 with two DLT episodes among 12 patients treated with 34 cycles at this dose level. On the day-15 schedule, delivery of the planned docetaxel doses was not feasible because of thrombocytopenia and hepatic dysfunction. Hematologic toxicities included grade 4 neutropenia in 16 patients, with three episodes of febrile neutropenia; grades 3 to 4 thrombocytopenia in nine patients; and anemia that required RBC transfusions in 10 patients. For patients treated at the highest docetaxel dose level, myelosuppression was not dose limiting and only one of 34 cycles was complicated by febrile neutropenia. The most common nonhematologic toxicities were asthenia, flu-like symptoms, and fluid retention. Antineoplastic activity was noteworthy, with partial responses in nine of 21 patients with pretreated non-small-cell lung cancer (NSCLC; 43%; 95% confidence interval, 22 to 66), in four of seven patients with breast cancer, and in one patient with esophageal adenocarcinoma. CONCLUSION: Gemcitabine 800 mg/m2 days 1,8, and 15 can be safely combined with docetaxel 100 mg/m2 day 1 of a 28-day cycle. The observed antitumor activity warrants phase II evaluation.

Adult↗

How to diagnose hypopituitarism. Learning the features of secondary hormonal deficiencies.

Hypopituitarism has many causes and various clinical presentations. Diagnosis depends on history taking, clinical suspicion, and an understanding of the hypothalamic-pituitary-target organ axes for proper interpretation of laboratory data. In the patient described in the case report, amenorrhea and inability to lactate were early clinical clues to a possible pituitary problem, but she felt otherwise fairly well over the years and did not seek evaluation. Thyroid-function tests showed normal thyrotropin measurements, but they were inappropriately low for the low T4 concentrations, indicating pituitary thyrotropin deficiency. Given the patient's obstetric history and overall clinical course, hypopituitarism resulting from postpartum pituitary necrosis was suspected. Magnetic resonance imaging of the pituitary was performed, and she was treated with glucocorticoids, T4 replacement, and estrogen-progesterone replacement. We expected her to do well. In general, the long-term outlook for patients with hypopituitarism is excellent, once the problem is diagnosed. Clinical signs and symptoms should be completely relieved by adequate hormone-replacement therapy, and with proper long-term follow-up and special attention during intercurrent illness, there should be no adverse outcomes.

Adrenal Insufficiency↗

Thyroid dysfunction: how to manage overt and subclinical disease in older patients.

Thyroid dysfunction is relatively common in older patients, but its clinical presentation varies. It may be obvious from the classic presenting symptoms, or it may be asymptomatic and discovered incidentally during routine testing. The clinical diagnosis of hypothyroidism and hyperthyroidism can be difficult in older patients, because many of the usual symptoms may be mistaken for the effects of aging or other medical conditions. Even so, these diseases in their overt forms are always significant and require treatment. On the other hand, subclinical hypo- and hyperthyroidism are often incidental biochemical abnormalities that may or may not require intervention.

Aged↗

Dacapo, a cyclin-dependent kinase inhibitor, stops cell proliferation during Drosophila development.

Most cell types in multicellular eukaryotes exit from the mitotic cell cycle before terminal differentiation. We show that the dacapo gene is required to arrest the epidermal cell proliferation at the correct developmental stage during Drosophila embryogenesis. dacapo encodes an inhibitor of cyclin E/cdk2 complexes with similarity to the vertebrate Cip/Kip inhibitors. dacapo is transiently expressed beginning late in the G2 phase preceding the terminal division (mitosis 16). Mutants unable to express the inhibitor fail to arrest cell proliferation after mitosis 16 and progress through an extra division cycle. Conversely, premature dacapo expression in transgenic embryos results in a precocious G1 arrest.

Amino Acid Sequence↗

Factors affecting treatment decisions and satisfaction of owners of cats with cancer.

Cancer in cats is being diagnosed with increasing frequency. Euthanasia or an active intervention such as chemotherapy, radiation therapy, or surgery are treatment choices for the owner at diagnosis of the cat's disease. In this study, 2 interviews with cat owners, one soon after diagnosis of cancer in the cat and one 6 months later, were used to identify owner characteristics associated with a decision of euthanasia or intervention, to identify factors associated with an owner's satisfaction with euthanasia or intervention, and to evaluate inappropriate expectations of the owners who selected an intervention. The study included 89 owners from 3 referral hospitals. In logistic regression analysis, significant factors were not found that affected the owner's decision to euthanatize the cat versus intervene. Satisfaction with the decision to euthanatize the cat was associated with the ability of the cat to groom itself, eat, and play at the first interview. Among owners who selected an intervention, 4 combinations of factors were associated with being satisfied. The first combination was clinic of origin (CLIN), having a live cat at the 6-month follow-up interview (LIVE), and understanding the number of return visits required for the intervention. The second was CLIN, LIVE, and type and frequency of adverse effects from the intervention at the 6-month interview. The third was CLIN, LIVE, and feeling guilty at the 6-month interview. The fourth was CLIN, LIVE, and whether the cat had a good or excellent quality of life at the first interview. Thirty percent (21/69) of the owners tended to overestimate their cats' life expectancy. Owners also felt they had reasonably accurate estimations of adverse effects of treatment and number of return visits, but underestimated the costs required for an intervention. For owners who elect an intervention, a reminder from the veterinarian that emotional upheavals may develop even after the decision has been made is important. To provide optimal patient care and client education, veterinarians must find a middle ground between being knowledgeable, practical, and informed, and being compassionate and approachable.

