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Biomedical subjects

D Donovan

Publications and source records attributed to D Donovan.

52 records · Page 3Linked to original sources

Interferon alfa-n1 (Wellferon) in juvenile onset recurrent respiratory papillomatosis: results of a randomized study in twelve collaborative institutions.

Sixty-six patients with clinically severe juvenile-onset recurrent respiratory papillomatosis (RRP) were entered into a 12-month randomized crossover study to evaluate interferon alpha-n1 Wellferon (WFN) as an adjuvant to CO2 laser surgical excision. Eligibility required disease onset to be before age 16, and an endoscopic excision requirement of at least three operations in the 6 months immediately prior to entry. Patients were randomized to Observation versus WFN at a dose of 5 MU/m2 daily for 28 days and three times weekly for 5 months. The patient groups were comparable in extent of disease at entry. Total extent of disease was determined by a composite score derived from the number of diseased anatomic sites and extent of surface area and lumen encroachment present at each site. Standard endoscopic excisions were performed every 2 months and clinical courses compared on a basis of composite scores determined at each endoscopy. Statistically significant improvement occurred in the patient group which received WFN. We conclude that interferon alpha n-1 is an effective adjuvant to surgery in RRP management.

Adolescent↗

Primary structure of histidine-tRNA synthetase and characterization of hisS transcripts.

Histidine-tRNA synthetase is one of the smallest bacterial aminoacyl-tRNA synthetases. It is less than one-half the size of the largest aminoacyl-tRNA synthetases. The entire nucleotide sequence of the Escherichia coli hisS locus was determined. The coding region is comprised of 424 codons, and the sequence was determined for 200 nucleotides on the 5'- and 3'-sides of the coding region. The translated nucleotide sequence was confirmed extensively by independent amino acid sequence information obtained by Edman degradations of purified peptides and by measurements of peptide masses by fast atom bombardment mass spectrometry. A significant sequence alignment of four bacterial aminoacyl-tRNA synthetases was reported recently (Webster, T., Tsai, H., Kula, M., Mackie, G., and Schimmel, P. (1984) Science 226, 1315-1317). Although the four enzymes vary considerably in length, this match occurs within the first 100 amino acids of each of the four enzymes and is in the segment believed to be part of the catalytic core. But no strong alignment could be found of the histidine sequence with these four tRNA synthetase sequences. This enzyme may be derived, therefore, from a different progenitor. Previous work suggested that three places in the hisS 5'-noncoding sequence could be promoter sites for RNA polymerase (Eisenbeis, S. J., and Parker, J. (1982) Gene 18, 107-114). We detected a 1400-nucleotide RNA species by RNA blot analysis with a hisS-specific probe. S1 nuclease mapping demonstrated a 5'-end to the RNA species occurs at -67 +/- 1, relative to the first nucleotide of the coding region. This position coincides with the predicted start site for transcription from one of the previously proposed promoter sites.

Amino Acid Sequence↗

Monoclonal antibodies to a glycolipid antigen on human neuroblastoma cells.

Using a somatic cell hybridization technique, four murine monoclonal antibodies (three immunoglobulin M and one immunoglobulin G3) were produced against a human neuroblastoma cell surface glycolipid antigen. They reacted strongly with all human neuroblastoma tumor-containing specimens and six of eight human neuroblastoma cell lines. More than 98% of each neuroblastoma cell population possessed this surface antigen, and in the presence of complement, 100% of them were killed. While melanoma and osteogenic sarcoma carried this antigen, leukemia and most Ewing's and Wilms' tumors did not. There was no cross-reaction with 30 normal or remission bone marrow samples and none with normal human tissues other than neurons in vitro. This antigen was neuraminidase sensitive, separable on thin-layer chromatogram, and did not modulate after combining with the monoclonal antibodies. These antibodies could detect less than 0.1% tumor cells deliberately seeded in the bone marrow samples. Because of their unique properties, these monoclonal antibodies may have diagnostic and therapeutic potentials.

Animals↗

Fetoscopic visualization in second-trimester pregnancies.

