A comparison of HLA-DRB1 alleles in three Lebanese villages reproductively isolated by geography and religion We
analyzed differences in HLA allele frequencies between small populations
of the same ethnic group. Our hypothesis was that, even if the ancestral
gene pools were identical, the effect of genetic drift and consanguinity
would result in variation in frequencies of shared alleles and/or the occurrence
of specific alleles. We tested this hypothesis by sampling 100 unrelated
subjects (50 husband/wife pairs) in three Lebanese villages reproductively
isolated by geography and religion. Niha El Shouff (NS), Kfarzubian (KF)
and Yohmor (YH). Blood samples from two children of each mating were obtained
for haplotype assignments. Successful PCR-SSOP DRB1, B3, B4, B5 typing
was obtained from 90 subjects (59 parents plus 31 on the volunteers) in
NS, and 92 and 81 parents in KZ and YH, respectively. Only 28 previously
reported DRB1 alleles were represented. The most frequently shared alleles
were 0701, 1104, and 1101; 66% of YH, 32% of NS, and 28% of KZ alleles.
1112, 0801 and 1103 were found only in NS, 6/28 alleles were observed only
once, and 2/28 were absent in this village. 1602 and 0405 were unique to
KZ, 3/28 were observed once, and 6/28 were absent. In YH, there were no
unique alleles; 5/28 were observed once and 8/28 were absent. Although
sample sizes are small, it is apparent that HLA allelic heterogeneity varies
among these ethnically similar, reproductively isolated villages. This
work was carried out in cooperation with the Immunogenetics Laboratory
at the Johns Hopkins University. W. Bias*, N. Nuwayri-Salti, B. Cissell*,
S. Berger* and B. Schmeckpeper. (Supported by Oussaymi Foundation;
Lebanese Ministry of Health.)
A comparative study of morphological alterations in the cardiovascular system of primary and secondary hypertensive rats There
have been only limited immunocytochemical studies of the histological structure
of the major vessels in hypertensive animals including the carotid body
and sinus. This comparative study aims to investigate the morphological
alterations of the vessel wall and heart in primary and secondary hypertension.
It will try to depict the various cell types and subsets populating these
vessels, and finally test the effect of various antihypertensive drugs
on such morphology. Such a study may shed further light on the biology
of advancing hypertension and possibly the relationship between the morphological
alterations and the pathogenesis of the two types of hypertension, primary
and secondary. These studies would also have implications in attempts to
prevent coronary artery disease by antihypertensive drugs. Finally, understanding
the possible role of immunoeffectors or mediators in the basic mechanism
of hypertension will stimulate the development of new therapeutic approaches
for this disease. A.R. Jurjus and H. Khansa*.
Direct transmission of Leishmania donovani in the absence of cutaneous lesions among mated mice We
studied the possibility of transmission of Leishmania parasites
in Balb/c mice injected intradermally with a strain of L. donovani.
The animals were mated with normal congeners and observed for disease progress.
The results and implications of this experiments are discussed in a publication
in preparation. N. Nuwayri-Salti. (Supported by LNCSR.)
The profile of leishmaniasis in Lebanon Studying
the populations around sentinel cases, we have formulated a reasonably
realistic picture about the prevalence of cutaneous leishmaniasis in north
Lebanon, the extent of spread in the animal reservoir and the species of
the phlebotomine vector which is the culprit (article in preparation).
N. Nuwayri-Salti, Z. Baydoun, K. Knio, E. Baydoun and E. Abou
Fakhr. (Supported by LNSCR; National Institute of Health.)
Major histocompatibility class I antigens in the Lebanese population Except
for scattered reports on Lebanese immigrants, so far there has not been
any studies on the major histocompatibility (MHC) antigens prevalent in
the Lebanese population. We describe the frequency distribution and linkage
disequilibrium of MHC class I antigens identified by serology and present
in the A, B and C loci based on data obtained from 200 healthy unrelated
individuals from different parts of Lebanon. The highest gene frequencies
were as follows: A2 (24.8%), B35 (17.9%) and CW4 (18.6%), making this haplotype
the commonest. Comparison of genetic distances revealed a pattern closer
to the Caucasoid population than to the Mongoloid, Oriental or Negro populations.
