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Biomedical subjects

J Patterson

Publications and source records attributed to J Patterson.

At least 91 records · Page 5Linked to original sources

Characterization of chromosomes with hybrid genes for Hb Lepore-Washington, Hb Lepore-Baltimore, Hb P-Nilotic, and Hb Kenya.

This study concerns the characterization of chromosomes with hybrid genes for Hb Lepore-Washington (44 chromosomes), for Hb Lepore-Baltimore (5 chromosomes), for Hb P-Nilotic (8 chromosomes), and for Hb Kenya (7 chromosomes) by determining a relatively large number of restriction enzyme polymorphism. Two, and possibly three, different Hb Lepore-Washington chromosomes were identified by specific haplotypes, while the haplotype of the Hb Lepore-Baltimore chromosome had its own characteristic pattern. A likely conclusion is that the crossovers leading to the formation of these chromosomes have occurred as independent events within the populations. Chromosomes with the delta beta-Lepore-Washington hybrid gene maintained specific characteristics (such as increased Hb F levels in heterozygotes, and high or low G gamma values in this Hb F) which have been observed in normal individuals with chromosomes having comparable haplotypes. Only one haplotype was observed for each of the chromosomes carrying either the beta delta-P-Nilotic hybrid gene or the A gamma beta hybrid gene of Hb Kenya.

Chromosome Mapping

Calcified renal masses.

A review of the literature and the University of Kentucky Medical Center/Lexington Veterans Administration Medical Center experience regarding calcification of renal masses was undertaken. Twenty per cent of calcified renal masses cannot be easily characterized by CT scan as malignant or benign and are indeterminate. These lesions must be followed closely with follow-up CT scanning or undergo surgical exploration, as 40 per cent may be malignant.

Calcinosis

Human cranial CSF volumes measured by MRI: sex and age influences.

Accurate measurements of CSF volumes would assist in the diagnosis of several important neurological conditions. Using Magnetic Resonance Imaging (MRI) we have devised a method to measure both total intracranial CSF volume and ventricular volume. This initial study, in normal humans, provides an answer to two longstanding questions: first, do these volumes differ between the sexes; second, do both total and ventricular CSF volumes increase with normal aging? We found that the total cranial CSF volume and skull size of males were significantly greater than those of females, but that there was not a statistically significant difference between the ventricular volumes of the sexes. Total cranial CSF volume increased steeply with age in both sexes but although there was an increase in ventricular volume with age in males, no significant increase with age could be demonstrated in females.

Adult

Translational requirement of La Crosse virus S-mRNA synthesis: in vitro studies.

The exceptional requirement of La Crosse virus mRNA synthesis for ongoing protein synthesis in vivo was examined in vitro by using purified virions and a reticulocyte lysate. Transcription from the S genome produced two incomplete transcripts (110 and 205 nucleotides [nt]) in the absence of the lysate, whereas S-mRNA (900 nt) was predominantly made when the lysate was present. The addition of drugs which inhibit protein synthesis also inhibited the synthesis of S-mRNA, and in some cases led to the reappearance of the 205-nt RNA. Reconstruction experiments demonstrated that the incomplete transcripts were not the result of rapid and selective degradation of S-mRNA but were due to premature termination of the polymerase at defined sites. The requirement for ongoing protein synthesis for productive transcription in vitro is not at the level of chain initiation but for elongation of the nascent RNA beyond these sites.

Animals

Magnetic resonance imaging in the management of resistant focal epilepsy: pathological case report and experience of 12 cases.

Clinical improvement in epilepsy following temporal lobectomy is more often obtained when an abnormality is found on subsequent histological examination. Pre-operative MRI demonstrated an abnormal signal in the temporal lobe of a patient with pathologically proven mesial temporal sclerosis with microvascular anomaly. MRI may therefore be helpful in the selection of patients for temporal lobectomy. MRI findings of 12 patients with resistant focal epilepsy are reviewed. A wide range of T1 and T2 weighting is suggested to maximise selection of patients.

