Biomedical subjects
Publications and source records attributed to M J Redmond.
The technique of computed-tomographic-directed stereotaxic biopsy of cerebral lesions is described, and our series of 24 procedures on 23 patients without mortality or morbidity is presented. This technique provides neurosurgeons with an improved method of performing cerebral biopsies.
The predictive algorithm Surfaceplot (J.M.R. Parker, D. Guo, and R.S. Hodges, Biochemistry 25:5425-5432, 1986) was used to examine glycoprotein D of herpes simplex virus type 1 (HSV-1) for amino acid residues with a high probability of being exposed on the molecular surface. Based on these data, 11 different peptides corresponding to 10-residue segments in the primary sequence of glycoprotein D and one 20-residue segment were synthesized, conjugated to carrier proteins, and used to generate specific antisera in rabbits. Two synthetic peptides predicted not to be on the surface of glycoprotein D were included as negative controls. The polyclonal antisera against individual synthetic peptide conjugates were in turn evaluated for their ability to recognize both isolated glycoprotein D and intact HSV-1 virions in an enzyme-linked immunosorbent assay. Based on Surfaceplot predictions, eight linear antigenic sites on glycoprotein D were thereby defined from the 12 antipeptide antisera prepared. Four of these sites contained epitopes to which complement-independent neutralizing antibodies could be generated. The latter sites corresponded to sequences 12 to 21, 267 to 276, 288 to 297, and 314 to 323 of the mature protein. An additional peptide sequence, 2 to 21, was found to generate antisera which had potent virus-neutralizing capacity in the presence of complement. Identification of a neutralizing epitope in the sequence 314 to 323 makes it likely that the membrane-spanning region of glycoprotein D is within the subsequent sequence, 323 to 339. Antipeptide antisera prepared in this study from 12 synthetic peptides contained 13 surface sites predicted by Surfaceplot, of which 7 were not predicted by the parameters of Hopp and Woods (Proc. Natl. Acad. Sci. USA 78:3824-3828, 1981). Of these seven sites not predicted by the Hopp and Woods plot, all generated antipeptide antibodies that bound to HSV-1 virions and three of these seven sites generated neutralizing antibodies. In total, 8 of 12 synthetic peptides containing surface regions produced antipeptide antibodies that bound to HSV-1 virions and 5 of these generated neutralizing antibodies. These results suggest the advantages of Surfaceplot in mapping antigenic determinants in proteins.
Based upon the use of a new predictive algorithm, three peptides were synthesized that correspond to likely antigenic sites of the cytotoxic T cell-specific protease cytotoxic cell protein 1 (CCP1). Antibodies raised against these peptides, under reducing conditions, bound to a single protein of m.w. 29,000 found in two actively cytotoxic T cells. This protein was absent from a "cytotoxic" T cell line that had lost its cytolytic properties. By using immunocytologic techniques, the protein was localized within cytoplasmic granules. In addition, granules purified from the cytoplasm of cytotoxic T cells were shown, by Western blot analysis, to contain the protein. The molecule detected by the antibodies behaves, upon reduction, similarly to a diisopropylfluorophosphate-binding protein. Thus, here we provide evidence that CCP1, a protein whose expression correlates with cytotoxicity, is contained within organelles which have been implicated in killing. These findings strongly suggest that CCP1 plays a key role in T cell-mediated target cell lysis.
This communication describes the application of Epstein-Barr virus lymphocyte transformation technology to the production of human monoclonal antibodies specific for human cytomegalovirus. A group of such IgG antibodies have been characterized in terms of subclass, light-chain composition, specificity for particular viral proteins and neutralizing capacity. These results have shown that the production of antibodies by transformed lymphocytes is representative of the in vivo human immune response; the antibodies produced may therefore be of therapeutic value. This approach should prove to be useful for the identification of specific virion proteins which are antigenic in humans and for the in vitro evaluation of the immune responses to synthetic peptide vaccines.
Elephantiasis verrucosa nostrum occurs when lymphatic obstruction of sufficient magnitude causes back pressure in the lymphatic channels forceful enough to produce superficial vessel dilation which has a "pebbly" or cobble-stone appearance. Unchecked this can progress to a marked verrucous or mossy appearance, frequently complicated by infection, with swelling and gross deformity. The patient presented here was both post-phlebitic and post-lymphatic with significant deformity. He showed dramatic improvement on a regimen of antibiotics and elevation followed by decompression and routine use of pressure-gradient support garments. This has not recurred and he has remained under control since 1979.
