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N R Jones

Publications and source records attributed to N R Jones.

At least 37 records · Page 2Linked to original sources

Characterization of the mononuclear cell infiltrate and HLA-Dr expression in 19 oligodendrogliomas.

We have studied frozen tissue from 19 oligodendrogliomas with a panel of antibodies to lymphocytes and their subsets, macrophages, natural killer cells, and HLA-Dr antigens. Macrophages were detected in moderate numbers in 60%-100% of tumors depending on the antibody used. T lymphocytes were fewer in number than macrophages and were present in 62% of cases. Most of the T lymphocytes were of the CD8 phenotype. CD4 lymphocytes were very few in number and present in only 18%. B cells and natural killer cells were absent from all cases. HLA-Dr antigens were expressed by macrophages in all cases but never on tumor cells. The implications of these findings are that macrophages and, to a lesser extent, CD8 lymphocytes are the predominant cells infiltrating oligodendrogliomas and that they may exert cellular immune functions.

Antibodies, Monoclonal↗

Mononuclear cell infiltrate and HLA-Dr expression in intra- and extradural secondary carcinomas.

Frozen sections from 30 secondary carcinomas (22 intra- and 8 extradural) were reacted with a panel of monoclonal antibodies to macrophages, lymphocytes, NK cells and HLA-Dr invariant chain. A moderate number of macrophages was demonstrated in 91% of tumours. CD 8 and CD 4 lymphocytes were detected in smaller numbers in 68% and 28% of tumours respectively. B lymphocytes were present in only one tumour and NK cells were absent. There was no significant difference between the mononuclear cell infiltrate in the intra- and extradural tumours and in respect to the histological tumour type. HLA-Dr antigen was expressed by macrophages in most cases and by tumour cells in 5/22 (22%) (4 adeno and 1 anaplastic carcinoma; of which one adenocarcinoma was extradural and the remaining intradural). The results may represent evidence for a degree of cellular immune response to secondary carcinomas which is independent of the intra- or extradural location of the tumour.

Antibodies, Monoclonal↗

Arachnoid cyst presenting as an extradural haematoma.

A case of extradural haematoma as the presenting feature of an arachnoid cyst is described. Haemorrhagic complications of arachnoid cysts are well known, but extradural haematoma is rare. A possible pathogenetic mechanism is proposed and the treatment of asymptomatic arachnoid cysts is discussed.

Adolescent↗

Mononuclear cell infiltrate and HLA-Dr expression in 28 pituitary adenomas.

Frozen sections from 28 pituitary adenomas were reached with a panel of monoclonal antibodies to macrophages, lymphocytes and HLA-Dr invariant chain. A low number of macrophages were demonstrated in all tumors, mainly perivascular. CD8 and CD4 lymphocytes were detected in even smaller numbers in 80% and 14% of tumors respectively. B lymphocytes were present in only 1 case. An occasional NK cell was present in 1/13 cases studied. HLA-Dr antigen was expressed by macrophages in all cases and by tumor cells in 2 growth hormone-producing adenomas/19 adenomas. These findings may represent evidence for a low degree of cellular immune response to pituitary adenomas.

Adenoma↗

Epidermal growth factor receptor expression in 72 meningiomas.

The expression of epidermal growth factor receptor (EGF-R) was studied immunohistochemically in 72 meningiomas using two monoclonal antibodies with specificities to protein and carbohydrate components, respectively, of the external domain of the EGF-R. One third of the tumors had cytoplasmic and membrane positivity with the protein-specific antibody but in none were there positive tumor cells with the carbohydrate-specific antibody which recognizes the blood group A antigen. There was no difference in EGF-R expression between typical and aggressive meningiomas. No evidence was found to support previous reports of specific EGF-R immunoreactivity in the vascular endothelial cells of meningiomas. The authors believe this discrepancy to be due to detection of normal blood group A antigen attached to endothelial cells in patients of blood group A or AB. This occurs because many monoclonal anti-EGF-R antibodies are specific for A antigen which is found on the EGF-R of A431 cells but has not been reported on EGF-R elsewhere.

