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Biomedical subjects

K Burman

Publications and source records attributed to K Burman.

16 recordsLinked to original sources
PubMed2006

The relative frequency in which empiric dosages of radioiodine would potentially overtreat or undertreat patients who have metastatic well-differentiated thyroid cancer.

The dosage of (131)I for the treatment of metastatic well-differentiated thyroid cancer is typically selected empirically. Benua and Leeper implemented a method to estimate the maximum dosages of (131)I that could be administered to a patient so as not to exceed a maximum tolerated radiation absorbed dose (MTD), which was defined as 200 rads (cGy) to the blood. The objective of this study was to determine the frequency of (131)I treatments in which the patient (1) would have exceeded the MTD (i.e., overtreatment) or (2) would have been able to receive higher dosages of (131)I thereby delivering a potentially higher radiation absorbed dose to their metastases (i.e., undertreatment) had the patient been administered various assumed empiric dosages of (131)I. The dosimetrically-determined maximum tolerated radioactivities (MTA) to deliver 200 rads to the blood (MTD) were tabulated at our facility. Data were then grouped to determine the percentage of patients who would have received less than or more than the MTD for various assumed empiric dosages of (131)I. A total of 127 dosimetries were performed. For assumed empiric dosages of (131)I (100 mCi, 150 mCi, 200 mCi, 250 mCi, and 300 mCi), the percentage of treatments for which patients would have exceeded the MTD were less than 1%, 5%, 11%, 17%, and 22%, respectively, and could have received a higher dosage of (131)I were more than 99%, 95%, 89%, 83%, and 78%, respectively. A significant number of patients receiving various empiric dosages of (131)I may exceed 200 rads (cGy) to the blood (potential overtreating). Likewise, the majority of patients may be able to receive much higher dosages of (131)I relative to empiric dosages thereby delivering potentially higher radiation absorbed doses to the metastases without exceeding 200 rads (cGy) to the blood (potential undertreating).

Adult↗
PubMed2002

Apparent increase in type I 5'-deiodinase activity induced by antiepileptic medication in mentally retarded subjects.

BACKGROUND/OBJECTIVES: Thyroid function measurements in 3 mentally retarded patients treated with antiepileptic drugs (phenytoin or carbamazepine) showed normal thyroid-stimulating hormone (TSH) responses in spite of markedly low levels of total thyroxine (T(4)), triiodothyronine (T(3)), and free thyroxine (FT(4)) concentrations; free triiodothyronine (FT(3)), as well as mean thyroxine-binding globulin (TBG) concentrations were normal. The objective of the present investigations was to determine if antiepileptic medication in these patients contributed to the disparate TSH and thyroid hormone (TH) levels. METHODS: Thyroid tests and other laboratory parameters were measured by conventional techniques. RESULTS: Circulating TH changes noted in retarded patients were similar to those observed in control subjects receiving carbamazepine alone. Reverse T(3) (rT(3)) levels in all patients were either undetectable or below the normal range. CONCLUSIONS: As type I 5'-deiodinase has a higher affinity for rT(3) than T(4), an increased activity of this enzyme would enhance rT(3) deiodination and reduce serum rT(3) concentration whereas enhanced T(4) deiodination would aid in normalizing intracellular FT(3) concentration. The finding of normal serum FT(3) concentration was consistent with normal TSH response and clinical euthyroidism in both retarded and control subjects. While phenytoin-induced increase in type I 5'-deiodinase has been previously noted, the present studies demonstrate a similar effect of carbamazepine on 5'-deiodinase.

Adult↗
PubMed2000

Macaque red nucleus: origins of spinal and olivary projections and terminations of cortical inputs.

The cerebellar, spinal, bulbar, and cortical connections of the mammalian red nucleus imply a motor role. However, what information the red nucleus receives, processes, and distributes is poorly understood, partly because the rubral microcircuitry, especially in primates, remains incompletely defined. Multiple retrogradely transported fluorescent tracers were injected into the spinal cord and inferior olive of the macaque to label rubrospinal and rubroolivary neuron populations, respectively. Anterograde dextran amines were used to label the terminals of corticorubral neurons. These data provided the topographic framework for examining the morphology of rubral neurons in the accompanying paper (Burman et al. [2000]). Soma profiles of rubrospinal and rubro-olivary neurons were respectively segregated in the magnocellular and parvocellular nuclei. A subpopulation of neurons (DL-spinal cells) with their somas immediately dorsolateral to the rostral magnocellular nucleus and its capsule, also projected to the spinal cord, as did clusters of neurons in the periaqueductal grey matter. Terminals of corticorubral axons originating from ipsilateral primary motor area 4 (the densest projection), the supplementary motor area, cingulate area 24, area 8, and posterior parietal area 5, were each mapped in the parvocellular red nucleus. Only area 4 projected to the magnocellular red nucleus, and this projection as small. DL-spinal neurons had no cortical input. The somatotopic organization of rubral connections was examined only in (a) the corticorubral input from motor area 4, and (b) the rubrospinal and DL-spinal projections. These connections and their somatotopic alignment, were mapped in a 3-dimensional reconstruction of the red nucleus.

