Pion absorption followed by multinucleon emission.
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Journal Article↗
Biomedical subjects
S Hyman
Publications and source records attributed to S Hyman.
Neutron and proton transition densities from 32,34S(p,p') at Ep=318 MeV. I. Isoscalar densities for 32S.
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Journal Article↗
Neutron and proton transition densities from 32,34S(p,p') at Ep=318 MeV. II. Neutron densities for 34S.
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Journal Article↗
Vasopressin uptake by hypothalamopituitary axis and pineal gland in guinea pigs.
The uptake of circulating arginine vasopressin (AVP) by the pituitary gland (anterior lobe), pineal gland, and hypothalamus (ventromedial part) was investigated in an isolated in situ perused brain of anesthetized guinea pig. Kinetic experiments revealed saturable AVP uptake in all studied regions with Km values of 0.79, 0.19, and 0.76 microM and maximum velocity values of 22, 2.1, and 1.6 pmol.min-1.g-1 for the pituitary gland, pineal gland, and hypothalamus, respectively. The nonsaturable components (diffusion constants) were not significantly different from zero. Peptide fragments, L-phenylalanine, and Bestatin (an aminopeptidase inhibitor) did not interfere with AVP uptake. However, uptake of AVP was strongly inhibited in the presence of the V1 antagonist [1-(beta-mercapto-beta-beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine]AVP at 2.7 microM, and regional Ki values, assuming that the observed inhibitions were purely competitive, ranged between 0.32 and 2.23 microM. The V2 agonist 1-desamino-8-D-AVP at 2.7 microM produced only a weak inhibition of AVP uptake, and regional Ki values ranged between 9.56 and 21.3 microM. It is concluded that specific uptake mechanisms in the hypothalamopituitary axis and pineal gland are sensitive enough to detect blood-borne AVP under the physiological hormonal state. It is suggested that AVP binding in situ is primarily related to V1 receptors, which may be involved in mediating the central effects of this circulating peptide.
Animals↗
Kinetics of circulating vasopressin uptake by choroid plexus.
Uptake of circulating arginine vasopressin (AVP) by choroid plexus was studied by means of the in situ brain perfusion technique in anesthetized guinea pig and by means of single-circulation paired-tracer dilution technique in isolated perfused sheep choroid plexus. Kinetic analysis revealed saturable AVP uptake with Michaelis constant (Km) values of 32 +/- 4 and 31 +/- 5 nM and maximal saturable influx rate (Vmax) of 0.45 +/- 0.06 and 12.1 +/- 0.67 pmol.min-1.g-1 in guinea pig and sheep choroid plexus, respectively. The peptide fragments AVP-(1-8) and [pGlu4,Cyt6]AVP-(4-9), the amino acids L-phenylalanine, L-tyrosine, and 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid, and the aminopeptidase inhibitors Bestatin and bacitracin did not influence hormone kinetics. However, the V1 antagonist [(1-beta-mercapto-beta,beta-cyclo-pentamethylenepropionic acid)-O-methyl-Tyr2]AVP significantly inhibited AVP uptake with inhibitor constant (Ki) values of 0.19 +/- 0.03 (guinea pig) and 0.07 +/- 0.01 microM (sheep). The V2 agonist 1-desamino-8-D-AVP and pressinoic acid produced weak inhibitions only in guinea pig choroid plexus, and Ki/Km ratios indicated 220 and 310 times lower affinities than for AVP, respectively. It is suggested that the membrane mechanism responsible for AVP uptake in choroid plexus has a binding site with properties similar to those of V1 receptor.
Animals↗
Orthodromic vs. antidromic latencies.
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Adult↗
Kinetics of arginine-vasopressin uptake at the blood-brain barrier.
