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Biomedical subjects

E Johnson

Publications and source records attributed to E Johnson.

At least 325 records · Page 18Linked to original sources

Testosterone, 17 beta-hydroxy-5 alpha-androstan-3-one and 4-androstene-3, 17-dione in the plasma of male and female grey squirrels (Sciurus carolinensis).

Extracts of squirrel plasma have been chromatographed on partition columns (using a hydrophilic stationary phase) at atmospheric pressure (Celite support) and a reversed phase system at high pressure (HPLC). Both methods effectively separated testosterone, 17 beta-hydroxy-5 alpha-androstan-3-one (DHT) and 4-androstene-3,17-dione; they gave elution patterns that differed considerably. Chromatographic mobility of the three androgens on the two systems was identical with that of fractions of squirrel plasma extracts that gave responses measured by appropriate androgen radioimmunoassays; good evidence for the occurrence of these androgens in squirrel plasma is thus provided. Plasma testosterone levels were 300 pmol/l in juvenile males, 800-7000 pmol/l in sexually-active males but undetectable (less than 50 pmol/l) in sexually-regressed males. Plasma DHT levels were also high in sexually-active males, but undetectable in other males except for one regressed individual. Plasma androstenedione was higher in juvenile males than in adult males, in which it was similar whether or not they were sexually regressed. Plasma testosterone and DHT, unlike androstenedione, were totally dependent on the presence of the testes. In females testosterone and DHT were undetectable in plasma but androstenedione levels were high, especially at oestrus. Androstenedione was dependent on the presence of the ovaries.

Androstenedione↗

Attachment and phagocytosis by salmon macrophages of agarose beads coated with human C3b and C3bi.

Agarose beads (diameter 5-10 micron) preincubated in human serum became associated (attached and ingested) to 50-60% of the salmon macrophages within 60 minutes. However, Beads preincubated in serum treated with heating (50 degrees C, 20 min) or with EDTA (10 mM) to inhibit the activation of alternative complement pathway, were not associated to the phagocytes. Furthermore, agarose beads coated with human C3b and C3bi after incubation with isolated complement factors (C3, D, B), were associated to 30-40% of the phagocytes. About 80% of the cell-associated agarose beads was intracellularly located. Conversion by trypsin treatment (0.01%) of agarose bound C3bi to C3d, abolished the association of such beads to the macrophages. The results demonstrate that salmon macrophages possess complement receptors that bind human C3b and C3bi. Agarose beads coated with these ligands (C3b and C3bi) are attached and ingested by the phagocytes.

Animals↗

Misonidazole combined with hyperfractionation in the management of malignant glioma.

Multiple daily fractionated radiation therapy (MDF) may be more effective than conventionally fractionated radiation therapy (CF) in the treatment of malignant glioma. The hypoxic cell sensitizer misonidazole (MISO) could be more effective when employed with small fractions of radiation every 4 hours to take advantage of the long half-life of the drug. To evaluate MDF and MDF in combination with MISO, a randomized prospective trial was initiated. Between January 1981, and December 1982, patients with histologically verified astrocytoma with anaplastic foci or glioblastoma multiforme were randomized to CF (5800 cGy, 30 fractions, 6 weeks), MDF (6141 cGy, 69 fractions, 4 1/2 weeks, at 89 cGy every 4 hours 3 times daily) and MDF in combination with MISO (1.25 gm/M2 three times weekly for the first 3 weeks). In January 1983, the CF arm was dropped and a high dose MDF arm added (7120 cGy, 80 fractions, 5 1/2 weeks, at 89 cGy per fraction every 4 hours 3 times daily). CCNU chemotherapy was given at the time of tumor progression. One hundred and twenty-eight patients were evaluated (38 CF, 42 MDF, 37 MDF plus MISO, and 11 high dose MDF). Median survival was 29 weeks for CF, 45 weeks for MDF and 50 weeks for MDF plus MISO. Survival was significantly improved for patients treated with MDF compared to patients treated with CF (p less than .002). The addition of MISO to MDF did not result in further improvement in survival. Acute toxicity was acceptable. No clinically apparent delayed toxicity was observed.

Adolescent↗

Phagocytosis by human monocytes of particles activating the alternative pathway of complement.

