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Biomedical subjects

A L Rosenberger

Publications and source records attributed to A L Rosenberger.

At least 19 recordsLinked to original sources
PubMed1994

Locomotion in captive Leontopithecus and Callimico: a multimedia study.

Video studies, gait analysis, footprint tracks, and observational scan sampling show that, in comparably furnished enclosures, Leontopithecus rosalia and Callimico goeldii are superficially similar in their use of predefined locomotor patterns but differ profoundly in many underlying details which reflect differences in postcranial morphology. Each uses pronograde arboreal quadrupedal walking, quadrupedal bounding, and vertical climbing with comparable frequency, and both shift to bounding while moving quadrupedally at high speeds. In walking, both species use a diagonal sequence gait. However, in Callimico the distance per bout traveled while walking or running is shorter than in L. rosalia and there is an emphasis on leaping (from a stationary position) and bounding-leaps (saltational extensions of pronograde quadrupedalism), in contrast with the basically quadrupedal style of L. rosalia. This dichotomy is consistent with anatomical specializations, such as forelimb elongation in Leontopithecus and hindlimb elongation in Callimico. In vivo hand- and footprint studies demonstrate grasping halluces in both species while walking. Limb stances in L. rosalia during "transaxial bounding" involve an overstriding hindlimb, a predominance of oblique rather than in-line travel, and unique hand and foot positions. Anatomically, this locomotor style may be associated with reduced dexterity of the elongate hands and a relatively short hallux. The captive locomotor profiles for both species probably reflect biased samples of the locomotor repertoire of their wild counterparts. Nevertheless, these data reflect species-specific integrations of locomotor behavior and morphology, and corroborate expectations of locomotor diversity among callitrichine primates, even those of similar body size. It is suggested, however, that conventional quantitative studies of locomotor profiles may prove inadequate for resolving subtle aspects of locomotor morphology and behavior.

Animals↗
PubMed1992

Evolution of feeding niches in New World monkeys.

The adaptive radiation of modern New World monkeys unfolded as the major lineages diversified within different dietary-adaptive zones predicated upon a fundamentally frugivorous habit. The broad outlines of this pattern can be seen in the fossil record, beginning in the early Miocene. Cebids are obligate frugivorous predators. The smallest forms (Cebuella, Callithrix) are specialized exudativores, and the largest (cebines) are seasonally flexible omnivores, feeding particularly on insects (Saimiri) or "hard" foods, such as pith and palm nuts (Cebus), when resources are scarce. The smaller-bodied atelids (Callicebus, Aotus) may use insects or leaves opportunistically, but pitheciins (saki-uakaris) specialize on seeds as their major protein source. The larger atelines (Alouatta, Brachyteles) depend on leaves or on ripe fruit (Ateles). Locomotion, body size, and dietary adaptations are linked: claws and small body size opened the canopy-subcanopy niche to callitrichines; climbing and hanging, the fine-branch setting to the atelines; large size and strength, semiprehensile tails, and grasping thumbs, the extractive insectivory of Cebus; deliberate quadrupedalism, the energy-saving transport of folivorous Alouatta. Body size increases and decreases occurred often and in parallel within guilds and lineages. Conventional dietary categories, particularly frugivory, are inadequate for organizing the behavioral and anatomical evidence pertinent to evolutionary adaptation. Related models of morphological evolution based on feeding frequencies tend to obfuscate the selective importance of "critical functions," responses to the biomechanically challenging components of diet that may be determined by a numerically small, or seasonal, dietary fraction. For fossils, body size is an unreliable indicator of diet in the absence of detailed morphological information. More attention needs to be given to developing techniques for identifying and quantifying mechanically significant aspects of dental form, the physical properties of primate foods, their mode of access, and the cycles of availability and nutritional value.

Adaptation, Physiological↗
PubMed1991

Laventiana annectens, new genus and species: fossil evidence for the origins of callitrichine New World monkeys.