Uptake of arginine-vasopressin, VP, at the luminal side of the blood-brain barrier (BBB) was studied by means of an in situ brain perfusion technique in the guinea-pig. Kinetic experiments revealed a saturable peptide influx into the parietal cortex, caudate nucleus and hippocampus with Km between 2.1 and 2.7 microM, and Vmax ranging from 4.9 to 5.6 pmol.min-1.g-1. The non-saturable component, Kd, was not significantly different from zero. Influx of VP into the brain was not altered by the presence of the peptide fragments: VP-(1-8), pressinoic acid and [pGlu4,Cyt6]VP-(4-9) at 4.5 microM, nor yet by the aminopeptidase inhibitor, bestatin (0.5 mM) and the L-amino acid transport system substrates, L-tyrosine and L-phenylalanine at 5 mM. At a perfusate concentration of 4.5 microM, the V1-vasopressinergic receptor antagonist, d(CH2)5[Tyr(Me)2]VP, reduced VP influx; regional Ki values, assuming that the observed inhibitions were purely competitive, ranged between 4.7 and 8.5 microM. It is concluded that there is an apparent cerebrovascular permeability to circulating VP due to the presence of a carrier-mediated transport system for the peptide located at the luminal side. The mechanism for VP BBB uptake exhibits no affinity for peptide fragments and large neutral amino acids, but requires reception of the intact molecule, which may be the same initial step for both the BBB VP transporter and the V1-receptor.
Animals↗
The Rett syndrome: progress report on studies at the Kennedy Institute.
Clinical, biochemical and pathological studies in patients with the Rett syndrome (RS) are presented. The neuropathological changes and alterations in neurotransmitter markers are particularly interesting and provide valuable information that may be helpful in understanding the behavior and neurological phenotype of RS.
Adolescent↗
A controlled trial of fluvoxamine in obsessive-compulsive disorder: implications for a serotonergic theory.
Thirty-eight patients with primary obsessive-compulsive disorder participated in a 10-week, double-blind, placebo-controlled trial of the potent, selective serotonin reuptake inhibitor fluvoxamine. Fluvoxamine was significantly better than placebo on two of three measures of improvement in obsessive-compulsive symptoms. The authors also compared studies of the serotonergic agents fluvoxamine, sertraline, fluoxetine, and clomipramine and found that a greater effect size was associated with less serotonergic specificity and that some ability to affect other neurotransmitter systems may be a necessary but not sufficient requirement for antiobsessional activity. These data lend only partial support to a serotonin hypothesis of obsessive-compulsive disorder.
1-Naphthylamine↗
Circulating neuroactive peptides and the blood-brain and blood-cerebrospinal fluid barriers.
Interactions of radiolabelled circulating neuroactive peptides: enkephalin-leucine (Enk-Leu), delta sleep inducing peptide (DSIP), thyrotropin-releasing hormone (TRH) and vasopressin-arginine (VP-Arg) with the blood-brain and blood-cerebrospinal fluid barriers were studied by mean of: 1. a vascular perfusion technique in the guinea-pig using multiple-time brain uptake analysis, 2. a vascular perfusion technique of the in situ isolated choroid plexus from sheep using single-circulation paired-tracer dilution or steady-state analysis. It has been demonstrated that Enk-Leu, DSIP and VP-Arg were taken up intact at the luminal side of the blood-brain barrier and blood-tissue interface of the blood-cerebrospinal fluid barrier by a saturable mechanism. On the other hand, a non-saturable mechanism as well as possible enzymatic degradation were shown during TRH interactions with either the blood-brain or blood-cerebrospinal fluid barriers. It is concluded that both, facilitated and simple diffusion, govern circulating neuroactive peptide uptake into the central nervous system.
Animals↗
In vivo assessment of 111In-labeled hematoporphyrin derivative in breast tumor-bearing animals.
The biological behavior of 111In-labeled HPD has been investigated in tumor-bearing animals. Mice mammary adenocarcinomas and 7,12-dimethylbenz(a)anthracine induced breast tumors in Sprague-Dawley female rats were clearly visualized by 111In-HPD nuclear scintigraphy. Optimal scans were obtained after a 48 h delay. In normal and tumor-bearing animals, the highest uptake of 111In-HPD 72 h post-injection was found in the liver, the spleen and the kidneys. Depending on the size and the extent of necrosis, the uptake of 111In-HPD by malignant breast tumors varied from 2.5% injected dose (ID) (range 0.14-5.3% ID) in mice to 1% (range 0.22-8.1% ID) in rats. Benign breast tumor uptake of 111In-HPD was less than 1% ID. No significant amount of the radiopharmaceutical was found in pulmonary abscesses and abdominal cysts (less than 0.1% ID). Scintigrams of these infectious or inflammatory lesions were normal. Malignant tumor to blood, heart and lung ratios averaged 50:1, 10:1 and 3:1 respectively. Tumor to brain ratio ranged from 72 to 444:1.
