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Biomedical subjects

M L Weiss

Publications and source records attributed to M L Weiss.

At least 55 records · Page 3Linked to original sources

[Reoperations in primary hyperparathyroidism].

We report on 14 patients suffering from persistent (n = 13) and truly recurrent (n = 1) primary hyperparathyroidism. Reoperations were successful in 13 cases. Cervical reexploration was only required for 5 patients who had previous operations by unexperienced surgeons in other clinics. In 5 out of 7 patients operated by us, the causes of the persistent primary hyperparathyroidism were 4 adenomas and one hyperplastic gland in the mediastinum found by median sternotomy. The remaining cases were a rare ectopic location of the inferior glands and an inadequate resection in four-gland-hyperplasia. Preoperative localization procedures were carried out for most patients. 201-Tl/99m-Tc-subtraction scintigraphy has proved for localization in both the cervical region and the mediastinum to be a highly sensitive method. Reoperative parathyroid surgery can be reduced with thorough initial cervical exploration by experienced surgeons in specialized clinics.

Adenoma↗

Collateral input to the paraventricular and supraoptic nuclei in rat. II. Afferents from the ventral lateral medulla and nucleus tractus solitarius.

In the rat, medullary afferents to the hypothalamic magnocellular nuclei mediate the baroreceptor reflexes of vasopressinergic neurons and the cholecystokinin- or gastric distention-induced excitation of oxytocinergic neurons. One strategy that reflexes such as these may use to coordinate the activity of magnocellular neuroendocrine neurons is collateral branching of input. Previous work has shown that the distributions of medullary neurons projecting to the paraventricular and the supraoptic nuclei overlap and that their axons branch. Thus, we hypothesized that single neurons in the ventral lateral medulla and/or the nucleus tractus solitarius would project to both the paraventricular and supraoptic nuclei via collateral branches of their axons. Medullary afferent neurons were retrogradely labeled after injection into the paraventricular and the supraoptic nucleus on one side of the brain with two different fluorescent tracers: Fluoro-Gold or rhodamine-labeled latex microspheres. The topographic distribution of labeled cells in the medulla containing either a single fluorescent tracer or both tracers were plotted. Of these labeled neurons, a small percentage (7%) contained both dyes, suggesting that they send collateral branches to both of the magnocellular neuroendocrine nuclei injected. Single labeled cells were both ipsi- and contralateral to the injected side (53% ipsilateral), but most double-labeled cells were ipsilateral (84%). In rats, areas that project to both the paraventricular and the supraoptic nuclei may act upon both nuclei together. Thus, afferent inputs, in conjunction with the known inter- and intracellular changes that take place within the magnocellular nuclei, may be involved with the coordinated responses throughout magnocellular neuroendocrine system during medullary reflexes, i.e., the baroreceptor-mediated reflexes or the gastric distention reflexes.

Afferent Pathways↗

Collateral input to the paraventricular and supraoptic nuclei in rat. I. Afferents from the subfornical organ and the anteroventral third ventricle region.

Injections of two fluorescent retrograde tracers were used to investigate the existence of collateral branching of input to the hypothalamic magnocellular neuroendocrine neurons. Injection of one tracer (either Fluoro-Gold or rhodamine-labeled microspheres) into the supraoptic nucleus and the other tracer into the ipsilateral paraventricular nucleus produced labeled neurons within the subfornical organ and the anteroventral third ventricle area. Some labeled cells were found to contain both fluorescent tracers (double-labeled cells), suggesting that they project to both the paraventricular and supraoptic nuclei via branching axons. Most double-labeled cells were found within the subfornical organ. Fewer of these cells were located within the nucleus medianus preopticus, and still fewer were distributed in the organum vasculosum lamina terminalis, the bed nucleus of the stria terminalis, and the medial and the lateral preoptic areas. These data present the first direct evidence that single cells may provide input to more than one magnocellular neuroendocrine nucleus. Hypothetically, hormonal release would require coordinated firing of many magnocellular cells. Thus, the branched input to these neurons may assist in the organization and the timely activation of this system in response to physiological stimuli.