Animals↗
PubMed2000

Geometry of rubrospinal, rubroolivary, and local circuit neurons in the macaque red nucleus.

The primate red nucleus consists of three main neuron subpopulations, namely, rubrospinal neurons in the magnocellular nucleus, rubroolivary cells in the parvocellular nucleus, and local circuit neurons in both subnuclei: Each subpopulation has unique cerebellar and neocortical inputs. The structural framework for the interactions of these rubral subpopulations remains poorly defined and was the focus of this study in six macaques. Somata of rubrospinal neurons, dorsolateral-spinal (DL-spinal) neurons, as defined in the accompanying paper (Burman et al. [2000] J. Comp. Neurol., this issue), and rubroolivary neurons were labeled retrogradely first with Fast Blue injected either into the cervical spinal cord or the inferior olive. The soma/dendrite profiles of selected cells (53 rubrospinal, 19 DL-spinal, and 17 rubroolivary cells) were visualized by the intracellular injection of Lucifer Yellow/biocytin in fixed slices (400 microm thick) of midbrain. The descriptive statistics of the somata and the dendritic arborization of each rubral neuron type were established. Projection neuron subpopulations had similar but differentiable soma/dendrite profiles, with four to six slender, spine-bearing dendritic trees radiating out approximately 400 microm from the soma. Twelve presumed interneurons, all in the parvocellular nucleus, differed from projection neurons in that they had smaller somata and many slender, spine-bearing segments that constituted the multibranching dendrite profile that radiated out approximately 250 microm from the soma. A tentative model of the macaque rubral microcircuitry was developed, and its functional implications were explored. It incorporated 1) the known topography of the nucleus and its connections, 2) our data specifying the soma/dendrite morphology of the three main rubral neuron types, and 3) the ultrastructure reported by other laboratories of intrarubral synaptic connections.

Animals↗
PubMed1999

Parallel pathways mediating manual dexterity in the macaque.

Transmission of information along appropriately structured parallel pathways ensures that a great deal of information can be transferred from the source to the target very quickly, and with great security-essential features of any motor control system. Studies over the last two decades have established that the corticospinal and corticocerebellar pathways mediating manual dexterity in the primate are structurally organized to sustain the parallel transmission of sensorimotor information in multiple pathways. Serial, hierarchical control systems now seem insufficient to regulate voluntary hand movements. To achieve the required coordination, and precision and speed of execution, they must be combined with parallel control systems, which themselves incorporate elaborate feedforward and feedback controls. To illustrate these issues, two aspects of the structural organization of parallel sensorimotor pathways mediating manual dexterity in the macaque are reviewed. First, we examine the structure of the multiple corticospinal neuron subpopulations projecting from different areas of the frontoparietal cortex and how they are modified following hemisection of the cervical spinal cord. The remarkable recovery of hand function following spinal hemisection, despite the absence of any structural 'bridging' of the interrupted spinal pathways, and the fact that this is accountable in a parallel but not in a purely serial transmission system, are then reviewed. The second aspect of parallel distributed transmission examined is its occurrence within a single population of relay neurons. Our recent structural analysis of the somatic/dendritic organization of rubrospinal neurons in macaque red nucleus is used. The very large dendritic fields of individual neurons, extending over one-third or more of the nucleus, provide a framework for extracting precise somatotopic information from an input population whose axon terminal arbors overlap extensively, and, which, without effective filtering, would provide poor spatial resolution.

Animals↗
PubMed1993

Ipsilateral cortical projections to areas 3a, 3b, and 4 in the macaque monkey.