A previously unidentified middle Miocene primate from the La Venta deposits of Colombia is intermediate between squirrel monkeys (Saimiri) and callitrichines (marmosets and tamarins) in the morphology of the lower molars, mandible, and talus. Laventiana annectens is closely related to Saimiri and to Cebus (capuchin monkeys) yet resembles the probable callitrichine morphotype, demonstrating that archaic relatives of a Saimiri-like stock were suitable structural ancestors for the enigmatic callitrichines. Laventiana is also more primitive than Saimiri (= Neosaimiri) fieldsi from the same fauna, further increasing the likelihood that the latter is a lineal ancestor of modern squirrel monkeys.

Animals↗
PubMed1990

Effects of three irreversible inhibitors of ornithine decarboxylase on macrophage-mediated tumoricidal activity and antitumor activity in B16F1 tumor-bearing mice.

The objective of the present investigation was to compare the effects of three ornithine decarboxylase inhibitors on tumoricidal macrophage and antitumor activities in vivo. alpha-Difluoromethylornithine (DFMO), (2R,5R)-6-heptyne-2,5-diamine, and alpha-(fluoromethyl)dehydroornithine methyl ester (delta MFMOme) were administered continuously in drinking water starting on Day 1 to B16F1 tumor-bearing mice. DFMO, (2R,5R)-6-heptyne-2,5-diamine, and delta MFMOme reduced B16F1 tumor growth, measured on Day 18, up to 87, 79, and 95%, respectively. Similarly, all three ornithine decarboxylase inhibitors reduced B16F1 putrescine and spermidine levels. delta MFMOme was substantially more effective both as an antitumor agent and in reducing polyamines. Both DFMO and delta MFMOme augmented macrophage tumoricidal activity directed against B16F1 target cells. MAP had no effect on macrophage tumoricidal activity. Lipopolysaccharide-stimulated macrophages from delta MFMOme-treated mice also exhibited an increase in interleukin and tumor necrosis factor levels. Furthermore, treatment with a known macrophage activator, gamma-interferon, enhanced the antitumor activity of delta MFMOme. delta MFMOme did not alter natural killer cell activity; however, cytolytic T-lymphocyte induction was reduced by 40 to 50%. These results demonstrate that, in addition to their established antitumor activity, ornithine decarboxylase inhibitors may also potentiate specific tumoricidal effector cell generation in vivo.

Alkynes↗
PubMed1989

Effect of murine alpha-, beta-, and gamma-interferons in combination with alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, on the tumor growth and metastasis of B16 melanoma and Lewis lung carcinoma in mice.

We have previously established that type I interferon (IFN), a mixture of alpha- and beta-IFN, augments the antitumor activity of alpha-difluoromethylornithine (DFMO), an inhibitor of polyamine biosynthesis, against B16 melanoma. The objective of the present investigation was to extend these earlier observations to metastatic Lewis lung carcinoma and to determine specifically which component(s) of type I IFN potentiates the antitumor activity of DFMO. Furthermore, we wanted to determine whether type II (gamma) IFN can also potentiate the antitumor activity of DFMO. Treatment of animals bearing Lewis lung carcinoma with DFMO, 2% in drinking water (3 g/kg/day), or IFN-alpha/beta (1000 units/mouse) given subcutaneously on alternate days for a total of ten doses alone resulted in 42 and 5% inhibition of tumor growth, respectively. A combination of DFMO and interferon brought about complete elimination of tumors in 12 of the 18 animals, and 94% inhibition of tumor growth in the remainder. DFMO or type I IFN administered alone caused 94 and 26% inhibition of metastasis, respectively. Combination treatment with these two agents resulted in complete elimination of visible metastases. Treatment of mice bearing B16 melanoma with DFMO resulted in 81% inhibition of tumor growth compared to controls. The administration of interferons alone resulted in tumor growth inhibition of 15, 3, 1, and 43% for type I, alpha-, beta-, and gamma-interferons, respectively. Treatment of animals with combination of DFMO and various interferons resulted in inhibition of 94, 93, 86, and 94% of B16 tumor growth for type I, alpha-, beta-, and gamma-interferons, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, augments cyclosporin A inhibition of cytolytic T lymphocyte induction.