The authors report the results of a retrospective study conducted in an effort to define the results and risks of transsphenoidal surgery for patients whose prior therapy had failed. In a series of 1210 patients undergoing transsphenoidal surgery during a 10-year period, 158 had received prior therapy: 127 for pituitary adenoma, 20 for craniopharyngioma, and 11 for other lesions. Prior therapy was considered "direct" when it consisted of craniotomy or transsphenoidal surgery (either open or stereotaxic), and "indirect" when it consisted of radiation therapy, adrenalectomy, or bromocriptine therapy. The current transsphenoidal operation was performed for persistent hyperfunctioning endocrinopathy in 63 patients, for visual loss in 72 patients, and for cerebrospinal fluid (CSF) rhinorrhea in 21 patients. Success rates were as follows: normalization of endocrinopathy was achieved in 35% of cases; improvement or stabilization of vision in 59%; and successful repair of CSF rhinorrhea in 74%. The risks associated with repeat transsphenoidal surgery are significantly greater than the same procedure in a previously untreated patient.
Intraspinal arachnoid diverticula are unusual lesions that may demonstrate significant mass effects. A 15-year-old boy with upper lumbar discomfort and progressive spastic paraparesis also demonstrated a sensory deficit at T-10 as well as a severe lower extremity dorsal column deficit. Radiographic evaluation demonstrated interpedicular widening from T-2 to T-9. Myelography revealed a triloculated arachnoid diverticulum, with major collections at C-7 to T-2, T-3 to T-5, and T-8 to T-10. An eight-level laminotomy (T-2 to T-9) was performed, leaving the spinous processes and interspinous ligaments intact. The inferior collection was completely extradural, with a diverticular neck leaving the right nerve root sleeve at T-8. The other loculations were intradural. The lesion was excised without difficulty, and the laminae were replaced. The postoperative course was unremarkable, in that recovery occurred almost immediately, and the patient's strength was essentially normal on discharge. In treating such lesions, replacement laminotomy is the best approach.
Seven labeled sulfonanilide analogs of dipamine were synthesized and their tissue distribution in rats were determined as a function of time. The methanesulfonanilide derivative, NP-27, showed significant uptake and retention in the rat adrenal, with 0.66% dose/gm at 5 min and 0.27% dose/gm at 24 h. The 24-hr target-to-nontarget concentration ratios for the adrenal versus liver, blood, kidney, and heart were 13, 27, 30, and 60, respectively. These results compared reasonably with the corresponding target-to-nontarget ratios of 23, 45, 8, and 15 obtained for 14C-dopamine. The six other analogs showed considerably less uptake and retention. Further evaluation of NP-27 in dogs indicated selective uptake in the adrenal medulla.
Carbon-14-diphenylhydantoin (DPH) concentrated maximally in pancreatic islet cells of the toadfish 10 min after its intravenous administration. The islet cell-to-acinar-tissue ratio at this time was 6:1. The islet cell-to-liver ratio was 20:1. Iodine-125-paroiodo-DPH at 10 min in the toadfish showed an islet cell-to-acinar-tissue ratio of 1.7:1 and an islet cell-to-liver ratio of 2.3:1. When 14C-DPH was given to four patients 10-17 min before removal of norma pancreatic tissue and of an insulinoma in three of the patients, the concentration of radioactivity in the insulinoma was never greater than in the pancreas and concentrations in insulinoma and pancreas were always less than in liver in the same individual. Forty-five to 90 min after administration of 131I-DPH, the liver and pancreas were delineated in three patients but the insulinoma was not imaged. Five days after administration of 131I-DPH, the concentration of 131I radioactivity in excised tissue was greater in the insulinomas than in the pancreas of two patient but not sufficient to produce positive images of the insulinoma in the pancreas.
A synthetic peptide corresponding to bovine rotavirus C486 (BRV) VP4 amino acid sequence 232-255 (VP4-peptide) was studied with the objective of defining the origin of the protective immune response reported previously by Ijaz et al. (J. Virol. 1991, 65, 3106-3113). Pretreatment of MA-104 cells with the VP4-peptide before infection with rotavirus prevented both the attachment of 35S-labelled virus and plaque formation in vitro. In vivo studies using a murine rotavirus model demonstrated that intragastric administration of VP4-peptide protected subjects from challenge with virulent rotavirus. These results clearly indicate the importance of this epitope in virus-cell interactions and their potential as a rotavirus vaccine candidate.