9,10-Dimethyl-1,2-benzanthracene↗
Scintigraphic detection of atherosclerotic plaques in rabbits with 111In-labeled hematoporphyrin derivative.
The efficacy of 111In-labeled hematoporphyrin derivative (HPD) in localizing and detecting atheromas had been investigated with 10 atherogenic New Zealand white rabbits. Atherosclerotic plaques surgically induced in the abdominal aorta showed selective uptake of 111In-HPD over normal blood vessels averaging 0.01% ID/g tissue (range 0.003-0.023% ID/g). Normal aorta and thoracic artery concentrated an average of 0.0026% ID/g which is less than the mean blood activity of 0.0034% ID/mL. Statistical analysis demonstrated significant difference in the uptake of 111In-HPD by the atherosclerotic plaque segments as compared to normal abdominal aorta (P = 0.0023) and normal thoracic artery (P = 0.0012). In hypercholesteremic rabbits, the mean plaque segment to normal blood vessels ratio was 4:1 (range 2 to 9:1) sufficiently high to permit plaque delineation in the scintigram. Although 111In-HPD showed promise as a plaque imaging agent, further investigation with large animal models such as primates is needed to confirm current findings.
Animals↗
CSF production in acute ventriculitis.
Clinically, there appears to be a significant reduction in cerebrospinal fluid (CSF) formation during acute ventriculitis--an observation that has not been well documented by experimental studies. To examine this phenomenon, an inoculum of Escherichia coli was injected into the lateral ventricles of New Zealand White rabbits. Approximately 18 hours later, the survivors (64%) underwent a 3-hour ventriculocisternal perfusion of carbon-14-dextran (MW 7 X 10(4)) as a reference marker for CSF formation. On the average, CSF formation in this experimental group was reduced by one-half to two-thirds of normal, confirming the clinical observation. Histologically, the stroma of the choroid plexus was the site of an extensive inflammatory infiltrate. Meningitis, ependymitis, and focal encephalitis completed the picture. Vasculitis was not present in the choroid plexus. The epithelium of the choroid plexus underwent patchy cellular swelling or frank necrosis and destruction. It is postulated that the changes in the choroid plexus caused by the inflammatory process were responsible for the diminished CSF formation in this acute setting. Reduced choroidal blood flow and/or enterotoxin may play a role in these alterations.
Acute Disease↗
Ultrastructure of the orbital pathway for cerebrospinal fluid drainage in rabbits.
An increasing number of physiological and morphological studies indicate that cerebrospinal fluid (CSF) drains via nonarachnoidal pathways in several mammalian species. Ultrastructural tracer studies were undertaken to examine the orbital route for CSF absorption in the rabbit. At the termination of the optic nerve subarachnoid space, an area of connective tissue containing numerous small tortuous channels is present. Ferritin (molecular weight 400,000) infused into the ventricles at normal and increased intraventricular pressure was present in these channels by 15 minutes postinfusion, and subsequently reached the intraorbital connective tissue. Elevating the intraventricular pressure did not noticeably alter the morphological appearance of this region or change the gross distribution pattern of the ferritin. Ferritin did not penetrate the scleral barrier to reach the choriocapillaris, nor did it breach the arachnoid barrier layer proximal to the transitional zone at the optic subarachnoid space to reach the dura mater. These results are very similar to those described for the hamster orbital region and the rabbit cribriform region. These experiments support the concept that macromolecules exit the subarachnoid space at the termination of the optic nerve via open channels, and that no significant barrier to drainage of macromolecules in CSF is present at this location.
Animals↗
Hematoporphyrin uptake in atherosclerotic plaques: therapeutic potentials.
Atherosclerotic plaques were induced in abdominal aortas of rabbits. At 8 weeks, 5 mg of dihematoporphyrin ether (Photofrin II) per kg was injected intravenously followed by sacrifice of the animal, fluorescence microscopy, and quantitative assay of porphyrin in the plaque-containing aortas at 1, 12, 24, 48, and 72 hours. Photofrin II was taken up preferentially by the plaque, with the highest plaque to normal wall ratio occurring at 48 hours. Phototherapy was carried out in 13 animals in each of which two plaques had been induced. With a 630-nm light source 48 hours after the infusion of Photofrin, one of the pair of plaques was treated while the other served as a control. Animals were killed at 2, 4, and 6 weeks. The 6-week specimens showed the most dramatic reduction in plaque in comparison to controls. Photodynamic therapy may provide an alternate strategy in dealing with focal atherosclerosis.
