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Biomedical subjects

T J Lee

Publications and source records attributed to T J Lee.

At least 19 recordsLinked to original sources

Alpha 2-adrenoceptors mediate norepinephrine constriction of porcine pial veins.

The adrenergic innervation and alpha-adrenoceptor agonist-induced constrictions in isolated medium-size pial veins (OD 734 +/- 18 microns) of the pig were investigated. Using in vitro tissue bath techniques, we noted exogenously applied norepinephrine (10(-9) to 10(-5) M) induced venoconstriction with EC50 values of 1.71 x 10(-7) M, where EC50 is the concentration that produced 50% of (non-KCl) agonist-induced maximum constriction. The constriction was mimicked by clonidine but not by phenylephrine and was more effectively blocked by yohimbine than by prazosin. Results from histochemical studies demonstrated that porcine pial veins received a denser plexus of catecholamine fluorescence fibers than do pial arteries with similar outer diameter. These results suggest that norepinephrine-induced pial venoconstriction is mediated predominantly by alpha 2-adrenoceptors and that porcine pial veins have significantly greater sensitivity to the alpha-action of norepinephrine than that reported in pial arteries. These results add further support for adrenergic innervation in pial veins being of importance in regulating cerebral blood volume and intracranial pressure.

Adrenergic alpha-Agonists

Regional variation in acute vascular homologous tachyphylaxis.

The development of tachyphylaxis or desensitization in a tissue upon repeated application of an agonist is a well-established phenomenon. To investigate the possible basis of vascular homologous tachyphylaxis, vasomotor responses in isolated cerebral and peripheral blood vessels from the cat, dog and rabbit upon repeated application of several agonists were examined using in vitro tissue bath techniques. Tachyphylaxis to vasodilator responses developed to repeated application of vasoactive intestinal polypeptide (VIP) but not to beta adrenergic agonist, forskolin, 8-bromo-cyclic AMP, sodium nitroprusside or 8-bromo-cyclic GMP in feline cerebral arteries. The tachyphylaxis to VIP-induced responses varied among regions and was greatest in the internal carotid artery (ICA), followed by the middle cerebral artery and least in the basilar artery (BA). Cerebral arteries also developed significant tachyphylaxis to constriction induced by repeated applications of neuropeptide Y (NPY), alpha-1 adrenergic agonist, but not to alpha-2 adrenergic agonist, acetylcholine (ACh) or KCl. The tachyphylaxis to constrictions induced by repeated application of neuropeptide Y (NPY) also varied among regions, but was different from that induced by VIP; it was greatest in the BA, followed by the middle cerebral artery and least in the ICA. Similar results were obtained in arteries without endothelial cells. The density of regional innervation of NPY-immunoreactive fibers, which is densest in ICA and sparsest in BA, parallels that of VIP-immunoreactive fibers in these three regions. There is no positive correlation between density of catecholamine fluorescence fibers and degree of tachyphylaxis to noradrenaline-induced constriction in cat ICA, dog saphenous arteries and rabbit ear arteries either.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Bone modulation in sustained hematopoietic stimulation in mice.

To understand the etiology of bone modulation and hypercalcemia observed in granulocytosis of a tumor-bearing animal model and to gain insight into the implication of sustained hematopoietic stimulation on the bone tissue, in vivo responses of normal mouse hematopoietic and bone tissues to long-term injections of recombinant human and murine granulocyte colony-stimulating factor (G-CSF), murine granulocyte-macrophage CSF (GM-CSF), and human erythropoietin were quantitatively analyzed. Osteoclast activation was estimated by the osteoclast-endosteal ratio, determined by morphometric analyses of femoral sections. Medullary and bone areas were measured on transverse ground bone sections of the tibia. Recombinant murine G-CSF provoked marked granulocytosis associated with significant increases in the number of marrow granulocytes and their progenitors, and caused expansion of granulopoietic marrow into fatty marrow. The bone of G-CSF-treated mice showed a significant increase in endosteal osteoclast numbers with medullary area enlargement and a reduction in the bone thickness; indicative of endosteal bone resorption. Although GM-CSF had little effect on granulopoiesis, it caused peritoneal macrophages to increase and induced similar bone changes as those observed in G-CSF treatment. Enhanced erythropoiesis stimulated by erythropoietin was also associated with evidence of endosteal bone resorption. Bone changes induced by these growth factors were not associated with hypercalcemia. These animal studies document association of bone modulation in sustained stimulation of hematopoiesis, and implicate important physiologic effects of hematopoietic growth factors on skeletal tissue in vivo.