The objective of the present investigation was to examine the effect of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, in combination with the immunosuppressant cyclosporin A (CsA) on cytolytic T lymphocytes (CTL) induction in vitro and in vivo. Treatment with DFMO (0.2 mg/ml) or CsA (10 ng/ml) alone in vitro inhibited mitogen-induced CTL generation by 56% and 51%, respectively. Similarly, DFMO or CsA treatment alone inhibited alloantigen-induced CTL generation by 50% and 62%, respectively. Combination treatment with DFMO and CsA reduced mitogen- and alloantigen-mediated CTL induction by 79% and 90%, respectively. In vivo, DFMO treatment alone did not inhibit alloantigen induced CTL generation. However, DFMO potentiated the immunosuppressive effects of CsA in vivo on CTL induction. DFMO treatment reduced activated lymphocyte putrescine and spermidine levels by 81% and 91%, respectively. Combination treatment with DFMO and CsA, at concentrations that effectively inhibited CTL induction, did not further deplete polyamine levels beyond those levels observed with DFMO alone. CsA treatment with or without DFMO did reduce detectable levels of interleukin 2 (IL-2) activity. DFMO treatment alone did not impair IL-2 production. These results indicate that CsA and DFMO may inhibit different processes required for CTL induction, IL-2 production and polyamine biosynthesis. Therefore, inhibitors of polyamine biosynthesis may be useful in lowering the doses of CsA required to inhibit CTL induction.

Adenosylmethionine Decarboxylase↗
PubMed1987

Antimetastatic activity of DL-alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, in mice.

Our earlier studies indicated a role for polyamines (namely, putrescine, spermidine, and spermine) not only in tumor growth but also in tumor metastases. We have observed that administration of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, resulted in significant inhibition of visually detectable pulmonary metastases in mice implanted with Lewis lung carcinoma. The objective of the present study is to investigate the effect of DFMO on other spontaneous and experimental metastatic models and also to determine which step(s) in the tumor metastatic cascade is sensitive to DFMO. The results presented in this study with malignant mouse B16 amelanotic melanoma (B16a) showed a dose-dependent effect of DFMO on the inhibition of both tumor growth and grossly detectable pulmonary metastases. DFMO, when administered as 0.5, 1, and 2% solution in drinking water, resulted in 0, 24.5, and 60% inhibition of tumor growth, respectively, whereas at the same doses an inhibition of 55, 83, and 96% of visible metastases was observed. At treatment levels of 1 and 2% DFMO, 30 and 65% of the animals were free of metastases. DFMO, at 0.5%, did not show any effect on tumor growth, while a significant 55% inhibition of visible pulmonary metastasis was observed, suggesting a specific role for polyamines in tumor metastasis. DFMO treatment also resulted in a significant reduction of putrescine and spermidine levels with a slight increase in spermine concentration in the tumor tissue. DFMO administration did not inhibit the experimental metastases induced as a result of i.v. injection of B16 melanoma (line F10) tumor and Lewis lung carcinoma cells into the tail vein. These results provide preliminary evidence to indicate that tumor cell polyamine depletion by DFMO might affect the first step in the metastatic cascade, intravasation (i.e., prevent the invasion of metastatic tumor cells into lymphatics or blood vessels), although the effect of DFMO on other steps in the metastatic cascade cannot be ruled out.

Animals↗
PubMed1986

The effect of alpha-difluoromethylornithine on natural killer cell and tumoricidal macrophage induction by interferon in vivo.

