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Biomedical subjects

D W Anderson

Publications and source records attributed to D W Anderson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Motor neuron disease on Guam: geographic and familial occurrence, 1956-85.

We investigated the geographic and familial occurrence of motor neuron disease (MND) on Guam, and then considered etiologic hypotheses related to cycad use and metal intoxication. The research was based on 303 Chamorros from Guam and 3 Chamorros from other Mariana Islands, all with MND onset on Guam during 1956-85. Inarajan and Umatac, two southern districts, each had, for both sexes combined, an average incidence rate significantly higher than the corresponding overall rate for Guam. Also, for each sex, geographic patterns of incidence were significantly related to 1) socioeconomic level (men only), 2) cycasin concentrations in cycad flour samples (men and women), 3) iron concentrations in water samples (men and women), 4) silicon concentrations in water samples (men only), and 5) cobalt and nickel concentrations in soil samples (men and women). The MND risk in susceptible sibships was about 7-28 times greater than that in the general population. The cycad hypothesis conforms somewhat better than the metal intoxication hypothesis with the data presented.

Female↗
PubMed1996

Efficacy of synthetic peptide-containing surfactant in the treatment of respiratory distress syndrome in preterm infant rhesus monkeys.

Studies were conducted to assess the efficacy and safety of a synthetic peptide-containing surfactant in the treatment of respiratory distress syndrome (RDS) in preterm (approximately 80% of normal gestation) infant rhesus monkeys. Surfactant was prepared consisting of the phospholipids dipalmitoylphosphatidyl choline and palmitoyl-oleoyl phosphatidyl glycerol and a synthetic peptide modeled after surfactant protein B (SP-B), "KL4-Surfactant" contained a peptide having the sequence KLLLLKLLLLKLLLLKLLLLK, where "K" is lysine and "L" is leucine. The peptide was selected because it mimics the repeating stretches of hydrophobic residues with intermittent basic hydrophilic residues seen in SP-B. KL4-Surfactant was shown to have biophysical activity assessed as the ability to lower surface tension at an air-liquid interface in a pulsating bubble surfactometer. Thirty premature rhesus monkeys were treated shortly after birth with one dose of KL4-Surfactant. The arterial to alveolar oxygen partial pressure ratio (a/A) was found to rise from a pretreatment level of 0.11 +/- 0.01 (mean +/- SEM), indicative of severe RDS, to 0.40 +/- 0.02 at 12-13 h post-treatment. The improvement in oxygenation persisted throughout the study period, with a mean a/A at 22-23 h of 0.45 +/- 0.07. Chest radiographs and gross and microscopic examination of the lungs all confirmed the reversal of the atelectasis seen before treatment. Animals treated with a dose of 200 mg/kg showed a faster, more consistent, and greater response than did a group treated with an average dose of 127 mg/kg. There was no evidence of toxicity after treatment with the higher dose as demonstrated by physiologic, hematologic, biochemical, and pathologic data. The importance of the peptide in the synthetic surfactant was apparent from the results obtained with a control group of nine premature monkeys treated with a non-peptide-containing surfactant; the a/A of this group was 0.15 +/- 0.03 at nine hours of age as compared with a value of 0.38 +/- 0.02 for 30 comparable animals receiving KL4-Surfactant.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

Functional results in oral cavity reconstruction using reinnervated versus nonreinnervated free fasciocutaneous grafts.

Recent advances in free-tissue transfer have given the otolaryngologist--head and neck surgeon a number of reliable options for reconstruction of the oral cavity following ablative procedures. One recent modification has been the transfer of free reinnervated fasciocutaneous grafts in the hope of enhancing oral rehabilitation following surgery. To assess the efficacy of this modification, a protocol was established to retrospectively evaluate patients that received either reinnervated or non-reinnervated free-tissue transfers. Factors including site, surgical resection, type of tissue transfer, and follow-up period were controlled. Evaluation of free-graft sensory return and quality of life was carried out through physical examination and patient interview. Speech assessment was carried out using standardized tests of intelligibility administered by a speech pathologist. Swallowing assessment was carried out with videocinefluoroscopic and scintigraphic techniques, and the oropharyngeal swallow efficiency was calculated. Sensory return in the reinnervate free grafts was superior; however, there was not statistical difference between groups in the speech and swallowing tests. Quality of life was judged to be good in both groups. Sensory return and functional outcome in intraoral reconstruction after tumour ablation was reviewed and discussed

Adult↗
PubMed1995

Constrained peptide analogues of transforming growth factor-alpha residues cysteine 21-32 are mitogenically active. Use of proline mimetics to enhance biological potency.

