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Biomedical subjects

W W Johnson

Publications and source records attributed to W W Johnson.

At least 19 recordsLinked to original sources

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

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

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

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

Acute toxicity of phosphate ester mixtures to invertebrates and fish.

The acute toxicity of three commercial phosphate ester mixtures (hydraulic fluids) was tested against two invertebrates and four fishes. Pydraul 50E was more toxic than Houghtosafe 1120 in static and flow-through tests; Pydraul 115E was the least toxic. In flow-through tests these phosphate esters were less acutely toxic than PCB's. However, sublethal reactions to the phosphates suggest a need for chronic toxicity studies.

Animals

Treatment strategy for nodular renal blastema and nephroblastomatosis associated with Wilms' tumor.

Nodular renal blastema and nephroblastomatosis were present in 8 of 118 patients (6.8%) with Wilms' tumor. Five of these 8 patients (63%) had bilateral Wilms' tumors. Two had hemihypertrophy. Preoperative renal angiograms were accurate in detecting these metanephric anomalies. The surgical approach consisted of removal of the most diseased kidney and biopsy for diffuse tumors and wedge resections for localized tumors for the remaining kidney. Postoperatively, radiation was administered when tumor extended outside the kidney. Chemotherapy consisted of vincristine and dactinomycin for 18 mo and adriamycin for 6 mo. This method of management resulted in tumor-free survival of these 8 patients for 1--44 mo (median 24 mo). Nodular renal blastema and nephroblastomatosis may possibly develop into Wilms' tumor. All of these three conditions respond to surgery, chemotherapy, and radiation. When a Wilms' tumor is encountered, it is better to explore and possibly biopsy the opposite kidney. There is a place for second-look laparotomy in this spectrum of congenital anomalies.

Child

Ultrastructure of malignant histiocytoma arising in the acromion.

The ultrastructural features of a malignant histiocytoma of the acromial process of the scapula were studied. Material was obtained from two surgical biopsy specimens and an amputation specimen from the tumor. Cells possessing characteristics of histiocytes, fibroblasts, xanthoma cells, and multinucleated giant cells were present throughout the tumor. Smaller numbers of undifferentiated cells and lymphocytes were also observed. Intimate cytoplasmic interdigitations between adjacent tumor cells were found, and instances of degenerating intracytoplasmic cells, possibly representing phagocytosis, were observed. Specimens stained with periodic acid-Schiff reagent with and without exposure to diastase, examined by light microscopy, showed that numerous cells contained phagocytized material consisting of degenerating cells rather than cytoplasmic glycogen. Intraumor lymphocytes apparently represented an inflammatory reaction to the tumor. The tumor giant cells and xanthoma cells were probably modified histiocytes. Results of the study were compared with previous reports of ultrastructural studies of malignant histiocytoma of soft tissues. Fundamental similarities between such studies and this one suggested that the progenitor cell is a histiocyte, whether arising in bone or in soft tissues, and that the progenitor cell is capable of differentiation in both histiocytic and fibroblastic directions.

Acromion

An ultrastructural basis for electrocardiographic alterations associated with Duchenne's progressive muscular dystrophy.

Electrocardiographic abnormalities were identified in 63 (84%) of 75 patients with Duchenne's progressive muscular dystrophy. A tall R wave over V1 with an abnormal R/S ratio was seen in 64% of the patients, a deep and narrow Q wave greater than 4 mm over leads I, V5, and V6 in 44%, sinus tachycardia in 32% and right axis deviation in 16%. Other ECG abnormalities included an abnormal PV1 index in 14% of patients and a short P-R interval in 6%. Ultrastructural characteristics of the heart were determined for two patients with characteristic electrocardiographic abnormalities. Common to both hearts was a total loss of thick as well as thin myofilaments, which gave a "moth-eaten" appearance to the myofiber. This feature, combined with preservation of the transverse tubular system, formed the most characteristic ultrastructural finding and was seen most consistently in the posterobasal area of the left ventricle. Alterations of Z-band material; accumulation of mitochondria, occasionally containing electron-dense bodies and showing loss or discontinuity of cristae; dilatation of sarcoplasmic reticulum with striking ectasia of cisternae; depletion of glycogen particles; a paucity of lipoid or lipochrome granules; and the absence of virus-like particles were other consistent ultrastructural features. Comparison of skeletal and cardiac muscle disclosed identical subcellular changes. These observations support the contention that the distinctive ECG pattern associated with Duchenne's dystrophy results from multifocal degenerative changes involving myocardium, predominantly the posterobasal region of the left ventricle and the posterior papillary muscle.

