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Biomedical subjects

A Zweig

Publications and source records attributed to A Zweig.

At least 19 recordsLinked to original sources
PubMed1992

Characterization of a digitonin-solubilized bovine brain H3 histamine receptor coupled to a guanine nucleotide-binding protein.

The H3 receptor is a high-affinity histamine receptor that inhibits release of several neurotransmitters, including histamine. We have characterized H3 receptor binding in bovine brain and developed conditions for its solubilization. Particulate [3H]histamine binding showed an apparently single class of sites (KD = 4.6 nM; Bmax = 78 fmol/mg of protein). Of the detergents tested, digitonin at a detergent/protein ratio of 1:1 (wt/wt) yielded the greatest amount of solubilized receptors, typically 15-30% of particulate binding. Neither equilibrium binding of [3H]histamine to receptors (KD = 6.1 nM; Bmax = 92 fmol/mg of protein) nor the inhibitor profile was substantially altered by digitonin solubilization. However, solubilization did increase the rate of [3H]histamine association with and dissociation from the receptor. Size-exclusion chromatography indicated an apparent molecular weight of 220,000 for the solubilized receptor, and peak binding from this column retained its guanine nucleotide sensitivity. These last two observations are consistent with the solubilized receptor occurring in complex with a guanine nucleotide-binding protein.

Animals↗
PubMed1990

Biexponential kinetics of (R)-alpha-[3H]methylhistamine binding to the rat brain H3 histamine receptor.

The H3 histamine receptor is a high-affinity receptor reported to mediate inhibition of CNS histidine decarboxylase activity and depolarization-induced histamine release. We have used (R)-alpha-[3H]methylhistamine, a specific, high-affinity agonist, to characterize ligand binding to this receptor. Saturation binding studies with rat brain membranes disclosed a single class of sites (KD = 0.68 nM; Bmax = 78 fmol/mg of protein). Competition binding assays also yielded an apparently single class of sites with a rank order of potency for ligands characteristic of an H3 histamine receptor: N alpha-methylhistamine, (R)-alpha-methylhistamine greater than histamine, thioperamide greater than impromidine greater than burimamide greater than dimaprit. In contrast, kinetic studies disclosed two classes of sites, one with fast, the other with slow on-and-off rates. Density of (R)-alpha-[3H]methylhistamine binding followed the order: caudate, midbrain (thalamus and hippocampus), cortex greater than hypothalamus greater than brainstem greater than cerebellum. These data are consistent with an H3 histamine receptor, distinct from H1 and H2 receptors, that occurs in two conformations with respect to agonist association and dissociation or with multiple H3 receptor subtypes that are at present pharmacologically undifferentiated.

Animals↗
PubMed1990

Identification of two H3-histamine receptor subtypes.

The H3-histamine receptor provides feedback inhibition of histamine synthesis and release as well as inhibition of other neurotransmitter release. We have characterized this receptor by radioligand binding studies with the H3 agonist N alpha-[3H]methylhistamine ([3H]NAMHA). The results of [3H]NAMHA saturation binding and NAMHA inhibition of [3H]NAMHA binding were consistent with an apparently single class of receptors (KD = 0.37 nM, Bmax = 73 fmol/mg of protein) and competition assays with other agonists and the antagonists impromidine and dimaprit disclosed only a single class of sites. In contrast, inhibition of [3H]NAMHA binding by the specific high affinity H3 antagonist thioperamide revealed two classes of sites (KiA = 5 nM, BmaxA = 30 fmol/mg of protein; KiB = 68 nM, BmaxB = 48 fmol/mg of protein). Burimamide, another antagonist that, like thioperamide, contains a thiourea group, likewise discriminated between two classes of sites. In addition to differences between some antagonist potencies for the two receptors, there is a differential guanine nucleotide sensitivity of the two. The affinity of the H3A receptor for [3H] NAMHA was reduced less than 2-fold, whereas [3H]NAMHA binding to the H3B receptor was undetectable in the presence of guanosine 5'-O-(3-thiotriphosphate). The distinction between H3A and H3B receptor subtypes, the former a high affinity and the latter a low affinity thioperamide site, draws support from published in vitro data.

Animals↗
PubMed1988

Examination of mouse and rat tissues for evidence of dual forms of the fatty acid cyclooxygenase.

