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Biomedical subjects

R E Weller

Publications and source records attributed to R E Weller.

At least 55 records · Page 3Linked to original sources

Mortality and body weight changes in Aotus nancymai shipped from Iquitos, Peru to Richland, Washington.

Four hundred and fifty wild-caught owl monkeys (Aotus nancymai) were shipped from Iquitos, Peru to Richland, Washington. Mortality and body weight changes from the time of shipment to 30 days after arrival were evaluated using age, sex, and transit time as comparison criteria. No association between mortality and sex, age, or transit time was observed. The mortality percentage from shipment to 30 days after arrival was 2.44%. Both age and transit time had a significant effect on weight changes, but sex did not. Shipping procedures are described.

Age Factors↗

Cholelithiasis in owl monkeys: seven cases.

Spontaneous cholelithiasis was found in seven owl monkeys (Aotus spp.) at necropsy. There were four male and three female animals. Antemortem clinicopathologic findings included weight loss, anemia, increased alanine aminotransferase and gamma glutamyl transpeptidase, and hyperbilirubinemia in several animals. Choleliths ranged in size from sand-like particles to 5 mm in diameter. Gallstones from five animals were analyzed by accepted analytical methods. Results showed the gallstones to be composed primarily of cholesterol (89%). The gallbladder was histologically normal in all cases examined. The etiopathogenesis of cholelithiasis in the owl monkey is unknown.

Animals↗

Relationship of serum total calcium and albumin and total protein in owl monkeys (Aotus nancymai).

A positive linear relationship was found between total calcium and albumin and between total calcium and total protein in the serum of 205 owl monkeys. Adjustment formulas for calcium were derived: adjusted calcium (mg/dl) = measured calcium (mg/dl) - 0.84 [albumin (g/dl)] + 3.8 and adjusted calcium (mg/dl) = measured calcium (mg/dl) - 0.82 [total protein (g/dl)] + 6.5. Adjusted calcium calculations for monkeys based on albumin concentration were similar to those for man and dogs, but different from those based on total protein.

Animals↗

Hypercalcemia and disseminated histoplasmosis in an owl monkey.

An adult male owl monkey (Aotus nancymai) had hypercalcemia associated with a disseminated case of histoplasmosis (Histoplasma capsulatum var. capsulatum). Histopathologic examination of tissues at necropsy showed moderate to marked numbers of small granulomas involving multiple organs. The granulomas contained numerous round, basophilic, intracellular structures, 1-2 microns in diameter, that stained positive in Periodic acid-Schiff and Gomori's methenamine silver tests. The hypercalcemia in this case was attributed to enhance conversion of dietary vitamin D to 1,25-dihydroxycholecalciferol by the granulomas.

Adrenal Glands↗

Parameters affecting the loss of ganglion cells of the retina following ablations of striate cortex in primates.

Partial lesions of striate cortex were made in newborn and adolescent or young adult macaque monkeys, one newborn squirrel monkey, and adult squirrel and owl monkeys. After survival times ranging from 3 1/2 weeks to 8 years, the retinas were examined for transneuronal retrograde ganglion cell loss and retinal projections to the dorsal lateral geniculate nucleus, and other targets were examined for changes. After lesions in infant macaque monkeys and long postoperative survivals, nearly 80% of the ganglion cells were lost in the altered portions of the retinas. The degeneration appeared to be exclusively of ganglion cells projecting to the parvocellular layers of the lateral geniculate nucleus, and the loss of this class of cell appeared to be complete or nearly complete for the affected portions of the retina. Cases with shorter survivals showed that nine-tenths of the potential loss occurred within 6 months, and about half of the potential loss took place within one month. In cases where lesions were placed in adolescent and young adult macaque monkeys, the loss also was of ganglion cells projecting to the parvocellular layers. However, the rate of cell loss was slower so that little or no cell loss was apparent after six months, and only one-third to three-fourths of the potential loss occurred within 12-14 months. A cell loss of 22% was measured in the altered portions of the retina of a squirrel monkey lesioned as an infant and surviving for 6 months, but no regions of ganglion cell loss were apparent in the retinas of owl and squirrel monkeys lesioned as adults and surviving as long as two or more years. We conclude that nearly 80% of the ganglion cells project to the parvocellular layers in macaque monkeys, and that the ultimate survival of these ganglion cells depends on the presence of target neurons in the parvocellular layers. Age is important in that the loss of ganglion cells proceeds rapidly in infant macaque monkeys, but slowly in older animals. Infant New World monkeys, judging from one squirrel monkey, are also susceptible to ganglion cell loss, although apparently at a rate comparable to older macaque monkeys. Finally, adult New World monkeys do not appear to be susceptible to ganglion cell loss. These age and species differences in rates of loss and susceptibility to loss challenge a "sustaining collateral" hypothesis proposed earlier (Weller et al., 1979), and suggest alternatives and modifications.