Two proline mimetics, the enantiomers of 2-aza-bicyclo[2,2,1]heptane-3-carboxylic acid, have been incorporated in place of Pro30 into synthetic peptides based on the B-loop beta-sheet sequence of human transforming growth factor-alpha (TGF-alpha) (residues Cys21-Cys32). The peptides were further modified by inclusion of an N-terminal phenylalanine and constrained by formation of an intramolecular disulfide bond. While no mitogenic response was observed in the parental NR6 cell line, the peptides stimulated DNA synthesis in NR6/HER cells (NR6 fibroblasts transfected with the human epidermal growth factor receptor). Induction of DNA synthesis was dose dependent, with EC50 values in the range 130-330 microM; in the presence of low doses of TGF-alpha, the mitogenic effect of the peptides was additive, up to the plateau response achieved by maximal doses of TGF-alpha alone. These effects are consistent with the peptides acting via the same mechanism as TGF-alpha. Analysis of the structure of the peptides by NMR indicated that the presence of the mimetics significantly increased the propensity of the peptidyl-proline bond to adopt the cis conformation. These data confirm the role of the beta-sheet in receptor activation, and emphasize the importance of presentation of peptides in an appropriate conformation for recognition.

Amino Acid Sequence↗
PubMed1995

Aberrant splicing of the type III procollagen mRNA leads to intracellular degradation of the protein in a patient with Ehlers-Danlos type IV.

Ehlers-Danlos syndrome type IV (EDS IV) is an autosomal dominant disorder characterized by fragile skin, blood vessels, and internal organs and associated with decreased production, secretion, or thermal stability of type III procollagen. Mutations in the gene for type III procollagen have been identified in patients exhibiting decreased secretion or thermal stability of the protein, but no defect has been elucidated to explain the decreased production of type III procollagen in some patients with EDS IV. We report on a patient with a moderate case of EDS IV who produced decreased amounts of type III procollagen despite normal levels of translatable type III procollagen mRNA. S1 nuclease analysis of the type III procollagen mRNA indicated a defect in the region encoding exon 27. Sequence analysis of cDNA clones and genomic fragments generated by polymerase chain reaction amplification revealed that sequences encoded by exon 27 were absent from 3 out of 5 cDNA clones and that a G at the +5 position of the splice donor site in intron 27 was changed to an A in one allele of the patient's type III procollagen gene. Using a cDNA-genomic DNA hybrid probe in S1 nuclease analysis, fragments consistent with mRNA species containing and lacking exon 27 were detected in a 1:1 ratio. Pulse label and chase experiments in the presence or absence of brefeldin A indicated that most of the type III procollagen molecules synthesized by the patient's fibroblasts were not secreted into the medium but were degraded in the endoplasmic reticulum-Golgi compartment by a nonlysosomal mechanism.

Adult↗
PubMed1995

A primary immunodeficiency syndrome in Shar-Pei dogs.

A multiple immunodeficiency, involving antibody- and cell-mediated responses in 10 Chinese Shar-Pei (CSP) dogs is described. Abnormal levels of serum IgM and IgA in most cases, and IgG in fewer cases characterized the immunoglobulin deficiencies. Decreased in vitro proliferative responses of pokeweed mitogen (PWM)-stimulated peripheral blood mononuclear cells (PBMC) were found in nine cases. Clinical presentation involved several organ systems and was associated with recurrent infections and malignancy. Sera from affected dogs suppressed PWM-stimulated cell proliferation of affected and normal dogs, but not cultures stimulated with PWM followed by recombinant IL-2 (rIL-2). In vitro supplementation of PBMC cultures with immunomodulatory guanosine analogs (GA) resulted in increased de novo IgG and/or interleukin-6 (IL-6) synthesis. Cells from five immunodeficient dogs showed in vitro evidence of GA- or rIL-2-dependent enhanced immunological responses. Since rIL-2-mediated activation of the IL-2 receptor and GA-mediated immunomodulation are reported to act through protein kinase C (PKC)-independent pathways, it is concluded that the IL-2 receptor is functional in these dogs and that cell activation through alternative pathways may restore immune responses in affected CSP dogs.