Animals↗

Investigation of the expression of epidermal growth factor receptor and blood group A antigen in 110 human gliomas.

The presence of epidermal growth factor receptor (EGF-R) and blood group A antigen was studied immunohistochemically in a series of 110 malignant gliomas using monoclonal antibodies. Fifty-seven percent of the tumours strongly expressed EGF-R on the malignant cells. Although blood group A antigen is present on EGF-R of A431 cells (a cell line derived from a human epidermoid carcinoma), in gliomas it was found only on vascular endothelial cells of tumours from blood group A patients. The results suggest that the EGF-R present in gliomas differs from that in A431 cells in the type or amount of the carbohydrate chains. This is in contrast to previous reports which have suggested that A antigen is present on EGF-R in gliomas. This has relevance in the choice of monoclonal antibodies used to study the EGF-R, as those directed against the A antigen component of the A431 cell EGF-R will not recognize EGF-R elsewhere and may cause normal blood group A antigen to be mistaken for EGF-R.

ABO Blood-Group System↗

Cervical myelopathy in C.P.P.D. deposition disease.

Cervical Myelopathy is a rare manifestation of calcium pyrophosphate dihydrate (C.P.P.D.) deposition disease. A case is presented where radiographically noncalcified extradural masses containing C.P.P.D. crystals were present at the C7 level, producing cord compression and neurological symptoms. These masses are thought to represent para-articular deposits related to the adjacent facet joints.

Aged↗

A double blind placebo controlled trial of the calcium entry blocking drug, nicardipine, in the treatment of vasospasm following severe head injury.

A double blind, placebo controlled trial of nicardipine in the treatment of high Doppler Flow Velocity (DFV) following severe head injury (Glasgow Coma Score (GSC) less than or equal to 8) was performed. Thirty patients with high DFV (greater than or equal to 100 cm/s for 6 h duration) on transcranial Doppler ultrasound, were treated with nicardipine or placebo for 24 h (2.5 mg/h, increasing in steps of 2.5 mg/h at 2 h intervals (maximum rate 7.5 mg/h) depending on response of DFV). DFV was measured hourly for 24 h and then every 12 h for 2 days. Nicardipine significantly reduced DFV below the threshold of 100 cm/s (16/19 cf placebo 3/11, chi-square p less than 0.001). In the nicardipine treated group maximum DFV was significantly reduced (p less than 0.001) and time with DFV below 100 was significantly longer. Rises in DFV were significantly reduced by the drug if the DFV was normal at the time of entry. High DFV returned on cessation of the infusion. No unexpected or adverse side effects were seen. No clinical benefit was demonstrable.

Adolescent↗

Mononuclear cell infiltrate, HLA-Dr expression and proliferation in 37 acoustic schwannomas.

Frozen sections from 37 schwannomas of the VIII nerve were reacted with a panel of monoclonal antibodies to macrophage, lymphocyte, HLA-Dr invariant chain and nuclear proliferation antigens. A moderate number of macrophages was demonstrated in 96% of tumours. CD8- and CD4-lymphocytes were detected in slightly smaller numbers in up to 87% and 23% of tumours respectively. B-lymphocytes were present in only 2/32 cases and NK-cells were absent from all 16 cases tested. HLA-Dr antigen was expressed by macrophages in most cases and by tumour cells in 13/24 tumours. These findings may represent evidence for a degree of cellular immune response. Occasional cells featuring nuclear proliferation were detected in 15/27 cases.

Cell Nucleus↗

The mononuclear cell infiltrate compared with survival in high-grade astrocytomas.

Frozen samples from 92 malignant astrocytomas were stained with a panel of monoclonal antibodies directed against macrophages and lymphocytes. A follow-up to death was available on 68 cases which form the basis of this study. Large numbers of macrophages were found in all cases; T lymphocytes, mostly of the CD8 phenotype were also seen in moderate numbers in 70% of cases. CD4-positive cells were present in small numbers in 32% and B cells were seen in only 8% of cases. Analysis of the survival showed no demonstrable correlation between the numbers of macrophages or CD4 lymphocytes and survival. The survival curves for parenchymal CD8 infiltration diverged after 9 months suggesting increased survival for those patients without such an infiltration but the difference failed to reach statistical significance (P = 0.37). No correlation between lymphocytic cuffing and survival was seen after studying all paraffin-embedded material. We conclude that there is no significant statistical correlation between survival and the various types of mononuclear cell infiltrating malignant astrocytomas.

