Biomedical subjects

J T Paine

Publications and source records attributed to J T Paine.

13 recordsLinked to original sources

PubMed1994

Intratumoral administration of tumor necrosis factor-alpha for malignant gliomas--two case reports.

Two patients with histologically verified glioblastoma multiforme and anaplastic astrocytoma were treated with four courses of intratumoral administration of human natural tumor necrosis factor-alpha (TNF) (specific activity 2.0 x 10(6) Japan reference unit [JRU]/mg protein) at intervals of 3-5 months. Each consisted of eight to 10 serial injections, ranging from 5 x 10(3) to 10(4) JRU/injection, at intervals of 3-5 days. There was no simultaneous administration of steroids. Serial neurological examinations and neuroimaging studies with computed tomography and magnetic resonance imaging demonstrated partial responses ranging from 28 and 36 months in duration. No significant TNF-related brain edema, intracerebral bleeding, or neurotoxicity occurred. Local immunotherapy with TNF may be used safely to contribute to therapeutic efficacy.

Adult↗

PubMed1993

Chemotherapeutic effects of intra-arterial administration of ACNU in primary intracerebral non-Hodgkin's lymphoma.

The authors report five patients with primary intracerebral non-Hodgkin's lymphoma who were treated with several cycles of intra-arterial injection of 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) at doses of 80 to 100 mg/m2/injection at several monthly intervals. There was no simultaneous use of steroids, and no patients had concomitant immunosuppression; no patient was human immunodeficiency virus positive. This therapy was initially used in four patients with advanced recurrent lymphoma. These patients experienced tumor progression despite our institutional standard therapy comprising cranial irradiation followed by repeated courses of systemic multi-agent chemotherapy (cyclophosphamide, vincristine, adriamycin, and prednisolone) more than 3 months previously. Based upon brain computed tomography scans and clinical neurologic examinations, three of the four cases showed partial responses ranging from 10 to 12 months in duration, whereas the other patient remained stable without worsening for 8 months. A fifth case was particularly noteworthy; this patient had no prior therapy and intra-arterial chemotherapy alone induced an 18-month, disease-free remission. No significant therapy-related complications nor neurotoxicity were seen. These results suggest that intra-arterial administration of ACNU may be a potential candidate for intracerebral lymphoma therapy.

Adult↗

PubMed1993

Role of histocompatibility antigen gene and protooncogene expressions in intracerebral tumorigenicity of mouse neuroblastoma.

The role of N-myc, c-src, and major histocompatibility complex (MHC, H-2 in the mouse) class I antigen gene expressions in dimethyl sulfoxide (DMSO)-induced differentiation and intracerebral tumorigenicity was examined using a mouse MNB85 neuroblastoma cell line. A fluorescence-activated cell sorter disclosed cell-surface MHC enhancement by DMSO, causing an increase in cytotoxic T-lymphocyte sensitivity. Southern blot analysis verified a single copy of the proto-oncogenes and MHC deoxyribonucleic acids in both untreated and DMSO-treated MNB85 cells. Northern blot analysis indicated that DMSO treatment induced a decrease in N-myc and an increase in c-src and MHC messenger ribonucleic acids. Nuclear run-off transcription assay revealed down-regulation of N-myc at a posttranscriptional level, contrasted with primary up-regulation of c-src at a transcriptional level. Immunoprecipitation after treatment with enzyme endo-beta-N-acetyl-glycoseamidase H proved that the terminal glycosylation of MHC heavy-chain gene products normally occurs in the Golgi apparatus of MNB85 cells. Intracerebral tumorigenicity assay showed that cells highly MHC-expressed by DMSO were less tumorigenic than untreated cells in association with DMSO-augmented cytotoxic T-lymphocyte susceptibility. These results suggest that proto-oncogenes may be linked to cellular differentiation, while cell-surface MHC gene expression influences intracerebral immunosurveillance.

Animals↗

PubMed1992

A morphological and ultrastructural investigation of normal mouse brain tissue after intracerebral injection of tumor necrosis factor.

Morphological and ultrastructural changes in normal mouse brain tissue were investigated after intracerebral stereotactic injections of tumor necrosis factor (specific activity: 2.0 x 10(6) U/mg protein) into the right frontal lobe. The mice received either a single infusion or multiple tumor necrosis factor infusions in three different dose groups (10, 100, or 500 U). Compared with sham-treated control mice that received adjusted intracerebral injections of purified albumin, the tumor necrosis factor-treated mice in all dose groups did not show any specific in vivo behavioral abnormalities during the 2 months of study following the infusions. Histological studies revealed hemorrhage attributable to the mechanics of the intracerebral infusions, a thickening of the arachnoid membranes, a reactive gliosis, and neutrophilic and/or mononuclear cell infiltration along the infusion pathway. A local neutrophilic response was prominent 1 day after tumor necrosis factor injection. An immunohistochemical analysis indicated that the mononuclear cell infiltration consisted of lymphocytes and macrophages. Except for the transient neutrophilic infiltration, these histological alterations did not differ from those seen in the sham-treated control groups, and most nonspecific reactive changes disappeared within 8 weeks after the injections. Furthermore, an ultrastructural study showed no apparent pathological changes in the cytoplasmic organelles of neuronal, glial, and endothelial cells in the tumor necrosis factor-injected mouse specimens. These results suggest that the tumor necrosis factor injections caused no specific toxicity and did not alter the parenchymal and stromal cells comprising normal mouse brain tissue.

