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Biomedical subjects

W W Johnson

Publications and source records attributed to W W Johnson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Association between relapsing polychondritis and systemic lupus erythematosus.

Relapsing polychondritis (RP) is an autoimmune disorder with chondritis as a prominent clinical feature. This disease has been found to coexist in some patients with systemic lupus erythematosus (SLE) or vice versa. We report a patient with clinical criteria fulfilling the diagnosis of RP. She had elevated levels of anti-dsDNA and decreased levels of CH50 during the 6-month observation, without clinical manifestations of SLE except for arthritis. We also reviewed all 16 cases of previously described patients with RP and SLE. From our study, we conclude that chondritis is rare in patients with SLE. If immunologic abnormalities usually found in SLE are detected in patients with RP, clinicians should observe patients for other manifestations of SLE.

Adult↗
PubMed1993

Tyrosine 115 participates both in chemical and physical steps of the catalytic mechanism of a glutathione S-transferase.

The participation of the hydroxyl group of tyrosine 115 in the catalytic mechanism of isoenzyme 3-3 of rat glutathione (GSH) S-transferase is implicated by x-ray crystallographic analysis of a product complex and confirmed by comparison of the catalytic properties of the native enzyme and the Y115F mutant. Tyrosine 115 is located in domain II of the protein (the xenobiotic substrate binding domain) and is the first residue in this domain to be shown to play a direct role in catalysis. The 1.8-A structure of isoenzyme 3-3 in complex with (9S,10S)-9-(S-glutathionyl)-10-hydroxy-9,10-dihydrophenanthrene, one of the diastereomeric products of the reaction of GSH with phenanthrene 9,10-oxide, indicates that the hydroxyl group of Tyr115 is within hydrogen-bonding distance of the 10-hydroxyl group of the bound product and, by implication, is proximal to the oxirane oxygen of the substrate in the Michaelis complex. Site-specific replacement of Tyr115 with phenylalanine has profoundly different effects on catalysis depending on the type of reaction and whether the rate-limiting step in catalysis is a chemical step or a physical step. Stopped flow measurements of the rate constants for product release and viscosity effects on the steady-state kinetics establish that the rate-limiting step in catalysis with phenanthrene 9,10-oxide (kcat = 0.4 s-1) is probably a chemical one, whereas the physical step of product dissociation (koff) is rate-limiting in the reaction of 1-chloro-2,4-dinitrobenzene (kcat = 20 s-1). The Y115F mutant is severely impaired in catalyzing the addition of GSH to phenanthrene 9,10-oxide (kcat = 0.0044 s-1), evidence that the -OH of Tyr115 provides electrophilic assistance in the epoxide ring opening. In contrast, the Y115F mutant is a better catalyst toward 1-chloro-2,4-dinitrobenzene (kcat = 72 s-1) than is the native enzyme. The enhanced rates of product release in the mutant are ascribed to the loss of hydrogen bonds between the -OH of Tyr115 and the side chain -OH and main chain NH of serine 209, interactions that block the channel to the active site or inhibit the segmental motion of the protein.

Amino Acid Sequence↗
PubMed1993

Composite microfiller content and its effect on fracture toughness and diametral tensile strength.

Previous studies have examined the relationship between total filler content in hybrid restorative composites and some of their mechanical properties. This investigation evaluated the effect of varying the amount of microfiller in an experimental hybrid composite on fracture toughness (single edge-notch technique) and diametral tensile strength. The microfiller content in the experimental hybrid composite was varied from 0-44 wt% for seven specimen groups, while the total filler content ranged from 77-84 wt%. It was found that 9 wt% microfiller loading produced the highest mean fracture toughness (1.33 MPa.m(1/2)) and 44 wt% loading produced the lowest mean value (0.80 MPa.m(1/2)). Only the 9 wt% microfiller content group differed significantly in fracture toughness from the other specimen groups. The diametral tensile strength displayed only small differences for the range of microfiller content studied with mean values ranging from 42.1-49.6 MPa. Additional research on the viscoelastic properties of these heavily filled hybrid composites may provide some insight into the differences for the fracture toughness and diametral tensile strength results.

Bisphenol A-Glycidyl Methacrylate↗
PubMed1992

Contribution of tyrosine 6 to the catalytic mechanism of isoenzyme 3-3 of glutathione S-transferase.