Animals↗
PubMed1995

Motor neuron disease on Guam: temporal occurrence, 1941-85.

Using a case registry, we investigated the temporal occurrence of motor neuron disease (MND) on Guam. MND with onset during 1941-85 was documented in 434 Chamorros and 9 non-Chamorro migrants who had lived on Guam before onset. Increased median age at onset and decreased age-adjusted incidence rates (since the early 1960s) were observed for Chamorros of both sexes. Our evidence about MND on Guam is consistent with: 1) The latent period duration has varied from years to decades; 2) With time, the exposure period or latent period, or both, have lengthened; 3) The high risk of acquiring the condition has been reduced since, at least, the early 1950s, and the most recent years of meaningful risk were the early to middle 1960s; 4) The critical age for acquiring the condition is in adolescence and adulthood; 5) Change of environment from Guam to overseas during childhood resulted in decreased risk of acquiring the condition.

Adult↗
PubMed1995

Methods for a prevalence survey of neurological disorders in Junín, Buenos Aires, Argentina.

A two-phase prevalence survey of major neurological disorders was conducted in the city of Junín, Buenos Aires, Argentina. In phase 1, a sample of households was screened to identify persons who possibly had a disorder of interest. In phase 2, persons screened as positive in phase 1 were clinically examined by neurologists. This article describes the survey methods used, discusses related methodologic issues (e.g., the problem of false negatives), and presents demographic findings and attrition tallies. A brief account of the pilot investigations is also included as an appendix.

Adolescent↗
PubMed1995

Case finding for epidemiological surveys of multiple sclerosis in United States communities.

In regard to prevalence surveys of MS in US communities, this article considers the relative merits of case finding through hospitals, physicians, MS service organisations, neurology practices, death certificates, chronic care facilities and media announcements and lay referrals. The current value of hospitals and non-neurological practitioners for case finding is questionable, given the changes in clinical practice with respect to MS and the data collection problems inherent with surveys of physicians. We suggest giving priority to the following case-finding methods: manually reviewing patient records of neurology practices, screening patient rolls of local MS service organisations and surveying chronic care facilities. In some US communities, these methods may need to be augmented by also surveying internists, general practitioners and family practitioners. Capture-recapture methodology offers a way to evaluate the completeness of case ascertainment.

Death Certificates↗
PubMed1995

Oncogenic osteomalacia: evidence for a humoral phosphaturic factor.

Oncogenic osteomalacia is a syndrome characterized by phosphaturia, hypophosphatemia, reduced vitamin D levels, and osteomalacia. The cause is not known, but all patients have had a tumor; usually of mesenchymal origin. Removal of the tumor reverses the metabolic abnormalities. We report a patient with osteomalacia, severe hypophosphatemia, elevated alkaline phosphatase, low 1,25-dihydroxyvitamin D3, and phosphaturia. A tumor was identified in the infratemporal fossa. The tumor was removed, and all of the biochemical abnormalities resolved over the subsequent 8 months. The bone density returned to normal values. The tumor had the appearance of a paraganglioma and was used to establish a cell culture line called JH-55. Electron microscopy of the original tumor and the JH-55 cells demonstrated the presence of neurosecretory granules. A bioassay using opossum kidney cells was used to evaluate phosphate transport. Conditioned medium from the JH-55 cells inhibited phosphate reabsorption by the kidney tubular cells. Maximal inhibition required a 24-h incubation period and was not altered by the presence of an inhibitor of protein synthesis (10 micrograms/mL cycloheximide). Immunoassays revealed no detectable PTH-related peptide or intact PTH in the JH-55 medium. The cause of this paraneoplastic syndrome is not known, but all of the evidence is consistent with the action of a hormone that produces phosphaturia. This putative factor is distinct from other hormones that cause phosphaturia.

Animals↗
PubMed1995

Sampling lymph node content of human immunodeficiency virus type 1 nucleic acids and p24 antigen by fine-needle aspiration in early-stage patients.