N. Nuwayri-Salti and M. Chaya. (Supported by the Oussaymi
Foundation.)
Immunogenetic markers associated with organ specific autoimmune disease: IDDM We
have completed the work on Class I and II serologic profile of the antigens
encoded by MHC loci I and II on a sample of 42 patients. DQ and DR residues
and alleles which seem to associate (predispose?) with disease expression
have been analyzed and sorted out on 16 out of the 42 patients only. DRB,
DQA and DQB features of the remaining 26 patients are in preparation. N.
Nuwayri-Salti, G. Halabi, I. Salti, M. Shoucair and P. H. Torbey*.
(Supported by URB.)
Behavior of Leishmania donovani sensu lato in BALB/c mice: Behavior in a mouse model of isolates of Leishmania donovani sensu lato cultured from the blood of patients with chronic cutaneous lesions Our
objective was to characterize biologically in an animal model, two isolates
of Leishmania parasites obtained unexpectedly from circulating blood
in two patients with chronic cutaneous Leishmaniasis. Both isolates were
classified by cellulose acetate electrophoresis as belonging to the
donovani complex (donovani sensu lato). We elected to use an animal
model established for several strains of this parasite, among which is
L. major, known to be dermotropic in man. We used BALB/c mice, an inbred
strain which has been proven to be exquisitely sensitive to L. major.
Our study demonstrated that for the same number of parasites used by intradermal
injection, the course of illness observed in the group which received the
donovani strain was totally different from what developed in the
animals which received the L. major strain. N. Nuwayri-Salti,
M. Matta, Z. Shbaklo, M. Lakkis* and Z. El-Jissr Kabbani*. (Supported
by LNCSR.)
Canine leishmaniasis in northern Lebanon In
recent years, a number of cases of human infection with Leishmania parasites
have been reported from Lebanon. As part of a campaign by the health authorities
to eradicate stray dogs, a total of 26 dogs that were caught were used
in this study. Leishmania antibodies were tested by immuno-fluorescence
and ELISA on the collected sera. Sera from three dout of the 26 were positive
for anti-Leishmania antibodies by the above two methods. Cultures
from tissues from one dog (whose serum was positive by both above serologic
tests) grew Leishmania parasites. The cultured promastigotes were
subjected to RAPD analysis which confirmed the identity of the parasite
as being of the L. infantum species (member of the L donovani
complex). These preliminary results are the first report on the animal
reservoir for Leishmania in Lebanon. N. Nuwayri-Salti, R. Nasr,
K. Haddad*, S. Chamat and J. Usta. (Supported by LNCSR.)
Anti rk39 antibodies in sera of Lebanese patients with cutaneous leishmaniasis We
are determining the level of antibodies to one component specific to a
strain of Leishmania parasites. rK39 is a recombinant polypeptide
which represents a highly conserved repeat in Leishmania donovani
kinesin-related gene and which was shown to be a specific and sensitive
screening antigen for antibodies present in the blood of patients with
active visceral leishmaniasis. N. Nuwayri-Salti, Y. Skeiky and S.
Reed*. This work was carried out at Corixa Corporation, Seattle. (Supported
by the National Institute of Health.)
Hematogenous spread of L. dononvani parasites in a child with acute cutaneous leishmaniasis Cutaneous
leishmaniasis is highly endemic in the countries bordering the eastern
Mediterranean shore. The established agents in this derangement are either
Leishmania tropica or Leishmania major organisms. We are
studying a case of a young girl with acute cutaneous leishmaniasis where
the agent is cultured both from the lesion and the blood stream. N.
Nuwayri-Salti, S. Salman, N. Mansour Shahine* and J. Malak.
(Supported by LNSCR; National Institute of Health.)