Aging↗

Functionally distinct groups of X-cells in the lateral geniculate nucleus of the cat.

The latencies and visual response properties of 202 X-cells in the A-laminae of the cat dorsal lateral geniculate nucleus (LGN) were examined to investigate the recent claim (Mastronarde, '85,'87a) that functionally different groups of X-cells reside there. Two groups of X-cells were found, which differed in their extracellularly recorded responses to spots of light flashed within their receptive fields. One group, constituting one-third of the sample, responded to spot onset with a profound and often long-lasting dip in discharge rate, such that cell discharge usually did not reach half maximum until greater than or equal to 100 msec after spot onset. About 70% of these cells also displayed a transient discharge at spot onset. These cells correspond to Mastronarde's lagged X-cells, and we similarly refer to them as XL-cells. The second group, constituting the remainder of the X-cell population, generally responded to spot onset with a short latency (less than or equal to 60 msec) brisk discharge, no detectable XL-type dip, and a rapid reduction in firing at spot offset. We refer to these neurons as nonlagged (XN) X-cells; this group probably encompasses all of Mastronarde's non-XL-cells. Despite some overlap, the XL- and XN-cells differed in numerous other features. Compared to XN-cells, XL-cells exhibited: 1) lower peak rates of discharge and more uniform firing during spot onset; 2) slightly longer latencies and markedly lower probabilities of discharge to optic chiasm stimulation; 3) consistently lower geniculocortical conduction velocities; and 4) markedly lower optimal temporal frequencies when tested with drifting sine wave gratings. No differences were found between the two cell groups in optimal spatial frequency, spatial resolution, or receptive field center size, and there were equal proportions of on- and off-center types of XL- and XN-cells. Analyses of one- and two-dimensional plots of the physiological measures indicate that XL- and XN-cells constitute a physiological continuum. However, the two groups occupy opposite sides of the continuum on many of the measures, with little overlap and with few (less than 5%) cells with intermediate properties. Therefore, XL-cells may be considered a distinct, readily identifiable group. These findings confirm and extend Mastronarde's ('87a) observations on functional differences among geniculate X-cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Structural correlates of functionally distinct X-cells in the lateral geniculate nucleus of the cat.

