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Biomedical subjects

J Patterson

Publications and source records attributed to J Patterson.

At least 73 records · Page 4Linked to original sources

The application of prolonged electroencephalographic monitoring and video recording to the diagnosis of epilepsy.

This study reports the results of the application of intensive monitoring by electroencephalogram (EEG) combined with video recording as an aid to the diagnosis of epilepsy. A group of 622 patients was investigated; useful information was obtained in approximately 50% of these patients. Ten per cent of the patients with suspected epilepsy had a seizure during the period of recording. The combined analysis of the video recording and the EEG provided valuable evidence in the analysis of complex partial seizures and highlights the high prevalence of pseudoseizures in patients who are suspected of having epilepsy.

Adolescent

The contribution of large granular lymphocytes to B cell activation and differentiation after T-cell-depleted allogeneic bone marrow transplantation.

Immunoglobulin and specific antibody levels are well maintained in the recipients of T-cell-depleted allogeneic bone marrow transplants (BMT), even though up to 99% of mature T cells are removed from the donor graft. For 3-8 weeks after the procedure, natural killer (NK) cells with an activated pattern of target cell killing have been shown to circulate in the recipient. This study investigates whether these recipient NK cells spontaneously secrete lymphokines that modulate B cell function in a way analogous to that of in-vitro-activated NK cells from normal individuals. Large granular lymphocytes (LGLs) (which contain a high proportion of NK cells) have been prepared from the peripheral blood of 11 recipients of T-cell-depleted major-histocompatibility-complex-matched allografts. In the first 4-6 weeks after BMT these LGLs were found spontaneously to secrete interleukin 2, interferon gamma and B cell differentiation factor. While secretion of these factors declines by 20-24 weeks after BMT, the quantities are still greater than those seen from control donors. Patient LGLs are also able to activate autologous (donor) B cells, rendering them potentially responsive to the secreted factors. It appears likely that activated NK cells (or LGL) play a significant role in maintaining B cell function in vivo after T-cell-depleted BMT.

Antigens, Differentiation, B-Lymphocyte

The significance of host haemopoietic cells detected by cytogenetic analysis of bone marrow from recipients of bone marrow transplants.

Bone marrow from 39 patients who received a bone marrow transplant (BMT) from a matched donor of different sex were studied by chromosome analysis for evidence of mixed haemopoietic chimaerism (MC). Recipient metaphases were detected in the bone marrow of 10 patients after BMT. Patients in whom MC was detected within 6 weeks of BMT did not all have a poor outcome. Two of seven are disease-free survivors at greater than 470 and greater than 632 d. All three patients in whom MC was diagnosed more than 6 weeks after BMT subsequently relapsed. Four factors appear to be important in determining the probability of relapse when MC is detected in a patient after BMT: the timing of detection of residual recipient cells; the proportion of these cells in the bone marrow; persistence of these cells in increasing proportions; and the karyotype of the recipient metaphases detected. Cytogenetic assessment may provide the earliest indication of relapse in these patients. In addition, this study provides further evidence that cyclophosphamide and total body irradiation, as used in these patients, may be inadequate conditioning therapy for BMT.

Adolescent

Natural killer cell activity following T-cell depleted allogeneic bone marrow transplantation.

We have examined the recovery of natural killer (NK) cell function in seven recipients of MHC matched T cell depleted bone marrow allografts. NK cell activity against the erythroblastoid line K562 recovers 2-3 weeks after transplantation. Recipients also show a high level of killing of the T cell target HSB2 and of EBV transformed lymphoblastoid cell lines (B-LCL). This activity peaks at 4-6 weeks and declines towards normal by 12-14 weeks after transplantation. Although killing of HSB2 and B-LCL is usually the property of activated NK cells, few of these patients had any obvious 'trigger' of such activation: none had CMV infection, there were no episodes of graft rejection, and only two patients had mild and transient grade I graft versus host disease (GvHD). We conclude that T cell depletion does not affect the reconstitution of NK cell function and that NK cell activation occurs after T depleted bone marrow transplantation even in the absence of clinically detectable GvHD, graft rejection or CMV infection.

Adolescent

Graft rejection following HLA matched T-lymphocyte depleted bone marrow transplantation.