Animals↗

Supraoptic nucleus afferents from the main olfactory bulb--I. Anatomical evidence from anterograde and retrograde tracers in rat.

The morphological features of a putative connection between the main olfactory bulb and the supraoptic nucleus of the rat was studied using a combination of anatomical techniques. Immunocytochemistry of neurophysin-containing processes were employed to delineate morphological features of supraoptic dendrites. Main olfactory bulb efferents to the supraoptic nucleus were studied by injection of the anterogradely transported substances, wheatgerm agglutinin conjugated horseradish peroxidase or Phaseolus vulgaris leucoagglutinin, into the main olfactory bulb. To confirm the results of these studies, the distribution of retrogradely labeled cells within the main olfactory bulb was determined after injection of rhodamine-labeled latex microspheres or Fluoro-Gold into the supraoptic nucleus. Neurophysin immunocytochemistry revealed the supraoptic nucleus dendritic plexus which coursed anteroposteriorly beneath supraoptic somata. Additionally, a portion of this plexus also projected ventrolaterally into periamygdaloid areas, a feature of supraoptic architecture which is not generally appreciated. The anterograde tracers labeled main olfactory bulb efferents including a dense plexus of terminals and fibers ventrolateral to the ipsilateral supraoptic nucleus. The pattern of anterogradely labeled fibers and terminals appeared to overlap with the distribution of ventrolaterally projecting neurophysin-containing processes. Since the latter consists of dendritic processes of supraoptic origin, this suggests that the main olfactory bulb projects to the supraoptic nucleus. Injections of rhodamine-labeled latex microspheres or Fluoro-Gold resulted in retrogradely labeled mitral cells throughout the ipsilateral main olfactory bulb. Taken together, these anatomical studies demonstrate a direct projection from the main olfactory bulb to the supraoptic nucleus of the rat. A comparison electrophysiological study confirmed these results.

Animals↗

Magnocellular tuberomammillary nucleus input to the supraoptic nucleus in the rat: anatomical and in vitro electrophysiological investigations.

Anatomical and electrophysiological methods were used to investigate the existence and role of inputs from the magnocellular tuberomammillary nucleus to the supraoptic nucleus. After injecting either Fluoro-Gold or rhodamine-labeled latex microspheres into the supraoptic nucleus, consistent patterns of retrogradely labeled neurons within the tuberomammillary nucleus were observed. The results indicate that both subdivisions of the supraoptic nucleus, the tuberal and the anterior, receive input from the tuberomammillary nucleus. Injections into the tuberal supraoptic nucleus tended to label more cells in the contralateral tuberomammillary nucleus, while injections into the anterior supraoptic nucleus may label more cells on the ipsilateral side. The in vitro intracellular electrophysiological results support the anatomical findings and extend them in several ways. Some tuberomammillary neurons were found to project to the supraoptic nuclei on both sides of the brain. Intracellular Lucifer Yellow injections into tuberomammillary cells after electrophysiological recording revealed labeled axons that were traceable into the supraoptic nucleus, where apparent varicosities (possible en passant terminals) were seen. Magnocellular tuberomammillary nucleus neurons had characteristic passive and active membrane properties and morphology, similar to histaminergic neurons in this area studied by other workers. Finally, in two of the 21 cases, Lucifer Yellow injection into one neuron revealed dye-coupled pairs of tuberomammillary neurons. Previous work by others has shown that histamine excited cells in the tuberal subdivision of the supraoptic nucleus, stimulating vasopressin release, and that the tuberomammillary nucleus provides histaminergic input to the anterior portion of the supraoptic. The present findings show that the tuberomammillary nucleus supplies input to both subdivisions of the supraoptic nucleus and that this input is provided bilaterally. Taken together with previous work, these data suggest that the tuberomammillary nucleus provides histaminergic input to the supraoptic nucleus and may be involved specifically with vasopressin release.

