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Biomedical subjects

D Lee

Publications and source records attributed to D Lee.

At least 469 records · Page 26Linked to original sources
PubMed1990

Ocular toxicity of multiple intravitreal DHPG injections.

Intravitreal 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (DHPG) has been advocated as an alternative mode of therapy in cytomegalovirus (CMV) retinitis in the acquired immunodeficiency syndrome (AIDS) because of toxic neutropenia which is a complication of systemic intravenous DHPG. The recommended regimen requires injection of 200 micrograms DHPG intravitreally twice a week for a period of several weeks to months to control the progression of CMV retinitis. A previous study performed to determine the safe dose of intravitreal DHPG was based on a single intravitreal dose study; it does not consider the toxicity which may arise from multiple intravitreal injections of DHPG as it is utilized in the treatment of patients with CMV retinitis. In our study, intravitreal injections of 1000, 400, 200, 100, 50, and 25 micrograms DHPG were administered weekly for a period of 5 weeks in rabbit eyes. Ocular toxicity was monitored using slit-lamp biomicroscopy, indirect ophthalmoscopy, electroretinography, and light and electron microscopy. Electroretinographic evidence of retinal toxicity was found with doses as low as 100 micrograms. Electron-micrographic studies of retinal tissue from the eyes injected with even lower doses (as low as 25 micrograms) also showed evidence of toxic vacuolization in the inner segments of the photoreceptor.

Animals↗
PubMed1990

Effects of ascorbate on myogenesis in micromass culture.

Micromass cultures from stage 23 and 24 chick wing mesenchyme were grown in serum-containing medium with or without additional ascorbic acid. It was found that ascorbic acid administered as a single pulse or present continuously throughout culture, in concentrations as low as 25 micrograms/ml, was sufficient to abolish 80% of myogenesis as assessed by immunolocalization using muscle-specific antibodies. This effect was not significantly altered when cultures were maintained in a serum-free medium that promotes myogenesis. In contrast to the above findings, spectrophotometric analysis of accumulated sulphated glycosaminoglycans, an indicator of chondrogenesis, was elevated by ascorbate treatment. Furthermore, a similar level of glycosaminoglycan stimulation was found in ascorbate treated stage 23 distal-tip limb cultures that were essentially free of myogenic cells. We conclude, therefore, that the presence of myoblasts in whole-limb cultures has no appreciable inhibitory effects on chondrogenesis.

Animals↗
PubMed1990

Mutagenesis of the a subunit of the F1F0-ATP synthase from Escherichia coli in the region of Asn-192.

Site-directed cassette mutagenesis was used to generate a series of amino acid substitutions in the a subunit of the Escherichia coli F1F0-ATP synthase. The following substitutions for Asn-192 were analyzed and shown to inhibit partially the ATP-dependent proton translocation without disrupting F1-F0 interactions: Leu, Val, Pro, Ser, Thr, and Arg. A group of multiple substitutions at residues Gln-181, Asn-184, and His-185 had no significant effect on ATP synthase function, as judged by growth yields, or by assays of ATP-dependent proton translocation, indicating that this region of the a subunit is not involved in function. Three double mutants were constructed in order to assess the independence of residues Asn-192, Glu-196, and Asn-214. Results of proton translocation assays of membranes from cells containing these double mutations are consistent with the interpretation that each of these residues is involved with proton movement, and that residues Asn-192 and Glu-196 may be coupled. Finally, the relationship between the mechanism of proton translocation by the E. coli ATP synthase and the chloroplast enzyme was probed by constructing variants of the E. coli a subunit containing several features of homologous chloroplast proteins. It was determined that these chloroplast features, in the region of Glu-196 of the E. coli a subunit,, were detrimental to ATP synthase function.

Amino Acid Sequence↗
PubMed1990

Improved contrast at 1.5 tesla using half-Fourier imaging: application to spin-echo and angiographic imaging.

