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Biomedical subjects

R C Griffith

Publications and source records attributed to R C Griffith.

At least 37 records · Page 2Linked to original sources

Acute renal rejection versus acute tubular necrosis in a canine model: MR evaluation.

Findings of magnetic resonance (MR) imaging in acute renal rejection and acute tubular necrosis (ATN) were studied in dogs. On T1-weighted images, corticomedullary differentiation was absent in kidneys undergoing acute rejection. The loss of corticomedullary differentiation in these kidneys was secondary to a decrease in the relative signal intensity of the cortex, indicating prolongation of the T1 relaxation time of the cortex. In contrast, corticomedullary differentiation was preserved on T1-weighted images of autotransplanted kidneys and kidneys with ATN. MR imaging findings correlated with changes in water content in these three groups of kidneys. Kidneys undergoing acute rejection showed a marked increase in water content compared with kidneys in the other two groups. No change in fat content was found in any group.

Acute Kidney Injury

The changing management of Wilms' tumor over a 30-year period. 1949-1978.

Seventy-four patients with histologically confirmed diagnoses of Wilms' tumor were treated between 1949 and 1978 at the Mallinckrodt Institute of Radiology and St. Louis Children's Hospital. The results have been divided into two eras of therapy, i.e., before and after 1965, when chemotherapy became a major modality for Wilms' tumor therapy. Analysis at 5 years by era of therapy has shown similar disease-free survival results for Stage I ("prechemotherapy" era 67% versus "chemotherapy" era 75%), whereas the Stage II ("prechemotherapy" era 33% versus "chemotherapy" era 100%) and Stage III ("prechemotherapy" era 0% versus "chemotherapy" era 70%) are significantly different (P less than 0.001). This suggests that chemotherapy has substituted for postoperative irradiation in Stage I patients; whereas in Stage II and III, improved survival occurs as a result of the eradication of subclinical metastatic disease. The patterns of failure by era of treatment are presented and the literature is discussed.

Adolescent

Angiofollicular lymph node hyperplasia (Castleman's disease) associated with vertebral destruction.

A 45-year-old man presented with lower thoracic pain, proteinuria, and destruction of thoracic vertebra from an adjacent unresectable paraspinal mass which, on biopsy, demonstrated angiofollicular lymph node hyperplasia (AFLNH). The patient received 3939 rad in 22 fractions to the mass and associated area of vertebral destruction. The patient is currently asymptomatic without recurrence of pain or progression of neurologic symptoms 5 years after radiotherapy. There has been resolution of the previous proteinuria. Serial computerized tomography scans and x-rays show no change in the paraspinal mass nor resolution of the vertebral destruction adjacent to the mass. A search of the English literature has failed to identify any previous association of AFLNH and bone destruction.

Humans

A single common electrophoretic abnormality of glucocorticoid receptors in human leukemia cells.

We determined the mol wt of glucocorticoid receptors in human leukemia cells in order to detect glucocorticoid receptor defects that might cause glucocorticoid resistance. Glucocorticoid receptors in intact cells were affinity labeled with [3H]dexamethasone-21-mesylate and were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Receptors in normal human peripheral blood mononuclear cells and six human leukemia cell lines had mol wt of 97,000. Malignant cells from ten of 25 patients with leukemia contained electrophoretically abnormal glucocorticoid receptors having mol wt of 55,000 in addition to normal size receptors (Mr = 97,000). The receptor abnormality was not restricted to a particular type of leukemia and was seen in cells from both newly diagnosed patients and patients who had received prior chemotherapy, including prednisone. The abnormal receptor was not generated when cells having only normal size receptors were assayed under conditions that favor proteolysis or when cytosol from cells containing the abnormal receptor form was mixed with cytosol from cells containing only normal size receptors. The mol wt of the abnormal receptors in human leukemia cells was the same as the mol wt of receptors in mutant mouse lymphoma cell lines, S49 143R and S49 55R, which have the nuclear transfer-increased phenotype of glucocorticoid resistance. This work describes for the first time a single common electrophoretic abnormality of glucocorticoid receptors in human leukemia cells. Further investigation of glucocorticoid receptor defects in human leukemia cells could lead to an improved understanding of the mechanisms of glucocorticoid resistance in leukemia as well as a method of predicting which patients are likely to be resistant to glucocorticoid therapy.