The phagocytosis of particles activating the alternative pathway of complement by human monocytes cultured under serum-free conditions was studied. In contrast to native zymosan particles, which were easily ingested, rabbit erythrocytes and agarose beads had to be coated with C3b or C3bi to be engulfed by the monocytes. The binding and ingestion by monocytes of particles coated with C3bi were greater than for the same particles coated with the equivalent amount of C3b. The binding and uptake of rabbit erythrocytes and agarose beads were proportional to the amount of C3b or C3bi on the particles. In contrast to the complement activator particles, C3b- and C3bi-coated sheep erythrocytes, which are non-activators, were not ingested by the monocytes, although attachment to the monocytes took place. The presence of methylamine or cobra venom factor, which are complement inhibitors, strongly reduced the ingestion of native zymosan by the monocytes, whereas the uptake of C3b- or C3bi-coated zymosan particles were only weakly affected. This suggests that the binding of native zymosan to monocytes is sensitive to interference from a cell-derived alternative pathway C3 convertase (C3bBb). Binding and uptake of activators by human monocytes via complement receptor(s) are discussed.

Animals↗

Fibronectin promotes binding but not ingestion of agarose beads by mouse macrophages adn human monocytes.

We have examined to what extent human fibronectin associated with agarose beads with a 5- to 10-micron diameter mediates binding and uptake of the beads by mouse macrophages and human monocytes. Native agarose beads preincubated with 125I-fibronectin were neither associated with nor taken up by mouse macrophages after 30 min of incubation under serum-free conditions. When fibronectin was cross-linked to cyanogen bromide-activated agarose beads or incubated with gelatinized beads, this resulted in a significant increase in particle binding by macrophages and monocytes as compared with gelatinized beads, whereas the fraction of cells with ingested particles remained unaltered. Native agarose beads activated by cyanogen bromide and treated with ethanolamine were to a greater extent associated with and taken up by phagocytes than fibronectin- or gelatin-coated beads. Our results indicate that fibronectin acts as an adhesive glycoprotein and not as an opsonin. Since agarose beads are activators of the alternative pathway of complement, and fibronectin is reported to bind to factor C3, we speculate that cell-derived C3b is bound to the beads and fibronectin-coated beads are ingested by the phagocytes via complement C3b receptors on the cells.

Animals↗

Uterine estrogen and progesterone receptors in an estrogen- and progesterone- "resistant" primate.

The squirrel monkey, a New World primate, has elevated plasma estradiol and progesterone concentrations compared to those in the cynomolgus macaque, an Old World primate. We previously reported that uterine progesterone receptor concentrations examined in ovariectomized squirrel monkeys 2 days after estrogen treatment were about one eighth those in identically treated cynomolgus macaques. To examine this in greater detail, we gave estradiol (10 micrograms/kg X day) to ovariectomized squirrel and cynomolgus monkeys for various lengths of time (0, 2, 4, 7, and 14 days), followed by measurement of uterine estrogen and progesterone receptors and assessment of endometrial histology (including glycogen and peroxidase strains), vaginal histology, and cytology. Endometrial and vaginal morphologies showed adequate estrogen effects, as did glycogen and peroxidase stains. Two days of treatment were sufficient to induce both estrogen and progesterone receptors to maximal binding of [3H]moxestrol and [3H]R5020, respectively, in both species. Squirrel monkeys had about one third and one eighth the estrogen and progesterone uterine receptor concentrations, respectively, of cynomolgus monkeys. Receptor affinities in both species were similar. Neither [3H]moxestrol nor [3H]R5020 bound to uterine cytosols from untreated monkeys. We conclude that the increased plasma concentrations of estradiol and progesterone in the squirrel monkey compensate for the decreased estrogen and progesterone receptors in this species.

Animals↗

Comparison of the Du Pont aca and Dow methods for determination of high-density lipoprotein cholesterol.

We compared the Du Pont aca (phosphotungstate-enzymic cholesterol) and the Dow (dextran sulfate/Mg2+-enzymic cholesterol) methods for the determination of high-density lipoprotein cholesterol (HDLC) and total cholesterol in serum from 113 patients. The aca results for both total cholesterol and HDLC were significantly greater (p less than 0.0001) than the Dow results, the aca method overestimating the HDLC concentration (mean recovery 107.2% in serum samples with values assigned by the Centers for Disease Control). The precision of the aca method for HDLC was essentially the same as that of the Dow method. Bilirubin (up to 0.17 g/L), hemoglobin (up to 4 g/L), and slight lipemia (triglycerides up to 5.4 g/L) did not interfere with the aca method.