Half-Fourier imaging is useful for reducing imaging time by requiring less than the usual number of phase-encoding steps. This increase in speed can be traded off for longer repeat times, TR, for improved contrast-to-noise in the same imaging time or to collect short asymmetric echoes. Consequently, it is shown to be especially useful for long TR spin-echo imaging where at 1.5 T a repeat time of 4 sec is recommended for a double-echo TE = 30/90 sequence or 3 sec for a double-echo TE = 15/90 sequence. Short TR FLASH imaging also benefits from a longer TR since there is more time to spoil the signal. In both cases, there is the advantage when a multislice acquisition mode is used that more slices (and hence, a larger volume) can be taken. Another application is to apply half-Fourier imaging in the read direction to avoid spin dephasing and motion artifacts. This is particularly useful in angiographic imaging where smaller pixel sizes and shorter echo times both reduce pixel dephasing. Again, even though taking less than the usual number of data points leads to a reduction in S/N, the improved signal and resolution for blood vessels can more than compensate this loss.

Adult↗
PubMed1990

Comparisons of glycosylated and nonglycosylated amniotic fluid prolactins in normal second- and third-trimester pregnancies.

Prolactins in glycosylated and nonglycosylated form were isolated from 218 second- and third-trimester amniotic fluid samples by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, electrotransferred to nitrocellulose paper, and probed with anti-human prolactin serum and protein A labeled with iodine 125. The glycosylated and nonglycosylated prolactin bands were exposed by autoradiography. The bands were analyzed by densitometry, and the ratio of glycosylated to total (glycosylated + nonglycosylated) prolactin was calculated (glycosylated/total ratio) and compared with matched prolactin radioimmunoassay measurements. Both radioimmunoassay-measured and nonglycosylated prolactin decreased from the second to the third trimester whereas glycosylated prolactin concentrations remained unchanged. Concomitantly, glycosylated/total prolactin ratios increased significantly (p less than 0.001). The correlation of radioimmunoassay-measured prolactin was closer to nonglycosylated prolactin (r2 = 0.32, p = 0.00001) than to glycosylated prolactin (r2 = 0.02, p = 0.06). We suggest that the proportion of amniotic fluid glycosylated prolactin increases with length of gestation and that glycosylation of prolactin is inversely related to total prolactin secretion. Furthermore, prolactin's immunoreactivity correlated more closely to the nonglycosylated-prolactin variant, suggesting that radioimmunoassay of prolactin poorly recognizes the glycosylated prolactin form.

Amniotic Fluid↗
PubMed1990

Influences of flexor sheath continuity and early motion on tendon healing in dogs.

The healing response of flexor tendons treated with either sheath reconstruction or sheath excision, and early passive motion rehabilitation was investigated in a canine model. Flexor sheath repair, sheath excision, and autogenous sheath grafting were compared for biomechanical characteristics, and biochemical and ultrastructural alterations at the repair site at intervals over a 12-week period. No significant differences could be found in tendons treated with either sheath repair or sheath excision by biomechanical, biochemical, or morphologic assessments. Although ultimate load and linear slope values increased significantly in both groups at each interval (p less than 0.05 for each comparison), there were no significant differences in angular rotation of the distal interphalangeal joint over time. Biochemical findings showed high levels of reducible Schiffbase crosslinks through 12 weeks, indicating a repair process undergoing active remodeling. Ultrastructural studies showed active fibrinogenesis and early evidence of longitudinal alignment of collagen fibrils in the extracellular matrix. In the sheath graft group, strength characteristics did not increase over time, and there was a high degree of disorganization of collagen fibril orientation. These findings demonstrate that reconstruction of the tendon sheath, either by suture or autogenous graft, does not improve significantly the biomechanical, biochemical, or morphologic characteristics of repaired tendons treated with early motion rehabilitation.

Animals↗
PubMed1990

Comparison of false-positive reactions in direct-binding anti-HIV ELISA using cell lysate or recombinant antigens.