In the companion paper (Humphrey and Weller, '88), we demonstrated 2 physiologically different groups of X-cells (XL and XN) in the A-laminae of the cat lateral geniculate nucleus. In order to investigate their possible morphological correlates, we iontophoresed horseradish peroxidase intracellularly into physiologically identified XL- and XN-cells and examined their light microscopic appearance. The 11 HRP-labeled XL-cells constituted the smallest relay neurons in the A-laminae, and were similar morphologically. All had small somata (mean soma size = 236 micron2), very thin (less than 1.0 micron) axons, few primary dendrites, and narrow, sinuous distal dendrites, which usually formed trees that were oriented perpendicular to laminar borders. The dendrites could be smooth or display beadlike varicosities, hairlike appendages, and/or occasional complex stalked appendages, but their most consistent feature was numerous clusters of grapelike dendritic appendages located at or near dendritic branch points. The 14 labeled XN-cells were structurally more heterogeneous, and they included relay neurons and interneurons. Eight of 11 XN-relay cells differed markedly from the XL-cells. These XN-cells were multipolar neurons with medium to large somata (mean soma size = 365 micron2), small to medium-size axons (1.0-2.0 micron), numerous primary dendrites, and straight distal dendrites that formed radially symmetric trees. The dendrites of the cells were largely smooth, except for occasional spines and/or hairs, and they were devoid of grapelike and other complex appendages. The three other XN-relay neurons had morphologies either similar to XL-cells or intermediate between XL-cells and more simple, multipolar XN-relay cells, but two of these cells had larger somata and axons than most XL-cells. Finally, three XN-cells were intrageniculate interneurons, which possessed small somata (mean soma size = 174 micron2), fine sinuous dendrites covered with beadlike varicosities on stalked appendages, and no obvious axon. These results reveal that, despite minor overlap, there are marked structural differences between XL- and XN-cells. Among the relay cells, these differences relate to soma and axon diameter, dendritic orientation, and the presence or absence of grapelike dendritic appendages. Our finding that interneurons were strongly excited at short latencies by spot onset supports the hypothesis (Mastronarde, '87a; Humphrey and Weller, '88) that such interneurons provide the major inhibitory input to XL-cells, and that this input is important in generating the spot-induced early dips in XL-cell discharge.

Animals↗

A novel class of unstable 6-thioguanine-resistant cells from dog and human kidneys.

Thioguanine-resistant primary clones were grown from single cell suspensions obtained from dog and human kidneys by enzymatic digestion. In medium containing a relatively high concentration (10 micrograms/ml) of thioguanine, thioguanine-resistant primary clones arose from each source at frequencies ranging from 10(-4) to 10(-5). A reduction in total hypoxanthine uptake was found in the thioguanine-resistant primary clones which had developed in thioguanine medium, consistent with a reduction in hypoxanthine phosphoribosyltransferase activity. When these thioguanine-resistant primary clones were subsequently grown in the absence of thioguanine and assayed for the thioguanine-resistant phenotype and hypoxanthine phosphoribosyltransferase activity, it was found that most were now thioguanine-sensitive and yielded cell-free extracts with substantial amounts of hypoxanthine phosphoribosyltransferase activity. In contrast, thioguanine-resistant human clones grown continuously in the presence of thioguanine yielded cell-free extracts with little or no detectable hypoxanthine phosphoribosyltransferase activity. Southern blot analysis demonstrated no structural alterations in the hypoxanthine phosphoribosyltransferase gene in thioguanine-resistant primary human kidney clones. These results suggest that a novel mechanism(s) for thioguanine resistance and the control of hypoxanthine phosphoribosyltransferase expression may occur in dog and human kidney cells.

Animals↗

Subdivisions and connections of inferior temporal cortex in owl monkeys.

Patterns of cortical connections and differences in architectonic appearance were used to subdivide inferior temporal cortex of owl monkeys into four main regions. These regions were named by location: ITC (the caudal subdivision of inferior temporal cortex), ITR (the rostral subdivision of inferior temporal cortex), ITP (the polar subdivision of inferior temporal cortex), and ITM (the medial subdivision of inferior temporal cortex). Two of these regions may contain further subdivisions--ITC, separate dorsal and ventral areas, and ITM, medial and lateral areas. The most caudal subdivision, ITC, was defined in an earlier report (Weller and Kaas: J. Comp. Neurol. 234:35-59, '85) as the projection zone of the dorsolateral visual area (DL). ITC occupies roughly the caudal half of the architectonic zone temporal area E (TE) (after von Bonin and Bailey: The Neocortex of Macaca mulatta. Urbana: University of Illinois Press, '47). TE is characterized by a dense, broad layer IV of granule cells and a dark inner band of myelination. Injections of 3H-proline in ITC demonstrated major projections to a more rostral division of the temporal lobe, ITR. Other projections were to the frontal eye field (FEF), a more ventral region of frontal cortex (FV), and a medial division of inferior temporal cortex, ITM, on the ventral surface of the temporal lobe. Feedback projections of ITC were to DL and adjoining temporal-parietal cortex (TP), while interhemispheric projections were to ITC and ITR. Connections between dorsal and ventral ITC, together with earlier evidence for two projection zones of DL in ITC (Weller and Kaas: ibid., '85), suggest that dorsal and ventral sectors of ITC are separate visual areas. The rostral division of inferior temporal cortex, ITR, was defined as the projection zone of ITC. ITR occupied the rostral half of the architectonic region TE. Slight differences in cortical architecture between ITC and ITR were noted, but an architectonic border between the two fields could not be reliably distinguished. Injections in ITR demonstrated projections to the rostral pole of temporal cortex, ITP, feedback projections to ITC, and inputs to FEF, FV, dorsomedial frontal cortex, and the rostroventral superior temporal gyrus. Interhemispheric projections were to ITR and ITP. The projections of ITR to the rostral pole defined ITP. ITP has broad, less distinct layers of cortex and appears to correspond to temporal area G (TG) of von Bonin and Bailey (ibid., '47). The only known input to ITP is from ITR, and its projections have not yet been determined.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗

Callosal and ipsilateral cortical connections of the body surface representations in SI and SII of tree shrews.

Injections of horseradish peroxidase (HRP) were used to study the connections of the first and second somatosensory areas (SI and SII) in tree shrews. The locations of callosally projecting neurons in SI were determined by placing large injections of HRP in the SI region of one cerebral hemisphere and determining the organization of SI of the other cerebral hemisphere with microelectrode mapping. Many callosally projecting neurons were revealed in lateral SI representing the face, especially the glabrous nose. A sparse scattering of callosally projecting neurons were located more centrally in SI in portions representing the forepaw; these neurons tended to be in cortex devoted to the dorsal hand and pads of the palm rather than the digits. Part of medial SI, representing the forelimb and trunk, had a moderately dense distribution of callosally projecting neurons. More restricted injections in SI indicated that callosally projecting neurons were largely within comparable portions of contralateral SI, although a few neurons projecting callosally to SI were located in SII and cortex caudal and rostral to SI. Large injections of HRP in SII labeled neurons throughout contralateral SII, including representations of the forepaw and hindpaw. More restricted injections in SII labeled neurons in somatotopically comparable parts of the contralateral SII. A few labeled neurons were also seen in somatotopically matched parts of contralateral SI. The results also demonstrated strong somatotopically organized connections between SI and SII of the same hemisphere, and connections of SI and SII with adjoining subdivisions of parietal and frontal cortex. The major thalamic projections to both SI and SII originated in the ventroposterior nucleus.

Afferent Pathways↗

Morphology of retinogeniculate X and Y axon arbors in monocularly enucleated cats.

We examined the terminal arbors of single, physiologically identified retinogeniculate X and Y axons from the remaining retinas of adult cats raised from birth with monocular enucleation. These were compared with arbors of X and Y axons in normally reared cats. We used intra-axonal injections of horseradish peroxidase to label each axon after recording its response properties. While the axons in monocularly enucleated cats exhibited normal response properties, both X and Y axons in these cats had abnormally large terminal arbors. Each of the hypertrophied X arbors appeared to be completely confined to the single geniculate lamina A or A1 appropriate to its eye of origin (i.e., lamina A for the contralateral retina and lamina A1 for the ipsilateral retina). In contrast, in addition to their normal terminations, most of the Y arbors seemed to extend well into laminae normally innervated only by the retina that was removed. Thus most or all of the translaminar sprouting previously reported for monocularly enucleated cats appears to reflect extensions of Y axon arbors. These data, in addition to earlier, analogous data from young kittens and cats reared with monocular lid suture, suggest the following sequelae during postnatal development: the retinogeniculate X arbors mature first and develop exuberant arbors that are later competitively pruned as the Y axons expand their innervation of the lateral geniculate nucleus; monocular lid suture prevents the Y axons from succeeding in this competition, so they fail to establish normal arbors and cannot reduce the exuberant X arbors; monocular enucleation offers a less resistant path in the denervated laminae for the rapidly growing Y arbors from the remaining eye, and the expansion of these arbors there reduces the competitive pressure on the exuberant X arbors. Thus, in monocularly enucleated cats, sprouting is limited to Y axons, either because only they possess the capacity to sprout or because they are in the midst of a period of relatively rapid growth at the time of the neonatal enucleation. The X axon arbors are also abnormally large within their appropriate laminae. This occurs presumably because they are able to maintain their immature exuberance, although we cannot rule out the possibility that they are pruned and later regrow to the final size seen in our experiments.