The objective of the present investigation was to evaluate the effect of DFMO (DL-alpha-difluoromethylornithine HCl H2O) administration on tumoricidal effector cell generation by IFN or IFN inducers in vivo. DFMO administration reduces both splenic leukocyte and peritoneal macrophage polyamine levels. In tumor bearing (B16 melanoma) mice, DFMO administration did not impair splenic natural killer (NK) cell augmentation, assessed against NK sensitive YAC-1 target cells, by IFN alpha/beta or the IFN inducers tilorone and polyriboinosinic: polyribocytidilic acid (poly I:C). Tumoricidal macrophage activation by IFN alpha/beta was similarly uninhibited by DFMO. However, only tumoricidal macrophage not NK cell activity was observed which could kill the B16 melanoma target cells. These results indicate that DFMO is not immunosuppressive regarding antitumor cytolytic cell induction in vivo.

Animals↗
PubMed1985

The effect of combination treatment with alpha-difluoromethylornithine and Corynebacterium parvum on B16 melanoma growth and tumoricidal effector cell generation in vivo.

The objective of the present investigation was to establish whether a known lymphoreticular-stimulating agent Corynebacterium parvum would augment the established antitumor activity of alpha-difluoromethylornithine in vivo. Furthermore, since C. parvum is known to boost cell mediated cytotoxicity, the effect of DFMO (DL-alpha-difluoromethylornithine X HCl X H2O) treatment was evaluated on macrophage and natural killer (NK) cell tumoricidal activity. DFMO administered alone, 1% or 2% in drinking water, inhibited 49.4% or 88.0% of B16 melanoma growth in vivo, respectively. Administration of C. parvum alone, three doses of 300 micrograms each, inhibited tumor growth 57.4%. When administered together, DFMO and C. parvum treatment resulted in 89.8% (1% DFMO) or 97.4% (2% DFMO) inhibition of melanoma growth depending upon the dose of DFMO. C. parvum-treated animals had increased levels of macrophage-mediated tumoricidal activity directed against B16 melanoma cells in vitro, however, NK cell activity was reduced. DFMO treatment alone had no effect on macrophage or NK cell tumoricidal activity. In animals receiving both C. parvum and DFMO treatments macrophage-mediated tumoricidal activity was augmented. These results demonstrate that C. parvum can augment the antitumor activity of DFMO in vivo, possibly through macrophage activation. Furthermore, in contrast to many other cancer chemotherapeutic drugs, DFMO is apparently not immunosuppressive regarding tumoricidal effector cells.

Animals↗
PubMed1984

Potentiation of antitumor and antimetastatic activities of alpha-difluoromethylornithine by interferon inducers.

The objective of the present investigation was to study the potentiation of antitumor and antimetastatic activities of DL-alpha-difluoromethylornithine (DFMO) by inducers of interferon, namely, tilorone and polyriboinosinic:polyribocytidilic acid complex [poly(l) X poly(C)]. The results of this study indicate that these interferon inducers enhance the antitumor activity of DFMO against B16 melanoma and Lewis lung carcinoma in mice. In B16 melanoma, DFMO, tilorone, or poly(l) X poly(C), when administered alone, showed 85, 39, and 39% of inhibition of tumor growth, respectively. However, a combination of DFMO and tilorone or poly(l) X poly(C) resulted in 98 and 95% inhibition of growth, with about 20% of animals showing no detectable tumors. This potentiation appears to be related to the ability of the compounds to induce interferon, since an analogue of tilorone, MDL 10,842, neither induced interferon nor potentiated the antitumor activity of DFMO. The data also indicate that this combination is particularly effective when the tumor burden is relatively low. When tilorone was given 7 days after tumor inoculation, it did not show any potentiation of antitumor activity of DFMO. The studies with Lewis lung carcinoma also showed that the interferon inducers potentiated both the antitumor and antimetastatic activities of DFMO. DFMO or tilorone administered alone showed 28 and 46% inhibition of tumor growth and 80 and 58% inhibition of metastases, respectively. Poly(l) X poly(C) by itself did not have any effect on the tumor growth and metastases. However, a combination of DFMO and tilorone brought about 78% inhibition of tumor growth and 99.5% inhibition of metastases, with 87% of the animals free of any metastases. A combination of DFMO and poly(l) X poly(C) also showed a potentiation of both antitumor activity (58% inhibition) and antimetastatic activity (94% inhibition), with 62% of the animals free of any detectable metastases. The mechanism underlying this tumor suppression by combination of DFMO and interferon inducers is not yet known. Enhancement of host immune response or interferon-mediated cytotoxicity could account for the observed marked suppression of tumor growth. Previous studies using interferon and the data reported here with interferon inducers, along with the relatively nontoxic nature of DFMO, suggest a potential use for the inhibitors of polyamine biosynthesis in combination with interferon or interferon inducers in cancer chemotherapy and other proliferative states.