In a 2-year study of false-positive anti-HIV-1 tests in blood donors at Manchester and Lancaster Blood Banks, the reactions associated with a HIV-infected cell lysate antigen were compared with those using recombinant-antigen-based tests. In year 1 (cell lysate test) at Manchester BTS 0.21% of 119.178 donations were repeatedly reactive, compared with 0.53% of 119,004 donations in year 2 (recombinant antigen). Reactive sera were tested at Manchester PHL by three different immunoassays. Referred specimens were classified as anti-HIV positive (95-100% reactive in all the assays), equivocal or negative (negative results in all three immunoassays). Two donors were confirmed to be anti-HIV positive over the 2-year period. Most sera were negative by confirmatory immunoassays in years 1 and 2. In year 1, a study of 60 referred sera with sex- and age-matched controls showed high correlation between a reactive anti-HIV-1 screening test and indeterminate anti-HIV-1 patterns on Western blot showing reactions with HIV gag-coded proteins. In year 2, less than 10% of referred sera were reactive by Western blot, and there was no correlation between a reactive screening anti-HIV test, the strength of signal in the test or a reactive Western blot. Follow-up showed that donors whose sera were reactive in years 1 and 2 by the anti-HIV-1 screening test formed almost two different populations. Four donors with equivocal anti-HIV-1 confirmatory tests had anti-HIV 'envelope' reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Western↗
PubMed1990

Vagus nerve morphology in diabetic gastropathy.

Two patients were treated with gastroenterostomy and vagotomy for intractable vomiting due to diabetic gastropathy. A morphometric examination of nerve fibres and capillaries in their resected abdominal vagi was performed and the results were compared with findings from two diabetic and two non-diabetic patients undergoing gastroenterostomy and vagotomy for duodenal ulceration. All four diabetic patients had pathological changes of a similar character: reduced myelinated fibre density, degeneration and regeneration of unmyelinated fibres, and capillary basement membrane thickening. Abnormalities were more pronounced in the two diabetic patients with gastropathy but intact and regenerating nerve fibres were still present. The findings support the view that vagal neuropathy could be a causal factor in diabetic gastropathy but imply that severe gastropathy with vomiting is not simply a consequence of autovagotomy. The morphological observations indicated that structural changes can occur in the autonomic nerves of diabetic patients who do not develop autonomic symptoms or have easily detectable abnormal autonomic physiology.

Adult↗
PubMed1990

Cloning, sequencing, and expression of a xylanase gene from the anaerobic ruminal bacterium Butyrivibrio fibrisolvens.

A gene coding for xylanase activity, xynA, from the anaerobic ruminal bacterium Butyrivibrio fibrisolvens 49 was cloned into Escherichia coli JM83 by using plasmid pUC19. The gene was located on a 2.3-kilobase (kb) DNA insert composed of two adjacent EcoRI fragments of 1.65 and 0.65 kb. Expression of xylanase activity required parts of both EcoRI segments. In E. coli, the cloned xylanase enzyme was not secreted and remained cell associated. The enzyme exhibited no arabinosidase, cellulase, alpha-glucosidase, or xylosidase activity. The isoelectric point of the cloned protein was approximately 9.8, and optimal xylanase activity was obtained at pH 5.4. The nucleotide sequence of the 1,535-base-pair EcoRV-EcoRI segment from the B. fibrisolvens chromosome that included the xynA gene was determined. An open reading frame was found that encoded a 411-amino-acid-residue polypeptide of 46,664 daltons. A putative ribosome-binding site, promoter, and leader sequence were identified. Comparison of the XynA protein sequence with that of the XynA protein from alkalophilic Bacillus sp. strain C-125 revealed considerable homology, with 37% identical residues or conservative changes. The presence of the cloned xylanase gene in other strains of Butyrivibrio was examined by Southern hybridization. The cloned xylanase gene hybridized strongly to chromosomal sequences in only two of five closely related strains.

Amino Acid Sequence↗
PubMed1990

Effects of ethnicity and physical disability on academic and social ratings of photographs.

120 college students used academic and social bipolar descriptors to rate color photographs of a male person which were varied to test the effect of ethnicity and physical disability of the photographic stimuli on evaluations. Analysis yielded significant main effects for disability and ethnicity on social ratings and a main effect for disability on academic ratings. No significant interactions were found.