Animals↗

PubMed1990

Focal subarachnoid hematoma: an unusual cause of delayed third cranial nerve paralysis.

We report a case of delayed onset of ultimately permanent oculomotor nerve palsy following a focal aneurysmal hemorrhage into the adjacent interpeduncular cistern. Operative inspection revealed no direct nerve compression by the aneurysmal fundus. Third cranial neuropathies following subarachnoid hemorrhage can occur independently of direct aneurysmal mechanical compression.

Aged↗

PubMed1990

Intracerebral malignant lymphoma with fluctuating regression and spatial evolution.

Seven patients with histologically proven primary intracerebral malignant lymphoma, characterized by a fluctuating nature with both transient regression and spatial evolution of the tumors without contiguity to the initial lesion, are presented. Although the overall outcome was unfavorable, two cases had a long-term survival of 3 years or more and one of them showed a good quality of life. Correlation among characteristic clinical presentations, computed tomography scans, and prognostic factors after management with surgery, radiation, and chemotherapy, including steroids, is discussed.

Aged↗

PubMed1989

Murine intracerebral interleukin-2 injection: pathological and immunological effects.

The authors have investigated whether specific pathological changes and antibodies against interleukin-2 (IL-2) are induced after intracerebral administration of recombinant IL-2 (rIL-2). In addition, IL-2 receptor (IL-2R) expression was checked on the cell surface of normal brain tissues before and after the intracerebral infusion. Reconstituted rIL-2 (specific activity 1.2 x 10(7) U/mg protein) was injected into the right cerebral hemisphere of normal adult C57BL/6 mice in three different dose groups, each receiving single or multiple infusions of 8, 32, or 80 U. In sham control experiments, mouse albumin purified by gel filtration and ion exchange chromatography and adjusted to the same concentration of protein as rIL-2 was injected into mice at various doses. Anti-IL-2 antibodies were measured by an enzyme-linked immunosorbent assay concurrently with assessment of IL-2 activity in serum. The IL-2R expression was determined by using immunofluorescence techniques with monoclonal antibodies against mouse IL-2R. Since histological alteration after rIL-2 injection did not differ from that in the sham control preparations, it seems that there is no direct toxic action of rIL-2 on normal brain tissues. Interleukin-2 antibodies were produced at low levels only in mice injected repeatedly at the maximum dose, and levels were insignificant in other groups. Serum levels of IL-2 activity remained low. The IL-2R expression within the brain was not enhanced within 8 weeks following the intracerebral administration of rIL-2, suggesting that direct intracerebral infusion of rIL-2 may be safely used in the immunotherapy of brain tumors.

Animals↗

PubMed1988

Intraoperative ventricular puncture.

Modern neuroanesthetic techniques frequently provide the neurosurgeon with adequate brain relaxation for an atraumatic frontotemporal or transylvian dissection. Circumstances such as recent subarachnoid hemorrhage with brain edema and acute hydrocephalus can mandate significant frontal lobe retraction before access to cerebrospinal fluid (CSF) drainage from the basal cisterns is gained. A simple technique can give the "early" aneurysm surgeon reliable access to the frontal horn of the lateral ventricle for intraoperative drainage of CSF before brain retraction.

Cerebral Ventricles↗

PubMed1987

Malignant melanoma metastatic to sphenoid bone with an unknown primary origin: report of a case with an immunohistochemical analysis of the infiltrating lymphocytes.

A rare case of hemorrhagic malignant melanoma from an unknown primary origin to the right sphenoid bone in a 37-year-old woman is presented. The tumor occupied an extensive intracranial extradural space with a mild orbital infiltration, but little involvement of the leptomeninges and parenchymal tissues. Immunohistochemical analysis of the tumor-infiltrating lymphocytes showed that the majority expressed pan-T or Leu-1 surface antigens and that the lymphocytes bearing the Leu-3 antigen, or helper phenotype, were predominant compared to the Leu-2 population representing both suppressor and cytotoxic T cells. Furthermore, most of the T lymphocytes stained with HLA-DR antigens. Because few B cells were seen, this observation indicates the presence of T cells in an activated state. The literature pertinent to associated organ involvement of metastatic melanomas and the correlations between the tumor and immunological cellular responses are discussed.

