Biomedical subjects
Publications and source records attributed to D A Johnson.
A 45-year-old woman with a long history of propoxyphene abuse was successfully detoxified with clonidine. She had no significant withdrawal symptoms and hospitalization was brief. Controlled study of clonidine for propoxyphene withdrawal is an area for further investigation.
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Localized asymptomatic soft tissue swellings developed in a 20-year-old woman, Type I juvenile-onset diabetic, at the site of repeated insulin injections. Histopathologic examination of specimens from these lesions in three patients showed chronic inflammatory changes and exogenous foreign material that was thought to be silicon. Lipodystrophic changes associated with insulin therapy are briefly reviewed.
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Cobra alpha-toxin purified from Naja naja siamensis venom was labeled with near stoichiometric quantities of fluorescein isothiocyanate. A monofluorescein alpha-toxin was separated in 50-60% yield from unconjugated alpha-toxin and other reaction products by ion exchange chromatography. The isolated mono-conjugated alpha-toxin electrofocuses largely as a single entity with 92% appearing with a pI of 9.6. The unmodified toxin has a pI of 10.7. Thermolysin digestion and subsequent high pressure liquid chromatography of the peptides yield two dominant fluorescent peaks, both of which can be traced to the labeling of lysine 23. The NE-fluorescein isothiocyanate (FITC)-Lys-23 alpha-toxin shows an apparent reduction in quantum yield when compared with either free FITC or the denatured and reduced NE-FITC-Lys-23 alpha-toxin. The reduction of fluorescence is likely to be due to static quenching of the fluorescein by the tryptophanyl and tyrosyl residues (25 and 21, respectively) in the "central loop" region. Binding of the NE-FITC-Lys-23 alpha-toxin to the membrane-associated acetylcholine receptor is accompanied by a 95 +/- 22% increase in fluorescence which probably reflects perturbation of the beta-pleated sheet character of the region containing residues 20-25 of the alpha-toxin. Steady state fluorescence polarization measurements of NE-FITC-Lys-23 alpha-toxin yield a rotational correlation time of 3.7 ns, suggesting FITC is largely immobilized on the alpha-toxin. The NE-FITC-Lys-23 alpha-toxin binds with a dissociation constant of 4 nM determined by fluorescence polarization.
Five fractions of basic proline-rich proteins were isolated from rat parotid saliva, obtained by surgical cannulation of the ducts. The purification procedures employed DEAE-Sephadex to isolate a heterogeneous break-through fraction containing the basic proline-rich proteins, followed by gel filtration on Sephadex G-200 to separate the high molecular weight glycoprotein, fraction A, from the other basic proline-rich proteins which were resolved into four additional fractions, SP-1 to SP-4, by ion exchange chromatography on SP-Sephadex. The proteins differed in their amino acid composition and content of neutral and amino sugars. All the proteins were characterized by a high proportion of proline (approx. 40 mol per cent) and glycine (11-23 mol per cent). Four of the fractions were also enriched in glutamic acid/glutamine (19-26 mol per cent). The exception was fraction SP-4, which contained lower levels of glutamic acid/glutamine and has no counterpart in human basic proline-rich proteins. Fraction A, the basic glycoprotein, was heavily glycosylated (59 mol per cent), whereas SP-2 and SP-4 were less glycosylated. Fractions SP-1 and SP-3 contained low levels of neutral and amino sugars. Basic proline-rich proteins constitute a smaller percentage of the total protein in rat parotid saliva than they do in human parotid saliva (10.5 versus 40 per cent). Rat basic glycoprotein fraction constitutes less than 1 per cent whereas the human glycoprotein fraction constitutes 17 per cent. Rat basic proline-rich proteins appear to be larger and less basic than most of the human basic proteins, and they resolve into fewer protein fractions (4 versus 9) with SP-Sephadex chromatography.
Hairless (hr/hr) mice segregating for SJL/J and HRS/J genes (SJL-HRS) were compared to their haired counterparts with respect to immune responsiveness, tumour development and ecotropic murine leukemia virus (MuLV) expression. Homozygosity at the hairless locus did not affect expression of MuLV. There was however, a significant depression of the cellular immune response of these mice as characterized by depressed reactions in phytohemagglutinin, concanavalin A and mixed leukocyte assays. Haired and hairless mice did not differ significantly in response to B-cell mitogens or in production of cytotoxic antibody. The depressed cellular immune response in hr/hr mice is associated with a distinctive histologic type of spontaneous reticulum cell sarcomas. The importance of these results in relation to previous studies of HRS/J hairless mice is discussed.
The object of the present study was to determine of the secretory proteins of rats parotid saliva were altered following parotid gland atrophy induced by feeding rats a liquid stock diet which eliminated mastication. Compared to rats fed the pelleted stock diet, the parotid glands of rats fed liquid stock diet showed 40% to 55% reductions in gland weight and content of RNA, amylase, and protein. Gland DNA content was reduced by 26%. The concentration of protein and the activities of three secretory enzymes in parotid saliva were reduced by 40% to 70%. The secretory enzymes were affected in a nonparallel manner so that per milligram of secretory protein DNase was increased, while RNase and amylase were reduced. Examination of the protein composition by acrylamide gel electrophoresis showed that several secretory proteins were no longer present. This study showed that feeding rats a standard stock diet, but in liquid form to eliminate mastication, results in a reduction in the protein concentration of parotid saliva, a loss of several secretory proteins and nonparallel changes in some of the proteins which remain.