Animals↗
PubMed1983

Tale of tails: parallelism and prehensility.

The occurrence of prehensile tails among only five platyrrhine genera--Cebus, Alouatta, Lagothrix, Ateles, and Brachyteles--might be interpreted as evidence that these are a closely related, possibly monophyletic group. In the absence of behavioral data, it is impossible to test whether all possess equivalent biological roles; such would lend credence to the idea that their tails evolved from an homologous, derived character complex. Contrariwise, the tendency for species of Cebus to have "averagely" proportioned or relatively short tails, in contrast to the relatively elongate tails of howlers and other atelines; osteological differences in caudal and sacral morphology; and a lack of ateline-like tail/neocortex correlates in Cebus, all imply that prehensility has evolved twice in parallel: once (homologously) in atelines and again in capuchins.

Alouatta↗
PubMed1979

Cranial anatomy and implications of Dolichocebus, a late Oligocene ceboid primate.

THE very scarce fossil record of Cainozoic New World monkeys(1,2) has contributed little to knowledge of the history of platyrrhine primates, an important element of both the neotropical mammal fauna(3) and the pantropical primates, as a whole. Only the affinities of the Middle Miocene Colombian fossils Neosaimiri, Stirtonia and Cebupithecia seem reasonably well established(4), though not without dissent(5), and these are clearly linked with the modern squirrel, howler and sakiuakari monkeys, respectively. After completion of a survey of the morphology and interrelationships of the platyrrhines, to be detailed elsewhere (A. L. R., in preparation), it is now possible to discuss the evolutionary implications of the terminal Oligocene Dolichocebus gaimanesis of Patagonia, represented by a nearly complete cranium only recently prepared fully, although first described in 1942 (ref. 6). This specimen strongly suggests that Dolichocebus is a member of the Saimiri lineage, which thus becomes the oldest generic lineage known for the primates, dating from about 25 Myr ago(7). Its affinities also imply that the two major monophyletic divisions of Ceboidea were already established by late Oligocene times, as were the marmosets and tamarins.

Journal Article↗
PubMed1976

Functional patterns of molar occlusion in platyrrhine primates.

Mechanico-functional features of molar form were studied in Callithrix, Alouatta, Pithecia and Cebus. Molars of Callithrix and Alouatta are adapted to loading foods under relatively high occlusal pressure; those of Pithecia and Cebus, under relatively low occlusal pressure. General functional considerations suggest that these taxa are adapted to insectivorous, folivorous, frugivorous and omnivorous diets, respectively. The physical properties of foods, principally mechanical strength and deformability, determine the selective pressures involved in the evolutionary adaptation of molar form. A dietary classification based upon percentages of foods eaten does not always reflect morphological adaptations. Homologous parts of teeth and homologous parts of the masticatory cycle do not always subserve equivalent functions. The relevance of functional occlusal analysis for deciphering phylogeny and explaining evolutionary grades is stressed.

Adaptation, Physiological↗