Animals

GABAergic innervation in cerebral blood vessels: an immunohistochemical demonstration of L-glutamic acid decarboxylase and GABA transaminase.

The presence of GABAergic innervation in cerebral arteries of several species was investigated by an immunohistochemical method using antibodies against glutamic acid decarboxylase (GAD) and GABA transaminase (GABA-T). Both GAD and GABA-T immunoreactivities were found to be associated with large bundles and single fibers in the adventitial layer of arteries examined. The density and distribution pattern of both GAD- and GABA-T-immunoreactive fibers were found to be comparable at most regions examined. Both fibers were found to be most dense in the anterior cerebral artery and its adjacent part of the circle of Willis. Several peripheral arteries were found to receive very sparse or no GAD- and GABA-T-immunoreactive fibers. Superior cervical ganglionectomy did not appreciably affect the distribution of both fibers. Cold-storage denervation, however, resulted in a drastic decrease in both fibers. At ultrastructural levels, both GAD- and GABA-T-immunoreactive nerve profiles were found to be very close to the smooth muscle cells. These results demonstrate the presence of a potentially functional GABAergic innervation in cerebral circulation. On few occasions, GAD immunoreactivities were also found in some endothelial cells, suggesting that a nonneuronal GABA system may also be present in cerebral arteries.

4-Aminobutyrate Transaminase

VIP-ergic and cholinergic innervations in internal carotid arteries of the cat and rat.

Using immunohistochemical methods, choline acetyltransferase and vasoactive intestinal polypeptide immunoreactive (ChAT-I and VIP-I) fine fibers with varicosity-like structures were observed in the rat and cat cerebral arteries. Acetylcholine (ACh) induced dual responses in endothelium-intact internal carotid arteries of the cat; it induced vasodilation at low concentrations and constrictions at high concentrations (greater than 10(-6) M). ACh induced contraction exclusively in endothelium-rubbed preparations. Atropine (10(-7) M) blocked ACh-induced constriction and dilatation. ACh-induced vasodilation was potentiated by M & B 22,948 (2 x 10(-5) M), a selective cyclic GMP phosphodiesterase inhibitor. Vasoconstriction induced by ACh was inhibited by neomycin (3 x 10(-3) M), an inositol phosphate synthesis inhibitor, which did not affect the neuropeptide Y-induced contraction. VIP-induced dilation of the cat internal carotid arteries was not affected by removing the endothelial layer, but was blocked by VIP receptor antagonist ([Ac-Tyr1, D-Phe2]-GRF 1-29 amide) and potentiated by cilostazol (2 x 10(-5) M), a selective cyclic AMP phosphodiesterase inhibitor. These results are consistent with previous findings that cerebral blood vessels receive cholinergic and VIP-ergic innervations, and that ACh-induced endothelium-dependent vasodilation is mediated by cyclic GMP synthesis, and that VIP-induced endothelium-independent vasodilation is mediated by cyclic AMP synthesis. The present study, however, demonstrates for the first time the presence of varicosity-like structure associated with ChAT-I fibers, suggesting the presence of cholinergic nerve terminals and that ACh-induced cerebral vasoconstriction is mediated by phosphatidyl-inositide turnover.

Acetylcholine

A single-stage two-flap method of total ear reconstruction.

A single-stage two-flap method of total ear reconstruction in congenital microtia is reported. This method was derived from the one-stage reconstruction described by Song and Song. Two flaps defined by vascular basis were elevated on the mastoid area: the superficial skin flap supplied mainly by subcutaneous pedicled arteriole perforators from the posterior auricular artery and the deeper axial-pattern fascial flap including the posterior auricular artery itself. The ear framework, exaggeratedly carved using autologous rib cartilage, could be inserted easily between the two flaps, simultaneously producing the auriculocephalic angle and the conchal wall. Intraoperative expansion of the skin flap and postoperative external ear molding also were performed to create aesthetically pleasing ears.

Adolescent

Zinc status in human immunodeficiency virus infection.