Autoanalysis↗

Aromatic-dependent Salmonella typhimurium as modified live vaccines for calves.

Strains of Salmonella sp with complete nonreverting aromatic biosynthesis (aro) defects are expected to be nonvirulent, in respect to invasive infection, because they need the aromatic metabolites paraaminobenzoate (for making folate) and dihydroxybenzoate (for making enterochelin) which are not available in host tissues. Derivatives with transposon-generated complete nonreverting aro-defects were prepared from 3 mouse-virulent strains of S typhimurium, namely, FIRN, WRAY, and UCD. The latter 2 parent strains originally were isolated from calves and are known to be calf-virulent. The resultant aromatic-dependent (aro-) strains were used to vaccinate 27 calves (2 to 3 weeks old), usually giving 2 doses by the IM route (10(9) bacteria) or orally (1.5 X 10(11)). Vaccination did not cause severe ill effects in any calf. Thus aro- defects cause loss of virulence for calves, as previously shown for mice. Vaccinated and control calves were challenge exposed, usually at 5 weeks of age, by feeding 1.5 X 10(11) cells of 1 of 2 calf-virulent S typhimurium strains, either UCD 108-11 or SL1323. Of the 16 challenge-exposed control calves, all became anorectic and depressed (CNS), and 15 had diarrhea. Fourteen of the 16 died; all tested tissues were bacteriologically culture-positive for Salmonella at necropsy. Vaccination with the live UCD aro- vaccine strain, SL1479 by either of 2 schedules (IM or orally) appeared effective.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Reactivity of monoclonal antibody F36/22 with human ovarian adenocarcinomas.

Monoclonal antibody F36/22 recognizes high-molecular-weight glycoprotein components associated with neoplastic development of the ovary. Indirect immunoperoxidase staining techniques were performed on a panel of nonmalignant ovarian tissues, primary ovarian tumors, exfoliated ascitic tumor cells, and metastatic lesions. Normal ovarian tissue components (n = 20) failed to exhibit detectable levels of antigen, whereas benign ovarian tissues show a low incidence of immunostaining (three of 26) restricted to some ductal elements. One hundred % (19 of 19) of the immunopositive primary malignant tumors were histologically classified as adenocarcinomas. Each of the predominant adenocarcinoma histotypes consistently showed expression of the antigen with 30 to 100% of the tumor cells scored as immunopositive. Ascitic tumor cells obtained from all of the ovarian adenocarcinoma patients examined (47 of 47) displayed immunopositive reactions, whereas normal mesothelial cells in these specimens exhibited undetectable staining. In addition, ovarian adenocarcinoma metastases (12 of 12) exhibited very intense immunoreaction products. No detectable antigen was expressed by nonadenocarcinoma ovarian tumor cells.

Adenocarcinoma↗

Relationship of cutaneous delayed hypersensitivity to protection from challenge exposure with Salmonella typhimurium in calves.

The purpose of this investigation was to relate cutaneous delayed hypersensitivity reactions to the degree of immunity induced in calves given a live virulent or a modified-live strain of Salmonella typhimurium. Calves were placed into 1 of 5 groups on the basis of the vaccinal strain given and route of the vaccination: (I) nonvaccinated controls, (II) vaccinated twice by IM inoculation with small doses of the live virulent strain, (III) vaccinated (IM) twice with the modified-live strain, (IV) vaccinated (orally) twice with the modified-live strains, and (V) vaccinated (IM, and then orally) twice with the modified-live strain. Skin testing was performed by intradermal injection of fragmented S typhimurium as antigen. Double skin fold thickness and visual assessments were recorded at 3, 6, 24, 48, and 72 hours after antigen was administered. Biopsy samples for histopathologic evaluation were obtained. After vaccination and skin testing were complete, calves were orally challenge exposed with 1.5 X 10(11) virulent S typhimurium. Cutaneous delayed-type hypersensitivity reactions (48 hours) were observed in all except controls (group I) and 2 of 3 calves vaccinated orally with the modified-live vaccine strain (group IV). Significant correlations between positive skin tests and protection from challenge exposure were observed except in group V calves, in which positive skin test results were seen, but adequacy of the immunity (or survival after challenge exposure) was inconsistent.

