Health status among prehistoric Eskimos from Point Hope,Alaska

Using the protocol outlined in The Backbone of History: Health and Nutrition in the Western Hemisphere (BBH) (Steckel and Rose. 2002a. The backbone of history: health and nutrition in the Western Hemisphere. Cambridge: Cambridge University Press), this project compares the Mark I Health Index (MIHI) scores of the Ipiutak (n = 76; 100BCE–500CE) and Tigara (n = 298; 1200–1700CE), two samples of North American Arctic Eskimos excavated from Point Hope, Alaska. Macroscopic examination of skeletal remains for evidence of anemia, linear enamel hypoplasias (LEH), infection, trauma, dental health, and degenerative joint disease (DJD) was conducted to assess differences in health status resulting from a major economic shift at Point Hope. These data demonstrate that despite differences in settlement pattern, economic system, and dietary composition, the MIHI scores for the Ipiutak (82.1) and Tigara (84.6) are essentially equal. However, their component scores differ considerably. The Ipiutak component scores are suggestive of increased prevalence of chronic metabolic and biomechanical stresses, represented by high prevalence of nonspecific infection and high frequencies of DJD in the hip/knee, thoracic vertebrae, and wrists. The Tigara experienced more acute stress, evidenced by higher prevalence of LEH and trauma. Comparison of overall health index scores with those published in BBH shows the MIHI score for the Ipiutak and Tigara falling just above the average for sites in the Western Hemisphere, adding support to the argument that the human capacity for cultural amelioration of environmental hardships is quite significant. Am J Phys Anthropol, 2011. © 2011 Wiley‐Liss, Inc.     

Somatic mosaicism for deletion of the entire NF1 gene identified by FISH

We report a young child with a large congenital cervical plexiform neurofibroma and multiple café-au-lait spots in a generalized distribution who has mosaicism for complete deletion of the NF1 gene. The deletion was demonstrated with intragenic cosmid probes as well as YACs spanning a 700-kb contig including NF1, by two-color FISH with an NF1 and a control probe. Using different intragenic probes, deletion was found in 77–84% of cultured peripheral blood lymphocytes but not in cultured skin fibroblasts. Neither parent has signs of neurofibromatosis type 1 (NF1) or a gene deletion. This is the first report of mosaicism for complete deletion of the NF1 gene. The child did not have typical NF1 or display segmental features of NF1. Received: 6 June 1996 / Revised: 2 October 1996     

Determinants of spatial distribution in a population of the subalpine butterfly Oeneis chryxus

Summary This paper describes temporally varying determinants of the spatial distribution of adults in an insect population and the relationship between that distribution and the mating system. Male Oeneis chryxus butterflies were distributed nonrandomly throughout a sloping Colorado meadow divided horizontally by a dirt road into an upper and lower slope. Over an eight-year period of intensive study, the proportion of males located on the road, the upper slope, and the lower slope varied as a function of population size and sex ratio. In each year, more than half of the male population aggregated on sections of the road in a distinct and recurring pattern that was not correlated with the distribution of any food resource or thermal regime. Females were usually extremely scarce and not distributed in any pattern apparent from the few observations of them. Areas densely occupied by males were associated with visual landmarks. We hypothesize that the male distribution is determined by a pattern of movement of receptive females toward these landmarks. The road offers a thermally favorable environment with an unobstructed view in which to await the passage of scarce females. The mating system in this population has several lek-like features and supports the prediction that landmark mating is a favored strategy under conditions of female scarcity and wide dispersal of resources.     

Meloxicam Blocks Neuroinflammation,but Not Depressive-Like Behaviors,in HIV-1 Transgenic Female Rats

Adolescents living with human immunodeficiency virus (HIV) comprise approximately 12% of the HIV-positive population worldwide. HIV-positive adolescents experience a higher rate of clinical depression, a greater risk of sexual and drug abuse behaviors, and a decreased adherence to highly active antiretroviral therapies (HAART). Using adolescent HIV-1 transgenic rats (HIV-1 tg) that display related immune response alterations and pathologies, this study tested the hypothesis that developmental expression of HIV-1-related proteins induces a depressive-like phenotype that parallels a decrease in hippocampal cell proliferation and an increase in pro-inflammatory cytokine expression in the hippocampus. Consistent with this hypothesis, adolescent HIV-1 tg rats demonstrated a depressive-like behavioral phenotype, had decreased levels of cell proliferation, and exhibited elevated expression of monocyte chemotactic protein-1 (Mcp-1) in the hippocampus relative to controls. Subsequently, we tested the ability of meloxicam, a selective COX-2 inhibitor, to attenuate behavioral deficits via inflammatory mechanisms. Daily meloxicam treatments did not alter the behavioral profile despite effectively reducing hippocampal inflammatory gene expression. Together, these data support a biological basis for the co-morbid manifestation of depression in HIV-positive patients as early as in adolescence and suggest that modifications in behavior manifest independent of inflammatory activity in the hippocampus.     

