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Biomedical subjects

D Johnson

Publications and source records attributed to D Johnson.

At least 613 records · Page 34Linked to original sources

Dupuytren's disease: comparative growth dynamics and morphology between cultured myofibroblasts (nodule) and fibroblasts (cord).

The excised palmar fascia of 11 patients with Dupuytren's disease was separated clinically into nodules and cords. Myofibroblasts were seen by light and electron microscopy in each of the nodules, but the cords generally lacked myofibroblasts. Only one cord specimen had microscopic features that were intermediate between nodule and cord. Electron microscopy demonstrated that in vivo differences between myofibroblasts from nodules and fibroblasts from cords and control skin samples could be preserved in vitro. Growth studies showed slower growth of cultured myofibroblasts (mean +/- SD generation time 68.7 +/- 15 h) than cord-derived fibroblasts (mean +/- SD generation time 51.5 +/- 0.9 h). These data suggest that the life cycle of the myofibroblasts from Dupuytren's disease nodules differs from that of fibroblasts found in cordlike tissues. These myofibroblasts have biological characteristics nearly identical to those of myofibroblasts found in other contracting tissues, such as granulating wounds and breast cancer.

Biopsy↗

Altered blood T-cell subsets in patients with multiple sclerosis.

We have found an alteration in T-cell subsets in patients with active multiple sclerosis, specifically an increase in the T4:T8 ratio. These findings have been reproducibly obtained over the past four years, occurring in the majority of acute patients tested early in the course of an attack and in between 25 and 40% of chronic progressive patients, depending on their stage of illness. These changes correlate with pleocytosis in spinal fluid and with other abnormalities of immune function, such as spontaneous immunoglobulin production. They have been helpful in assessing disease activity in patients being treated on a variety of protocols and as part of research studies of immunoregulatory abnormality in multiple sclerosis, but have not been helpful as a diagnostic test for multiple sclerosis. The decrease of these cells in the peripheral blood of patients with active disease may be secondary to migration of these cells to the central nervous system, where they are sequestered.

Animals↗

Familial third-fourth pharyngeal pouch syndrome with apparent autosomal dominant transmission.

A family is presented in which both siblings and their father had evidence of third-fourth pharyngeal pouch syndrome (DiGeorge syndrome). All three individuals had hypocalcemia and unusual facies. Both infants had truncus arteriosus. One infant had evidence of impaired cell-mediated immunity; the father had a relatively decreased number of T-lymphocytes. The syndrome is uncommon, most cases being isolated, and familial presentations are even rarer. Two recent reports described several affected individuals who also had partial deletions of chromosome 22. Chromosome banding studies in our family were normal. Thus our family demonstrates an autosomal dominant pattern of inheritance, although it cannot be proved that this is a single gene defect. We propose that inasmuch as the presentation of the syndrome is quite varied, thorough family investigation including high-resolution cytogenetic analysis is necessary. Familial cases may be more common and require genetic counseling.

Chromosome Aberrations↗

Endocrine pancreas in cystic fibrosis: an immunohistochemical study.

The pancreases of 17 patients who had cystic fibrosis with and without diabetes mellitus were evaluated at autopsy by routine staining and immunohistochemical methods for insulin, glucagon, somatostatin, and pancreatic polypeptide. Qualitative assessment of the number of islets of Langerhans and the degrees of exocrine pancreatic atrophy, fibrosis, and fat replacement was made for each pancreas. Quantitative assessment of islet composition was performed in 15 of the 17 based on the immunochemical reactivity of each cell type. Nondiabetic patients with cystic fibrosis in the latter part of the first decade of life have classic fibrocystic changes of the pancreas, with some persisting exocrine tissue, islets that appear normal, and prominent nesidioblastosis. The latter process may protect these patients from glucose intolerance. Young adult diabetic patients with cystic fibrosis have total loss of exocrine pancreas with fat replacement, lack of nesidioblastosis, a qualitative decrease in the number of islets, fibrosis of and amyloid deposits in islets, decreased numbers of insulin-containing cells in each islet, and atrophy of islet cells, probably resulting from progressive ischemia. Although the potential exists for an increasing incidence of diabetes mellitus in patients with cystic fibrosis as their life spans increase, individual variation occurs in this disease.