Animals

Spinal Ewing sarcoma: misleading appearances.

The plain radiographic and computed tomographic (CT) findings in two unusual cases of spinal Ewing sarcoma are reported. Radiographic features resembling neuroblastoma in one case and aneurysmal bone cyst in the other were present. These findings may be misleading and distinguishing characteristics in each case are discussed.

Aneurysm

cis-1,3,4,6,7,11b-Hexahydro-2-methyl-7-phenyl-2H-pyrazino[2,1-a] isoquinoline: a new atypical antidepressant.

Molecular modelling studies suggested the synthesis of cis-1,3,4,6,7, 11b-hexahydro-2-methyl-7-phenyl-2H-pyrazino[2,1-a]isoquinoline (7a) as a rigid analogue of the atypical antidepressant mianserin. Acylation of 2,2-diphenylethylamine with chloroacetyl chloride gives the chloroacetamide (2). Cyclization of 2 with P2O5 in xylene provides 1-(chloromethyl)-3,4-dihydro-4-phenylisoquinoline (3). Amination of 3, followed by reduction, gives the isomeric (aminomethyl)tetrahydroisoquinolines (4a and 5). Treatment of 4a with diethyl oxalate, followed by reduction of the diamide with borane, provides 7a. A variety of N-substituted, aromatic substituted, and optically resolved derivatives were prepared and evaluated for anticholinergic, antihistaminic, and antidepressant activity. In particular, the target cis isomer 7a as predicted from the modelling studies appears to possess excellent atypical antidepressant activity. This activity resides in the (+)-S,S optical isomer 10, which has the same absolute configuration as (+)-mianserin.

Animals

Cystographic contrast media: clinical and experimental studies.

Cysto-Conray II 17.2% (81 mg l/ml), diluted Cysto-Conray 10% (47 mg l/ml), and Hypaque-Cysto 10% (47 mg l/ml) produced no histologic effects on rat bladders. Simulated ureters in water phantoms were well shown with lower concentrations of cystographic solutions including those of 5% (24 mg l/ml). In clinical studies there was little difference between Cysto-Conray II 17.2% and Hypaque-Cysto 10% for delineating refluxing ureters, bladder margins, and the urethra. Intraluminal filling defects in dog bladders were demonstrated best with cystographic concentrations of less than 10% (47 mg l/ml).

Animals

A unique DR-related B cell differentiation antigen.

The Ia or class II molecules in both mouse and man are the basis for the genetic control of the immune response. In addition to DR, other class II antigens have been described in man. We describe a new human Ia antigen K19, recognized by three monoclonal antibodies (HK-9, HK-19, and HK-20). This antigen has the general biochemical characteristics of an Ia antigen but is different from a DR antigen. Further, this antigen is found only on mature B lymphocytes and not on monocytes and activated T cells. Thus, this antigen may represent a new Ia-like molecule that is preferentially expressed on mature B cells.

Animals

Non-Hodgkin's lymphoma of the stomach.

