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Biomedical subjects

R M Davis

Publications and source records attributed to R M Davis.

At least 19 recordsLinked to original sources

Morphological differentiation and proteoglycan synthesis regulate Alzheimer amyloid precursor protein processing in PC-12 and human astrocyte cultures.

A morphologically differentiated strain of rat pheochromocytoma (PC-12H) metabolically labeled with [35S]methionine and incubated with a phorbol ester displayed reduced 140-kDa and increased 15 kDa bands relative to cells incubated without phorbol ester after immunoprecipitation with antisera elicited by the C-terminal peptide of the Alzheimer amyloid precursor protein (APP). These bands correspond to glycosylated full length APP and a C-terminal fragment previously reported by Anderson et al. (Neurosci. Lett. 120:126-128, 1991) to result from a cleavage within the amyloidotic A4 region of APP, which releases a 120 kDa extracellular fragment. The 15 kDa fragment, not immunoprecipitated with an antisera elicited by the N-terminal portion of A4 amyloid, is nonamyloidogenic. Incubation of these cells with p-nitrophenylxyloside, known to inhibit proteoglycan formation, also increased this nonamyloidogenic cleavage of APP. In contrast to these results, an undifferentiated low passage PC-12-L strain constitutively displayed rapid nonamyloidogenic APP cleavage. Incubation of PC-12-L with phorbol ester did not affect the relative abundance of 140 or 15 kDa bands. Growth of PC-12-L with 7 S NGF or dibutyryl cAMP resulted in increased morphological differentiation and decreased APP cleavage which was now phorbol-inducible. Similar analyses of dividing and senescent human astrocytes and normal and F-AD fibroblasts indicate 5-fold lower rates of mid-A4 APP cleavage. Phorbol esters decreased the 140 kDa APP band without affecting the intensity of the 15 kDa band in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid beta-Protein Precursor

Comparison of intraocular lens fixation techniques performed during penetrating keratoplasty.

We reviewed the charts of 41 patients who had undergone penetrating keratoplasty, anterior vitrectomy, and placement or exchange of an intraocular lens during a two-year period with a median follow-up time of 15 months (range, five to 26 months). The median preoperative visual acuity was 20/400 (range, 20/40 to hand motions). The median postoperative visual acuity was 20/70 (range, 20/25 to hand motions). Of 41 corneal grafts, 38 (93%) remained clear. New intraocular lenses were inserted by anterior chamber, iris, or transscleral fixation. The median visual acuity was 20/70 for the anterior chamber lens group, 20/100 for the iris fixation group, and 20/70 for the transscleral fixation group. Analysis of variance demonstrated no significant difference by type of fixation in postoperative visual acuity, central corneal thickness, and intraocular pressure.

Adult

Assessing community interventions to reduce smoking.

Few major, community-based antismoking programs have undergone specific evaluation in developed countries; the number is even lower in developing countries. Yet not all evaluation need be elaborate, expensive, or overly time-consuming. Data on tobacco trade, import and export, taxation, mortality, and morbidity may already exist within government departments and can be used for evaluation. Published information from the tobacco industry may be obtained easily in trade journals and annual reports. Universities and international and overseas national health agencies may offer information, assistance, and expertise. Indirect evaluation of the importance of any particular antismoking intervention can be measured by how strongly the tobacco industry opposes that measure.

Community Participation

Isolation and characterization of a new human microsporidian, Encephalitozoon hellem (n. sp.), from three AIDS patients with keratoconjunctivitis.

A new human microsporidian was isolated from cultures of Madin-Darby canine kidney cells incubated with conjunctival scrapings or corneal tissues from three AIDS patients with keratoconjunctivitis. The three isolates were morphologically similar to Encephalitozoon cuniculi. The spores averaged 1 x 1.5-2.0 microns, had six to eight polar filament coils, displayed monokaryotic nuclei, and possessed relatively thick endospores with irregularly shaped exospores. Organisms developed within a parasitophorous vacuole. By SDS-PAGE analysis, the three isolates appeared to be identical but were different from E. cuniculi. Identical banding patterns on Western blots of the three isolates were expressed by each patient's serum. By Western immunoblotting, murine antisera to E. cuniculi reacted to several antigens of the new AIDS-related microsporidian, whereas murine antisera bound weakly to Nosema corneum. The name Encephalitozoon hellem (n. sp.) is proposed to identify this new human microsporidian.

Acquired Immunodeficiency Syndrome

Ciliary sulcus anatomical dimensions.