Adult↗

Processing of cues for stop consonant voicing by young hearing-impaired listeners.

To assess whether young hearing-impaired listeners are as sensitive as normal-hearing children to the cues for stop consonant voicing, we presented stimuli from along VOT continua to young normal-hearing listeners and to listeners with mild, moderate, severe, and profound hearing impairments. The response measures were the location of the phonetic boundaries, the change in boundaries with changes in place of articulation, and response variability. The listeners with normal hearing sensitivity and those with mild and moderate hearing impairments did not differ in performance on any response measure. The listeners with severe impairments did not show the expected change in VOT boundary with changes in place of articulation. Moreover, stimulus uncertainty (i.e., the number of possible choices in the response set) affected their response variability. One listener with profound impairment was able to process the cues for voicing in a normal fashion under conditions of minimum stimulus uncertainty. We infer from these results that the cochlear damage which underlies mild and moderate hearing impairment does not significantly alter the auditory representation of VOT. However, the cochlear damage underlying severe impairment, possibly interacting with high signal presentation levels, does alter the auditory representation of VOT.

Adolescent↗

A new spinal brace for use in Duchenne muscular dystrophy.

Nine boys with Duchenne muscular dystrophy, chairbound but without scoliosis, were fitted with a recently developed brace of metal and moulded medium-density polyethylene, the modified Calot brace. Each was also fitted with a wrap-around, moulded leather jacket. Each brace held the relaxed lumbar spine in an angle of lordosis similar to that achieved by a brief active effort to sit erect without a brace. Over-all, they proved equally acceptable to patients and carers. The modified Calot brace caused substantially less restriction of pulmonary function and so may be preferable to the moulded leather jacket.

Braces↗

[Experimental study of postvaccinal immunity to sheep-pox].

Two live virus sheep-pox vaccines have been prepared on lamb testicular cells from strains Perego and RM65. Inocuity and activity have been compared to those of a commercial vaccine on a small number of lambs. Immunogenicity has been studied through neutralizing and precipitating antibodies, and through challenge resistance (strain Held), using a protective index. Results show that Perego vaccine titrated at 10(4) DICT50 gives a reliable immunity and does not provoke severe reaction post-inoculation. RM65 vaccine of which protection index is lower, only avoid infection to generalize. Although some correlation exists between seroneutralizing titers and protective index, virulent challenge appears and seems to give better data with regards to the level of protection conferred.

Animals↗

Catabolism of exogenously supplied thymidine to thymine and dihydrothymine by platelets in human peripheral blood.

The interference of platelets with the estimation of unscheduled DNA synthesis in human peripheral mononuclear leukocytes following genotoxic exposure was studied. A 96% reduction in the unscheduled DNA synthesis value was achieved by incubating [3H]thymidine with platelet-rich plasma for 5 hr at 37 degrees. Using radioactive thymine-containing compounds, together with quantitative analyses based on thin-layer and ion-exchange chromatographies, we have shown that thymidine was converted to thymine which, in turn, was converted to dihydrothymine in platelet-rich plasma. The enzymes responsible were separated from platelet lysates by gel filtration and were identified as thymidine phosphorylase and dihydrothymine dehydrogenase. The phosphorylase reversibly catalyzed the formation of thymine from thymidine and converted bromodeoxyuridine to bromouracil. The dehydrogenase reversibly catalyzed the interconversion of thymine and dihydrothymine in a reaction dependent on NADP(H), and it was inhibited by diazouracil and by thymine. Nearly all the thymidine-catabolizing activity found in whole blood samples supplied exogenously with thymidine was accounted for by the platelets. Since most genetic toxicological tests that use blood samples do not involve removing platelets from the blood cell cultures, then it is concluded that precautions should be taken in the future to determine the influence of platelets on these test systems. This is particularly true for methods dependent on thymidine pulses such as unscheduled DNA synthesis, or those dependent on bromodeoxyuridine, such as sister chromatid exchanges, since this nucleoside is also a substrate for thymidine phosphorylase.