Animals↗

On talc translocation from the vagina to the oviducts and beyond.

The objective of this study was to investigate whether multiple vaginal depositions of neutron-activated talc in the cynomolgus monkey result in the translocation of this material to the uterus and beyond. Within a 45-day period, six monkeys received 30 applications of 125 mg neutron-activated talc, suspended in 0.3 ml physiological saline solution containing 1% carboxymethyl cellulose as a suspending agent. The suspension was deposited in the posterior vaginal fornix of the sedated monkeys. Two days after the final talc application, the animals were anaesthetized. Abdominal lavage was performed and the lavage fluid collected for gamma-ray analysis. Also collected for gamma-ray analysis were the following tissues/organs: ovaries, oviducts, uterus, and vagina with cervix. Six untreated control monkeys underwent the same procedures. The radioisotopes 46Sc, 60Co, 59Fe and 51Cr in the activated talc served as tracers. Only the samples containing vagina and cervix from the dosed monkeys contained varying quantities of talc. This demonstrates that no measurable quantities of talc, deposited by multiple applications in the vaginal fornix of the cynomolgus monkey, translocated to the uterus or beyond.

Animals↗

Cortical projections of the dorsolateral visual area in owl monkeys: the prestriate relay to inferior temporal cortex.

The dorsolateral visual area (DL) is one of a number of visual areas that have been defined by electrophysiological mapping procedures and cortical architecture in the extrastriate cortex of owl monkeys. The projections of DL were determined by the intra-axonal transport of 3H-proline, 3H-acetyl-wheat germ agglutinin, and horseradish peroxidase after cortical injections. The major ipsilateral projection of DL defined a new subdivision of the visual cortex in owl monkeys, the caudal inferior temporal cortex. Single injections in DL sometimes produced label in two separate regions in the caudal inferior temporal cortex, suggesting that functional subdivisions exist in this projection zone. Other targets of DL included the region of the frontal eye fields, the dorsomedial visual area, the dorsointermediate visual area (DI), a region of the cortex rostral to DI which we call the temporoparietal cortex, and possibly the ventral (V) and posterior parietal areas. A major feedback projection of DL was to V-II. Projections from DL to V-II and the dorsomedial visual area were roughly retinotopic. Projections from DL to the contralateral cerebral hemisphere were to DL and the inferior temporal cortex. Overall, the results support the concept that a major relay of visual information proceeds from V-I to V-II to DL and then to the inferior temporal cortex. In addition, similarities in connection patterns of DL in owl monkeys and V4 in macaque monkeys suggest that DL and much or all of V4 are homologous.

Animals↗

Do particles translocate from the vagina to the oviducts and beyond?

To investigate whether particles deposited in the vagina translocate to the oviducts, 0.3 ml of a 4% bone black suspension was deposited in the posterior vaginal fornix of each of five cynomolgus monkeys (Macaca fascicularis) during their mid-menstrual cycle. Simultaneously, each animal received 10 units of oxytocin by intramuscular injection. The oviducts of three animals were removed 1 hr after administration of the bone black, while those of the remaining two animals were removed 72 hr after dosing. The removed oviducts were flushed with Hank's solution and then with collagenase solution. The solutions were collected in clean vials and filtered. The filters were examined for bone black particles by light microscopy, as were filters through which solution blanks (negative controls) had been passed. Particles resembling bone black were found on all filters. There were no appreciable differences in the number or shape of these particles between the solution-blank filters and the oviduct-flush filters. The particles on both the solution-blank filters and on the oviduct-flush filters probably originated from environmental contamination by ubiquitous carbon particles. While these results suggested that no translocation took place, translocation could not be ruled out with certainty in the absence of quantitative analyses. A more definitive pilot study was then conducted with two dosed monkeys and one control, using talc labelled by neutron activation to circumvent the problem of environmental contamination. Gamma-Ray analysis of tissue and peritoneal lavage samples for the radionuclides 46Sc, 59Fe and 60Co indicated that no measurable quantities (i.e. greater than 0.5 micrograms) of talc translocated from the deposition site in the vagina to the uterine cavity and beyond.