Antibodies, Monoclonal↗

Diffuse axonal injury in head trauma.

Diffuse axonal injury (DAI) as defined by detailed microscopic examination was found in 34 of 80 consecutive cases of head trauma surviving for a sufficient length of time to be clinically assessed by the Royal Adelaide Hospital Neurosurgery Unit. The findings indicate that there is a spectrum of axonal injury and that one third of cases of DAI recovered sufficiently to talk between the initial head injury producing coma and subsequent death. The macroscopic "marker" lesions in the corpus callosum and dorsolateral quadrants of the brainstem were present in only 15/34 of the cases and represented the most severe end of the spectrum of DAI.

Axons↗

Intracranial haemorrhage from meningiomas: a report of five cases.

Intracranial haemorrhage from meningiomas is rare and carries a mortality of over 40%. The authors present five cases presenting with intratumoral, intracerebral, subarachnoid or subdural haemorrhage. The relevant literature is reviewed and the pathology and possible mechanisms of haemorrhage in these tumours are discussed.

Adult↗

A comparison of the intracellular uptake and radiosensitization efficiency in different media of uncharged 2-nitroimidazoles of varying lipophilicity.

The effect of varying octanol: water partition coefficients, P, (range 0.026-260) on the uptake of uncharged 2-nitroimidazoles into Chinese hamster V79 379A cells has been studied. Average intracellular concentrations were measured by high performance liquid chromatography after centrifuging cells through oil or an aqueous medium. The ratio of intracellular concentration of radiosensitizer to extracellular concentration (Ci/Ce) for misonidazole (P = 0.43) was 0.85 for the oil method and 0.68 for the aqueous method. For values of P less than about 0.05 uptake was initially very slow and Ci was always less than Ce. When P greater than or equal to 0.1 uptake was rapid and then remained unchanged for times up to 3 h; for P greater than or equal to 10, Ci/Ce increased rapidly as P increased. Ro 31-1405 (P = 260) concentrated by a factor of 7 inside the cell. Although uptake was identical for cells suspended in full growth medium and PBS, radiosensitization was greater for cells in PBS: 1 mmol dm-3 misonidazole produced an enhancement ratio of 1.6 in full growth medium and 1.9 in PBS. This increase in radiosensitization could not be accounted for by protein binding. However, measurements on cellular non-protein sulphydryl (NPSH) demonstrated the levels to be reduced to about 60 per cent for cells in PBS. Similar reductions in NPSH levels have previously been shown not to increase the radiosensitivity of control cells but to increase greatly the effectiveness of nitroimidazole radiosensitizers.

Animals↗

Radiosensitization of Chinese hamster cells by oxygen and misonidazole at low X-ray doses.

The radiosensitization of Chinese hamster V79 cells in vitro by air and misonidazole at low X-ray doses (0.2-6.0 Gy) had been studied. These survival data, together with high-dose data, were fitted to the linear quadratic model ln S = -(alpha D + beta D2), deriving estimates of alpha and beta by six different methods to illustrate the influence of the statistical treatment on the values so derived. This in vitro study clearly demonstrated that the survival parameters alpha and beta are dependent to some degree on the method of analysis of the raw survival data; however, their ratios, the values of oxygen enhancement ratios (OERs) and radiosensitizer enhancement ratios (SERs) derived from the different methods, are similar. All methods of analysis give reduced OERs at low radiation doses for combined low- and high-dose X-ray data. However, the OERs are still appreciably high, ranging from 2.45 to 2.50 for an oxic dose of 2 Gy. All methods of analysis gave reduced SERs at low doses for combined low and high X-ray dose data for hypoxic cells irradiated in 1 mmol dm-3 misonidazole. At survival levels corresponding to doses of 2 Gy in the presence of 1 mmol dm-3 misonidazole and SERs ranged from 1.2 to 1.5.