Animals↗

Post-transcriptional stimulation of transforming growth factor beta 1 mRNA by TGF-beta 1 treatment of transformed human osteoblasts.

Following exogenous administration of transforming growth factor-beta 1 (TGF-beta 1) polypeptide to the human osteosarcoma cell line TE-85, we observed a 2- to 6-fold stimulation of steady-state TGF-beta 1 mRNA. The stimulation was dose- and time-dependent, as judged from Northern blot hybridization analyses. A 2- to 6-fold increase of the TGF-beta 1 polypeptide was also found in the media of these cells after TGF-beta 1 treatments. The autostimulation of TGF-beta 1 mRNA was nullified by cycloheximide treatment of the cells. The in vitro transcription rates of the TGF-beta 1 gene by isolated nuclei were not altered by TGF-beta 1 treatment. Under conditions of transcriptional inhibition, the stability of TGF-beta 1 mRNA was enhanced nearly two-fold by TGF-beta 1 treatment. Our findings indicate that TGF-beta 1 can stimulate autologous gene expression and subsequent polypeptide translation by a post-transcriptional mechanism requiring protein synthesis in human osteoblast-like cells. The recognized versatility of TGF-beta 1 autostimulation mechanisms (transcriptional and post-transcriptional) in other mesenchymal cells may apply also to skeletal cells, further underscoring the broad and potent activities of this cytokine.

Cell Line, Transformed↗

Skeletal response to immobilization in Paget's disease of bone: a case report.

The authors discuss a case of Paget's disease of the forearm in which the Pagetic radius and non-Pagetic ulna responded differently to immobilization. The high turnover state of Pagetic bone is more sensitive to physical unloading than normal bone, and thus more rapidly develops osteopenia of immobilization. The different responses to immobilization between Pagetic bone and site controlled normal bone illustrate how physical and metabolic factors interact at a skeletal site to regulate bone remodeling and bone mass.

Bone Remodeling↗

Cytogenetic and histologic findings in 17 pulmonary chondroid hamartomas: evidence for a pathogenetic relationship with lipomas and leiomyomas.

Pulmonary chondroid hamartomas (PCH) are benign tumors that contain mesenchymal and epithelial components. In this series, we identified clonal chromosome aberrations in mesenchymal cells from 10 of 17 PCH. Chromosome band 12q15 was rearranged most frequently (N = 4), and one case had a t(12;14)(q15;q24) that was identical cytogenetically to the characteristic translocation in uterine leiomyomas. Histologic review revealed diverse mesenchymal populations, including undifferentiated cells, cartilage, adipose tissue, and smooth muscle, in most of the PCH. These findings suggest that PCH result from neoplastic transformation of a primitive mesenchymal cell that differentiates along chondroid, adipose, and smooth muscle pathways.

Adult↗

Olfactory performance during childhood. II. Developing a discrimination task for children.

OBJECTIVES: (1) To create a match-to-sample odorant discrimination task (MODT) for children and adolescents; (2) to assess whether nonolfactory factors affect olfactory performance more on an identification task than on the MODT; (3) to evaluate subjects with olfactory dysfunction; and (4) to create age-appropriate sets of odorants for use in the MODT format to test children of different ages. STUDY DESIGN: We tested 75 normal children, aged 2 to 18 years, and 17 other subjects, aged 7 to 53 years, with known or suspected olfactory dysfunction, with the MODT. We compared the age trends in variability of scores on the MODT with those on an odorant identification task, using a weighted linear regression analysis. RESULTS: The MODT was useful in children aged 5 years and older, but not generally in the 2- to 4-year-old children. There was an appreciable age trend in the variability of the scores on the identification task but not on the MODT. Mean MODT scores for subjects with suspected or known olfactory dysfunction were far below average. Finally, we created four sets of odorants that will likely be sensitive to age-specific changes in olfactory performance. CONCLUSIONS: The MODT appears to be a suitable test instrument to assess olfaction in children aged 5 and older and is less likely to be influenced by nonolfactory factors than an identification task. According to our preliminary results, it is likely that the MODT will allow us to detect olfactory deficits in children of many ages.

Adolescent↗

Assessment of an abbreviated odorant identification task for children: a rapid screening device for schools and clinics.

To validate the level of olfactory performance of children, we tested 825 volunteers, aged 4-17 years, with an abbreviated form of our pediatric odorant identification task. The test consisted of sniffing and identifying five odorants (baby powder, bubble gum, candy cane, licorice and peach). Mean olfactory scores increased as a function of age, reaching a plateau of about 94-95% correct at 8 years of age. In general, girls out-performed boys. Physicians require a test instrument such as the one we have devised to allow them to diagnose olfactory dysfunction in children. The present task is particularly applicable in screening large numbers of children in clinics or schools because it can be administered easily and rapidly. Adult subjects with olfactory dysfunction also performed poorly on this odorant identification task designed for children. Therefore, we expect that our odorant identification task will also detect children with severe olfactory dysfunction.

Adolescent↗

Gastrointestinal perforation or vascular injury? A diagnostic dilemma for computed tomography in blunt abdominal trauma.

The authors describe an unconscious 20-year-old woman with Crohn's disease who was examined after a motor vehicle accident. During dynamic computed tomography after intravenous and oral administration of contrast material, contrast agent was observed in the peritoneal cavity. The source of the free contrast material was active bleeding, but it was initially mistaken for extravasation from the bowel. Exploratory laparotomy revealed transection of the superior mesenteric vein.

Abdominal Injuries↗