The role of the hydroxyl group of tyrosine 6 in the catalytic mechanism of isoenzyme 3-3 of rat glutathione S-transferase has been examined by x-ray crystallography and site-specific replacement of the residue with phenylalanine and evaluation of the catalytic properties of the mutant enzyme. This particuar tyrosine residue is conserved in the sequences of all of the cytosolic enzymes and is found, in crystal structures of both isoenzyme 3-3 from the mu-gene class and an isoenzyme from the pi-gene class, to be proximal to the sulfur of glutathione (GSH) or glutathione sulfonate bound at the active site. The 2.2-A structure of the binary complex of isoenzyme 3-3 and GSH indicates that the hydroxyl group of Tyr6 is located 3.2-3.5 A from the sulfur of GSH, well within hydrogen bonding distance. Removal of the hydroxyl group of Tyr6 has essentially no effect on the dissociation constant (22 +/- 3 microM) for GSH. Nevertheless the Y6F mutant exhibits a turnover number which is only about 1% that of the native enzyme when assayed at pH 6.5 with either 1-chloro-2,4-dinitrobenzene (CDNB) or 4-phenyl-3-buten-2-one. UV difference spectra of the binary enzyme-GSH complexes suggest that the predominant ionization state of GSH in the active site of the Y6F mutant is the neutral thiol (e.g. EY6F.GSH) which is in contrast to the native enzyme in which the thiol is substantially deprotonated (e.g. E.GS-). Spectrophotometric titration suggests that the pKa of the thiol is 6.9 +/- 0.3 in the E.GSH complex and greater than or equal to 8 in the EY6F.GSH binary complex. In addition, the pH dependence of kcat/KmCDNB reveals that the reactions catalyzed by the native enzyme and the Y6F mutant are dependent on a single ionization in the E.GSH and EY6F.GSH complexes with pKa = 6.2 +/- 0.1 and 7.8 +/- 0.3, respectively. The results suggest that the hydrogen bond between Tyr6 and the enzyme-bound nucleophile helps to lower the pKa of GSH in the binary enzyme-substrate complex.

Animals↗
PubMed1992

Oral amalgam pigmentations (tattoos): a retrospective study.

Oral amalgam tattoos are typically asymptomatic, benign, solitary or multiple clinical lesions produced by inadvertent placement of dental silver amalgam restorative material into the oral soft tissues. Diffuse lesions often display a grayish brown discoloration while other tattoos present a darker blue-black contrast. One hundred sixty-eight biopsy reports that confirmed the diagnosis of amalgam tattoo were analyzed to find age, sex, and race of the patients and size, location, and duration of occurrence of the lesions. Among the 168 cases, 235 individual tissue specimens were identified. A majority of the specimens were taken from the buccal mucosa, gingiva, and alveolar mucosa. The most common site for the lesion was the mandibular arch. The size of the individual specimens ranged from 0.10 cm to 1.50 cm. Almost two thirds of the specimens were 0.40 cm or less.

Adolescent↗
PubMed1991

Soft tissue myofibroblastomas.

Five well-circumscribed solitary soft tissue tumors composed of myofibroblasts are described and termed myofibroblastomas. By light microscopy these lesions are characterized by short, intersecting, or crisscrossing fascicles of spindle cells, sometimes associated with foci of necrosis and/or mitotic activity with less than three mitoses per 10 high power fields. Myofibroblastomas show well-defined myofibroblastic differentiation ultrastructurally with peripheral myofilaments and vimentin, actin, and desmin immunocytochemistry positivity. The five tumors described occurred in patients of various age groups, including one congenital, and in a variety of soft tissue locations. It is important to recognize this benign soft tissue neoplasm to avoid confusion with other soft tissue tumors and to separate this lesion from other myofibromatosis. This study elucidates the spectrum of light microscopic, ultrastructural, and immunocytochemistry findings of soft tissue myofibroblastomas and establishes this soft tissue tumor as a specific clinico-pathologic entity.

Actins↗
PubMed1990

Organ preservation injury in small bowel transplantation.

Histological features of preservation injury were studied in a dog model of total small bowel transplantation. It was remarkable that substantial microscopic injury was evident during cold ischemia, unlike in other organ systems. This was early in onset and was related to the duration of cold storage. There was further progression of injury during reperfusion, as expected. Nevertheless, the small bowel was noted to have substantial ability to recover from this storage- and reperfusion-related injury. Histological features of damage and recovery are described in detail.

