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Biomedical subjects

B H Smith

Publications and source records attributed to B H Smith.

At least 127 records · Page 7Linked to original sources

Refractory Cushing's disease caused by multinodular ACTH-cell hyperplasia.

A patient with pituitary-dependent hypercortisolism, unresponsive to resection of nodules in the anterior lobe, is described. Histochemical stains of the nodules showed multiple, focal, cellular expansions of the fibrovascular stroma. Transitions between normal and expanded adenohypophysial acini were present. Immunoperoxidase stains for ACTH and other pituitary hormones revealed that these multiple foci contained an excess of ACTH-positive cells. Less than 10% of the cells in these foci were negative for ACTH and positive for other hormones. Serial sections showed that these foci of predominantly ACTH-producing acini were not connected. Clinical, morphological, and immunohistochemical data indicated that ACTH-cell hyperplasia caused Crushing's disease in this patient. Pathologic study of individual cases should concentrate on determining whether hyperplasia or adenoma exist at the time of surgical exploration of the pituitary gland, since this determination is important to proper treatment. Tentative criteria to recognize ACTH-cell hyperplasia are: 1. Multiple foci of ACTH laden cells. 2. A minor subpopulation of cells of alternate hormone series. 3. Expansion without destruction of acini in the adenohypophysis.

Adenoma↗

Products of cultured neuroglial cells. III. Release of an 85,000 molecular weight glycoprotein by C6 glioma cells in vitro.

With [3H]fucose as a marker, C6 glioma cells in culture released an 85,000 molecular weight molecule into the medium as the major extracellular glycoprotein. The quantity and extracellular/cytoplasmic ratio of this glycoprotein suggest that its cellular processing is different from that of five other released glycoproteins of molecular weights 55,000, 115,000, 130,000, 150,000, and 170,000. Nearly 40% of newly synthesized glycoproteins in the cells was released into the culture medium. Major glycoproteins retained by the cells migrated electrophoretically to molecular weight positions of 82,000, 110,000, 120,000, 140,000, and 160,000, and approximately one-third of these returned glycoproteins were labile to trypsinization. Both synthesis and release of these macromolecules were inhibited more than 95% with cycloheximide treatment, demonstrating that nearly all fucosylation was linked to protein synthesis. Since 40% of all glycoproteins was released under conditions of more than 99% cellular viability, it is likely that these extracellular glycoproteins are physiological products of membrane turnover and secretion, but not of cell lysis. The results provide a basis for the further study of glial differentiation and of shed glioma antigens.

Animals↗

Work in progress: [18F] fluorodeoxyglucose and positron emission tomography in the evaluation of radiation necrosis of the brain.

Five patients who had undergone radiation therapy for cerebral tumors and whose conditions were deteriorating were examined by means of positron emission tomography (PET) with [18F] fluorodeoxyglucose. All five cases had similar clinical and computed tomographic findings. Using the PET technique the two cases of radiation necrosis were distinguished from the three recurrent tumors. In the two cases of radiation necrosis the rate of glucose utilization in the lesion was markedly reduced compared with the normal brain parenchyma. In the recurrent gliomas, however, the glucose metabolic rate was elevated. All five diagnoses were confirmed by biopsy or autopsy.

Astrocytoma↗

Glucose utilization of cerebral gliomas measured by [18F] fluorodeoxyglucose and positron emission tomography.

Positron emission tomography was used to measure local cerebral glucose utilization by the 1-[18F]fluoro-2-deoxy-D-glucose technique in 23 patients with cerebral gliomas. All 10 high-grade (III and IV) astrocytomas demonstrated a region of high activity with a glucose consumption of 7.4 +/- 3.5 (SD) mg/100 gm per minute. The 13 low-grade (I and II) gliomas had a glucose metabolic rate of 4.0 +/- 1.8 mg/100 gm per minute, with no distinctly visible hot spot. Thus, we found a correlation between rate of glycolysis and malignancy in primary cerebral tumors. Cerebral cortical glucose utilization was often depressed in areas adjacent to or neurally connected to the tumor site, and there was focal irregular delta wave EEG activity in these areas.

Adult↗

Immunological, biochemical, ultrastructural, and electrophysiological characteristics of a human glioblastoma-derived cell culture line.

This report presents the results of a study using multiple techniques of the established human cell line, LM, which has been developed in culture medium from a patient with a right temporoparietal glioblastoma. This cell line has human subtetraploid karyotype and has several features of a transformed line in culture. These include continuous propagation for 10 years, ability to form tumor nodules when transplanted into immunologically suppressed hamsters, and pleomorphic appearance. Ultrastructurally, it is characterized by multiple nuclei, few actin cables, and numerous surface-membrane microvilli, as well as abundant 9- to 10-nm cytoplasmic filaments. By its immunological reactivity, the line can be shown to contain glial fibrillary acidic protein at low levels, consistent with its glial origin and continued nature. Dibutyryl cyclic adenosine monophosphate (db-cAMP) induces formation of long astrocytic-like processes as well. Its membrane electrical characteristics include a low resting membrane potential and short time constant. Used in a microtiter antiglioma antibody cytotoxicity assay, LM yields a positive reaction to antibodies in the sera of 80% of patients with astrocytomas and only 9% of normal blood-bank donors, suggesting that it shares common antigens with other astrocytic tumor lines. The varied characteristics of this glioblastoma-derived line emphasize the "multiforme" nature on the neoplasm and suggest that for characterization of any such line, multiple parameters are necessary to allow comparison with other long-term glioblastoma lines in the literature. The usefulness of the LM line in in vitro cell biological, immunological, chemotherapeutic, and radiobiological studies of gliomas makes such efforts very worthwhile.