The potential of lymph node fine-needle aspiration (LNFNA) for sampling viral load was evaluated in excised, peripheral lymph nodes from five patients with early-stage human immunodeficiency virus type 1 HIV-1 disease (asymptomatic, CD4 cells > 300/mm3). The preponderance (> 80%) of viral RNA was within follicular germinal centers as noted by in situ hybridization on lymph node frozen sections (LNFSs) as well as within cohesive groups of 10-20 lymphoid cells (microfragments) in LNFNA preparations. Quantification of cells expressing HIV-1 RNA by in situ hybridization, quantification of HIV-1 gag RNA and gag DNA per 10(5) cells by polymerase chain reaction, and measurement of p24 antigen per 10(5) cells yielded similar values for LNFNA, lymph node mononuclear cells (LNMCs) from tissue homogenates by Ficoll-Hypaque separation, and LNFS. Sampling of lymph node viral load by LNFNA appears to capture viral components associated with both individual expressing cells and follicular germinal centers. Due to the advantages in terms of patients' morbidity, repeatability, and cost, assessment of lymphoid tissue viral load by LNFNA warrants an in vivo feasibility trial as an alternative to lymph node biopsy.

Adult↗
PubMed1994

Attrition and use of proxy respondents and auxiliary information in the Sicilian Neuroepidemiologic Study.

Two-phase prevalence surveys with screening (phase 1) and examination (phase 2) are useful for some chronic diseases. Attrition, which may bias estimates, occurs in either phase because some eligible subjects die before contact, some refuse to cooperate, some are incapacitated, and some are unreachable. This investigation relates to a survey of neurologic diseases conducted in three municipalities of Sicily (prevalence date, November 1, 1987) and considers the attrition experienced and the use of proxy respondents in phase 1 and auxiliary information in phase 2 to offset, in part, this attrition. Regarding case finding, the salvage effort was more productive for decreased and incapacitated subjects. The age, sex, and household size of the subject were related to phase 1 attrition, but only age was related for all four attrition groups--deceased, refusing, incapacitated, and unreachable subjects. On the basis of information from proxy respondents, the educational levels of refusing and unreachable subjects were compared with those of subjects screened directly. Refusing subjects were less educated, and unreachable subjects were more educated. The proxy respondent performance, as indicated by "don't know" responses, was better with screening items concerning facial paralysis and mouth drooping (and not limb sensory abnormalities or impaired consciousness), better with younger subjects, and worse with refusing or incapacitated subjects.

Adolescent↗
PubMed1994

Reticulocyte measurements as a bioassay for erythropoietin.

The possibility of using reticulocyte counts in peripheral blood to assay erythropoietic activity of recombinant human erythropoietin (r-HuEPO) was evaluated in normal mice. Mice were injected subcutaneously with r-HuEPO on days 0, 1 and 2 and bled on day 4 for reticulocyte count determinations, using an automated counting system with thiazole orange fluorescent staining and flow cytometric analysis. Reticulocyte counts increased in a dose-dependent fashion upon administration of r-HuEPO. The reticulocyte count was unaffected by asialylated EPO as well as other substances tested (interleukin-1, interleukin-3, dexamethasone, human chorionic gonadotropin). These data demonstrate the usefulness of employing reticulocyte counts as a rapid, specific and reproducible assay for in vivo erythropoietic activity of r-HuEPO.

Animals↗
PubMed1994

Tepoxalin: a dual cyclooxygenase/5-lipoxygenase inhibitor of arachidonic acid metabolism with potent anti-inflammatory activity and a favorable gastrointestinal profile.

Tepoxalin [5-(4-chlorophenyl)-N-hydroxy-(4-methoxyphenyl)-N-methyl-1H- pyrazole-3-propanamide] is a potent inhibitor of sheep seminal vesicle cyclooxygenase (CO) (IC50 = 4.6 microM), rat basophilic leukemia cell (RBL-1) lysate CO (IC50 = 2.85 microM) and CO from intact RBL-1 cells (IC50 = 4.2 microM). The compound inhibits the production of thromboxane B2 (TxB2) in Ca++ ionophore A-23187-stimulated human peripheral blood leukocytes (HPBL; IC50 = 0.01 microM) and human whole blood (IC50 = 0.08 microM) and is a potent inhibitor of epinephrine-induced human platelet aggregation (IC50 = 0.045 microM). Tepoxalin inhibits lipoxygenase (LO) in RBL-1 lysates (IC50 = 0.15 microM) and intact RBL-1 cells (IC50 = 1.7 microM) and inhibits the generation of leukotriene B4 (LTB4) in calcium ionophore A-23187-stimulated HPBL (IC50 = 0.07 microM) and human whole blood (IC50 = 1.57 microM). Human platelet 12-LO (IC50 = 3.0 microM) is inhibited, but 15-LO is only weakly so (IC50 = 157 microM). In vivo, tepoxalin, administered orally, demonstrated potent anti-inflammatory activity in the established adjuvant arthritic rat (ED50 = 3.5 mg/kg) and potent analgesic activity in the acetic acid abdominal construction assay in mice (ED50 = 0.45 mg/kg). In an ex vivo whole blood eicosanoid production assay, tepoxalin produces a dose-related inhibition of prostaglandin (PG) and LT production in dogs (PGF2 alpha - ED50 = 0.015 mg/kg; LTB4 - ED50 = 2.37 mg/kg) and adjuvant arthritic rats following oral administration. In adjuvant arthritic rats, tepoxalin is devoid of ulcerogenic activity within its anti-inflammatory therapeutic range (1-33 mg/kg p.o.) and does not exhibit ulcerogenic activity in normal rats at doses lower than 100 mg/kg (UD50 = 173 mg/kg p.o.). Tepoxalin represents a new class of anti-inflammatory drugs which may exhibit less gastrointestinal toxicity and may be efficacious in immunoinflammatory disease states where excessive PG and LT production has been implicated and may offer a significant alternative to nonsteroidal and corticosteroidal anti-inflammatory therapy.