Action Potentials↗

A retinal projection to the paraventricular nuclei of the hypothalamus in the Syrian hamster (Mesocricetus auratus).

The retino-hypothalamic tract of the Syrian hamster (Mesocricetus auratus) was examined using intraocular injections of horseradish peroxidase conjugated to cholera toxin. In addition to the retinal input to the suprachiasmatic nuclei (SCN), a retinal projection to the caudal paraventricular nuclei was identified. This projection may mediate some effects of light upon pineal gland physiology independently of the SCN and the circadian-rhythm generating system.

Afferent Pathways↗

Nucleotide sequence analysis of the lemur beta-globin gene family: evidence for major rate fluctuations in globin polypeptide evolution.

Lemur beta-related globin genes have been isolated and sequenced. Orthology of prosimian and human epsilon-, gamma-, and beta-related globin genes was established by dot-matrix analysis. All of these lemur globin genes potentially encode functional beta-related globin polypeptides, though precisely when the gamma-globin gene is expressed remains unknown. The organization of the 18-kb brown lemur beta-globin gene cluster (5' epsilon-gamma-[psi eta-delta]-beta 3') is consistent with its evolution by contraction via unequal crossing-over from the putative ancestral mammalian beta-globin gene cluster (5' epsilon-gamma-eta-delta-beta 3'). The dwarf lemur nonadult globin genes are arranged as in the brown lemur. Similar levels of synonymous (silent) nucleotide substitutions and noncoding DNA sequence differences have accumulated between species in all of these genes, suggesting a uniform rate of noncoding DNA divergence throughout primate beta-globin gene clusters. These differences are comparable with those observed in the nonfunctional psi eta pseudogene and have therefore accumulated at the presumably maximal neutral rate. In contrast, nonsynonymous (replacement) nucleotide substitutions show a significant heterogeneity in distribution for both the same gene in different lineages and different genes in the same lineage. These major fluctuations in replacement but not silent substitution rates cannot be attributed to changes in mutation rate, suggesting that changes in the rate of globin polypeptide evolution in primates is not governed solely by variable mutation rates.

Amino Acid Sequence↗

Interference with central actions of angiotensin II suppresses sodium appetite.

We have proposed that sodium appetite is aroused by a synergy in the brain of angiotensin II and aldosterone. This hypothesis was tested with 1) chronic intracerebroventricular infusion of captopril, which blocks the conversion of angiotensin I to angiotensin II, or 2) intracerebroventricular injection of eight-substituted analogues of angiotensin II, which block its receptors. Both treatments resulted in a suppression of the sodium appetite induced by sodium deficiency. The suppression was specific for the deficiency-induced appetite, because spontaneous ingestive behaviors were not changed nor was sodium excretion. In addition, the rats continued to express a sodium appetite aroused by pharmacological doses of deoxycorticosterone acetate when they received the highest dose of chronic intracerebroventricular captopril. These results offer compelling evidence for the idea that angiotensin II action in the brain is necessary for expression of sodium appetite.

Angiotensin II↗

Plasmodium berghei: ectopic antibody synthesis in splenectomized rodents.

Jirds (Meriones unguiculatus) were able to maintain acquired antimalaria immunity independent of the spleen approximately 4 months after initial infection. The memory cells appeared to become peripheralized, and persist outside the spleen for +/- 10 months if no further antigenic stimulus is applied. With regular stimulation, immunity was maintained indefinitely. In immune splenectomized jirds, the secondary, splenic germinal center function appeared to be taken over by cellular infiltrates in the liver that are organized as "pseudofollicles." They were comprised of macrophages that contained very finely divided malaria pigment and functional B and T cells. These pseudofollicles were located at the vascular triangles of the hepatic lobules. Strings of plasma cells appeared to be differentiated at the edges of the pseudofollicles. Like the splenic germinal centers, the pseudofollicles appeared largest about 10 days after challenge and became completely resorbed after 3 weeks. Similar structures were observed in asplenic aged rats, whether the spleen was removed before or after initial infection. However, rats splenectomized prior to infection developed low-grade chronic parasitemias; rats splenectomized later remained solidly immune, confirming the view that the pseudofollicles replace only the secondary, humoral response of the splenic germinal centers. It is not known at which site the memory for sterilization locates after peripheralization. The liver also appears to assume the splenic function of storage, and possibly detoxification, of clumps of indigestible malaria pigment. The pigment is located in clusters of macrophages dispersed throughout the parenchyma.