Trans-scleral ciliary sulcus and iris suture fixation of posterior chamber intraocular lenses (IOLs) in eyes without posterior capsular support are techniques gaining wider acceptance. Primary indications are IOL exchange in pseudophakic bullous keratopathy and secondary IOL insertion in aphakia. Accurate placement of the posterior chamber lens loops within the ciliary sulcus is based on knowledge of ciliary sulcus anatomy. Nineteen postmortem eyes were sectioned in the coronal plane to expose the posterior iris border and the ciliary body. Ciliary sulcus diameters were measured, and the mean diameter was 11.0 +/- 0.37 mm. The mean limbus-ciliary sulcus distance was then measured by passing 26-gauge needles through the ciliary sulcus and sclera. The mean limbus-ciliary sulcus distance was 0.9 mm. These measurements may guide ophthalmic surgeons in choosing appropriate IOL designs for IOL exchange or secondary IOL procedures.

Ciliary Body

National programs for smoking cessation.

The smoking cessation effort has made tremendous progress since the 1964 Report of the Surgeon General described the health hazards of smoking. The impact of these efforts on smoking is particularly impressive when the current smoking level is compared with levels of smoking projected from trends apparent before that 1964 report, levels that might have been reached if there had been no national stop-smoking campaign. Because of the campaign, an estimated 35 million Americans were nonsmokers in 1985 who would otherwise have been smokers. If these figures are projected to the year 2000, the campaign will have postponed more than 2 million deaths. Therefore, reducing the prevalence of smoking in adults from about 40% in 1964 to 29% in 1987 can be considered a tremendous public health achievement. Among those who did take up smoking, there is also reason for some optimism. By 1987, more than 38 million Americans had quit smoking; this figure represents nearly half of all living adults who ever smoked. The 1990 Report of the Surgeon General gave a positive message to the 50 million Americans who continue to smoke by describing the health benefits of quitting for all the major smoking-related diseases.

Female

Quitting smoking in the United States in 1986.

In an analysis of recent behavior with regard to quitting smoking, detailed histories were obtained on a representative sample of 5,623 Americans who had smoked in the year preceding the 1986 Adult Use of Tobacco Survey. An estimated 55.8 million Americans smoked regularly for some period during the year prior to the survey. Approximately one third (34.8%) quit for at least a day during the year prior to the survey, 28.3% quit for at least 7 days during the year prior to the survey, and 16.2% were still not smoking at the time of the survey. Of those who quit for a day, 54% had relapsed by the time of the survey. Demographic characteristics, such as age, sex, race, marital status, and education, were evaluated as predictors of making a major attempt to quit for 7 days or more. Among those who had made a major attempt, a similar analysis was done predicting success in maintaining cessation for 3 months or more. Ordinal logistic regression analyses showed that younger age and higher education predicted a major attempt to quit. There was only one group who differed markedly from all others: those who were younger and were more highly educated. Older age and being white predicted those who abstained for 3 months or longer.

Adolescent

'Common courtesy' and the elimination of passive smoking. Results of the 1987 National Health Interview Survey.

The tobacco industry recommends "common courtesy" as the solution to potential conflicts over smoking in public places and as an alternative to policies that restrict or ban smoking. Specifically, the industry suggests that nonsmokers "mention annoyances in a pleasant and friendly manner" and that smokers ask others, "Do you mind if I smoke?" We analyzed data for 22,000 adults who responded to the 1987 National Health Interview Survey of Cancer Epidemiology and Control to determine if common courtesy is being used in passive-smoking situations. Almost half (47%) of smokers said they light up inside public places without asking if others mind. When someone lights up a cigarette inside a public place, only 4% of nonsmokers ask the person not to smoke despite the fact that most nonsmokers consider secondhand smoke harmful and annoying. We compared these data with similar data collected by the Roper Organization in the 1970s and found that smokers today are less likely to smoke inside public places. However, nonsmokers' actions in response to secondhand smoke have changed very little. These findings show that the common courtesy approach endorsed by the tobacco industry is unlikely, by itself, to eliminate exposure to environmental tobacco smoke. Though no one would oppose the use of common courtesy, we conclude that legislative or administrative mechanisms are the only effective strategies to eliminate passive smoking.

Adult

Human neuroectoderm-derived cell line secretes fibronectin that shares the HNK-1/10C5 carbohydrate epitope with neural cell adhesion molecules.