Immunogenetic markers associated with some autoimmune disorders: Grave’s disease We
are reporting the profile of HLA Class I antigens in 40 Lebanese patients
with Grave’s Disease. The above were determined serologically using commercially
available One-Lambda trays. Statistical analysis of our results revealed
a higher prevalence of this derangement in subjects with the expression
of certain antigens: B39 and A2403 exhibited an odds ratio (OR) of 9.6
and 10.1 respectively. B41 seems to play the same role though not as dramatically
with an OR of 2.3. On the other hand, A24 antigen (split of A9) seems to
have a somewhat protective effect with an OR less than 1. We are also reporting
the titers of the following autoantibodies in the above patients: Anti-TPO;
Anti-TG and TRAB. N. Nuwayri-Salti, M. Shoucair, S. Azar, R. Jaber,
I. Salti and G. Halabi*. (Supported by URB.)
Immunogenetic markers associated with multisystem autoimmune disorders: Behç et disease and rheumatoid arthritis So
far, we have the results on 23 patients. More samples should be determined
before a meaningful statistical analysis is carried out to determine which
MHC antigens predispose and favor this disease and which, if any, have
a protective effect. N. Nuwayri-Salti, I. Uthman and F. Nasr.
(Supported by URB.)
Reciprocal interconnection between the dorsal column and the vestibular nuclei; an anatomical and electrophysiological study Using
electrophysiological and modern tracing techniques, horse redish peroxidase
(HRP) and wheat germ aglutinate-horse redish peroxidase (WGA-HRP), this
study investigates the possible existence of reciprocal projections between
the dorsal column and vestibular nuclei and the possible role of this loop
in the modulation of sensory-motor behavior. N.E. Saadé, N. Bahuth
and S.J. Jabbur. (Supported by URB; Diana Tamari Sabbagh Fund.)
Effects of selective chemical lesions placed in the basal ganglia or the substantia nigra Previous
work from our laboratory has shown that surgical and/or chemical lesions
of either the cerebral cortex or the striatum produced significant inhibition
of autotomy behavior (model for chronic deafferentation pain) and nociceptive
reflexes (models for acute pain) in rats. These data provided experimental
evidence on the role of the basal ganglia in the processing of nociceptive
information and their involvement in the control of pain related behavior.
Furthermore, these results provide neural substrates to the recent clinical
observation showing an involvement of the neostriatum in the frontal lobe
syndrome. N.E. Saadé, S.J. Jabbur and S.F. Atweh.
(Supported by URB; Diana Tamari Sabbagh Fund.)
Hyperalgesia induced by local inflammation: upregulation of cytokines and neurotrophins and induction of fos-like immunoreactivity in the central nervous system Intraplantar
and intraperitoneal injections of inflammatory or proinflammatory agents
produce hyperalgesia as assessed by various acute pain tests. This hyperalgesia
is characterized by an increase in the levels of interleukin 1b
, tumor necrosis factor and nerve growth factor in the peripheral tissues.
These peripheral events play a major role in the induction of fos gene
expression at the level of the central nervous system and especially in
specific areas known to be involved in the processing of nociceptive information.
N.E. Saadé, B. Safieh-Garabedian, S. Kanaan, S.F. Atweh and
S.J. Jabbur. (Supported by URB; Diana Tamari-Sabbagh Fund.)
Vascular and myogenic anatomic variations The
identification and documentation of the anatomic variations in muscles
and vessels are helping to clarify and expand our incomplete knowledge
of the structure of the human body. The ongoing project is a micro/mascroscopic
study of selected cadaveric material, previous findings having already
been published. F. Saadeh, R. Bergman*, F. Haikal* and J.
Hawi. (Funded by Department of Human Morphology.)