Adolescent

Factors leading to delay in the diagnosis and affecting survival of children with head and neck rhabdomyosarcoma.

Rhabdomyosarcoma of the head and neck often presents with vague symptoms which mimic other disease conditions. These factors lead to undue delay in the establishment of the correct diagnosis and the delivery of acceptable therapy, including surgery, radiation therapy, and chemotherapy. There is, however, evidence of improved results of treatment of these tumors since the addition of multiple drug chemotherapy to surgery and radiotherapy.

Adolescent

Methotrexate-induced sudden fatal pulmonary reaction.

A teenage girl in bone marrow remission with acute lymphocytic leukemia died suddenly from pulmonary edema. She had taken her first oral dose of methotrexate and cyclophosphamide 10 hours previously when she was feeling well and was asymptomatic. One week previously she had received the last of four intrathecal injections of methotrexate. Autopsy showed marked pulmonary edema as well as chronic lung changes, as previously described in patients with methotrexate pneumonitis. There is usually at least a 12-day interval from the onset of administration of methotrexate to the onset of the lung toxicity. The authors suggest the patient was sensitized by the intrathecal methotrexate and then reacted with angioneurotic edema of the lung when given the first oral dose of methotrexate. Careful examination for infectious agents, including electron microscopy, was negative.

Adolescent

Colorectal carcinoma in adolescents implications regarding etiology.

Between October, 1974 and December, 1976, 13 adolescent patients with far-advanced, poorly differentiated colorectal carcinoma had been referred to a pediatric cancer center. All patients received chemotherapy with vincristine, methyl-CCNU and 5-fluorouracil. Five of 13 patients are living, one of whom remains disease-free after 12 months of chemotherapy. Four of the patients were from urban areas and nine from rural areas. One of four from urban areas had intimate exposure to chemicals used in the production of cotton and soy beans. Eight of nine patients from rural areas also had exposure to farm or agricultural chemicals, and three of these patients were intimately involved with the spraying operations. Suggestions regarding etiology and causative factors for the development of carcinoma of the colon in adults have previously been advanced. Results of these studies suggest that alternate etiologies must be suggested for adolescent colorectal carcinoma.

Adenocarcinoma, Mucinous

Citric acid consumption and the human dentition.

The habitual and abusive use of fruits and foods containing citric acid can cause serious dissolution effects on human tooth enamel. Because these effects can occur so easily, this paper suggests that foods and fruits containing citric acid, as well as other acids, could be definite contributors to the many other forms of idiopathic erosion so often observed by the dentist. There is a need for continued research and study in this area.

Adult

Bioaccumulation of chlorinated paraffin residues in fish fed chlorowax 500C.

Fingerling rainbow trout were fed a diet fortified with 10 ppm Chlorowax 500C, a chlorinated paraffin, for up to 82 days. Chlorinated paraffin residues as high as 1.1 ppm (tissue basis) were found. Recoveries from fortified fish tissue were greater than 92%, and the method sensitivity (tissue basis) is at least 0.5 ppm. Ultraviolet irradiation of the sample extracts and microcoulometric gas chromatography minimized interferences. No gross toxicological effects were noted in the experimental fish, although their weight gain was less than that of the controls.

Adipose Tissue