Animals↗
PubMed1993

Experimental antiasthmatic activity of RWJ 22108: a bronchoselective calcium entry blocker.

RWJ 22108 (N-benzyl-N-methylaminoethyl 9-(2-chloro-6-fluorophenyl)-2,3,4,5,6,9-hexahydro-7-methyl-1, 1-dioxothiacyclohepteno-[3,2-b]pyridine-8-carboxylate) is a new bronchoselective calcium entry blocker with potential use as an antiasthmatic agent. Previous studies have shown that RWJ 22108 is a potent calcium entry blocker in vitro and demonstrates tissue selectivity for airway smooth muscle over vascular smooth muscle. The current study demonstrates the in vivo activity of RWJ 22108 in several different models of airway obstruction and asthma. RWJ 22108 relaxes preconstricted airways in dogs with little effect on blood pressure when administered by aerosol. In addition, it inhibits airway obstruction induced by antigen, histamine and exogenous leukotriene D4 in guinea pigs. In a conscious sheep model of allergic asthma, aerosol RWJ 22108 inhibits antigen-induced early and late phase airway obstruction and also the cellular infiltration associated with late phase. Total leukotrienes production is decreased in the guinea pig model probably as a result of fewer inflammatory cells infiltrating the lungs as shown in the sheep model of late phase. These data suggest that RWJ 22108 may have pharmacological potential in the clinical management of asthma.

Airway Obstruction↗
PubMed1993

Quality assurance study of cardiac isoenzyme utilization in a large teaching hospital.

Guidelines for diagnosis of acute myocardial infarction recommend that, if acute myocardial infarction is suspected, creatine kinase (CK)-MB levels should be measured on admission and again at 12 and 24 hours. In light of these recommendations, we conducted a quality assurance study to determine whether utilization of CK-MB tests in our institution, a large, university-affiliated teaching hospital, was consistent with current guidelines. Also, several years ago, we had established a policy of cancelling lactate dehydrogenase isoenzyme orders if the request originated from an unauthorized location, unless it was approved by a laboratory staff. Since this policy led to a greater than 90% reduction in the requests for lactate dehydrogenase isoenzyme testing, an additional objective was to reevaluate this policy. Of 774 patients evaluated with CK-MB tests, 294 (38%) received only a single test. Of these single tests, 277 had normal results (CK-MB < 5%). For the remaining 17 patients, the single CK-MB test findings were abnormal (CK-MB > 5%) without follow-up testing. Only two CK-MB tests were ordered for 187 patients (24%). Three or more CK-MB tests were obtained in 293 cases (38%). When two or more CK-MB tests were ordered, the time interval between the first and second tests was inappropriately short in 70% and long in 24%. The recommended timing for the third CK-MB was followed in only 4% of cases. Review of 32 cancellations of lactate dehydrogenase isoenzyme tests disclosed that lactate dehydrogenase isoenzyme tests were requested when unnecessary in 26 cases. Despite published guidelines for use of CK-MB for acute myocardial infarction, physicians at our institution continue to use these tests inappropriately by ordering only single CK-MB tests or by ordering repetitions of CK-MB tests at excessively short or long intervals.

Clinical Enzyme Tests↗