Bone marrow graft rejection following HLA-matched bone marrow transplantation (BMT) for leukaemia has been a rare problem. However, with the introduction of T-lymphocyte depleted BMT, graft rejection is recognized as a new complication. At the Royal Free Hospital (RFH) in London T-depletion is achieved using two monoclonal antibodies with complement mediated lysis. The methodology was extended to other centres and in total 56 patients have received T-depleted, HLA matched BMT. Twelve of 56 patients have had graft rejection. At the RFH three of 41 (7%) patients have had rejection whereas at collaborating centres nine of 15 (60%) patients have had rejection. We have investigated these rejections in order to identify factor(s) responsible. Rejection was not restricted by patient or donor characteristics, nor disease status. Patient management, chemotherapy conditioning, efficiency of T-depletion, graft versus host disease (GvHD), and infection post BMT, were not consistently implicated. The major difference between the RFH and all other centres was in the radiotherapy (RT) conditioning: The RFH prescribed a single fraction of 7.5 Gy total body irradiation (TBI) whilst collaborating centres gave 10 or 12 Gy fractionated TBI. We conclude that the different incidence of rejection (7% v. 60%) relates primarily to the RT conditioning although the mechanisms(s) of rejection remain unknown. We conclude that where T-depleted BMT is used, compensation by more intensive RT conditioning is required in order to avert graft rejection.

Adolescent

Standardization of T-cell depletion in HLA matched bone marrow transplantation.

The IBM 2991 Blood Cell Processor has been used to isolate a mononuclear cell (MNC) fraction from the marrow of 31 allogeneic donors. The MNC fraction was then incubated with a combination of two murine monoclonal antibodies MBG6 (CD6) and RFT8 (CD8) followed by two rounds of treatment with rabbit complement resulting in a marrow inoculum significantly reduced in the number of T-lymphocytes. We report here new specifications for the use of Ficoll-Metrizoate, the method used to calculate T-lymphocyte depletion and the details of our attempts to improve T-depletion. Following marrow transplantation with this T-depleted fraction, 29 patients are evaluable for engraftment, one patient failed to engraft and one died too early for evaluation. Twenty-two had no acute graft-versus-host disease (aGvHD), at a minimum of 60 d, six had grade I acute GvHD and one grade III. No correlation was found between the absolute number of MNC infused and time to engraftment, nor any relationship between the number of residual viable T-lymphocytes in the infused marrow and the incidence of GvHD, but the patient with the most severe aGvHD also had the highest number of T-lymphocytes infused.

Antibodies, Monoclonal

Recovery of immunoglobulin isotypes following T-cell depleted allogeneic bone marrow transplantation.

After conventional bone marrow transplantation serum IgG, IgM and IgA levels fall from pre-transplant levels and may not return to normal for 3-12 months. In contrast IgE may rise to supranormal levels, an event that may be associated with graft-versus-host disease. We have investigated the recovery of immunoglobulin isotypes in the recipients of allogeneic marrows depleted of T-cells to prevent graft-versus-host disease. We find that pre-transplant IgG, IgM and IgA levels are maintained throughout the post-transplant period but that there is a short-lived rise in IgE about 3 weeks after transplantation: this rise occurs in the absence of clinically detectable graft-versus-host disease. We conclude that specific T-cell depletion does not impair and may actually enhance the functional recovery of B cells after allogeneic BMT.

Adolescent

La Crosse virus small genome mRNA is made in the cytoplasm.

The cellular site of La Crosse virus S genome mRNA synthesis was examined by pulse-labeling infected cells for various times and determining the amount of labeled S mRNA in both the cytoplasmic and nuclear fractions. With pulse times as short as 3 min, La Crosse virus S genome transcription was found to be localized in the cytoplasm.

Animals

The dopamine withdrawal test following surgery for intracranial aneurysms.

Cerebral blood flow was measured in eight patients who were being treated with dopamine in order to maintain cerebral perfusion after the onset of delayed postoperative ischaemia following intracranial aneurysm surgery. Measurements were made whilst on treatment and repeated either during a reduction in the dosage or withdrawal of dopamine. There was a significant fall in cerebral blood flow in both hemispheres in all eight patients. Clinical deterioration was observed in seven of nine instances in which cerebral blood flow fell by 25% or more of the value while on dopamine treatment. There were no episodes of deterioration in six tests where the fall in cerebral blood flow was less than 25% of the starting value. It is suggested that cerebral blood flow measurement can be useful in predicting when it is safe to withdraw dopamine treatment in these patients. Hypertensive treatment should be maintained if a withdrawal test is associated with a fall in cerebral blood flow of 25% or more.