Blood Platelets↗

5-Fluorouracil + Oncovin + Adriamycin + mitomycin C (FOAM): an effective program for breast cancer, even for disease refractory to previous chemotherapy. A Northern California Oncology Group (NCOG) Study.

One hundred and thirty-one patients (118 evaluable) with disseminated breast cancer were treated with a combination of 5-fluorouracil + Oncovin + Adriamycin + mitomycin C (FOAM). The objective response rate for 82 evaluable patients whose disease was refractory to previous CMF or L-PAM chemotherapy was 35%; that for 36 evaluable patients who had not previously received chemotherapy, 56%. The hematologic toxicity of this therapy was generally mild and acceptable. It is believed that FOAM is an effective therapy for patients whose tumors are resistant to CMF.

Adult↗

Aqueous humor dynamics in Fuchs' uveitis syndrome.

We studied aqueous humor dynamics in ten subjects (four men and six women, ranging in age from 19 to 72 years) with unilateral Fuchs' uveitis syndrome. The unaffected fellow eyes served as controls. In two patients, the affected eye also had glaucoma. Fluorophotometry showed the blood-aqueous barrier to be abnormally permeable in the affected eyes. The calculated coefficient of exchange of fluorescein across the blood-aqueous barrier was 30.7 X 10(-4) min-1 in the affected eyes and 5.7 X 10(-4) min-1 in the unaffected eyes. The anterior chamber elimination coefficient of fluorescein, corneal endothelial permeability to fluorescein, and anterior chamber volume did not differ significantly in affected vs unaffected eyes. The rate of aqueous humor flow through the anterior chamber in the affected eyes appeared to be normal, as did the apparent resistance to the outflow of aqueous humor.

Adult↗

Function and fidelity of aging tRNA: in vivo acylation, analog discrimination, synthetase binding, and in vitro translation.

The liver transfer RNAs for valine and lysine were completely acylated in vivo, as judged by periodate oxidation, at 4 and 24 months of age in male Sprague-Dawley rats. In vitro acylation capacity for whole tRNA populations from rat livers is decreased, but this is evidently not deleterious in vivo. Several halogenated phenylalanines were synthesized and their effects upon acylation capacity for phenylalanine were examined. Synthetases bound to young (3 month) and old (24 month) tRNAs discriminated differently between p-chlorophenylalanine and authentic phenylalanine; synthetase with young tRNA was less able to discriminate than with old tRNA. Purified tRNAphe from old rats did not form ultraviolet-induced crosslinks to purified phenylalanyl tRNA synthetase as well as young tRNAphe. In vitro translation of encephalomyocarditis virus, hemoglobin, and ovalbumin mRNAs was effective, using tRNAs of young or old Sprague-Dawley or Fischer 344 rat livers, although, when the old tRNA was supplied, the product synthesized per unit tRNA was reduced. All of the protein products were synthesized with all tRNAs, as shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis. We conclude that tRNA is capable of normal functions in livers of aging rats, is probably modification deficient, and is unlikely to produce protein errors.

Acylation↗

The vascular supply to the skin: an anatomical and physiological reappraisal--Part I.

We present a new concept of vascular anatomy, proposing that a complex subcutaneous vascular network, located between the dense and loose adipose tissue, connects the larger subcutaneous vessels, the vertical perforators, and the subdermal plexus. Knowledge of the location of these vessels helps determine optimal flap design and level of elevation. In this first of two articles, we describe the experimental portions of our study. The sequel describes the human experience and clinical implications.

Animals↗