Adult

Syringomyelia: cyst measurement by magnetic resonance imaging and comparison with symptoms, signs and disability.

The severity and distribution of symptoms and signs in patients with syringomyelia is considered to be dependent on the longitudinal and transverse dimensions of the syrinx and it is thought that clinical examination can identify the extent of the cyst. Magnetic resonance imaging has made the anatomical localisation of intramedullary spinal lesions more exact and probably more specific than previous methods of investigation. Syrinx length, diameters, cyst:cord and cord:canal ratios have been studied in 12 patients with syringomyelia to assess whether the dimensions of the syrinx relate to the clinical findings. The length of syrinx appeared to be related to cyst diameter, cyst:cord and cord:canal ratios. Patients with a small syrinx tended to have a small cyst diameter, and small cyst:cord and cord:canal ratios. No significant relationship was found between muscle wasting or weakness, distribution of sensory loss, degree of disability or distress and the dimensions of the syrinx. These findings should be borne in mind when surgical management is being considered.

Adult

Haemorrhagic cystitis in bone marrow transplantation patients: possible increased risk associated with prior busulphan therapy.

Following bone marrow transplantation employing conditioning including 'high-dose' cyclophosphamide, 65 patients were studied for the subsequent development of symptomatic haemorrhagic cystitis. There was no protection from the urothelial toxicity of cyclophosphamide metabolites afforded by the concurrent administration of 2-mercaptoethane sodium sulphonate (mesna) if timing errors in administration were made. Other factors which might increase the risk of haemorrhagic cystitis due to cyclophosphamide administration include the prior administration of busulphan to patients with chronic granulocytic leukaemia, in whom the incidence of haemorrhagic cystitis was 36% compared with 4% in all other patients. We have also investigated the use of intravesical prostaglandin E2 as a treatment for haemorrhagic cystitis in eight patients, two of whom appeared to obtain major benefit.

Adolescent

Occupation and lung cancer risk among New Jersey white males.

The association of occupation with lung cancer risk was examined in a case-control study conducted in six areas of New Jersey. The study included 763 white males with incident histologically confirmed primary cancer of the trachea, bronchus, and lung and 900 general population white male controls selected from driver's license and death certificate files. Altogether, 27 employment categories had a smoking-adjusted odds ratio (OR) of 1.3 or greater; five of these with significantly high OR contributed to an occupational population attributable risk of 13%. Masons and tilesetters; janitors and cleaners; printing workers; and trucking service, warehousing, and storage workers had significantly high risks overall and for longer durations of employment. Shipbuilding workers had significantly high risk overall and for short duration of employment. Although the excess risk for all shipbuilding workers was primarily among those with reported exposure to asbestos, the risk was also high among welders, burners, sheet metal workers, and boilermakers with no reported asbestos exposure.

Asbestos

Use of magnetic resonance imaging to measure intracranial cerebrospinal fluid volume.

Magnetic resonance imaging was used to measure intracranial extraventricular and ventricular cerebrospinal fluid (CSF) volume. In 10 normal subjects lateral ventricular and extraventricular intracranial CSF volumes were 25.3 +/- 4.6 ml (mean +/- SD) and 97.6 +/- 6.6 ml, respectively (total 122.8 +/- 38.7). These volumes were measured in 4 patients and the results were: 11.0 ml ventricular volume, 68.7 ml total cranial CSF in the patient with benign intracranial hypertension; 606.6 ml ventricular, 174.1 ml total in the patient with hydrocephalus due to a blocked ventriculo-peritoneal (V-P) shunt; 83.4 ml ventricular, 108.5 ml total in the patient with normal pressure hydrocephalus; and 52.7 ml ventricular, 181.0 ml total in the patient with cerebral atrophy due to Alzheimer's disease. The technique gave highly reproducible results (SD less than 5.7% of mean value). It may be useful in differential diagnosis and as an objective means of monitoring therapy or progress in conditions such as cerebral atrophy, hydrocephalus, and benign intracranial hypertension.

Adolescent

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