Adult↗

PubMed1986

Brainstem glioma: an analysis of 85 cases.

The study analyses 85 cases of brainstem glioma in the past 35 years, 69 of which include patients under 16 years of age. The incidence of brainstem glioma was 2.4% of all intracranial tumours, and 9.4% of intracranial tumours in children. There were two peaks in age distribution, in the first and in the fourth decades. In children, the tumours were located mainly in the pons, so VIth and VIIth cranial nerve palsies, and pyramidal and cerebellar signs were frequently seen. In adult cases, the tumours ranged in location from the midbrain to the medulla, so neurological symptoms caused by lesions of the whole brainstem axis were seen. The left side was dominant in both age groups. The choice of treatment was steroid administration and radiation. Chemotherapy was not effective. Even after these treatments, the median survival period from onset was no longer than 10.5 months. We conclude that the treatment of brainstem gliomas in children should be distinguished from adult cases, which in the latter may be considered to be merely one of the gliomas which may occur at any other sites. Since brainstem gliomas in children may be congenital, we must redirect our treatment of these lesions to treatment of congenital tumours.

Adolescent↗

PubMed1986

Suprasellar germinoma with shunt metastasis: report of a case with an immunohistochemical characterization of the lymphocyte subpopulations.

A case of suprasellar germinoma metastatic to the peritoneum 3 years after the placement of a ventriculoperitoneal shunt is presented. The excised metastatic germinoma was analyzed immunohistochemically with monoclonal antibodies against human lymphocyte subpopulations. Approximately 80% of the lymphocytes expressed pan-T, or Leu-1, surface antigens, and 20% were B1+, or B cells. Approximately 30% of T cells were Leu-2+, or cytotoxic and suppressor cells; 70% were Leu-3+, or helper cells. The large number of T cells is consistent with their role in cell-mediated immunity; their subpopulation ratio approximated that of the circulation. The literature pertinent to germinoma shunt metastasis is also reviewed.

Adolescent↗

PubMed1986

Immunohistochemical analysis of infiltrating lymphocytes in central nervous system tumors.

To investigate cell-mediated immune responses to central nervous system tumors, we immunohistochemically analyzed 32 operative specimens, including 19 primary tumors, 5 recurrent tumors, and 8 metastases, for the presence of infiltrating T lymphocytes. In 1 patient, an additional sample of normal brain was studied. Using monoclonal antibodies against T lymphocyte surface markers with a peroxidase technique on frozen sections, we determined that a mild lymphocytic response was present in 3 of 7 primary glial tumors, 1 of 4 recurrent glial tumors, and in 3 of 9 primary meningiomas. The predominant subset was Leu 2, or suppressor/cytotoxic. In contrast, 5 of 7 intracranial metastatic tumors and 1 extracranial metastasis showed marked infiltration with an overall Leu 3, or helper/inducer, predominance. The remainder of the specimens, including 1 recurrent meningioma, 3 neurinomas, and the normal brain sample, were free of infiltrates. Permanent sections revealed an overall pattern of lymphocytic infiltration similar to that of frozen sections. Although additional studies such as electron microscopy are required to establish definitively the lymphocytic nature of the infiltrates, these results support the concept of the ability of the body to mount a cell-mediated response against central nervous system tumors and imply a differential response to primary and secondary tumors.

Adolescent↗

PubMed1986

Intracranial and orbital cavernous angiomas. A review of 30 cases.

The authors review 30 documented cases of intracranial and orbital cavernous angiomas treated at their institution between 1965 and 1984. The diagnosis was based on computerized tomography (CT) or surgery; three patients were treated in the pre-CT era (1965 to 1976) and 27 since the advent of CT. The number of cases diagnosed preoperatively markedly increased after the introduction of CT, and 22 cases were verified histopathologically at surgery. Six cases were in children (aged 2 months to 17 years) and 24 in adults (aged 19 to 73 years). There was no significant sex difference (male:female ratio was 14:16). Nineteen lesions were intraparenchymal, five were intraventricular, three were in the middle fossa, two were intraorbital, and one originated from the tentorium. Symptoms varied according to the site of the lesion; hemorrhage occurred in 11 cases. Calcifications were seen on CT scans in all cases, but on plain skull films in only two. Angiography revealed hypovascular masses in all cases excluding those with lesions in the middle fossa; in two cases, tumor stain could be detected only with prolonged-injection angiography. Radionuclide brain scanning showed a dense hot area in eight of 19 patients. Recent experience has shown that magnetic resonance imaging clarified anatomic relationships that were obscure on CT. The overall outcome was favorable except for one patient who died in the postoperative period. The clinical results in this series are summarized and some diagnostic and therapeutic problems are discussed.

Adolescent↗