Thirty-seven patients with non-Hodgkin's lymphoma of the stomach were treated with curative intent by several single and combined modality regimens. Twenty-two patients presented with stage IE and 15 with stage IIE disease. All but three patients underwent laparotomy. Of all diagnostic procedures used, x-ray of the upper gastrointestinal tract proved to be most helpful in diagnosing malignant lesions (87%). Gastric cytology was suspicious or diagnostic of malignancy in 35% of the patients. Twelve of 34 evaluable patients (35%) developed recurrence. Distant metastases (75%) was the most common mode of failure. The recurrence rates varied by the type of therapy and also the extent of initial disease. Four of 12 patients (33%) were salvaged with retreatment. The 5-year actuarial no evidence of disease survival for the entire group was 61% (stage IE-57%; stage IIE-67%). Patients receiving combined modality therapy had significantly (p = less than 0.05) higher survival than patients treated with single modality treatment. Three of 29 patients (10%) died of surgical complications after gastrectomy. Radiation treatment was well tolerated. Our data and a critical review of the literature do not support the reportedly high incidence of gastric perforation after radiation treatment. We recommend the use of adjuvant radiation for stage IE and adjuvant radiation plus chemotherapy for stage IIE gastric lymphoma.

Adult

Stereotactic surgical system controlled by computed tomography.

The three-dimensional data obtained by computed tomographic (CT) scanning offer an advantage in using this imaging technique for stereotactic surgical procedures. This requires interfacing of CT image data with a stereotactic guide. In the performance of functional procedures where the surgical target must be identified from brain landmarks, such as the anterior and posterior commissures, an image reconstruction technique that presents in an image high spatial resolution structural information must be used. The description of a fully hardware- and software-interfaced CT-directed stereotactic surgical system is presented. The logic of operation and examples of images reconstructed with a high spatial resolution algorithm are illustrated. The experimentally determined measurement of an electrode tip localization with this system is within 1 pixel or +/- 0.5 mm in any direction.

General Surgery

Regulation of anti-hapten antibody secretion by carrier-specific suppressor T cells.

Carrier-primed T lymphocytes can suppress high avidity IgG anti-hapten antibody secretion within 90 min. in vitro if the suppressor and target cells are primed with the same carrier determinants. Suppression seems to be directed to the antibody secreting cell since the effect is rapid and does not depend on macrophages or T cells in the target cell population. Suppression can be blocked by inclusion of soluble carrier in the cell mixture or by treatment of the target cells with anti-carrier antibody or pronase. Moreover, suppression can be augmented by PFC exposure to the soluble hapten-carrier conjugate. Finally, carrier specificity may be altered by preincubation of the target population with a hapten-heterologous carrier before addition of suppressor cells specific for the heterologous carrier. Thus, it is likely that high avidity suppression depends upon immunogen bound to the surfaces of antibody secreting cells which serves as a target for suppressor cells or molecules.

Animals

A morphologic study of intrahepatic portal-vein islet isografts.

Isologous pancreatic islets were implanted into the portal vein of rats with streptozotocin-induced diabetes. At intervals of from one to 32 days after transplantation, the intrahepatic islet grafts were examined histologically and ultrastructurally, and their vascular supply was determined by later perfusion studies. Implanted islets were found widely dispersed throughout the liver in peripheral interlobular portal venules and surrounded by vacuolated liver cells containing large stores of glycogen. The endocrine cells were structurally normal in each interval examined. By the third day after transplantation the beta cells were depleted of secretory granules in aldehyde-fuchsin preparations. Regranulation returned by the 14th day and was associated with secretory organelle hypertrophy and hyperplasia. Islet cells were found outside the portal areas in direct apposition to hepatocytes forming distinct desmosomes by the first day. While hemoperfusion of the grafts occurred from the moment of implantation into the portal venule, a dual vascular supply derived from periportal arterial and venous sources developed by the 11th day after transplantation, establishing full vascularization of the grafts. Preliminary work is presented to show that an active ingrowth of nerves in the islet graft occurs in association with the process of vascularization.

Animals

Cation transport in lymphoblastoid cell lines established from bipolar manic-depressive patients.

Lymphoblastoid cell lines established from patients suffering from bipolar manic depression have been used to study the possible involvement of cation transport in the aetiology of this illness. No significant difference was found in the K+ fluxes mediated by the ouabain-sensitive sodium pump, the diuretic-sensitive cotransport system and the passive leak pathway of cell lines established from either control or bipolar subjects. The mean value for the specific binding of 3H-ouabain (sodium pump site number) was significantly higher in the bipolar group (approximately 30%) than in the control group.