Human microvascular endothelial cells: Coordinate induction of morphologic differentiation and twofold extension of life span

Summary Human microvascular endothelial cells (HMVEC) from adult adipose tissue were cultured in MCDB 131 medium supplemented with 10% fetal bovine serum. Under these conditions, HMVEC from seven different donors had finite proliferative life spans ranging from 14.5 to 23.5 population doublings (PD), with a mean life span of 19 PD. Addition of 10% conditioned medium from activated human leukocyte cultures (BM Condimed^?) extended the life span of HMVEC to 31 to 41 PD, with a mean life span of 37 PD. At the end of lifespan, HMVEC cultures both with and without BM Condimed had very low labeling indices (0 to 5% [³H]thymidine labeled nuclei) and consisted of enlarged cells. However, the morphologies of the two types of HMVEC cultures were very different. Untreated HMVEC were polygonal endothelial cells that formed cobblestonelike monolayers with no cell overlapping. In contrast, BM Condimed-treated HMVEC were more elongated, less regularly shaped cells that were not strictly inhibited from overlapping. When old, these cells accumulated numerous vacuoles. The BM Condimed-treated HMVEC expressed Factor VIII antigen, which confirms their identity as endothelial cells. These cells reverted rapidly to the polygonal morphology of untreated HMVEC when they were removed from BM Condimed. Likewise, their proliferative capacity was not extended further once BM condimed was removed. These results suggest that HMVEC can exist in two distinct morphologic states in which the cells have different finite proliferative life spans. This work was supported by grants AG00947 and AG04811 from the National Institute on Aging, Bethesda, MD.     

SK HEP-1: A human cell line of endothelial origin

Summary SK-HEP-1 is an immortal, human cell line derived from the ascitic fluid of a patient with adenocarcinoma of the liver. We have determined that these cells are of endothelial origin. Despite the location of the tumor from which SK HEP-1 was derived, the cell line does not have properties of hepatocytes. Northern blot analysis of total cellular RNA shows no messenger RNA for the hepatic-specific proteins albumin, alpha-fibrinogen, or gamma-fibrinogen. Endothelial characteristics are seen by transmission electron microscopy. These features include numerous pinocytotic vesicles, electron dense granules consistent with Weibel-Palade bodies, and abundant intermediate filaments, identified immunocytochemically as vimentin. Cultures grown on plastic dishes grow in bundles of polygonal to spindle-shaped cells. Proteins characteristic for endothelial cells are identified by immunocytochemistry. Addition of basement membrane material (Matrigel) or type I collagen to the cultures induces these cells to organize into a tubular network.     

Limulus amebocyte clotting cascade: Roles of endotoxin and adenylate cyclase

Endotoxin, the lipopolysaccharide from the cell wall of Gram-negative bacteria, causes blood clotting in the horseshoe crab,Limulus polyphemus. Minute amounts of endotoxin stimulate the amebocytes in the blood to undergo exocytosis, which release the contents of their secretory granules to form a clot. An endotoxin-binding protein that possesses calmodulin-like activity has been isolated from the amebocyte plasma membrane. This endotoxin-binding protein can activate adenylate cyclase fromBordetella pertussis to the same extent as rat testes calmodulin. The effect of endotoxin and the endotoxin-binding protein on cyclic AMP synthesis inLimulus amebocytes was examined. Amebocytes exposed to endotoxin have increased levels of intracellular cyclic AMP. Amebocyte membranes contain an adenylate cyclase which is stimulated by NaF, guanosine (,r-imido)triphosphate, and for skolin. This adenylate cyclase is also stimulated by the endotoxin-binding protein and calcium. Exposure of amebocytes to forskolin or dibutyryl cyclic AMP are stimulated to secrete clot components. Activation of adenylate cyclasein vivo by endotoxin via the endotoxin-binding protein may be one of the ways in which endotoxin stimulates secretion. It is suggested that endotoxin may have two actions in theLimulus system: (1) binding of endotoxin to the endotoxin-binding protein activates adenylate cyclase, promoting secretion by the amebocytes; and (2) endotoxin catalyzes a reaction on the secreted material to form a blood clot. This latter reaction is not elicited by forskolin or dibutyryl cyclic AMP.A preliminary report of this work has been presented elsewhere (Liu and Liang, 1984).     