Adult

Accuracy of stereotaxic localisation using MRI and CT.

The accuracy of stereotaxic coordinates determined using the Leksell apparatus with CT and MRI was investigated using an Agar filled head phantom. Both imaging techniques were found to produce an accuracy of better than 2 mm with the exception of the Z coordinate as measured by CT (2.3 mm). This latter error is greater because of the 3 mm slice width used. Direct coronal views were used to determine Z more accurately using MRI. The measurement procedures are described and it is shown that the Leksell system of using orthogonal coordinates enables the scaling of images, which is particularly necessary with MRI, to be done easily.

Humans

Relative effectiveness of concurrent forward/backward versus simple forward and simple backward Pavlovian conditioning procedures.

Concurrent forward/backward Pavlovian conditioning procedures were compared with simple forward and simple backward procedures for differential excitatory and inhibitory conditioning. Four groups of dogs each received 30 shocks while restrained in a Pavlovian harness. One group of dogs (CON) received concurrent conditioning with a clicker signaling shocks and with a tone following shocks. For another group of dogs (SF), a clicker signaled the shocks, whereas the tone was randomly related to shocks. For a third group (SB), the tone followed shock termination, whereas the clicker was randomly related to shocks. For a fourth group (TRC), both the clicker and the tone were randomly related to shocks. All stimuli were then superimposed on a temporally paced avoidance baseline and their associative properties were assessed relative to the TRC group. Differential excitatory-inhibitory conditioning was significantly reduced in the concurrent procedure relative to that which occurred in the simple conditioning procedures despite exactly equal CS + -US and US-CS-contingencies. These results were interpreted with reference to contextual conditioning effects predicted by the Rescorla-Wagner conditioning model and the theoretical issue of independence vs. interdependence of CS-US associative strengths.

Acoustic Stimulation

Valproate metabolite concentrations in brain increase with chronic administration of sodium valproate.

Rats were treated chronically with sodium valproate for varying periods of time up to eight weeks. A statistically significant negative correlation between plasma concentrations of valproate-derived substances (VDS) and length of treatment was observed while a statistically significant positive correlation was found between brain VDS concentration and length of treatment. Liver VDS concentrations showed a tendency to decrease with time but this trend was not statistically significant. A new procedure was developed to measure the tissue levels of VDS.

Animals

Cerebral blood flow and CO2 responsiveness as an indicator of collateral reserve capacity in patients with carotid arterial disease.

Resting cerebral blood flow (CBF) and the response to inhalation of 7 per cent CO2 was measured in 74 patients with symptoms of cerebrovascular disease. In order to evaluate their role in the identification of patients with significant arterial lesions, these measurements were correlated with the angiographic appearances, the clinical picture and the presence or absence of infarction on CT scan. Patients with carotid stenosis of 60 per cent or more had normal resting flows, but reduced responsiveness to CO2 inhalation. Patients with carotid occlusion had both reduced resting flow and reduced CO2 responsiveness. Infarcts were visible in 25 per cent of the hemispheres studied, and were more common in patients with fixed neurological deficits, but were also present in 17 per cent of patients with transient ischaemic attacks (TIAs). Reduction in the collateral supply from the contralateral carotid artery via the Circle of Willis further reduced CO2 responsiveness with ipsilateral internal carotid occlusion. The normal increase in CBF which occurs with the inhalation of carbon dioxide is diminished with increasingly severe bilateral disease, with infarction and with a fixed neurological deficit.

Adult

Specificity in the reactivation of infant memory.

In three experiments the specificity of an effective reactivation stimulus, or reminder, was examined. Two weeks after learning to produce movement in a crib mobile by footkicking, 3-month-old human infants showed no retention of the response-reinforcer contingency. A reactivation procedure 24 hours prior to the long-term retention test was effective if the reminder was a brief noncontingent exposure to the original 5-component training mobile or a mobile containing one novel substitution. When more than one novel component were substituted into the original mobile, the reminder was ineffective. This was predicted by the discrimination function 24 hours following training. A reminder containing only a single familiar (predictive) component and four novel ones was also moderately effective. In subsequent studies, we explored different interpretations of the reminder specificity effect. We hypothesize that reminder specificity is of particular adaptive value for developing organisms in providing a buffer against memory retrieval in inappropriate contexts.