Fetoscopic visualization may be required for the prenatal diagnosis of external fetal malformations which cannot be clearly defined by ultrasound. The synchronous use of real-time ultrasound guidance during the fetoscopic procedure has permitted successful visualization to be achieved in pregnancies of greater than 18 weeks' gestation. The chances of successful visualization and the influence of advancing gestational age have been critically evaluated. Between 18 and 23 weeks', when these techniques were used, advancing gestational age did not appear to exert a significant effect on the chances of successful visualization. Analysis of placental position indicated that an anterior placenta did not significantly affect bloodstaining of the fluid or preclude access to placental vessels for blood sampling.

Adolescent↗

Fetoscopic photography.

Fetoscopic visualization may be used for the prenatal diagnosis of external structural malformations of the fetus. Objective documentation of these fetoscopic findings would be desirable. The photographic equipment and techniques required for fetoscopic photography have been investigated, and the results of these investigations with standard fetoscopic instruments in current clinical usage are described. The factors evaluated include the light source, camera equipment, camera settings and film.

Female↗

Mini alar myocutaneous flaps for nasolabial-columella reconstruction.

A new midfacial myocutaneous flap that is particularly useful in nasolabial-columella reconstruction is described. The mini alar flap is a randomized myocutaneous island flap incorporating portions of the orbicularis oris, levator labi superioris alae (labial portion), levator labi superioris, and zygomaticus minor, based on a vascular supply from the terminal branches of the facial artery. The flaps allow for a bilateral elipse of skin and underlying muscle to be transferred from the lateral nasal area into the midportion of the columella and the upper lip for reconstruction of ablative, traumatic, or congenital defects. The primary advantage of the mini alar flap lies in the ability to transpose moderate quantities of viable, well-matched tissue with minimal donor area deformity.

Female↗

Cognitive deficit in middle-aged alcoholics.

Two groups of male alcoholics with mean ages of 44 and 55 and two groups of matched control subjects were tested twice, one year apart. Comparisons on verbal and adaptive ability factors derived from the Wechsler Intelligence Scale and selected Halstead--Reitan neuropsychological tests found no differences on verbal abilities. Significant improvement for the younger alcoholics on retesting indicates that previous comparisons of the neuropsychological effect of aging and alcoholism may not have sufficiently taken into account the reversibility of an alcoholic deficit. For the age range studied here, it may be only older alcoholics who appear different from control subjects.

Adult↗

Hereditary tyrosinaemia. Clinical, enzymatic, and pathological study of an infant with the acute form of the disease.

A clinical, enzymatic, and pathological study of an infant with the acute form of hereditary tyrosinaemia is presented. Treatment with a diet low in methionine, tyrosine, and phenylalanine was unsuccessful. A selection of specific and nonspecific hepatic enzymes, obtained at necropsy within one hour of the infant's death at 9 1/2 weeks, were studied to try to throw light on the basic defect. The major pathological findings were those of a peculiar hepatic fibrosis associated with bile retention and an abnormal grouping of hepatocytes, islet-cell hyperplasia of the pancreas, and dilatation of the proximal renal tubules. Death was precipitated by bronchopneumonia and liver failure. The difficulty in diagnosing the acute form of tyrosinaemia is pointed out, especially in differentiating it from hereditary galactosaemia (transferase deficiency) and hereditary fructosaemia. All three may present with the same clinical symptoms and liver lesions, and the distinction must be made by enzyme studies and by therapeutic trial.

Amino Acid Metabolism, Inborn Errors↗

Normal inhibition of mammary tumor metastasis in C3H/He mice.

The blood of normal C3H mice contains molecular factors that can rapidly lyse mammary carcinoma cells that enter the circulation. The cytotoxic effect of blood on tumor cells during incubation was most clearly demonstrated if fibrin formation was prevented. The conversion of the mammary carcinoma cells to ascites growth increased both the resistance to lysis in plasma and the ability to form lung colonies after intravenous injection. Mice that were surgically cured of numerous 9 mm tumors and survived for an average 10 months had a lower incidence (36%) of spontaneous metastases than mice that experienced one 30 mm tumor and survived for an average 8 weeks (65%). This is interpreted to mean that mice that retained their vitality by early surgical cures, could suppress the development of metastases by the action of normal serum factors that can destroy neoplastic cells that enter the circulation.

Animals↗