In the macaque monkey area 3a of the cerebral cortex separates area 4, a primary motor cortical field, from somatosensory area 3b, which has a subcortical input mainly from cutaneous mechanoreceptive neurons. That each of these cortical areas has a unique thalamic input was illustrated in the preceding paper. In the present experiments the cortical afferent projections to these 3 areas of the sensorimotor cortex monkey were visualized and compared, using 4 differentiable fluorescent dyes as axonal retrogradely transported labels. The cortical projection patterns to areas 3a, 3b, and 4 were similar in that they each consisted of (a) a "halo" of input from the immediately surrounding cortex, and (b) discrete projections from one or more remote cortical areas. However, the pattern of remote inputs from precentral, mesial, and posterior parietal cortex was different for each of the 3 cortical target areas. The cortical input configuration was least complex for area 3b, its remote input projecting mainly from insular cortex. The pattern of discrete cortical inputs to the motor area 4, however, was more complex, with projections from the cingulate motor area (24c/d), the supplementary motor area, postarcuate cortex, insular cortex, and postcentral areas 2/5. Area 3a, in addition to the proximal projections from the immediately surrounding cortex, also received input from the supplementary motor area, cingulate motor cortex, insular cortex, and areas 2/5. Thus, this pattern of cortical input to area 3a resembled more closely that of the adjacent motor rather than that of the somatosensory area 3b. Contrasting with this, however, the thalamic input to area 3a was largely from somatosensory VPLc (abbreviations from Olszewski [1952] The Thalamus of the Macaca mulatta. Basel: Karger) and not from VPLo (with input from cerebellum, and projecting to precentral motor areas).

Aging↗
PubMed1992

Failure of Epstein-Barr virus-specific cytotoxic T lymphocytes to lyse B cells transformed with the B95-8 strain is mapped to an epitope that associates with the HLA-B8 antigen.

There are two types, A and B, of Epstein-Barr virus (EBV) and B95-8 represents the common type A laboratory strain. Herein, we show in a family study that paternal EBV-specific cytotoxic T lymphocytes (CTL) generated in short-term cultures following stimulation with the autologous B95-8-transformed lymphoblastoid cell line (LCL) or B cells freshly infected with the B95-8 isolate did not lyse haploidentical B95-8 LCL expressing the HLA-A1, -B8, -DR3 paternal haplotype. In contrast, the haploidentical B95-8 LCL expressing the HLA-A11, -B51, -DR7 paternal haplotype was strongly lysed. Moreover, paternal CTL generated in response to stimulation with the B95-8 LCL expressing the haploidentical HLA-A1, -B8, -DR3 paternal haplotype included an allogeneic response against the maternal haplotype but no EBV-specific response as shown by the poor lysis of the autologous LCL target cells. However, stimulation with the haploidentical HLA-A11, -B51, -DR7 paternal haplotype resulted in the generation of both an allogeneic and an EBV-specific response. CTL clones were generated from two HLA-B8+ donors in response to stimulation with the autologous type A LCL transformed with wildtype EBV. The clones were cross-reactive for an immunodominant B95-8-associated peptide epitope that interacted with the HLA-B8 allele but failed to lyse B95-8-transformed LCL targets unless the targets were pre-coated with the exogenous peptide. A CTL clone that was initially stimulated with the autologous BL74 LCL lysed the spontaneous autologous LCL and spontaneous LCL from an HLA-B8+ donor, but failed to lyse the B95-8 LCL from that donor. The observed haplotype preference can be explained in terms of sequence variation between the B95-8 and the corresponding wildtype epitope. Our findings may help to clarify the role of EBV in the pathogenesis of primary Sjögren's syndrome which is closely associated with HLA-B8.

Cell Transformation, Viral↗
PubMed1991

Composite response of naive T cells to stimulation with the autologous lymphoblastoid cell line is mediated by CD4 cytotoxic T cell clones and includes an Epstein-Barr virus-specific component.

We have approached the challenge of generating a primary T cell response to Epstein-Barr virus (EBV) in vitro by stimulating naive T cells with the autologous EBV-transformed lymphoblastoid cell line (LCL), a rich source of EBV-associated cytotoxic T lymphocyte (CTL) epitopes. Responsive T cells from three EBV-seronegative donors were cloned in agarose, phenotyped for T cell markers by flow cytometry, and their cytotoxic properties analyzed in the 51Cr release assay. Most clones (greater than 95%) expressed the CD4 phenotype and 59% of these clones showed cytotoxic properties. The dominant CTL response was specific for FCS-associated epitopes presented by FCS-grown autologous LCL target cells and was restricted by class II HLA antigens. Other clonal components included: (i) an EBV-specific response by HLA-restricted CD4 CTL clones that did not discriminate between A- and B-type EBV transformants; (ii) an EBV-specific response by an HLA-restricted CD4 CTL clone that discriminated between A- and B-type transformants, and (iii) a nonspecific cytotoxic response by CD3+,4+,8-, CD3+,4-,8-, and CD3-,4-,8- clones that were broadly allotypic or restricted to the lysis of K562 target cells. The EBV-specific CTL clones did not lyse the autologous EBV-negative B or T cell blasts and their specificity patterns of lysis were supported by the cold target competition data. These studies highlight the role of CD4 CTL in the establishment in vitro of a primary immune response to a human virus.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Interleukin-2 receptors in infectious mononucleosis.