Animals↗

Acute subdural haematomas: aetiology, pathology and outcome.

The aetiology, mechanisms of haemorrhage and results of treatment of a series of 63 consecutive cases of acute subdural haematoma are presented. Forty-six cases were due to trauma (46% mortality) and 17 cases were non-traumatic (41% mortality). Only 15 patients overall (24%) made a good recovery. The various mechanisms of venous and arterial bleeding leading to subdural haematoma are reviewed and the importance of brain swelling as a determinant of fatal outcome is stressed.

Adolescent↗

Human tumor cell destruction by distilled water. An in vitro evaluation.

A distilled water lavage is sometimes used during tumor surgery in an effort to kill tumor cells spilled into a cavity or wound. To test the efficacy of this technique, a model study utilized nine different human tumor cell lines, subjected in vitro to hypotonic exposure for 1 to 10 minutes. Only the carcinoid, multiple myeloma, leiomyosarcoma cell lines, and normal lymphocytes were destroyed by the treatment. Although breast, ovarian, gastric, bladder, and melanoma cell lines were damaged to varying degrees, viable cells persisted in all cases. These data suggest that hypotonic shock is not an effective method to kill human tumor cells.

Autoradiography↗

The effect of extracellular pH on radiosensitization by misonidazole and acidic or basic analogues.

The effect of extracellular pH (pHe) on the radiosensitization of hypoxic Chinese hamster V79 cells in vitro by the 2-nitroimidazole, misonidazole, and analogues substituted with basic or acid functions has been studied. Misonidazole (1 mmol dm-3) gave an enhancement ratio (e.r.) of 1.6 which remained unchanged over the pHe range of 3.8-9.5. Control hypoxic survival curves in the absence of sensitizer also remained essentially unchanged over this pHe range. These results contrast with those seen for 0.1 mmol dm-3 Ro 03-8799 (1-(2-nitro-1-imidazolyl)-3-N-piperidino-2-propanol), a base with pKa = 8.9): the ER increased from 1.4 to 2.1 as pHe increased from 5.6 to 8.4. However, with the weaker bases, Ro 03-8800 and nimorazole (morpholino derivatives with pKa = 6.3 and 5.2 respectively) the e.r. remained constant over a wide pHe range. Nitroimidazoles substituted with acidic functions gave decreasing sensitization with increasing pHe. For azomycin (pKa = 7.2) at 1 mmol dm-3 the e.r. decreased from 1.9 at pHe 4 to 1.0 at pHe 9. The effect of the proton conductor carbonyl cyanide-3-chlorophenylhydrazone (CCCP, 10 mumol dm-3) on radiosensitization by Ro 03-8799 (0.1 mmol dm-3) and misonidazole (1.0 mmol dm-3) was also studied. At pHe 6.67 the e.r. for Ro 03-8799 was increased from 1.36 to 1.76 by the presence of CCCP, whereas at pHe 7.33 the e.r. was unchanged. In contrast the e.r. for misonidazole was unchanged at pHe 6.65 and 7.33. These results are consistent with pH differentials across the cell membrane creating intracellular:extracellular concentrations gradients for radiosensitizers with acidic or basic functions.

Animals↗

Glutathione depletion in tissues after administration of buthionine sulphoximine.

Buthionine sulphoximine (BSO) an inhibitor of glutathione (GSH) biosynthesis, was administered to mice in single and repeated doses of 0.5, 1 and 5 mmol kg-1 (i.p.). The resultant pattern of GSH depletion was studied in liver, kidney, skeletal muscle and three types of murine tumor. Liver and kidney exhibited a rapid depletion to GSH levels of ca. 20% of controls after single doses of 1-5 mmol kg-1 BSO. Muscle was depleted to a similar level, but at a slower rate after a single dose. All three tumors required repeated administration of BSO over several days to obtain a similar degree of depletion to that shown in the other tissues.

Animals↗