Animals↗

Paraneoplastic disorders in dogs with hematopoietic tumors.

Often overlooked in the presence of neoplasia, PNDs constitute significant clinical entities in dogs with hematopoietic tumors. They may cause morbidity and mortality in such patients, with effects more severe than those caused by the associated tumor. Accurate clinical evaluation of these disorders is important in differential diagnosis and treatment, for failure to realize that cancer can produce many clinical signs similar to those of other diseases may lead to incorrect diagnosis and delayed therapy. Early recognition of the problem underlying the PND is essential to selecting the proper therapeutic approach and maximizing the patient's chances for remission and survival. The presence of these disorders may complicate or rule out the preferred therapy in some cases of hematopoietic neoplasia, because the addition of cytotoxic drugs may worsen the existing PND, predisposing the dog to a variety of complications. Appropriate management of the PND may be of more immediate importance than treatment of the tumor. The study and recognition of PNDs in dogs with hematopoietic tumors may be valuable for a number of reasons: to facilitate early diagnosis of the tumor, for the observed abnormalities may represent tumor cell markers; to allow assessment of premalignant states; to aid in the search for metastases; to help quantify and monitor response to therapy; to aid in the evaluation of tumor recurrence or progression; to aid in identifying specific pathophysiologic processes by which cancer produces systemic effects; and to provide insight into the study of malignant transformation. Recognition of PNDs is relevant to the diagnosis and treatment of many problems in veterinary cancer medicine. With increasing emphasis on diagnosis and treatment of canine hematopoietic tumors, PNDs will be recognized with greater frequency and will assume greater importance in the therapeutic management of those patients. Research in veterinary and human cancer medicine needs to be directed toward identifying more definitively those substances and pathways that are responsible for PNDs, because therapy directed toward arresting the specific pathophysiologic processes causing the PND may offer the best approach for successful management of cancer.

Anemia↗

Cortical connections of the middle temporal visual area (MT) and the superior temporal cortex in owl monkeys.

The connections of the middle temporal visual area (MT) and an adjoining superior temporal visual region (ST) were investigated with injections of 3H-proline and horseradish peroxidase (HRP) in adult owl monkeys. Injections in MT revealed an extensive pattern of intrinsic connections that appeared to be organized in a series of bands across MT. MT was found to project ipsilaterally to an array of visual areas including the first (V I) and second (V II) visual areas, the dorsolateral visual area (DL), and the dorso-medial visual area (DM). When injection sites and projection zones were related to previously described retinotopic maps, it was apparent that the projections of MT to these fields were largely homotopic. Other projections were to posterior parietal cortex, the dorsointermediate visual area (DI), the ventral visual area (V), and possibly the medial visual area (M). In addition, dense projections to cortex on the rostral border of MT were used to define a new subdivision of visual cortex, the superior temporal visual region (ST), as the major projection zone of MT. Callosal connections of MT were mainly to MT, with some terminations in DL and ST. Injections of 3H-proline into ST revealed a diffuse projection to largely layer I of MT, and dense projections to posterior parietal cortex, cortex in more rostral parts of the superior temporal sulcus, ventromedial inferior temporal cortex, and the region of the frontal eye fields. Callosal projections were largely to ST cortex of the other cerebral hemisphere. The results place MT and V II in distinctly different processing chains. While both MT and V II receive the major cortical outputs of V I, V II relays to DL and DL relays to subdivisions of inferior temporal cortex. In contrast, the most significant cortical target of MT appears to be to ST, which relays to posterior parietal cortex and other targets.

Animals↗