The majority of peripheral blood mononuclear cells (PBMC) from acute-phase infectious mononucleosis (IM) patients express high levels of T10 (CD38) and HLA-DR surface antigens, which are markers characteristic of activated T cells. However, Tac antigen (p55) expression on these cells was not detectable by flow cytometric immunofluorescence, and only a low level of specific interleukin-2 (IL-2) binding was found by Scatchard analysis. These results suggest that IL-2 receptors (IL-2R) are lost or down-regulated on activated T cells in acute IM. Since a large proportion of T cells die during the first 24 h of in vitro culture in the absence of exogenous IL-2, the data implicate a physiological role for the observed low levels of IL-2R on T cells.

Humans↗
PubMed1988

Cytotoxic T-cell clones discriminate between A- and B-type Epstein-Barr virus transformants.

Epstein-Barr virus (EBV) is the aetiological agent of infectious mononucleosis and is associated with Burkitt's lymphoma and nasopharyngeal carcinoma. The virus is harboured for life in all previously infected individuals and is apparently controlled by a population of EBV-specific memory T lymphocytes, specifically activated to recognize the functionally defined lymphocyte-detected membrane antigen. Two types (A and B) of EBV have been identified that show DNA sequence divergence within the BamH1 WYH region of the genome encoding the transformation-associated antigen, Epstein-Barr nuclear antigen 2 (EBNA 2) (ref. 4). To define the function of EBNA 2 in T-cell recognition, we have compared the ability of EBV-specific cytotoxic T-cell clones to distinguish between autologous B lymphocytes transformed by A- or B-type virus. We have now isolated both CD4 and CD8 cytotoxic T-cell clones that recognize autologous A-type but not B-type transformed lymphoblastoid cell lines, thus providing the first evidence that EBV-specific T-cell recognition can be mediated by EBNA 2. As this antigen is not expressed in Burkitt's lymphoma, this finding explains the failure of EBV-specific T-cell surveillance to eliminate the tumour.

B-Lymphocytes↗
PubMed1984

Differences in the reproductive endocrine status of ewes in the early post-partum period and during seasonal anoestrus.

More (P less than 0.05) post-partum acyclic ewes (8/9) showed evidence of pulsatile LH release than did seasonally anoestrous ewes (2/8). Mean plasma prolactin concentrations were higher (P less than 0.05) in the post-partum ewes than in the seasonally anoestrous ewes. Hypothalamic and pituitary cytosol oestrogen receptor number, median eminence GnRH content and pituitary LH, FSH and prolactin contents were similar in the two groups of ewes. The number of nuclear-bound oestrogen receptors was greater (P less than 0.01) in pituitaries from seasonally anoestrous ewes than in pituitaries from post-partum ewes. These data suggest that the basis of acyclicity in seasonally anoestrous ewes and in post-partum ewes is probably due to their inability to generate LH pulse frequencies similar to that in the follicular phase of the oestrous cycle. The higher LH pulse frequency in post-partum ewes, compared to that in seasonally anoestrous ewes, suggests that pregnancy may partly negate the reduction in LH secretion that is associated with photoperiod-induced acyclicity. The lower number of nuclear-bound oestrogen receptors in post-partum ewes suggests that there may be lower plasma oestrogen levels and less ovarian follicular growth than in non-suckling anoestrous ewes.

Anestrus↗
PubMed1981

Lack of effects of beta sympathetic blockade on the metabolic and respiratory responses to carbohydrate feeding.

Increases in metabolic rate, heart rate and ventilation occur following carbohydrate feeding or during beta sympathetic stimulation. Furthermore, insulin secretion and hypokalemia are features common to both which raises the question as to whether these effects of carbohydrate depend upon an intact sympathetic nervous system. Accordingly, in the present study, we measured the effects of carbohydrate feeding (250 gram meal) before and after chronic beta sympathetic blockade in sex normal men. Before blockade metabolic rate (O2 consumption) rose (P less than 0.05) from a fasting mean of 248 +/- 19.7 (SEM) ML O2/min to 292 +/- 15.2 at 1 hr. 269 +/- 13.7 at 2, and 262 +/- 18.0 at 3 hr following the meal. During blockade (oral propranolol 80 mg p.o. Q 6 h for 3 days) the post-prandial increase in O2 consumption was also significant (P less than 0.05) and almost identical to that found before blockade. A similar pattern was found for ventilation, heart rate, insulin secretion and hypokalemia, where the significant postprandial changes were not altered by blockade. A transient increase in serum triiodothyronine from a mean of 92 +/- 8.4 microgram/ML to 109 +/- 9.4 occurred at 1 hr (P less than 0.05) only during blockade. No other changes in thyroid hormonal concentrations occurred as a result of the meal. We conclude that although similarities exist between beta sympathetic stimulation and carbohydrate feeding, the post-prandial effects studied do not depend on intact beta sympathetic receptors.

Dietary Carbohydrates↗