Adult

Preclinical profile of remacemide: a novel anticonvulsant effective against maximal electroshock seizures in mice.

Anticonvulsant tests in mice revealed specific, potent actions of remacemide for protection of mice against maximal electroshock seizures (MES). Comparisons of oral efficacy to reference compounds yielded the following ED50 values (expressed as mg/kg): remacemide = 33, phenytoin = 11, phenobarbital = 20, carbamazepine = 13 and valproate = 631. The duration for protection by remacemide was longer than carbamazepine or valproate, but shorter than phenytoin or phenobarbital. In neural impairment tests (inverted screen or rotorod) to determine the oral toxic dose 50 (TD50) the following therapeutic indices (TD50/ED50) were obtained: (1) inverted screen--remacemide = 17.6, phenytoin = 57.4, phenobarbital = 5.1, carbamazepine = 10.2, and valproate = greater than 3; and (2) rotorod--remacemide = 5.6, phenytoin = 9.6, phenobarbital 4.8, and valproate = 1.9. Remacemide was devoid of sedative actions and possessed a favorable 28.1 margin of safety value (median estimated lethal dose/ED50 for MES). An intermediate potency against either audiogenic- or N-methyl-D-aspartate-induced seizures was exhibited by remacemide. Tolerance to MES was not apparent after 5 days of oral daily dosing of remacemide. Remacemide was inactive in vitro against gamma-aminobutyrate or benzodiazepine receptors and adenosine uptake mechanisms. Therapeutic utility for generalized tonic/clonic seizures is predicted for remacemide.

Acetamides

Preclinical profile of stereoisomers of the anticonvulsant remacemide in mice.

Stereoisomers of remacemide (racemate form) were compared for anticonvulsant efficacy and safety in mice. In the maximal electroshock seizure (MES) test for oral efficacy, the (-) stereoisomer, FPL 14145, was more potent than the racemate or the (+) stereoisomer, FPL 14144. Respective ED50 values (expressed as mg/kg) were: remacemide, 58; FPL 14145, 45; FPL 14144, 79. In 2 of 3 tests for neural impairment, FPL 14145 yielded significantly better therapeutic indices (toxic dose 50/ED50) than the racemate. The margin of safety (estimated median lethal dose ED50) was more favorable for FPL 14144: remacemide, 15.1; FPL 14144, 18.9; FPL 14145, 15.7. The duration of protection against MES indicated the stereoisomers were longer acting than the racemate. After intravenous administration the order of potency against MES was similar: FPL 14145 greater than remacemide greater than FPL 14144. Following daily administration of the oral ED98 for 4 days, with a dose response curve run on day 5, the MES ED50 values for all compounds were increased. The test indicates tolerance. In the pentylenetetrazol infusion test the racemate and FPL 14144 demonstrated more proconvulsant properties than FPL 14145. Intraperitoneal administration of 50 mg/kg or more produced changes in behavior with all compounds. At higher doses the racemate and FPL 14145 elicited more severe symptoms with death at 200 mg/kg.

Acetamides

Fluorescent in situ hybridization for assessing the proportion of cells with trisomy 4 in a patient with acute non-lymphoblastic leukemia.

A case of acute non-lymphoblastic leukemia is described in which fluorescent in situ hybridization (FISH) helped to resolve initially conflicting conventional cytogenetic results. Identification and assessment of the proportion of cells exhibiting trisomy of chromosome 4 in the patient's bone marrow were made using a probe which hybridizes to the centromeric region of chromosome 4. These FISH results were consistent with our retrospective GTG-banded analysis but differed from another study conducted elsewhere. Factors such as culture conditions and duration of culture which may have influenced the proportion of leukemic to nonleukemic cells are discussed. Fluorescent in situ hybridization is a powerful adjunct to conventional cytogenetic analysis and may prove to be a useful tool for monitoring minimal residual disease in this patient.

Adult