A human malignant melanoma cell line, Melur, secretes several glycoproteins that contain a unique carbohydrate epitope shared by neural cell adhesion molecules and recognized by the monoclonal antibodies HNK-1, L2, and 10C5. In this report, we present evidence that one of the major melanoma glycoproteins containing the HNK-1/10C5 epitope is the cell adhesion molecule, fibronectin, or a fibronectin-like molecule. Melanoma-derived fibronectin was isolated from serum-free conditioned medium by gelatin-Sepharose affinity adsorption and shown to react with monoclonal antibodies HNK-1 and 10C5 in Western blot analysis. HNK-1-containing fibronectin was purified on a gelatin-Sepharose column followed by an affinity column using a monoclonal antibody against the HNK-1 carbohydrate. The purified HNK-1-fibronectin then could be incorporated into the extracellular matrix of hamster fibroblasts in vitro, and such a matrix was detectable using the HNK-1 monoclonal antibody in an immunofluorescence assay. Of the seven neuroectoderm-derived tumor cell lines tested, only the Melur melanoma cell secreted fibronectin containing the HNK-1 carbohydrate. Identification of human neuroectoderm-derived fibronectin as a potential carrier of the HNK-1 carbohydrate suggests a new role for fibronectin in neural development and regeneration, and represents a new model for studying the function of this carbohydrate domain in neural cell adhesion.

Antigens, Differentiation

Information on tar and nicotine yields on cigarette packages.

We examined information on tar and nicotine yields on the packages of 160 cigarette brands, 58 percent of the 275 brands for which tar and nicotine yields were listed in a recent Federal Trade Commission report. The tar yield was indicated on 14 percent, the nicotine yield was indicated on 11 percent. As tar yield increased among brands, the yield was progressively less likely to be shown on the package and was not disclosed on the package of any cigarette yielding 11 mg or more of tar.

Humans

Corneal microsporidiosis. A case report including ultrastructural observations.

Stromal keratitis and iritis developed in the left eye of a healthy 45-year-old man with no history of ocular disease, trauma, or contact lens wear. The clinical course over a 2-year period was characterized by progressive central disciform keratitis, recurrent anterior stromal patchy infiltration, and iritis which was partially controlled with topical corticosteroids and broad-spectrum antibiotics. Results of bacterial, viral, fungal, and chlamydial cultures were negative. Results of histopathologic examination of a corneal biopsy specimen and, later, a penetrating keratoplasty specimen showed many extracellular and intracellular spores in degenerating keratocytes. By electron microscopy there were encapsulated oval structures measuring approximately 3.5 to 4 microns in length x 1.5 microns in width. Mature spores had well-developed cell walls that contained two abutted nuclei (diplokaryon) and a redundant polar tubule with six coils. These structures are characteristic of a protozoa in the genus Nosema.

Animals

Human carboxypeptidase M. Purification and characterization of a membrane-bound carboxypeptidase that cleaves peptide hormones.

A membrane-bound neutral carboxypeptidase B-like enzyme was solubilized from human placental microvilli with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) and purified to homogeneity by ion-exchange chromatography and affinity chromatography on arginine-Sepharose. It gave a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent Mr of 62,000 with or without reduction. The enzyme is a glycoprotein as shown by its high affinity for concanavalin A-Sepharose and reduction in mass to 47,600 daltons after chemical deglycosylation. It has a neutral pH optimum, is activated by CoCl2, and inhibited by o-phenanthroline, 2-mercaptomethyl-3-guanidinoethylthiopropanoic acid, or cadmium acetate, indicating it is a metallopeptidase. The enzyme cleaves arginine or lysine from the COOH terminus of synthetic peptides (e.g. Bz-Gly-Arg, Bz-Gly-Lys, Bz-Ala-Lys, dansyl-Ala-Arg, where Bz is benzoyl and dansyl is 5-dimethylaminonaphthalene-1-sulfonyl) as well as from several biologically active substrates: dynorphin A(1-13), Met5-Arg6-enkephalin (Km = 46 microM, kcat = 934 min-1), bradykinin (Km = 16 microM, kcat = 147 min-1), Met5-Lys6-enkephalin (Km = 375 microM, kcat = 663 min-1), and Leu5-Arg6-enkephalin (Km = 63 microM, kcat = 106 min-1). Although the enzyme shares some properties with other carboxypeptidase B-like enzymes, it is structurally, catalytically, and immunologically distinct from pancreatic carboxypeptidase A or B, human plasma carboxypeptidase N, and carboxypeptidase H ("enkephalin convertase"). To denote that the enzyme is membrane-bound, and to distinguish it from other known carboxypeptidases, we propose the name "carboxypeptidase M." Because of its localization on the plasma membrane and optimal activity at neutral pH, carboxypeptidase M could inactivate or modulate the activity of peptide hormones either before or after their interaction with plasma membrane receptors.

Carboxypeptidases