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Biomedical subjects

M A Hunt

Publications and source records attributed to M A Hunt.

At least 19 recordsLinked to original sources
PubMed1992

Differential localization of alpha 2-adrenergic receptor subtypes in brain.

The pharmacological identification and characterization of subtypes of alpha 2-adrenergic receptors have been confirmed by molecular biological investigations. Using receptor autoradiographic techniques, it has been possible to show regions of the brain where alpha 2 agonist binding ([3H]para-aminoclonidine) is preferentially labeling the presumed guaninenucleotide-sensitive, high-affinity conformations of the alpha 2 receptor. Careful examination of autoradiograms generated using the tritiated antagonists yohimbine, idazoxan, and rauwolscine also indicates some disparity in the regions occupied by these radiolabeled ligands. Inhibition of [3H]rauwolscine binding with the subtype selective compounds, ARC-239, or oxymetazoline demonstrates that there are discrete regions of the brain where one receptor subtype predominates over the other. These studies indicate that previous investigations utilizing the agonist para-aminoclonidine as the ligand for obtaining labeling of alpha 2 receptors have overlooked some regions of binding due to the subtype selectivity of this ligand. A more complete localization of alpha 2-adrenergic receptors can be obtained using the tritiated antagonist rauwolscine, and the differential distribution of at least two subtypes of the alpha 2 receptor can be obtained by selective inhibition of this binding.

Adrenergic alpha-Agonists↗
PubMed1992

Conformal static field radiation therapy treatment of early prostate cancer versus non-conformal techniques: a reduction in acute morbidity.

Patients with early prostate cancer have been definitively treated using our previously described technique of CT-based 3D treatment planning and beam's eye view techniques with patients immobilized in alpha cradle casts. An average of 14% bladder (range 6-31%) and 14% rectal (range 7-25%) volume receiving a given dose was eliminated using four conformally blocked fields, with a 1.5 cm margin around the prostate contour, when compared to stage matched controls. Treatment-related acute morbidity was compared for 26 patients treated by the conformal techniques (CG) since April 1989 and 20 consecutive patients treated immediately prior to the conformal techniques with prostate only fields from May 1985-March 1989 (NCG). Acute urinary symptoms (frequency, dysuria, hematuria) or acute rectal symptoms (diarrhea, tenesmus, blood) occurred in 77% (20/26) of the CG versus 80% (16/20) of the NCG patients. Only 31% (8/26) of the CG versus 60% (12/20) of the NCG patients (p < .05) experienced symptoms to a degree which prompted physician intervention (medication and/or interruption of treatment). Two of 26 CG patients (8%) required medication for both bladder and rectal symptoms compared to 5/20 (25%) NCG patients (p = .09). Symptoms persisted for an average of 2.5 weeks versus 3.5 weeks in the CG and NCG groups, respectively. Persistent symptoms at or beyond the 1 month follow-up were present in 3/26 (11%) CG patients (average duration 1.5 months) and were present in 4/20 (20%) of the NCG patients (average duration 2.5 months). Thus, although the percentage of patients who experience acute irritation of the bladder and/or rectum is similar in the two groups, it appears that the percentage requiring medication and/or interruption of treatment is significantly less when 3D treatment planning, rigid immobilization, and conformal blocks are used. The amount of bladder and rectal tissue that is eliminated by our conformal technique is important as shown clinically by the lesser severity and shorter duration of acute symptomatology.

Aged↗
PubMed1991

Downregulation of muscarinic receptors in the rat caudate-putamen after lesioning of the ipsilateral nigrostriatal dopamine pathway with 6-hydroxydopamine (6-OHDA): normalization by fetal mesencephalic transplants.

The autoradiographic distribution and density of muscarinic receptors was studied in the neostriatum of rats with long-term unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopaminergic pathway and in lesioned rats who had additionally received embryonic substantia nigra grafts in the dopamine denervated striatum. Muscarinic receptors were labeled with [3H]quinuclidinyl benzilate (QNB), M1 receptors were directly labeled with [3H]pirenzepine (PZ) and non-M1 receptors were labeled by the competition of 100 nM PZ with [3H]QNB. The density and distribution of muscarinic receptors were directly compared to the sodium-dependent, high-affinity, choline uptake sites as labeled with [3H]hemicholinium-3 (HC-3). In the 6-OHDA-lesioned animals, there was a 25% reduction in muscarinic receptors labeled with [3H]QNB. Subtype analysis showed that there was a reduction of both M1 (-26%) and non-M1 (-33%) receptors. A normal density of both muscarinic receptor populations was found in animals with successful transplants. Saturation analysis demonstrated that the changes, in muscarinic receptor density, were due to a change in receptor number (Bmax) and not affinity (Kd). There was no significant change in [3H]HC-3 binding in the 6-OHDA-lesioned or transplanted animals, indicating that alterations in muscarinic receptors were not due to transynaptic degeneration of striatal cholinergic interneurons. The findings of downregulation of muscarinic receptors following long-term dopamine denervation and the subsequent normalization of muscarinic receptor density after fetal mesencephalic transplantation suggests that transplanted substantia nigra cells are able to restore inhibitory control on striatal cholinergic interneurons.