Cues

Effect of mannitol on cerebral blood flow and cerebral perfusion pressure in human head injury.

Patients with severe head injury frequently have evidence of elevated intracranial pressure (ICP) and ischemic neuronal damage at autopsy. Mannitol has been used clinically to reduce ICP with varying success, and it is possible that it is more effective in some types of head injury than in others. The aim of the present study was to determine the effect of mannitol on ICP, cerebral perfusion pressure (CPP), and cerebral blood flow (CBF) in patients with severe head injury, and to discover if these effects differed in different types of injury. Measurements of CPP, ICP, and CBF were made in 55 patients with severe head injury. In general, the resting level of CBF was higher in patients with diffuse injury (mean 50.2 ml/100 gm/min) than in those with focal injury (mean 39.8 ml/100 gm/min). Mannitol consistently reduced ICP and increased CPP and CBF by 10 to 20 minutes after infusion. The lowest flows (31.8 ml/100 gm/min) were recorded from the most damaged hemispheres of patients with focal injuries and elevated ICP. The baseline levels of flow did not correlate with ICP, CPP, Glasgow Coma Scale score, or outcome. Only four of the 55 patients had a CBF of less than 20 ml/100 gm/min in either or both hemispheres. The few low CBF's in this and other studies may reflect the steady-state conditions under which measurements are made in intensive care units, and that these patients have entered a phase of reperfusion.

Adult

In situ study of T-cell subpopulations in cutaneous T-cell lymphoma. Diagnostic criteria.

The T-cell subpopulations present in skin biopsy specimens from 91 patients with cutaneous T-cell lymphoma (CTCL) and from 19 patients with benign lymphocytic infiltrates of the skin were examined in situ to define criteria for the differentiation of benign from malignant lymphocytic infiltrates. The monoclonal antibodies OKT 1 (pan T-cell), BE 3 (pan T-cell), OKT 4 (helper/inducer T-cell), OKT 6 (cortical thymocyte and Langerhans' cell), OKT 8 (suppressor T-cell), and OKT 10 (pan thymocyte) were used in direct or indirect immunoperoxidase reactions. Sections were examined at high magnification, and the distribution and percentage of cells reactive with each antibody were assessed. Three main patterns of staining were observed in the CTCL patients: (1) 64% of the biopsy specimens showed that 60% of the cells present in the dermis were T-cells that were OKT 1+ and BE 3+ and there was an even distribution of the different T-cell subpopulations, with 54% being OKT 4+ and 8% OKT 8+; (2) 21% patients showed selective loss of OKT 1 antigen, and 80% of these also showed loss of BE 3 antigen; and (3) 15% patients showed large numbers of OKT 8+ cells (range, 50%-90%) but the percentages of OKT 1+ and OKT 4+ cells were within the ranges seen in Group 1, indicating the presence of a population of T-cells simultaneously expressing OKT 4 (helper/inducer) and OKT 8 (suppressor) reactivity. In 95% of the CTCL patients, 3.5% OKT 6+ cells were present in the dermal infiltrate, and in 92% of patients, 3% OKT 10+ cells were present. Comparing sections from CTCL and benign dermatoses, no single diagnostic feature was identified, but helpful differentiating features were: (1) the even, rather than nodular, distribution of the T-cell subpopulation; (2) the selective loss of OKT 1 and BE 3 antigens; (3) the presence of T-cells simultaneously expressing OKT 4 and OKT 8 antigens; and (4) the presence of OKT 10+ cells.

Antibodies, Monoclonal

S1-hypersensitive sites in eukaryotic promoter regions.

We have examined by fine mapping the S1 nuclease-hypersensitivity of the 5' flanking regions of the human beta-globin and rat preproinsulin II genes and of the SV40 origin/enhancer region. In all cases S1-hypersensitive sites are located in known or presumed promoter/regulatory regions. Though a consensus DNA sequence is not evident, all of these sites reside in predominantly homopurine-homopyrimidine stretches. The alternate (non-B) DNA structure which is revealed by the enzymatic probe is a sequence-dependent feature of a short stretch of DNA, which is retained upon transplantation into a foreign environment. The alternate structure exhibits S1-nicking patterns uniquely different from those associated with the presence of Z-DNA.

Animals