Achievement↗
PubMed1990

Stereo-pair three-dimensional imaging of microvascular architecture in primate dental tissues.

The morphology of microvascular beds in dental tissues is poorly documented at the ultrastructural level. SEM stereo-pair imaging of microcorrosion casts reveals the markedly contrasting vascular architecture and capillary anastomoses within the nasopalatine foramen, soft palate and gingival regions of the marmoset. This primate was studied as an analogue for man to further our knowledge of periodontal anatomy and function.

Animals↗
PubMed1990

Vascular relationships of the vestibulocochlear nerve on magnetic resonance imaging.

Vascular compression of the vestibulocochlear (VIIIth) nerve may cause constant or recurrent positional vertigo, tinnitus, and/or hearing loss. At present the diagnosis is based upon history, physical findings, audiologic assessment, vestibular function testing, and auditory brainstem evoked responses. Delineation of the vascular and neural anatomy within the cerebellopontine angle (CPA) has not been part of the preoperative assessment. We recently treated a patient demonstrating the clinical features of this syndrome. A magnetic resonance imaging (MRI) study revealed a vascular loop of the anterior inferior cerebellar artery intimately associated with the VIIIth nerve at the porus acusticus. To better define the significance of this finding, we retrospectively reviewed the CPA neurovascular anatomy of 100 (200 sides) otherwise normal MRI scans performed for unrelated disorders. Vessels were identified on 59.9 percent of sides while nerves were seen on 40 percent of sides. Contact between vessel and nerve occurred on 12.5 percent of sides and when both nerve and vessels were seen concurrently, they were in contact 50 percent of the time. These findings may preclude the use of MRI as the definitive diagnostic test in the preoperative assessment of vascular VIIIth nerve compression.

Arteries↗
PubMed1989

Combined zidovudine and interferon-alpha therapy in patients with Kaposi sarcoma and the acquired immunodeficiency syndrome (AIDS)

STUDY OBJECTIVE: To evaluate the toxicity and potential clinical efficacy of combined therapy with zidovudine and interferon-alpha for patients with Kaposi sarcoma and the acquired immunodeficiency syndrome (AIDS). DESIGN: Nonrandomized, open trial study. SETTING: Outpatient clinic of a government referral-based research hospital. PATIENTS: Volunteer sample of 39 patients with human immunodeficiency virus (HIV) infection and Kaposi sarcoma. INTERVENTIONS: Patients received zidovudine, 250, 100, or 50 mg orally every 4 hours; 6 weeks after interferon-alpha was begun at a dose of 5 million U/d, and the dose was increased every 2 weeks until a maximum tolerated dose was determined. Patients then received the maximum tolerated dose of the combination for a minimum of 12 weeks before formal efficacy evaluations. MEASUREMENTS AND MAIN RESULTS: In the dose-escalation phase, the ability to tolerate interferon-alpha was clearly related to the zidovudine dose. Of the 13 patients receiving 250 mg of zidovudine, only 1 patient was able to tolerate at least 10 million U/d of interferon-alpha. Of the 12 patients receiving 100 mg of zidovudine, 8 tolerated 10 million U/d, 5 tolerated 15 million U/d, and none tolerated higher doses. Of the 12 patients receiving 50 mg of zidovudine, 8 tolerated 10 million U/d, 7 tolerated 15 million U/d, and 6 tolerated 20 million U/d or more. Dose-limiting toxicities included neutropenia (57%), fatigue (16%), thrombocytopenia (14%), and hepatic dysfunction (10%). Of the 22 patients who received a stable dose of both drugs for 12 weeks, 11 patients had a complete or partial tumor response and 8 showed an anti-HIV effect. Peak serum levels of interferon-alpha (32 to 250 U/mL) and zidovudine (0.40 to 3.85 microM) were in the ranges previously shown to be synergistic against HIV. CONCLUSIONS: Combination therapy with zidovudine and interferon-alpha can be administered to patients with HIV infection and Kaposi sarcoma in doses that effect antiviral and antitumor responses; it appears to have a potential role in managing such patients.

Acquired Immunodeficiency Syndrome↗