Acetylcholinesterase↗
PubMed1991

Functional recovery of supersensitive dopamine receptors after intrastriatal grafts of fetal substantia nigra.

Interruption of the ascending dopamine neurons of the nigrostriatal pathway, by 6-hydroxydopamine (6-OHDA) lesion in rats, produced a significant loss of the dopamine transport complexes labeled with the phencyclidine derivative [3H]BTCP. This loss of dopamine innervation in the striatum was present at least 12 to 14 months after lesioning and was functionally manifested by ipsilateral rotation of the animals in response to amphetamine. In these same animals, in comparison to controls, there was a significant increase in the number (Bmax) of [3H]SCH 23390-labeled D-1 receptors in the striatum (36.7%) and the substantia nigra (35.1%) and a 54.4% increase in the number (Bmax) of [3H]sulpiride-labeled striatal D-2 receptors without an apparent change in affinity (Kd). Ten to twelve months after the transplantation of homologous fetal substantia nigra into the denervated striatum, there was a significant decrease in amphetamine-induced turning behavior. In these animals, there was an ingrowth of dopamine nerve terminals in the striatum as demonstrated by a return of [3H]BTCP binding. Accompanying this reinnervation was the normalization of D-1 and D-2 receptors to control values in the striatum as well as the return of D-1 receptors to prelesion densities in the substantia nigra. In a subgroup of transplanted rats, amphetamine continued to induce ipsilateral turning. In these animals both D-1 and D-2 receptors remained supersensitive. These results support the hypothesis that the functional recovery of transplanted animals is due, in part, to reinnervation of the striatum. In addition, long-term alterations in receptor density may be related to the behavioral deficits that are associated with the 6-OHDA-lesioned rat. Furthermore, dopamine receptor plasticity may play a role in the functional recovery of substantia nigra transplanted animals and graft viability seems to be a prerequisite for behavioral recovery as well as receptor normalization.

Acetylcholinesterase↗
PubMed1991

Improved dose distributions for 3D conformal boost treatments in carcinoma of the nasopharynx.

This study was designed to demonstrate the feasibility of 3-dimensional (3D) treatment planning in patients with carcinoma of the nasopharynx, and to explore its potential therapeutic advantage over the traditional 2-dimensional (2D) approach in this disease. Qualitative and quantitative comparisons between the two techniques were made for the boost portion of the treatment (19.8 Gy of a total 70.2 Gy treatment schedule) in 10 previously untreated patients and for the entire treatment in 5 patients with locally recurrent disease. The 2D and 3D plans were compared in each patient using dose-volume histograms (DVH's), tumor control probabilities (TCP's), normal tissue complication probabilities (NTCP's), and a new biologic figure of merit that describes the probability of uncomplicated control. Although there was no attempt to optimize the 3D treatment approach by using this method throughout the total treatment course (rather than for the boost only), it was still found that for each of the endpoints examined the 3D approach resulted in improved plans. An average of 22% of the target volume was underdosed at the 95% isodose level with the 2D plans compared to 7% with the 3D plans. The improved treatment planning by 3D increased the mean dose to the tumor volume by an average of 13% over 2D planning. The dose to normal structures such as the mandible and parotid glands was reduced with the 3D plans while the brain stem and spinal cord remained within tolerance limits. The probability of uncomplicated tumor control was increased by an average of 15% with 3D treatment planning compared to the 2D approach. Our findings demonstrate the potential of 3D planning for improving the treatment of carcinoma of the nasopharynx, but prospective studies are required to define the true clinical advantages of this methodology.

Humans↗
PubMed1991

Clustering analysis and pattern discrimination of EMG linear envelopes.

A technique has been developed for performing pattern analysis of EMG activities generated during locomotion. In this development it was found that the shapes of the EMG linear envelopes (LE) are mainly determined by their phase spectra; their magnitude spectra are much less important. Autoregressive (AR) parametric models and discrete Fourier transform (DFT) approaches were tested and compared. The latter was proved to be a better way to describe the EMG LE's. Feature extraction and clustering were performed by doing DFT of EMG LE's, extracting part of the phase and magnitude spectra (in less important degree) as features, and using the percent powers to weigh the corresponding harmonics. The approach was applied to the clustering analysis of EMG LE's of normal and anterior cruciate ligament (ACL) injured subjects during walking.