Brain Neoplasms↗

Axoplasmic transport and neurological surgery.

Both the slow bulk flow (1 mm/day) of cytoplasm and the rapid transport of specific small molecules, as well as macromolecules (at rates of up to 410 mm/day), are known to occur in the neuronal cell body, axon, and dendrites. The basic phenomena as well as mechanisms of these transport phenomena and their implication for a variety of pathophysiological processes in the central and peripheral nervous system are reviewed. Brought to bear on a variety of neurosurgical problems, ranging from herniated discs to central pain, head injury, ablative surgery, and recovery from cerebrovascular insults, the principles of axoplasmic and dendritic transport suggest opportunities for neurosurgical research that should lead not only to improved understanding of pathophysiological mechanisms but also to the further elucidation of these important neuronal phenomena.

Animals↗

Enhancement of antibody production and protection against systemic anaphylaxis by large doses of vitamin C.

Male and female guinea pigs receiving, respectively, 100 and 280 mg/day Vitamin C throughout the duration of immunization showed enhanced humoral antibody production to bovine serum albumin (BSA) and, in castrated females, to penicilloyl-coupled guinea pig gamma-globulin. A significant degree of protection was afforded against fatal anaphylactic shock in passively sensitized males. Under appropriate conditions of sensitization with rabbit anti-HGG and challenge with human gamma-globulin, 8 of 20 unsupplemented animals died of shock, whereas in the group receiving 280 mg Na ascorbate/day for 4 days preceding passive transfer and again 60' before challenge, only 2 of 18 died. The rate of dose-dependent mortality observed when groups of passively sensitized animals were challenged with increasing doses of antigen was reduced in animals supplemented as above. Actively immunized guinea pigs were not protected by 5 daily doses of 280 mg Na ascorbate given prior to challenge. There were no significant differences in the total hemolytic activity of the serum nor in the C3 and C4 components of complement in immunized animals. There was no change in the concentration of Cl esterase in non-immunized controls, but immunization with BSA was followed by a rapid decline in Cl concentration, the decrease being greater in the ascorbate-treated group than in the unsupplemented controls, possibly reflecting a higher level of circulating immune complexes in the former case.

Anaphylaxis↗

Response of cultured human brain tumors to nitrosoureas: correlation with clinical data.

An in vitro microcytotoxicity assay was utilized to determine the sensitivity of 58 cultured human malignant gliomas to the chemotherapy agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Of 58 such tumors, 42 (72%) showed a statistically significant cytotoxic response to BCNU in this assay. For those responding tumor lines, the cytotoxic index ranged from 0.25 to 0.76, with most clustered at the 0.40 level. To determine the therapeutic predictive relevance of such microcytotoxicity testing, the clinical course of patients receiving postoperative radiation therapy plus two or more doses of nitrosourea chemotherapy, as well as two or more computerized tomographic scans, was evaluated. In the 14 patients meeting all these criteria, tumor size increased in all five patients whose tumors did not respond to BCNU in the microcytotoxicity test. Six of the nine patients whose tumors in culture showed significant sensitivity to BCNU in vitro showed a clear decrease in tumor size over periods ranging from 17 to 48 months. Tumors in two patients increased in size, and one remained unchanged over the interval studied. These data support the concept that in vitro microcytotoxicity testing can be predictive of clinical response. Further study of this correlation seems warranted.

Adult↗

High pressure liquid chromatographic method for indole in shrimp: development of method and collaborative study.

A collaborative study on the determination of indole in shrimp was conducted in which a high pressure liquid chromatographic (HPLC) method and a spectrofluorometric method were compared with the AOAC gas-liquid chromatographic (GLC) method (18.075-18.078, 13th ed.). In the HPLC method, 10 g shrimp was blended with methanol, an internal standard was added, and the extract was filtered. Indole was separated on an octadecylsilane reverse phase column, using 60% MeOH-H2O, and quantitated with a fluorescence detector (excitation 280 nm, emission 330 nm) by comparing the indole peak height with that of an internal standard, 2-methyl-indole. Recoveries at a 25 micrograms/100 g level averaged 104% with a range of 90-127%, and at a level of 35 micrograms/100 g averaged 102% with a range of 93-112%. In the spectrofluorometric method, 25 g shrimp was extracted with 2% EtOAc-hexane. After several washes, indole was partitioned into a saturated NaCl-MeOH solution and its fluorescence was measured (excitation 280 nm, emission 332 nm). Recoveries at a 25 micrograms/100 g level averaged 93% with a range of 0-255% and at a level of 35 micrograms/100 g averaged 64% with a range of 0-107%. Recoveries obtained by the AOAC-GLC method at a level of 25 micrograms/100 g averaged 96% with a range of 81-116% and at a level of 35 micrograms/100 g averaged 101% with a range of 81-119%. The coefficients of variation were 20, 10, and 64% at a 25 micrograms/100 g level for the GLC method, the HPLC method, and the spectrofluorometric method, respectively. The HPLC method was adopted as official first action for indole levels in shrimp exceeding 1 microgram/100 g.

Animals↗