Vascular patterns in myo-and fasciocutaneous flaps A
thorough knowledge of vascular patterns in myocutaneous and fasciocutaneous
flaps used in reconstructive surgery is extremely important. The ongoing
anatomic study evaluates the vascular basis for such flaps, especially
vessels that traditionally receive little attention in didactic teaching,
but could be invaluable to the surgeon. F. Saadeh, F. Haikal* and
S. Kawas. (Funded by University of Alexandria through F. Haikal.)
Regulation of vasomotor function by cell-cell communication Hypertension
is a well-recognized pathophysiological contributor to the progression
of coronary artery disease. A major focus of this laboratory is to evaluate
the role of cell-cell communication in the control of vasomotor function
and to utilize this knowledge for developing strategies for prevention
and effective therapeutic intervention in pathological situations. We use
laser confocal imaging microscopy and flowcytometry to study gap junctions
between EC and SMC in purified cell cultures of EC and SMC as well as in
cocultures. Disordered interaction between vascular cells could play a
role in the evolution of abnormal states of vasomotor function. An understanding
of normal coordination by cell-cell communication is necessary for the
task of unraveling the basis of altered regulation in disease. M. E.
El-Sabban.
Adhesion and gap junctional communication between macrophages and intestinal epithelial cells In
intestinal inflammation, inflammatory cell infiltrates are found juxtaposed
to the epithelial cell basolateral membranes. We have shown that specific
adhesion occurs between macrophages and intestinal epithelial cells (IEC).
In this joint project the study of the role of adhesion and gap junction-facilitated
communication of inflammatory cells with intestinal epithelial cells is
undertaken. The role of cytokines in the up-regulation of adhesion and
communication is studied and the nature of the message transmitted between
the two cell types is investigated The interaction between IEC and macrophages
through gap junctions could provide a means by which inflammatory cells
regulate IEC function. This may assist in devising new strategies for intervention
in inflammatory bowel diseases. M. E. El-Sabban and F.
R. Homaidan.
HLA class II DPB1 alleles found in families from three isolated Lebanese villages Samples
from families (2 parents and 2 children) were obtained from 3 villages
isolated by geography and religion, so that alleles found in these populationcould
be compared. DNA was amplified and probed with primers and sequence specific
oligonucleotides. Nine combinations of alleles could not be distinguished.
In village Yohmor (YH) 10 DBB1 alleles were identified in 39 parents who
were typed; 15 more parents had combinations. In village Kfarzubian (KZ)
11 DPB1 alleles were found in 46 parents; 17 more had combinations. In
village Niha Shouff (NS) 13 DPB1 alleles were found in 25 parents; 8 others
had combinations. The DPB1 allele frequencies in these 3 groups were calculated
(results not shown here). DBB1*0301 was fourth frequent in both KZ (0.06)
and NS (0.04). The 4 alleles: 0401, 0402, 0301 and 02012 account for 73-83%
of the total DBP1 alleles found in members of these 3 villages. This work
was carried out in cooperation with the Immunogenetics Laboratory at the
Johns Hopkins University. C. Ng-Wong*, N. Nuwayri-Salti, W. Bias*
and B. Schemeckpeper*. (Supported by the Oussaymi Foundation; Lebanese
Ministry of Health.)
HLA class II DRB and DBQ1 alleles found in families from three isolated Lebanese villages Samples
from families (2 parents and 2 children) were obtained from each of 3 villages
isolated by geography and religion, so that alleles found in these populations
could be compared. DNA was amplified and probed with primers and sequence
specific oligonucleotides. We also devised primers and probes to discriminate
ambiguous allele combinations, e.g. DRB4. In village Yohmor (YH) 21 DRB1
and 23 DQB1 alleles were found in 80 parents who were typed. In village
Kfarzubian (KZ) 24 DRB1 and 11 DQB1 alleles were found in 89 parents. In
village Niha Shouff (NF) 33 DRB1 and 12 DBQ1 alleles were found in 58 parents.
The allele frequencies of the 3 groups were calculated. We found that all
DRB1*04 and DRB1*0901 alleles were associated with DRB4*0103. The DRB4*0102
allele was not found. The DRB1*0701 was found with various DRB4 alleles
(results not shown here). The 3 groups (YH, KZ, and NS) have distinct DRB
and DQB1 allelic patterns. This work was carried out in cooperation with
the Immunogenetics Laboratory at the Johns Hopkins University. W. Wood
III*, B. Cissell*, N. Nuwayri-Salti, W. Bias*
and B. Schmeckpeper*. (Supported by the Oussaymi Foundation; Lebanese
Ministry of Health.)