Anterior Cruciate Ligament Injuries↗
PubMed1991

Relative affinity of quazepam for type-1 benzodiazepine receptors in brain.

Quazepam and its major metabolite, 2-oxoquazepam, were the first benzodiazepine (BZ) compounds shown to be capable of differentiating between central nervous system (CNS) subtypes of BZ receptors. Initial studies suggested that quazepam preferentially binds to the BZ1-receptor population with high affinity at relatively low doses. Subsequent binding experiments, performed in both human and rodent brain, confirmed this hypothesis for both the parent compound and its principal metabolite. Autoradiographic studies revealed a differential distribution of BZ1 and BZ2 receptors within regions of the brain associated with behavior, sensory input, control of movement, and coordination. BZ1 receptors are concentrated in specific, well-localized regions of the brain. BZ2 receptors are more widespread and diffusely localized throughout most brain regions. These observations suggest that a selective BZ1 agent such as quazepam might have a different pharmacologic profile than other nonselective benzodiazepines. Restricting the number of sites where BZ drugs act has been proposed as a strategy for producing a more circumscribed therapeutic effect; the BZ1 selectivity of quazepam embodies this concept.

Animals↗
PubMed1989

Localization of the dopamine uptake complex using [3H]N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine ([3H]BTCP) in rat brain.

[3H]N-[1-(2-Benzo(b)thiophenyl)cyclohexyl]piperidine ([3H]BTCP) is a novel phencyclidine derivative with considerable selectivity for dopamine uptake sites. [3H]BTCP was used to label dopamine uptake sites in vitro, in rat brain, and the regions containing these sites were visualized with an autoradiographic technique. The binding was found to be highest in the striatum, where greater than 90% of binding was specific. Furthermore, 6-hydroxydopamine lesions of the nigrostriatal pathway obliterated striatal [3H]BTCP binding ipsilaterally, whereas ibotenic acid injection into the caudate-putamen failed to significantly reduce [3H]BTCP binding in that structure. These results indicate that [3H]BTCP labels dopamine uptake sites in mammalian brain and that it can be employed for autoradiographic studies of this transport complex.

Animals↗
PubMed1989

Normalization of subtype-specific muscarinic receptor binding in the denervated hippocampus by septodiagonal band grafts.

Unilateral fimbria-fornix lesions were made by aspiration in female Sprague-Dawley rats. In a group of these rats, fetal septal tissue was transplanted into the lesion cavity. Lesion of the fimbria-fornix resulted in a reduction of cholinergic input to the hippocampal formation as indicated by the loss of acetylcholinesterase (AChE)-positive staining in all ipsilateral hippocampal laminae and a loss of [3H]hemicholinium-3 binding to cholinergic terminals in the strata oriens (82% reduction) and radiatum (77% reduction) of areas CA2 and CA3 and in the molecular layer of the dentate gyrus (83% reduction). In contrast, the density of muscarinic receptor binding ([3H]QNB) increased in the strata oriens (80% increase) and radiatum (70% increase) in areas CA2-CA4. This was shown to be due to an actual increase in receptor number (Bmax) and not to a change in affinity (KD). Analysis of muscarinic receptor subtypes indicated that the increase in receptor binding in the stratum radiatum was of the M-1 subtype ([3H]-pirenzepine) and in the stratum oriens was of the M-2 subtype ([3H]QNB + 100 nM pirenzepine). In the host hippocampus after fetal septal graft, the staining for AChE, the binding of [3H]hemicholinium-3, and the binding of muscarinic receptors (both the M-1 and M-2 receptor subtypes) were all comparable to nonlesioned control values. These data indicate that the fetal septal grafts have reinnervated the host hippocampus and have made synaptic contact with host cells in a manner capable of regulating postsynaptic muscarinic receptors.

Acetylcholinesterase↗
PubMed1989

The use of lymphoscintigraphy in treatment planning of primary breast cancer.

A technique is described for the use of lymphoscintigraphy in treatment planning of primary breast patients. During simulation of the treatment fields, the positions of the internal mammary nodes are projected back toward the source onto the patient skin surface and are marked by radio-opaque markers for visualization on films. Exact solutions for the coordinates of these surface projection points are derived. Approximate solutions are also given which are independent of the isocenter location and primarily dependent on the treatment field gantry angle. If a typical couch angle and field size are assumed, the projection points can be calculated for various gantry angles prior to simulation. Generally, a decision can then be made beforehand whether it would be better to use deep tangents or a separate field to treat the internal mammary nodes. During simulation, the surface projection points serve as visual and fluoroscopic guides to field design and optimization. A method is also presented for projecting the internal mammary node positions onto a single transverse patient contour for conventional 2-dimensional treatment planning. By accurately showing the projected location of the node with respect to the field edge, adequate treatment margin can be assured.