Human bronchial mucus contains an acid-stable proteinase inhibitor called bronchial mucous inhibitor (BMI) that apparently protects the upper airways from proteolysis by polymorphonuclear leukocyte (PMN) elastase and cathepsin G, and infections of Pseudomonas aeruginosa, which also produces an elastase, can result in considerable lung damage. The possible role of BMI in protecting the lung from proteolytic attack in the presence of P. aeruginosa elastase (a zinc metalloprotease) was investigated. The BMI not only failed to inhibit P. aeruginosa elastase but the ability of BMI to inhibit PMN elastase and cathepsin G was rapidly lost in the presence of the bacterial elastase. The P. aeruginosa elastase also freed active PMN elastase from complexes with BMI, resulting in elastin digestion by both enzymes. The proteolysis of lung tissue observed with P. aeruginosa infections may be caused by a combination of bacterial and PMN proteases. Elastase and cathepsin G released from leukocytes, attracted to P. aeruginosa infection sites, would be free to attack the bronchial tissues after BMI inactivation by P. aeruginosa elastase, adding to the damage caused by the bacterial protease(s).
The present study, along with others, shows that when the requirement of a diet for mastication is increased, enlargement of the parotid gland occurs. This study demonstrated for the first time that the magnitude of the gland enlargement is directly related to the amount of nonnutritive bulk incorporated into the diet, and that the concentration of protein is significantly increased in the parotid saliva of rats fed such a diet. The findings show that, although the concentration of protein is increased in the parotid saliva, the composition of proteins is unchanged, leading to the conclusion that all secretory proteins are increased in parallel. A comparison of the gland enlargement observed in response to the bulk diet with that observed in response to chronic isoproterenol treatment reveals many similarities. However, the fact that the protein composition of the parotid saliva is not altered when rats are fed the bulk diet is in marked contrast to the striking changes observed following chronic isoproterenol treatment. The reason for the dissimilar response is not known. However, an investigation into the differences that exist in the gland response to these two means of inducing gland enlargement may lead to a better understanding of the factors that regulate the size of the rat parotid gland and the complement of proteins in its secretion.
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One of the intriguing questions about the establishment of synaptic connections is how appropriate numbers of different axons come to innervate each target neuron. A reorganization of connections in early postnatal life appears to be an important aspect of this process, since many of the axons terminals that initially innervate target cells are subsequently lost. The rabbit ciliary ganglion is a remarkably simple neural ensemble in which to examine this rearrangement of developing synaptic connections. Using this system we have found that a reduction in the number of axons innervating each cell occurs without any change in the number of ciliary ganglion cells or preganglionic neurons; therefore the rearrangement is not based on cell death. The number of different axons that ultimately innervate each cell is, however, influenced in some way by the geometry of individual target neurons. Thus, mature ganglion cells that lack dendrites are generally innervated by a single axon, while neurons with increasingly complex dendritic arbors receive innervation from a commensurate number of different axons. At birth, on the other hand, neurons with or without dendritic processes receive about the same number of preganglionic inputs. These results suggest that the geometry of the target cell influences the competitive interaction between different axons innervating the same neuron. Indeed, an important function of dendrites may be to regulate the number of axons that innervate each nerve cell.
Rats were fed a stock pelleted diet (control diet) or the same stock diet to which 30 per cent non-nutritive cellulose had been added (bulk diet). The control diet and the bulk diet were fed to rats in two consistencies, pelleted or ground. Compared to the parotid glands of rats fed the pelleted control diet, those of rats fed either of the ground diets were not different, but parotid gland wet weight, DNA and RNA content and total gland amylase and protein were significantly greater in rats fed the pelleted bulk diet for 2 wk. The cell indices of RNA/DNA and amylase/DNA were significantly greater in rats fed the pelleted bulk diet, but were not significantly changed in rats fed the ground bulk diet. Thus there is a significant increase in cell number and cell content of amylase when rats are fed a bulk diet that is pelleted and no such increases are found when the bulk diet is ground. The findings support the contention that the physical consistency of the diet and its requirement for mastication are major factors contributing to the regulation of parotid-gland size and secretory-enzyme content.
The relative importance of dementia, gender, age and functional status (FS) was examined for relationships to mortality within five years after admission of the subjects to a New York City nursing home for the aged. Using a random sample of 212 of the nursing home's patients, a statistical model was developed to estimate the relative risk of mortality. When this model was cross-validated on an independent sample of 118 residents, it failed to show significant lack of fit. Given these results, an international model was developed by combining the New York City samples(N = 330) and comparing them to a sample (N = 363) from a nursing home in Tokyo, Japan. In the new York model, gender was the most important predictor, with age and dementia next in importance; FS was not a significant predictor. Despite the apparent differences in the types of dementia in the New York and Tokyo nursing homes, the mortality patterns were similar.
A survey of over two hundred patients attending fourteen family doctors in five different practices investigates the treatment in general practice of patients suffering from depressive illness. Medication was the principal treatment offered, but was often inadequate either because of prescription variables or because patients failed to comply with the treatment prescribed. The reasons for patient non-compliance fell into three main categories (a) side effects, (b) attitudes to drugs, (c) patient--doctor communication failure. It is suggested that a more extensive discussion of mental illness and its treatment is required as part of the total treatment of the individual, that the family doctor should take a more active role in the supervision of the treatment regimen, and that drugs with fewer side effects, particularly anticholinergic effects, are all required as essential measures to improve patient compliance with treatment.