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Biomedical subjects

R Anderson

Publications and source records attributed to R Anderson.

At least 163 records · Page 9Linked to original sources
PubMed1999

PrM- and cell-binding domains of the dengue virus E protein.

The E-prM proteins of flaviviruses are unusual complexes which play important roles in virus assembly and fusion modulation and in potential immunity-inducing vaccines. Despite their importance, little is known about the biogenesis and structural organization of E-prM complexes. Pulse-chase radiolabeling of dengue virus-infected Vero cells demonstrated a rapid interassociation of E and prM proteins, and sucrose gradient sedimentation analysis suggested that E-prM complexes progressed from simple heteromers to more densely sedimenting structures indicating increased multimerization. E-prM heteromers of even higher complexity were observed in virus particles, suggesting an intracellular assembly process which results in the networking of E-prM subunits into a lattice-like structure found in virus particles. Trypsin cleavage of E-prM-containing virus particles resulted in the release of a soluble 45-kDa fragment of the E protein which retained cell-binding activity. The results suggest that E-prM interactions in dengue virus particles are largely mediated by domains in the carboxy-terminal anchoring domain of E, while cell-binding activity is retained in a trypsin-releasable ectodomain of the E protein.

Animals↗
PubMed1999

Comparison of custom and prefabricated orthoses in the initial treatment of proximal plantar fasciitis.

Fifteen centers for orthopaedic treatment of the foot and ankle participated in a prospective randomized trial to compare several nonoperative treatments for proximal plantar fasciitis (heel pain syndrome). Included were 236 patients (160 women and 76 men) who were 16 years of age or older. Most reported duration of symptoms of 6 months or less. Patients with systemic disease, significant musculoskeletal complaints, sciatica, or local nerve entrapment were excluded. We randomized patients prospectively into five different treatment groups. All groups performed Achilles tendon- and plantar fascia-stretching in a similar manner. One group was treated with stretching only. The other four groups stretched and used one of four different shoe inserts, including a silicone heel pad, a felt pad, a rubber heel cup, or a custom-made polypropylene orthotic device. Patients were reevaluated after 8 weeks of treatment. The percentages improved in each group were: (1) silicone insert, 95%; (2) rubber insert, 88%; (3) felt insert, 81%; (4)stretching only, 72%; and (5) custom orthosis, 68%. Combining all the patients who used a prefabricated insert, we found that their improvement rates were higher than those assigned to stretching only (P = 0.022) and those who stretched and used a custom orthosis (P = 0.0074). We conclude that, when used in conjunction with a stretching program, a prefabricated shoe insert is more likely to produce improvement in symptoms as part of the initial treatment of proximal plantar fasciitis than a custom polypropylene orthotic device.

Adult↗
PubMed1999

Mouse primordial germ cells lacking beta1 integrins enter the germline but fail to migrate normally to the gonads.

Primordial germ cells are the founder cells of the gametes. They are set aside at the initial stages of gastrulation in mammals, become embedded in the hind-gut endoderm, then actively migrate to the sites of gonad formation. The molecular basis of this migration is poorly understood. Here we sought to determine if members of the integrin family of cell surface receptors are required for primordial germ cell migration, as integrins have been implicated in the migration of several other motile cell types. We have established a line of mice which express green fluorescent protein in germline cells that has enabled us to efficiently purify primordial germ cells at different stages by flow cytometry. We have catalogued the spectrum of integrin subunit expression by primordial germ cells during and after migration, using flow cytometry, immunocytochemistry and RT-PCR. Through analysis of integrin beta1(-/-)-->wild-type chimeras, we show that embryonic cells lacking beta1 integrins can enter the germline. However, integrin beta1(-/-) primordial germ cells do not colonize the gonad efficiently. Embryos with targeted deletion of integrin subunit alpha3, alpha6, or alphaV show no major defects in primordial germ cell migration. These results demonstrate a role for beta1-containing integrins in the development of the germline, although an equivalent role for * integrin subunit(s) has yet to be established.

Animals↗
PubMed1999

Expression of the homophilic adhesion molecule, Ep-CAM, in the mammalian germ line.