Forearm training attenuates sympathetic responses to prolonged rhythmic forearm exercise

Sinoway, Lawrence, Jeffrey Shenberger, Gretchen Leaman,Robert Zelis, Kristen Gray, Robert Baily, and Urs Leuenberger. Forearm training attenuates sympathetic responses to prolonged rhythmic forearm exercise. J. Appl.Physiol. 81(4): 1778-1784, 1996.We previouslydemonstrated that nonfatiguing rhythmic forearm exercise at 25%maximal voluntary contraction (12 2-s contractions/min) evokessympathoexcitation without significant engagement ofmetabolite-sensitive muscle afferents (B. A. Batman, J. C. Hardy, U. A. Leuenberger, M. B. Smith, Q. X. Yang, and L. I. Sinoway.J. Appl. Physiol. 76: 1077-1081,1994). This is in contrast to the sympathetic nervous system responsesobserved during fatiguing static forearm exercise wheremetabolite-sensitive afferents are the key determinants of sympatheticactivation. In this report we examined whether forearm exercisetraining would attenuate sympathetic nervous system responses torhythmic forearm exercise. We measured heart rate, mean arterial bloodpressure (MAP), muscle sympathetic nerve activity (microneurography),plasma norepinephrine (NE), and NE spillover and clearance (tritiatedNE kinetics) during nonfatiguing rhythmic forearm exercise before andafter a 4-wk unilateral forearm training paradigm. Training had noeffect on forearm mass, maximal voluntary contraction, or heart ratebut did attenuate the increase in MAP (increase in MAP: from 15.2 ± 1.8 before training to 11.4 ± 1.4 mmHg after training;P < 0.017), muscle sympathetic nerve activity (increase in bursts: from 10.8 ± 1.4 before training to6.2 ± 1.1 bursts/min after training;P < 0.030), and the NE spillover(increase in arterial spillover: from 1.3 ± 0.2 before training to0.6 ± 0.2 nmol ^· min^{1 ·} m²after training, P < 0.014; increasein venous spillover: from 2.0 ± 0.6 beforetraining to 1.0 ± 0.5 nmol ^· min^{1 ·} m²after training, P < 0.037) seen inresponse to exercise performed by the trained forearm. Thus forearmtraining reduces sympathetic responses during a nonfatiguing rhythmichandgrip paradigm that does not engage muscle metaboreceptors. Wespeculate that this effect is due to a conditioning-inducedreduction in mechanically sensitive muscle afferentdischarge.

     

Training-induced alterations of glucose flux in men

Friedlander, Anne L., Gretchen A. Casazza, Michael A. Horning, Melvin J. Huie, and George A. Brooks. Training-induced alterations of glucose flux in men. J. Appl.Physiol. 82(4): 1360-1369, 1997.We examined thehypothesis that glucose flux was directly related to relative exerciseintensity both before and after a 10-wk cycle ergometer trainingprogram in 19 healthy male subjects. Two pretraining trials [45and 65% of peak O₂ consumption(O_{2 peak})] andtwo posttraining trials (same absolute and relative intensities as 65%pretraining) were performed for 90 min of rest and 1 h of cyclingexercise. After training, subjects increasedO_{2 peak} by9.4 ± 1.4%. Pretraining, the intensity effect on glucose kinetics was evident with rates of appearance(R_a; 5.84 ± 0.23 vs. 4.73 ± 0.19 mg · kg¹ · min¹),disappearance (R_d; 5.78 ± 0.19 vs. 4.73 ± 0.19 mg · kg¹ · min¹),oxidation (R_ox; 5.36 ± 0.15 vs. 3.41 ± 0.23 mg · kg¹ · min¹),and metabolic clearance (7.03 ± 0.56 vs. 5.20 ± 0.28 ml · kg¹ · min¹)of glucose being significantly greater(P  0.05) in the 65% than the 45%O_{2 peak} trial. WhenR_d was expressed as a percentage of total energy expended per minute(R_{d E}), there was nodifference between the 45 and 65% intensities. Training did reduceR_a (4.63 ± 0.25),R_d (4.65 ± 0.24),R_ox (3.77 ± 0.43), andR_{d E} (15.30 ± 0.40 to12.85 ± 0.81) when subjects were tested at the same absolute workload (P  0.05). However, whenthey were tested at the same relative workload,R_a,R_d, andR_{d E} were not different,although R_ox was lowerposttraining (5.36 ± 0.15 vs. 4.41 ± 0.42, P  0.05). These results show1) glucose use is directly relatedto exercise intensity; 2) trainingdecreases glucose flux for a given power output;3) when expressed as relativeexercise intensity, training does not affect the magnitude of bloodglucose use during exercise; 4)training alters the pathways of glucose disposal.