The possibility that the enzymatic generation of prostaglandin E2 (PGE2) and PGF2 alpha results from the catalytic activity of two distinct forms of the fatty acid cyclooxygenase was studied in microsomes prepared from kidney, lung, and brain of the mouse and rat. Three criteria established previously to detect the dual cyclooxygenase forms in the rabbit brain were used in the present study: (1) different time course profiles of microsomal PGE2 and PGF2 alpha biosynthesis from exogenous arachidonic acid; (2) elimination of the synthesis of one PG in vitro by non-steroidal anti-inflammatory drug concentrations that did not affect the synthesis of the other PG and; (3) selective autocatalytic inactivation of one cyclooxygenase by preincubation with arachidonic acid. Incubations with PGH2 endoperoxide as substrate tested whether the altered PG biosynthesis resulted from an effect on the endoperoxide utilizing enzymes and not on the cyclooxygenase. Of the six tissues examined, only the mouse brain microsomes satisfied all the criteria. The microsomes prepared from the mouse kidney produced mixed results. We conclude that the mouse brain but not the rat brain gives evidence for two distinct forms of the fatty acid cyclooxygenase. Additional distinguishing features of the different cyclooxygenases are required to determine if the cyclooxygenase forms are found in mouse kidney.

Animals↗
PubMed1985

The early lethality of autosomal monosomy in the mouse.

Using male mice doubly heterozygous for pairs of Robertsonian translocation chromosomes that have one arm in common, mouse embryos monosomic for 11 of the 19 autosomes have been generated. All of these monosomies result in death prior to or during the implantation period, with only rare survivors being detected 6 days after fertilization. For some of the monosomies the onset of lethality can be detected during the third or fourth day of development, but others do not begin to die until sometime after the late blastocyst stage on day 4. Retardation of development, as revealed by decreased cell numbers, is often detectable prior to or after the onset of the lethal period. The period during which death occurs may spread over several days and does not coincide with any of the developmental landmarks of the pre- or peri-implantation period. Genetic factors that may affect the rate of cellular proliferation or other aspects of embryonic development appear to play an important role in determining exactly when individual monosomies result in death. The universal early lethality of the autosomal monosomies leads to the conclusion that a large number of loci scattered over all of the autosomes are involved in processes that are so concentration dependent that a 50% reduction is sufficient to produce very serious consequences.

Aneuploidy↗
PubMed1985

Iliopsoas injury in soccer players.

Injuries to the iliopsoas muscle are rarely mentioned in the literature dealing with soccer-related trauma. This report describes our experience in the successful diagnosis and treatment of iliopsoas injury in 40 professional soccer players. These injuries were not associated with direct external trauma to the muscle. Anatomical and functional characteristics of the iliopsoas are reviewed as they relate to the diagnosis and to the treatment by direct local injection with corticosteroids. A safe anatomical approach to the iliopsoas below the inguinal ligament is described.

Adrenal Cortex Hormones↗
PubMed1980

Arterial combat injuries of the upper extremity.

The results of treatment of 101 combat injuries of the upper extremities are reported. There were 84 acute injuries and 17 late complications. There was a high incidence of associated fractures (35%) and nerve lesions (51%). Over half the injuries were repaired by saphenous vein graft replacement. There were seven early amputations related to a long delay before treatment, extensive tissue damage, and sepsis with delayed hemorrhage. There were no late amputations, but residual neurologic damage gave a less than perfect result in 32 extremities. Two injuries resulted in Volkmann's contracture. Fracture specific to the management of upper-extremity arterial injuries are outlined.

Amputation, Surgical↗
PubMed1979

Saphenous neuralgia: a complication of vascular reconstructions below the inguinal ligament.

Although relatively frequent in our experience saphenous neuralgia (SN) is not usually reported as a complication of vascular operations below the inguinal ligament. In 55 patients undergoing extended deep femoral angioplasty (EDFA, n = 28) and femoropopliteal bypass graft (FPBG, n = 27) special attention was paid to incidence and severity of postoperative SN. Severe early postoperative SN was seen in 8/28 patients with EDFA and in 6/27 with FPBG. Milder SN was seen in 10 more patients with EDFA, and 3 other developed SN many months after surgery. The milder forms of SN and late SN were not encountered after FPBG. SN usually improved with the passage of time, and at last follow-up averaging 18 months for EDFA and 33 months for FPBG there remained only 23 patients with mild SN (15 after EDFA and 8 after FPBG). The etiology of SN appears to be trauma to the nerve sustained during operation. Age, sex, diabetes, or the addition of lumbar sympathectomy to the vascular operation did not affect the risk of sustaining early postoperative SN. Increased awareness of this complication may help to understand its pathophysiology better, and possibly to decrease its incidence.

Adult↗