Animals↗

Aromatic-dependent Salmonella dublin as a parenteral modified live vaccine for calves.

A virulent Salmonella dublin isolate was made histidine-requiring (his-) to allow recognition. The his- derivative, SL1367 (still calf-virulent), was then given by transduction and mutation, a transposon-generated non-reverting aromatic biosynthesis (aro) defect; this defect caused loss of virulence for the mouse. The his- aro- derivative strain, SL1438, was effective as a live vaccine in mice. Twenty male Holstein calves were divided into 4 groups. Groups I, II, and III were vaccinated IM at 2 weeks and at 3 weeks of age with aromatic-dependent (aro-) S dublin strain SL1438. Groups I and III received freshly prepared vaccine and group II received lyophilized vaccine. Serious adverse reactions to the vaccination were not seen. After vaccination, the mean maximum increase in rectal temperature was 1.8 C in group I and III calves and 0.6 C in group II calves. Fewer group II calves developed diarrhea (1 of 5) or positive blood cultures (0 of 5) after vaccination compared with group I and III calves (6 of 10 and 5 of 10, respectively). Postvaccination diarrhea was mild and of short duration. Group IV was comprised of 5 nonvaccinated calves. At 5 weeks of age, all calves were challenge exposed orally. Group I, II, and IV calves were challenge exposed with 10(11) virulent S dublin SL1367. Group III was challenge exposed with 10(11) virulent S typhimurium UCD 108-11. Subsequently, fever and diarrhea (lasting 1 to 3 days), but no deaths, were observed in the vaccinated calves. Four of the 5 nonvaccinated (group IV) calves died (P less than 0.001) within 8 days after challenge exposure. Aro- S dublin SL 1438 did not cause serious adverse effects and provided protection against oral challenge exposure with either virulent S dublin or S typhimurium.

Animals↗

The spirochetal etiology of Lyme disease.

We recovered a newly recognized spirochete from the blood, skin lesions (erythema chronicum migrans [ECM]), or cerebrospinal fluid of 3 of 56 patients with Lyme disease and from 21 of 110 nymphal or adult lxodes dammini ticks in Connecticut. These isolates and the original one from l. dammini appeared to have the same morphologic and immunologic features. In patients, specific IgM antibody titers usually reached a peak between the third and sixth week after the onset of disease; specific IgG antibody titers rose slowly and were generally highest months later when arthritis was present. Among 40 patients who had early disease only (ECM alone), 90 per cent had an elevated IgM titer (greater than or equal to 1:128) between the ECM phase and convalescence. Among 95 patients with later manifestations (involvement of the nervous system, heart, or joints), 94 per cent had elevated titers of IgG (greater than or equal to 1:128). In contrast, none of 80 control subjects had elevated IgG titers, and only three control patients with infectious mononucleosis had elevated IgM titers. We conclude that the I. dammini spirochete is the causative agent of Lyme disease.

Antibodies, Bacterial↗

Tracing the use of torture: electrically induced calcification of collagen in pig skin.

Reports of the use of electrical torture are usually denied, so that there is an urgent need of diagnostic methods to distinguish the consequences of electrical torture from other superficial injuries. The 'electrical group' of Anti-Torture Research (ATR) has accordingly studied the possibility of distinguishing between the sequelae of electrical and heat injury. Among the reported differences of the two types of injuries is the occurrence in epidermis, vessel walls and sweat glands of vesicular nuclei exclusively in electrically injured skin. On the basis of experiments with anaesthetized pigs, we now report that the late sequelae of electrical injury appear to include the deposition of calcium salts beneath the area of an electrical cathode.

Aggression↗

The electroencephalogram of elderly subjects revisited.

The EEGs of 98 elderly volunteers were compared with those of 84 patients with a recent cerebral infarction who had achieved a stable clinical course. All subjects were uniformly evaluated according to a special protocol. The elderly volunteers were accepted for the study if they had no history, signs or symptoms of central nervous system disease. The EEGs were found to be significantly different between the two groups of subjects in several aspects. These included not only possible abnormalities, focal or diffuse, but also some normal features, such as alpha frequency and responses to photic stimulation and to hyperventilation. Groups of these differentiating features were analyzed. Using the single variable of ER (evoked response), discrimination of 80% was achieved. The variables that distinguish the volunteers from the patients may be used in the future to determine whether they are helpful in differentiating normals from patients with conditions other than stroke.

Aged↗