During normal embryonic development, mammalian germ cells use both cell migration and aggregation to form the primitive sex cords. Germ cells must be able to interact with their environment and each other to accomplish this; however, the molecular basis of early germ cell adhesion is not well characterized. Differential adhesion is also thought to occur in the adult seminiferous tubules, since germ cells move from the periphery to the lumen as they differentiate. In a screen for additional adhesion molecules expressed by the germ line, expression of the homophilic adhesion molecule, Ep-CAM, was identified in embryonic, neonatal and adult germ cells using immunocytochemistry and flow cytometry with an Ep-CAM-specific monoclonal antibody. At embryonic stages, germ cells were found to express Ep-CAM during migration at embryonic day 10.5 and early gonad assembly at embryonic day 12.5. Expression of Ep-CAM was also found on neonatal male and female germ cells. In the adult testis, Ep-CAM was detected only on spermatogonia, and was absent from more differentiated cells. Finally, embryonic stem cells were shown to express this receptor. It is proposed that Ep-CAM plays a role in the development of the germ line and the behaviour of totipotent cells.

Animals↗
PubMed1999

Biomechanical assessment of gait in below-knee walking casts.

The introduction of modern synthetic casting bandages for splinting of fractures and soft tissue injuries has allowed the development of new casting techniques. Casts can be constructed with a greater degree of function so that controlled motion and stabilisation can be provided within the same cast. This study has shown that a very efficient gait can be achieved with modern synthetic bandages, if they are correctly applied. The authors have compared the gait of volunteer subjects fitted respectively with below-knee walking casts constructed from a rigid glass fibre bandage and a flexible glass fibre bandage which is reinforced. These casts were wrapped so that minimal amounts of bandage were used whilst appropriate strength and stiffness was provided. The temporal and spatial factors of cast gait were not statistically different from normal gait. The cast gait was found to be slightly more asymmetrical (dominant versus non-dominant leg) when a cast was worn and there was also a greater Physiological Cost Index (PCI). The flexible bandage has some advantages compared with the rigid bandage as normal footwear can be worn, the casts are more comfortable and they could be removed with shears, obviating the need for a power saw.

Adult↗
PubMed1999

Prostatitis unplugged? Prostatic massage revisited.

Repetitive prostatic massage is not a new tool in the urologists' armatarium. Once the most popular therapeutic maneuver used to treat prostatitis, it was abandoned as primary therapy almost 3 decades ago. Based on experience reported outside North America and anecdotal experiences of some patients and their physicians, it may be making a comeback. Unfortunately, there are almost no prospective data that would substantiate a claim as to its effectiveness. This article discusses the historic aspects of prostatic massage, suggests possible mechanisms of action, and describes the opinions of North American urologists who are associated with academic clinical research centers and are universally acknowledged as experts in the diagnosis and treatment of prostatitis. At this time, the science of prostatic massage must rely on anecdotal experiences, small, uncontrolled studies, and perhaps somewhat biased opinions of the major thought leaders in the field of chronic prostatitis/chronic pelvic pain syndrome.

Chronic Disease↗
PubMed1999

A new gas chromatography-mass spectrometry method for simultaneous determination of total and free trans-3'-hydroxycotinine and cotinine in the urine of subjects receiving transdermal nicotine.

trans-3'-Hydroxycotinine (THOC) has been recognized as the most abundant metabolite of nicotine. In an attempt to assess THOC and cotinine (COT) concentrations during nicotine transdermal therapy, we developed a new quantitative gas chromatography-mass spectrometry (GC-MS) method for simultaneous determination of total and free THOC and COT in human urine. The method utilizes the following: (a) hydrolysis of conjugated THOC and COT by beta-glucuronidase; (b) basic extraction of THOC and COT with mixed dichloromethane and n-butyl acetate; (c) derivatization of THOC with bis(trimethylflurosilyl)acetamide; and (d) separation and identification by GC-MS with selective ion monitoring. Lower limits of quantification for the assay were 50 and 20 microg/L for THOC and COT, respectively. The intra- and interassay CVs were 4.4% and 11% for THOC, and 3.9% and 10% for COT at 1000 microg/L. The results from six consecutive 24-h urine collections in 71 subjects administered daily transdermal nicotine doses of 11, 22, and 44 mg showed that, on average, free THOC was 76% of total THOC and free COT was 48% of total COT in all subjects. THOC is the major metabolite of nicotine and constitutes 20% of total nicotine intake at steady state, whereas urinary nicotine and COT excretion were 8% and 17%, respectively. The method is useful for simultaneous determination of free and total THOCand COT and can be used to assess the urinary excretion of these metabolites during transdermal nicotine therapy.

Administration, Cutaneous↗
PubMed1998

Loss of function of the tuberous sclerosis 2 tumor suppressor gene results in embryonic lethality characterized by disrupted neuroepithelial growth and development.