Animals↗
PubMed1989

Cognitive demands in automation.

As the nature of a task changes with increasing automation, so do the cognitive demands on the human operator. The present study examines the implications of such changes on subjective workload and automation design issues. A variety of tasks (continuous flight control, discrete target acquisition, and decision making) was used to tax the different cognitive systems. Each task could be performed alone or in combination with other tasks. Performance and subjective workload ratings, obtained by three workload scales, were examined as a function of the level of automation. Results demonstrated the usefulness of the multiple resource approach to task analysis. All three workload scales were found to be sensitive to the task demands. The Bedford scale was particularly impressive in distinguishing the different types of resources in demand. Both the multiple resource model's performance predictions and the subjective workload ratings were shown to be invaluable for decisions on how and what to automate.

Adolescent↗
PubMed1989

The visually guided control of simulated altitude.

Simulated "flights" over three different ground textures were used to examine people's ability to extract optical information useful for active regulation of altitude. The textures were regularly spaced lines as follows: 1) orthogonal to the direction of flight (latitude texture); 2) parallel to the direction of flight (meridian texture); and 3) both parallel and orthogonal (square texture). Visual constant velocity forward flight simulations were displayed on a CRT screen, and subjects asked to maintain one of three initial altitudes using a rate control stick. This task was made difficult by the presence of lateral (irrelevant) and vertical (relevant) "wind gusts." The attitude never varied as winds, forward speed, and vertical rate control resulted in only translational movements. Adjusted root mean square errors (ARMSE) showed altitude regulation was more difficult at higher altitudes and when flying over meridian textures. Refined analysis of a single subject's data showed that this was due both to poorer regulation of the vertical wind disturbance and to a tendency to confuse the lateral wind disturbance for a vertical disturbance.

Adolescent↗
PubMed1987

Total orthotopic small bowel allotransplantation in the dog. Features of atypical rejection and graft-versus-host reaction.

The critical histologic review of our experience with small bowel allotransplantation in the dog is presented. While "classical" rejection with dense small cell infiltration and mucosal destruction does occur, more common is the "atypical" rejection reaction in which cellular infiltration is sparse. This "atypical" rejection was characterized by a significant decrease of mucosal epithelial structures with increased mitotic figures in crypt cells and frequent vascular changes, including segmental fibrinoid necrosis and thrombosis with or without overlying mucosal destruction. Substantial regenerating capacity of bowel mucosa tends to compensate for the destruction, complicating the histology. The host lymph nodes and spleen present a histologic picture highly suggestive of GVH reaction. The reduction in host lymphocytes in these organs from karyorrhexis with replacement by histiocytes and subsequently by plasma cells is described. It is emphasized that rejection and GVH are not mutually exclusive and occur simultaneously. The decrease of functional mucosal mass could well account for the nutritional malsequelae. Also, the weakening of immune structures on the host and the graft side may predispose to catastrophic enterogenous infections, perhaps explaining the large number of animals that die without overt signs of rejection following small bowel transplantation.

Animals↗
PubMed1986

Cancer of the large bowel in children.

We present the morphologic and clinical features of large bowel carcinoma in 22 patients seen over 18 years at St. Jude Children's Research Hospital. We saw 18 cases of mucinous adenocarcinoma, three of well differentiated adenocarcinoma, and one case of poorly differentiated adenocarcinoma. The patients ranged in age from 9 to 19 years with a median age of 15. There were 12 female and ten male patients; 12 were black and ten were white. Eighteen patients had Dukes' stage C disease, with median survival of seven months and one patient alive 12 months after diagnosis. Three patients had Dukes's stage B disease, with two patients surviving 16 months each and one presently alive seven months after diagnosis. Only one patient had Dukes' stage A disease and is alive 121 months after diagnosis. Large bowel carcinoma in children is predominantly mucinous adenocarcinoma and occurs in the adolescent age group. Tumor distribution is fairly even throughout the large bowel, and all subtypes of the tumor are positive for carcinoembryonic antigen (CEA) on immunohistologic study. Active tumor and tumor regrowth are always accompanied by high serum levels of CEA. The tumor has no predilection for sex, but is significantly more frequent in blacks (P less than .05). Discovery of the tumor in an early stage improves the prognosis.

Adenocarcinoma, Mucinous↗