Breast Neoplasms↗
PubMed1988

Selective cortical infarction reduces [3H]sulpiride binding in rat caudate-putamen: autoradiographic evidence for presynaptic D2 receptors on corticostriate terminals.

Although the existence of presynaptic D2 dopamine receptors on corticostriate terminals has been supported by numerous receptor-binding studies, recent autoradiographic data has failed to demonstrate loss of striatal D2 receptors following cortical lesions. In the present study, Long-Evans rats were subjected to unilateral middle cerebral artery (MCA) infarction in order to produce reproducible lesions of the neocortex without damaging subcortical structures. Animals were sacrificed 2 and 4 wk following lesion and brains were prepared for receptor autoradiography. D2 receptors were studied using the selective ligand [3H]sulpiride, while D1 dopamine receptors were examined using [3H]SCH 23390. Sodium-dependent, high-affinity choline uptake sites were labeled with [3H]hemicholinium-3, thereby providing a quantitative measure of cholinergic neuronal integrity. Unilateral cortical infarction resulted in approximately a 20% reduction in [3H]sulpiride binding in several discrete regions of the ipsilateral caudate-putamen (CPu), but not in the nucleus accumbens. D2 receptor binding was also reduced significantly in some areas of the contralateral CPu when compared with [3H]sulpiride binding in sham-operated, control animals. In contrast, D1 receptors (as identified by [3H]SCH 23390 and high-affinity choline uptake sites (labeled with [3H]-HC-3) were not affected by the cortical lesion. The results provide autoradiographic confirmation of the existence of presynaptic D2 receptors on corticostriate terminals.

Animals↗
PubMed1987

Matchline dosimetry of a three field technique for breast treatment using cobalt or 6 MV X rays.

The matchline dose distribution between the tangential and supraclavicular fields used for treatment of breast cancer was investigated using 60Co and 6 MV X rays. Techniques which allow minimum, moderate, and maximum overlap between the fields as well as a geometric alignment technique were studied. For a given technique, comparable matchline widths and doses were obtained with either machine. Average matchline doses were slightly greater with 6 MV X rays, however, more tissue was irradiated to higher dose levels with 60Co. Among the techniques which do not geometrically align the three fields, doses as high as 150% or as low as 70% were observed depending on the amount of overlap between the fields. Matching the tangents 3.5 cm medial and lateral to the supraclavicular field center yielded average maximum and minimum matchline doses within ten percent of those with geometric alignment techniques. However, these distributions will vary with patient size and matchline length. Geometric alignment techniques offer the advantages of matchline dose uniformity and reproducibility over the patient population with maximum matchline doses of only 110-115%.

Breast Neoplasms↗
PubMed1987

Intratympanic injection of sodium arsanilate (atoxyl) solution results in postural changes consistent with changes described for labyrinthectomized rats.

Intratympanic injections of sodium arsanilate (atoxyl) have been shown to produce vestibular dysfunction in the rat. Unilateral and bilateral dysfunction can be distinguished by changes in the animals' postures. These changes are consistent with changes described for unilateral or bilateral labyrinthectomized rats. The intratympanic injection technique offers a simple yet effective alternative to labyrinthectomy.

Animals↗
PubMedDate not supplied

Electron backscatter corrections for parallel-plate chambers.

The wall of an ionization chamber is commonly assumed to have a negligible effect on chamber response in electron beams. For cylindrical chambers with thin walls this assumption is valid. However, parallel-plate chambers commonly possess large mechanical supports which may affect chamber response in a manner not accounted for in current dosimetry protocols. This is due to changes with energy in the relative backscattered electron fluence between chamber support and phantom materials. To investigate this effect, electron backscatter from low atomic number materials has been measured with electrons from 6 to 20 MeV. The effect of the diameter and thickness of the backscattering material has also been studied. Based on these data, Lucite and polystyrene chambers in water phantoms are expected to underrespond by 1% and 2% at 6 MeV. The expected underresponse decreases to 0.8% and 0.4% for polystyrene and Lucite at 12 MeV and is insignificant above 16 MeV. Two commercially available parallel-plate chambers were compared with a cylindrical chamber in electron beams from 6 to 20 MeV. Using the 20-MeV intercomparison, the expected chamber responses at the lower energies were calculated and compared with measurements. Both parallel-plate chambers underresponded by approximately 1% at 6 MeV and 0.5% at 9 MeV which is qualitatively consistent with the electron backscatter data. Recommendations for minimizing electron backscatter effects through chamber design are discussed.

Electrons↗