Animals↗
Blood-cerebrospinal fluid barrier alteration following intraventricularly administered cholera toxin.
Cholera toxin (CT) has been reported to double cerebrospinal fluid (CSF) formation following its introduction into the ventricular system of cats and dogs. In our laboratory we noted that CT used in a similar fashion in rabbits and cats resulted in only a slight increase in CSF formation and was associated with a steadily rising protein content in the cisterna magna effluent. To further investigate this finding, rabbits and cats underwent ventriculo-cisternal perfusions, one group with CT introduced into the ventricles and the other without. In the rabbit only, radioiodinated serum albumin (125I-RISA) was given i.v. Other groups of rabbits had 125I-RISA or 125I-CT injected into the ventricles. The group of rabbits receiving intraventricular CT experienced a 4-10-fold elevation in the amount of both protein and 125I-RISA in the cisterna magna effluent compared with the control group. Electrophoretic pattern of the protein present in the effluent was similar to that of rabbit plasma. Autoradiography of the brains of those animals given intraventricular 125I-CT were found to have a very high uptake of 125I-CT in the choroid plexus and along all exposed ventricular surfaces, a finding not evident when 125I-RISA alone was given intraventricularly. It is concluded that CT altered the blood-CSF barriers allowing the reference marker to penetrate these barriers and plasma to leak into the CSF. These findings appear to account for most if not all of what was thought to be an increase in CSF formation in response to intraventricular CT.
Animals↗
A clinical study of sensitivity to sodium nitroprusside during controlled hypotensive anesthesia in young and elderly patients.
Aging has important effects on the cardiovascular system; baroreceptor reflex function decreases and the elderly are more resistant to both beta-receptor agonists and antagonists. The purpose of the present clinical study was to determine the relationship between age and sensitivity to sodium nitroprusside in 16 patients during deliberate hypotensive anesthesia by determining the blood pressure changes in young and elderly patients to incremental increases in dose of sodium nitroprusside. A dose-response curve relating change in mean blood pressure to dose of sodium nitroprusside (microgram X kg-1 X min-1) was constructed for each patient; the slope of this line is a measure of "sensitivity." The change in mean arterial blood pressure per microgram X kg-1 X min-1 nitroprusside dose (i.e., slope), showed a significant correlation with age (r = 0.766, P less than 0.001), demonstrating that sensitivity to sodium nitroprusside increases with advancing years. The maximum change in heart rate produced by nitroprusside showed a reciprocal correlation with age (r = -0.791, P less than 0.001). There was no significant correlation between age and maximum change in plasma norepinephrine or epinephrine concentrations during nitroprusside infusion. The increased sensitivity to nitroprusside might have been due to diminished baroreflex activity, resistance of cardiac adrenergic receptors to catecholamine stimulation, or alteration in sensitivity to the direct vasodilating effects of sodium nitroprusside. Whatever the mechanism, however, this clinical study has shown that lower doses of nitroprusside should be used in elderly patients to achieve the same degree of hypotension achieved in younger patients.
Adolescent↗
Familial isolated aniridia associated with a translocation involving chromosomes 11 and 22 [t(11;22)(p13;q12.2)].
Isolated aniridia segregated as an autosomal dominant trait in a family with 11 affected members spanning five generations. Four of the eight individuals studied had aniridia associated with glaucoma and cataracts. Cytogenetic studies revealed an apparently balanced reciprocal translocation between chromosomes 11 and 22 [t(11;22)(p13;q12.2)], while four unaffected relatives had normal karyotypes. There is no evidence of Wilms tumor or genitourinary abnormalities in any members of the family. Restriction enzyme analysis of the human catalase gene revealed no abnormalities in the individuals with the translocation. A summary of phenotypic abnormalities in 61 cases associated with aniridia is presented, as well as a comparison of breakpoints in 44 cases of 11p deletion. These data indicate that single breaks at 11p13 are associated with isolated aniridia, while deletion of 11p13 results in aniridia combined with Wilms tumor, genitourinary abnormalities, and/or mental retardation.
Abnormalities, Multiple↗