Christ, G.J.*, Spray, D.C.*, El-Sabban, M.E., Moore, L.* and Brink, P.R.*, A review of gap junctions in vascular tissue: evidence for an obligatory role of heterotypic and homotypic intercellular communication in the modulation of vasomotor tone. Circulation Research, 79, 631-646, 1996. El-Sabban, M.E. and Pauli, B.U.*, Adhesion mediated gap junctional communication between lung-metastatic cancer cells and endothelium. Invasion and Metastasis, 14, 164-176, 1995. ———, Role of cell adhesion molecules in endothelial cell/tumor cell communication in tumor cell extravasation. Progress in Cell Research, 4, 87-92, 1995. Goetz, D.*, El-Sabban, M.E., Pauli, B.U.* and Hammer, D.*, Lu-ECAM-1 mediated adhesion of murine melanoma cells to endothelium under conditions of flow. International Journal of Cancer, 65, 1-8, 1996. Grummer, R.*, Hellman, P.*, Traub, O.*, Soares, M. J.*, El-Sabban, M. E. and Winterhager, E*., Regulation of Connexin 31 gene expression upon retinoic acid treatment in rat choriocarcinoma cells. Experimental Cell Research, 227, 23-32, 1996. Jurjus, A., Low Birth Weight in Lebanon: A morphological parameter and a health status indicator. Eastern Mediterranean Health Journal, 1 (2), 194-200, 1995. Kanaan, S.A., Saadé, N.E., Haddad, J.J., Abdelnoor, A.M., Atweh, S.F., Jabbur, S.J. and Safieh-Garabedian, B., Endotoxin-induced local inflammation and hyperalgesia in rats and mice: A new model for inflammatory pain. Pain, 66, 373-379, 1996. Nuwayri-Salti, N., Nasr, R., Haddad, K.*, Usta, J. and Shamat, S., Canine Leishmaniasis in Northern Lebanon. Annals of Tropical Medicine and Parasitology, 91 (2), 221-222, 1997. Saadé, N.E., Atweh, S.F., Bahuth, N. and Jabbur, S.J., Augmentation of nociceptive reflexes and chronic deafferentation pain by chemical lesions of either striatal dopaminergic terminals or midbrain dopaminergic neurons. Brain Research, 751, 1-12, 1997. Saadé, N.E., Shbeir, S.A., Atweh, S.F. and Jabbur, S.J., Effects of cerebral cortical and striatal lesions on autotomy following peripheral neurectomy in rats. Physiology and Behavior, 60, 559-566, 1996. Saadeh, F.A., Haikal, F.A., Kawas, S.H. and Hawi, J., The middle temporal artery: study of 48 cadaveric dissections. Journal of the Anatomic Society of India, 45 (2), 95-99, 1996. Safieh-Garabedian, B., Jalakhian, R.H., Saadé, N.E., Haddad, J.J., Jabbur, S.J. and Kanaan, S.A., Thymulin reduces hyperalgesia induced by peripheral endotoxin injection in rats and mice. Brain Research, 717, 179-183, 1996. Safieh-Garabedian,
B., Poole, S.*, Allchorne, A.*, Kanaan, S., Saadé, N.E. and Woolf,
C.J.*, Zinc reduces the hyperalgesia and upregulation of NGF and IL-1b
produced by peripheral inflmmation in the rat. Neuropharmacology,
35, 599-603, 1996.