Animals↗

The primate psi beta 1 gene. An ancient beta-globin pseudogene.

The human beta-globin gene cluster contains five functional genes plus a single pseudogene termed psi beta 1. Hybridization and comparative sequence analysis show that this pseudogene is not the product of a recent gene duplication, but is ancient and has been maintained in all major primate groups ranging from prosimians to anthropoids, at the same position as in man, between gamma- and delta-globin genes. In the lemur, a prosimian, the central exons of the psi beta 1 and delta-globin genes have undergone an unequal exchange, which has resulted in a contraction of the beta-globin gene cluster and the formation of a Lepore-type psi beta 1-delta globin pseudogene. Comparisons of defects shared by prosimian, New World monkey and human psi beta 1 sequences suggest that the ancestral primate gene was probably a pseudogene with an abnormal initiation codon but few if any additional defects, and that most contemporary pseudogene defects were accumulated relatively recently by slow neutral drift. We suggest that psi beta 1 arose early in primate evolution by silencing of a pre-existing discrete functional gene, and show that psi beta 1-related sequences are also present in other mammalian orders. In view of the antiquity of psi beta 1-related sequences, we propose that this gene be renamed the eta-globin gene.

Animals↗

The eta-globin gene. Its long evolutionary history in the beta-globin gene family of mammals.

In phylogenetic reconstructions by the parsimony method, utilizing 62 sequenced globin genes and pseudogenes (including 34 of the beta-globin gene family from eutherian orders Primates, Lagomorpha, Artiodactyla and Rodentia), the branch of primate psi beta pseudogenes and the goat embryonically expressed epsilon II gene group monophyletically together as orthologues of a common ancestral gene (labelled eta) distinct from orthologues of epsilon, gamma, delta and beta. This primate psi eta-goat eta branch is cladistically closer to epsilon and gamma than to delta and beta branches. In each eutherian order gene conversions replaced portions of delta by beta sequences, whereas in descent of Primates epsilon, gamma and eta mostly retained their separate ancient identities predating the radiation of Eutheria in all their exons and non-coding regions. The loci of the ancestral beta-globin gene cluster in basal eutherians and proto-primates, as deduced from beta-clusters representing the four eutherian orders, were linked 5'-epsilon-gamma-eta-delta-beta-3' with epsilon, gamma and eta being embryonically expressed genes, and delta and beta ontogenetically later expressed genes. Through deletions gamma was lost in artiodactyl evolution, eta in lagomorph and rodent evolution, and all DNA between exon 2 3' boundaries of eta and delta in prosimian lemuriform evolution (lemur having the hybrid pseudogene psi eta delta). Simian primates retained intact the five loci of the ancestral cluster. Not only did eta, after it became a pseudogene in the basal primates, persist intact in descent to present-day simians but in the line to hominoids it evolved during the last 40 million years at the decelerated rate of 1 X 10(-9) substitutions/site per year which is one-fifth the expected neutral rate. The possibility is suggested that the psi eta locus situated between fetal and adult chromosomal domains of the simian beta-globin gene cluster might play some role in a mechanism for ontogenetic switches of globin gene expression. However, not enough sequence data on genes and intergenic regions in DNA of species of primates and other mammals as yet exist to know if the slow rate of 1 X 10(-9) reflects the rate of a conserved functional gene or primarily reflects a decelerated neutral rate of hominoid DNA evolution, conceivably from enhanced DNA repair and longer generation times in hominoids. The further possibility is raised that gene correction (repair of damaged DNA that prevents emergence of new alleles) and gene conversion both more often involve strand copying of conserved than of rapidly evolving DNA.

Animals↗