Germline defects in the tuberous sclerosis 2 (TSC2) tumor suppressor gene predispose humans and rats to benign and malignant lesions in a variety of tissues. The brain is among the most profoundly affected organs in tuberous sclerosis (TSC) patients and is the site of development of the cortical tubers for which the hereditary syndrome is named. A spontaneous germline inactivation of the Tsc2 locus has been described in an animal model, the Eker rat. We report that the homozygous state of this mutation (Tsc2(Ek/Ek)) was lethal in mid-gestation (the equivalent of mouse E9.5-E13.5), when Tsc2 mRNA was highly expressed in embryonic neuroepithelium. During this period homozygous mutant Eker embryos lacking functional Tsc2 gene product, tuberin, displayed dysraphia and papillary overgrowth of the neuroepithelium, indicating that loss of tuberin disrupted the normal development of this tissue. Interestingly, there was significant intraspecies variability in the penetrance of cranial abnormalities in mutant embryos: the Long-Evans strain Tsc2(Ek/Ek) embryos displayed these defects whereas the Fisher 344 homozygous mutant embryos had normal-appearing neuroepithelium. Taken together, our data indicate that the Tsc2 gene participates in normal brain development and suggest the inactivation of this gene may have similar functional consequences in both mature and embryonic brain.

Animals↗
PubMed1998

The pathogenesis of Schmorl's nodes in relation to acute trauma. An autopsy study.

STUDY DESIGN: Seventy thoracolumbar spines from cadavers of individuals killed in motor vehicle accidents were examined pathologically and radiologically, particularly for the occurrence of acute Schmorl's nodes. OBJECTIVES: To document whether Schmorl's nodes occur acutely as a result of trauma. SUMMARY OF BACKGROUND DATA: Theories proposed to explain the pathogenesis of Schmorl's nodes include developmental, degenerative, traumatic, and disease influences. Few studies show a direct causal relation between a traumatic episode and acute Schmorl's node formation. METHODS: Thoracolumbar spines were removed at autopsy, underwent radiography in the anteroposterior and lateral planes, fixed, sagittally cut, and underwent radiography a second time. Pathologic and radiographic examinations were performed. RESULTS: Nine acute Schmorl's nodes were detected, most in association with other acute injuries to the spine. Most acute Schmorl's nodes were present in spines from individuals aged 11-30 years, with a male to female ratio of 9:1, and were localized to the T8-L1 region. Spines from motorcyclists showed the highest percentage of acute Schmorl's nodes. No acute Schmorl's nodes were detected radiologically. CONCLUSION: Schmorl's nodes do occur acutely as the result of a single traumatic episode, and are almost always associated with other acute spinal injury. The frequency and occurrence of acute Schmorl's nodes in motorcyclists suggest that axial loading is an important mechanism. Their predominance in the T8-L1 region suggests that this region is particularly susceptible to stress.

Acute Disease↗
PubMed1998

Alpha-tocopherol antagonizes the multidrug-resistance-reversal activity of cyclosporin A, verapamil, GF120918, clofazimine and B669.

The effects of the membrane-stabilizing agent, alpha-tocopherol (25 microg/ml), on the chemosensitizing interactions of cyclosporin A (5 microg/ml), verapamil (2 microg/ml), clofazimine (1 microg/ml), B669 (0.5 microg/ml) and GF120918 (0.015 microg/ml) with a P-glycoprotein-expressing human lung cancer cell line (H69/LX4) have been investigated in vitro. In an assay of cell proliferation, all the chemosensitizing agents restored the sensitivity of H69/LX4 cells to doxorubicin and vinblastine. The inclusion of alpha-tocopherol (25 microg/ml) antagonized the multidrug-resistance (MDR)-modifying activity of all five chemosensitizing agents, effectively preventing restoration of sensitivity to both doxorubicin and vinblastine in H69/LX4 cells.

Acridines↗
PubMed1998

Chaos, persistence, and evolution of strain structure in antigenically diverse infectious agents.

The effects of selection by host immune responses on transmission dynamics was analyzed in a broad class of antigenically diverse pathogens. Strong selection can cause pathogen populations to stably segregate into discrete strains with nonoverlapping antigenic repertoires. However, over a wide range of intermediate levels of selection, strain structure is unstable, varying in a manner that is either cyclical or chaotic. These results have implications for the interpretation of longitudinal epidemiological data on strain or serotype abundance, design of surveillance strategies, and the assessment of multivalent vaccine trials.

Alleles↗