Bejjani, G.*, Sullivan, B.*, Abello, J.*, Jurjus, A., Duong, D.*, Wright, D.*, and Sekhar, L.*, The exocranial portion of the lower cranial nerves: surgical landmarks. Proceedings of the American Association of Neurological Surgeons Annual Meeting, 167, 1253, 1997. ———, Surgical anatomy of the lower cranial nerves. Eighth Annual Meeting of the North American Skull Base Society. Skull Base Surgery, 7, suppl. 1, 34, 1997. Bias, W*., Nuwayri-Salti, N., Cissell, B*, Berger, B* and Schmeckpeper, B*., A comparison of HLA-DRB1 Alleles in three Lebanese villages reproductively isolated by geography and religion. Twelfth International Histocompatibility Workshop and Conference, Paris, France, 1996. Correa, R.*, Jurjus, A., and Walsh, R.*, A bilateral double axillary artery: Embryological basis and clinical implications. FASEB Journal, 11 (3), 1494, 257, 1997. Jurjus, A. and Walsh, R., Detection of substance P positive cells and nerve fibers in the rat thymus. The FASEB Journal, 11 (3), 1168, A201, 1997. Kanaan, S.A., Saadé, N.E., Jabbur, S.J., Atweh, S.F. and Safieh-Garabedian, B., Interleukin (IL)-10 reduces significantly endotoxin (ET)-induced peripheral hyperalgesia in mice. Society for Neuroscience, Abstracts, 22, 1812, 1996. Ng-Wong, C*., Nuwayri-Salti, N., Bias, W*., and Schmeckpeper, B*., HLA class II DPB1 alleles found in families from three isolated Lebanese villages. Twelfth International Histocompatibility Workshop and Conference, Paris, France, 1996. Nuwayri-Salti, N., The neuro-endocrine-immune axis: a novel control system. Second Annual Meeting of the Syrian Endocrine Society, Homs, Syria, November 21 - 22, 1996. ———, Genetics markers in patients with medullary thyroid carcinoma. Second Arab Congress on Thyroid Diseases, Bousra Aski-Sham, Syria, May 22-23, 1997. Nuwayri-Salti, N. and Fallah-Khansa, H.*, Direct transmission of Leishmania donovani in the absence of cutaneous lesions among mated mice. First World Congress on Leishmaniosis, 21 (1), 155, 1997. Nuwayri-Salti, N., Skeiky, Y.* and Reed, S.*, Anti-rk39 antibodies in sera of Lebanese patients with cutaneous Leishmaniasis. Forty-Fifth Annual Meeting Tropical Medicine and Hygiene, Baltimore, Maryland, 55 (2), 287, 1996. Nuwayri-Salti, N., Shoucair, M., Azar, S., Raiif, J, Salti, I and Halabi, G., Class I immunogenetic markers in Lebanese patients with Graves’ disease. Twelfth International Histocompatibility Workshop and Conference, Paris, France, 1996. Saadé, N.E., Illness-induced hyperalgesia: the effect of various anti-inflammatory and analgesic drugs. Second International Head and Neck Pain Symposium of the Middle East, Beirut, Lebanon, September 29-30, 1995. Saadé, N.E., Shbeir, S.A., Jabbur, S.J. and Atweh, S.F., Chemical lesions in the striatum inhibit nociceptive reflexes in rats. Society for Neuroscience, 21, 1164, 1995. Safieh-Garabedian, B., Kanaan, S., Haddad, J., Malik, S., Abdel Nour, A., Saadé, N.E. and Jabbur, S.J., Hyperalgesia produced by endotoxin (ET) injections: A new model for localized inflammatory pain in rats and mice. Society for Neuroscience, 21, 643, 1995. Wood,
W*.,Bias, W*., Nuwayri-Salti, N., Cissell, B.*, and Schmeckpeper, B*. HLA
class II DRB and DPQ1 alleles found in families from three isolated Lebanese
villages. Twelfth International Histocompatibility Workshop and Conference,
Paris, France, 1996.
Abou Jaoude, P., C-fos expression and cytokine secretion induced by local injections of endotoxin. Advisor: N.E. Saadé (1996). Rabah, D., Class I immunogenetic markers associated with some autoimmune diseases: Grave’s disease. Advisor: N. Nuwayri-Salti (1996). Lawand, H., Fos-protein immunoreactivity in the central nervous system of the rat induced by systemic and local injections of thymulin. Advisor: N.E. Saadé (1997). Nasr, R., Profile of canine leshmaniasis in Lebanon. Advisor: N. Nuwayri-Salti (1997).
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