Plasma zinc and copper concentrations, erythrocyte zinc concentration, copper-zinc superoxide dismutase activity and urinary zinc concentrations were determined for control subjects and individuals with AIDS, ARC, or asymptomatic HIV infection. Significant differences among the population groups were not noted for the above parameters with the exception of plasma copper which was higher in the AIDS group than in other patient groups. These results do not support the idea that zinc deficiency is a common contributory factor of HIV infectivity or clinical expression, nor that HIV infection induces a zinc deficiency.

AIDS-Related Complex

Structure of acid protease from Endothia parasitica in cross-linked form at 2.45-A resolution.

The structure of acid protease from Endothia parasitica in strongly cross-linked form is compared with that of the untreated protein at 2.45-a resolution. The only observed conformation change introduced by the cross-linking reaction is at the N terminal. Otherwise the two main chain structures are essentially identical. Approximately 2 molecules of the inhibitor, 1,2-epoxy-3-(p-nitrophenoxy)propane, are found to be incorporated into each protein molecule. They are covalently bound to the two aspartic residues at the active center.

Ascomycota

Neisseria meningitidis bacteremia in association with deficiency of the sixth component of complement.

The serum of a 26-year-old black man with a recent episode of meningococcemia complicated by meningitis and arthritis was found to lack hemolytic complement activity. The sixth component of complement was not detected by functional or immunochemical assays whereas other components were normal by hemolytic assay. His fresh acute-phase serum lacked complement-mediated bactericidal activity against the homologous strain of Neisseria meningitidis, but the addition of fresh normal serum or purified C6 restored bactericidal activity as well as hemolytic activity. The absence of C6 activity could not be accounted for on the basis of an inhibitor. Opsonization and chemotaxis functioned normally. Histocompatibility typing of family members did not demonstrate evidence for genetic linkage of C6 deficiency with the major histocompatibility loci. This report represents the first published case of C6 deficiency associated with bacteremic Neisseria infections in which antimeningococcal bactericidal antibodies have been definitively demonstrated against the homologous strain in the acute phase of the illness.

Adult

Neisseria meningitidis and Neisseria gonorrhoeae bacteremia associated with C6, C7, or C8 deficiency.

We summarize data from 24 previously described or newly diagnosed cases of homozygous deficiency of the sixth, seventh, or eighth components of complement. Thirteen of 24 patients had at least one episode, and usually two or more episodes of Neisseria meningitidis or Neisseria gonorrhoeae bacteremia, or both. Deficiency of C6, C7, or C8 is a meaningful risk factor for repeated neisserial bacteremia; conversely, hemolytic complement studies are indicated in patients who develop recurrent neisserial infections. When a person with C6, C7, or C8 deficiency is identified, family members should also be studied.

Adolescent

Mucocutaneous lymph node syndrome in a young adult.

Mucocutaneous lymph node syndrome (MLNS) is an acute febrile illness of unknown cause first described in Japan but more recently reported in the United States. The mean age in confirmed cases was 3.8 years (range, 3 months to 13 years), and the mortality is 1% to 2% when associated with coronary artery thrombosis and aneurysm. We describe the first case of MLNS in a young adult, with the additional clinical finding of associated arthritis.

Adolescent

Familial deficiency of the seventh component of complement associated with recurrent bacteremic infections due to Neisseria.

The serum of a 29-year old woman with a recent episode of disseminated gonococcal infection and a history of meningococcal meningitis and arthritis as a child was found to lack serum hemolytic complement activity. The seventh component of complement (C7) was not detected by functional or immunochemical assays, whereas other components were normal by hemolytic and immunochemical assessment. Her fresh serum lacked complement-mediated bactericidal activity against Neisseria gonorrhoeae, but the addition of fresh normal serum or purified C7 restored bactericidal activity as well as hemolytic activity. The absence of functional C7 activity could not be accounted for on the basis of an inhibitor. Opsonization and generation of chemotactic activity functioned normally. Complete absence of C7 was also found in one sibling who had the clinical syndrome of meningococcal meningitis and arthritis as a child and in this sibling's clinically well eight-year-old son. HLA histocompatibility typing of the family members did not demonstrate evidence for genetic linkage of C7 deficiency with the major histocompatibility loci. This report represents the first cases of C7 deficiency associated with infectious complications and suggests that bactericidal activity may be important in host defense against bacteremic neisseria infections.

Adult