EphB4 (HTK) and its ligand, ephrinB2, are critical for angiogenesis and result in fatal abnormalities of capillary formation in null mice. EphB4 was originally identified in human bone marrow CD34 ؉ cells by us and has since been reported to be expressed in erythroid progenitors, whereas the ligand ephrinB2 is expressed in bone marrow stromal cells. Reasoning that the developmental relationship between angiogenesis and hematopoiesis implies common regulatory molecules, we assessed whether EphB4 signaling influences the function and phenotype of primitive human hematopoietic cells. IntroductionHematopoietic stem cells (HSCs) have the capacity to self-renew and to differentiate along a number of pathways, thereby generating all blood cells. Understanding the molecular mechanisms that regulate the formation, growth, and differentiation of HSCs has become increasingly complex. 1 The bone marrow (BM) is a diverse environment that contains a variety of different cell types and extracellular matrix molecules. The BM microenvironment produces a wide range of stimuli to different hematopoietic cells, providing combinatorial relationships that result in the finely tuned hematopoietic system. How factors (in either membrane-bound or soluble form) produced by BM stromal cells regulate the balance of self-renewal and differentiation of specific blood cell lineages remains a major question.Eph receptor tyrosine kinases and their ligands, ephrins, play important roles in various processes during embryonic development, including the targeting behavior of migratory neurons, vascular cell assembly, and angiogenesis. 2 Fourteen Eph receptors have been catalogued into EphA or EphB subclasses based on their affinity for ligands. Eight ephrins have been identified to date. They are membrane proteins of either glycerophosphatidylinsitol (GPI)-linked (ephrinA) or transmembrane (ephrinB). 3 Rather than longrange communication, signaling from Eph receptors and their ligands is restricted to sites of direct cell-cell contact and is capable of inducing reciprocal bidirectional events between interacting cells. 4 Some Eph and ephrin molecules have been found to be expressed in the hematopoietic system. EphA3 (Hek) was originally cloned from a pre-B-cell leukemia and is expressed in some T-cell lines. 5 EphA1 (Esk), EphA2 (Eck), and EphB2 (Hek5) were reported to be expressed in thymus. 6-8 EphA4 (Hek8) and EphA7 (Hek11) appear to be expressed in human fetal bone marrow pro-B cells. 9 The receptor tyrosine kinase EphB4 (HTK) and its cognate ligand, ephrinB2 (HTKL) are widely expressed in fetal and adult tissues. 10,11 Unlike most of the Eph subfamily members, EphB4 does not appear to be expressed in the central nervous system. Recent studies have shown that EphB4 is specifically expressed at the venous endothelium, whereas ephrinB2 is specifically and reciprocally expressed on arterial endothelial cells at the earliest stages of vascular development. 12 Mice lacking either EphB4 or ephrinB2 display identical defects in angiogenesis by arteri...

In recent years, Alzlzeimer's disease lzcis becoiize well known both to the medical profession and to layinen cis an increasingly important cmse of inorbidity and mortality in the elderly. As interest in the disease has grown, so has the scient$ic literature. In the past four years, over 400 jotirnul (irticles in the English language alone have been publislzed on various aspects of Alzlzeiiner's rlisecise.Those pcirticipating in the Geriatric Medicine Fellowslzip Program at tlw Gainesville V A Mediccil Center have compiled an annotated list of 92 important references on Alzlzeimer's disease. These are class$ied into six major groups: General Review, Etiology, PatIzopRysiology, Diagnosis, Treutment, and Epidemiology. It is important f o r the practicing plzysician to be able to quickly find references to recent studies on various aspects of Alzkcimer's clisease, especicilly those related to treatinent possibilities. Family mcinbers of Alzkcimer's patients are particularly well infomned about this disease and are anxious to learn about tlze latest resecirclz advances from their physicians. I. CENEIIAL REVIEW 1. College Coininittee on Geriatrics: Organic mental impairment in the elderly. J 13 Coll Physicians Loiid 15:141-67, 1981 A romprclicnsive reiiort runsistiiig or llircc piirts: (1) siinininry or clisc~sc processes. pntlioloyy. nssessmctit. nnd tlicrupy crf the dcnic~itius: (2) iinnlysis or tlic prnvision of lienltli enre to the denicnted clclcrly in Great Uritnirr: nnil(3) grolwsnls for ccliieiition for Iicnltlr profcssioniils nnd tlic generid piil~lic to increase iinilerstiinding of incntnl iinpiiirincnt 111 tlic clclcrly. 2. Butler RN: Cliartiiig the conquest of senility. Bull NY Acnd Med 58:362-81, 1982 Cites the ~ieglcct orpsycliititryiind psycliology to ialdrcss IIIC probleiiis UIICI CIIIISCS ordcnletlti~i. nevic\vs h i c fentiires hlzlicinicr's iliseusc nnd discusses vnriniis cni~s:il tlicwrics. l~iiinlly revlcws llic c o i i~~~i i l i i r r~i t of tlic NIA to sponsor rcsciircli in tliis nren. 3. Glenner GG: Alzheimer's disease (senile dementia): a research update and critique with recommendations. J Am Geriatr SOC 3035942, 1982 Sumiiiurizcs llic latest rcscsreli findings in Alzliciiner's cliscnse and clisci~sses the ~l i l r i~~l t i~~ inlierent i n stiidyiiig this iliscnsc. Si~ggcstions iirc iniidc Cir ne\v uppronclws. itichiling enzyinc iiircl neirronnl rcccptar studies. 4. Bowen EM, Dnvison AN: The failing brain. J Chronic Dis 363-13, 1983 Describes progress nncl weas of contriivcrsy regarding i\lzlicinicr's iliswse. Cell loss. synoptogcncsis, Iiistopntliology. neiirotriuisiiiittcr metiibolisni. und bioclicniiciil chnngcs nrc ilisci~ssed. He\*icws ~ilinrinecologic IiBtcrveiition. 5. Hainill RW, Buell SJ: Dementia: clinical and basic science aspects. J Am Geriatr Soc 30:781-7, 1982 011tlitic~ ~IIC c l i~i i~~l lwturcs or SCIICSCC.IICC U I I~ dcincntin: dilli.rcntiiil diiignosis mid liistnclicniical niid ncii-roiritliolo~ic clinructcristics or Alzlieiiiicr's discese. G. Blass JP: Ileinentia. Med Clin...

Blood granulocyte-macrophage progenitor cells (CFU-GM) and myeloid differentiation were studied in 16 patients with hepatic cirrhosis by culturing blood mononuclear cells in semisolid and in liquid medium. The numbers of CFU-GM from normal and cirrhotic subjects were not significantly different, even when increased numbers of monocyte-macrophagic colonies and decreased numbers of granulocytic colonies were observed in cirrhotic patients. Significantly reduced granulocytic growth and increased monocyte-macrophagic cell growth were found in liquid culture of cirrhotic patients. These data seem to indicate that in hepatic cirrhosis, besides granulocyte sequestration within the spleen, there is a disorder of granulocytic versus monocyte-macrophagic differentiation.

No abstract