100 000. The overall mortality rate was 13,6 per 100,000 climbers. Conclusion: Although HAI
occurs frequently among climbers, fatal cases are rare. With an increased awareness of risks of
activities at high altitudes among tourists and tour guides, most fatal cases could be prevented on
Mt. Kilimanjaro.
72.
ADAPTING TO EXCESSIVE ERYTHROCYTOSIS IN MICE. Katja Heinicke
1
. Division of
Physiology, School of Medicine, University of California San Diego, CA
1
.
Erythropoietin (Epo) is the main regulator of red blood cell production. The oxygen-
dependent regulation of Epo is controlled by hypoxia-inducible factor alpha. Imbalanced
erythropoiesis leads to polycythemia that might result in hypertension and thromboembolism.
Nevertheless, excessive erythrocytosis in our transgenic mice (tg6) that, due to hypoxia-
independent overexpression of human Epo, reach hematocrit levels of 0.8 to 0.9 did not show
alterations in blood pressure, heart rate or cardiac output, nor could thromboembolism be
observed. We recently reported that adaptive mechanisms to the increased number of erythrocytes
involve elevated expression of nitric oxide (NO) and increased flexibility of tg erythrocytes that
lead to vasodilation and controlled elevation of blood viscosity, respectively. Despite these
adaptive mechanisms, the life span of tg6 mice was less than one year. Morphological and
functional examination of tg6 mice showed severe degenerative processes in the kidney including
(i) extensive iron deposition in tubules, (ii) dilatation of the Bowman's capsule and urinary space
accompanied by a progressive capillary retraction and (iii) increased permeability of the renal
endothelium. Moreover, increased lung volume in the tg6 mice suggested that emphysema might
develop. In addition, tg6 animals suffer from splenomegaly, and, to a given extent, liver and heart
hypertrophy, but did not show cerebral alterations. Interestingly, we observed an increased
capillary to fiber ratio, increased capillary density and decreased neuromuscular junction density
in the skeletal muscle as well as degeneration of the n. ischadicus. In summary, despite NO- and
viscosity-dependent adaptation, excessive erythrocytosis leads to early death due to multiple
organ failure.
73.
SUPPRESSION SUBTRACTIVE HYBRIDIZATION(SSH) FOR IDENTIFYING
DIFFERENTIALLY EXPRESSED GENES IN BONE MARROW OF HYPOXIA-ADAPTED
PEOPLE*. Xin Hong
1
, Zhonghai Xiao
1
, Zhaoyun Yin
1
, Xuetao Pei
2
. Tianjin institute of Health
and environmental medicine, Tianjin
1
, Beijing institute of transfusion medicine, Beijing
2
.
Polyadenylated RNA was isolated from bone marrow of hypoxia-adaptated Tibetan
volunteers and Han of sea level origin living on the Tibetan plateau, and SSH was performed
according to the instructions of the kit manufacturer. Second round PCR products were cloned to
T/A vectors to set up the subtractive library. Some clones underwent sequence analysis and
Northern blot to identify specifically expressed genes. The human hypoxia adaptated bone
marrow (HHABM) subtractive library with high subtractive efficiency contains 436 positive
clones. PCR analysis of the clones showed that the vectors in the clones contained 100- 600bp
inserts. Among sequence analysis gene clones, 2 are known genes which are Hembase in
Erythroid Precursor Cells; and hemoglobin beta mRNA, 8 sequences were of unknown function
and from hematopoietic related cDNA Library. They are cDNA clones from Bone marrow
CD34+ hematopoietic stem/progenitor cell; from Culture of Peripheral Blood Mononuclear Cells
EPO responsive CD71++++ Progenitor stage; from GPA++ Precursor erythroblasts; from TN
intrathymic T-cell CD3-4-8- triple negative stage; from Human fetal liver cDNA library; from
whole embryo cDNA; Human fetal kidney subtracted cDNA library; Human Fetal Pancreas
cDNA. The other 7 are tumor related gene, including Homo sapiens lung tumor, breast
adenocarcinoma, Human insulinoma, lung large cell carcinoma, moderately-differentiated
endometrial adenocarcinoma, Human Chondrosarcoma Grade 3 cell line mix cDNA clones. The
constructed cDNA subtractive library of HHABM lays a solid foundation for large scale
screening and cloning new and specific genes of hypoxia adaptation. Some of sequenced and
specifically expressed genes provided an important clue for studying the mechanisms of hypoxia
