IL-11, a pleiotropic cytokine: exciting new effects of IL-11 on gastrointestinal mucosal biology.

Recombinant human interleukin 11 (rhIL-11) is a pleiotropic cytokine that stimulates bone marrow stem cells to proliferate and decreases intestinal mucosal injury produced by cytoablative drugs and radiation in animals. The effects of rhIL-11 were studied in a hamster model of oral mucositis and in two rat models of inflammatory bowel disease (IBD). Oral mucositis was induced in male Golden Syrian hamsters with 5-fluorouracil 60 mg/kg intraperitoneal, days 0 and 2.

Resolution of cutaneous leishmaniasis: interleukin 12 initiates a protective T helper type 1 immune response.

Resistance to Leishmania major in mice is associated with the appearance of distinct T helper type 1 (Th1) and Th2 subsets. T cells from lymph nodes draining cutaneous lesions of resistant mice are primarily interferon gamma (IFN-gamma)-producing Th1 cells. In contrast, T cells from susceptible mice are principally Th2 cells that generate interleukin 4 (IL-4).

Analogues of platelet activating factor. 8. Antagonists of PAF containing an aromatic ring linked to a pyridinium ring.

A series of platelet activating factor (PAF) antagonists containing a quaternary pyridinium ring connected through an amide, imide, or carbamate linkage to a substituted aromatic ring was prepared. Of these compounds, those containing a branched imide linkage of the form (CON-(COCH3)CH2, 37-51, and 59) generally showed excellent PAF antagonist properties in vitro. Structure-activity relationships within this series of compounds were studied extensively with respect to substituents and the position of substitution in both the aromatic and pyridinium rings.

Recombinant human interleukin-11 stimulates megakaryocytopoiesis and increases peripheral platelets in normal and splenectomized mice.

The effects of recombinant human interleukin-11 (rhIL-11) on in vivo mouse megakaryocytopoeisis were examined. Normal C57Bl/6 mice and splenectomized C57Bl/6 mice were treated for 7 days with 150 micrograms/kg rhIL-11 administered subcutaneously. In normal mice, peripheral platelet counts were elevated compared with vehicle-treated controls after 3 days of rhIL-11 treatment and remained elevated until day 10.

Analogues of platelet activating factor. 7. Bis-aryl amide and bis-aryl urea receptor antagonists of PAF.

A series of bis-aryl amide (13-57 and 66-81) and bis-aryl urea (58 and 85) antagonists of platelet-activating factor (PAF) was prepared that contain, separating the two aromatic rings, linear amide linkages of the form -(CH2)nCONH- (n = 0-2), -OCH2CONH-, and -(CH2)nNHCO- (n = 0-1), branched amide linkages of the form -(CH2)nN(COR)- (n = 1-3, R = CH3 or n-C3H7), and -N(COCH3)CH2-, and urea linkages of the form -NHCONH- and -CH2N(CONHCH3)-. These compounds were examined for their ability to inhibit PAF-induced platelet aggregation of rabbit platelets. These in vitro data were compared to similar data obtained for a number of known PAF antagonists.

Studies of the effect of a platelet-activating factor antagonist, CL 184,005, in animal models of gram-negative bacterial sepsis.

The effect of CL 184,005, a potent and specific platelet-activating factor antagonist, has been examined in a variety of animal models relevant to gram-negative bacterial sepsis. Pretreatment of mice with CL 184,005 protected them from the lethal effects of platelet-activating factor. When rats or primates rendered hypotensive with endotoxin were treated with CL 184,005, blood pressure was normalized.

Optimal management of a ventricular assist system. Contribution of flow visualization studies.

The Novacor (Baxter Novacor, Oakland, CA) Left Ventricular Assist System (LVAS) incorporates a versatile microprocessor based controller that permits a variety of operating modes. These include internally triggered automatic synchronous counterpulsation, electrocardiogram triggered synchronous operation, and full to empty or fixed rate asynchronous operation. The aim of this pilot study was to determine the extent to which washing of the blood contacting surfaces of the pump may be optimized by suitable choice of operating mode.

Analogues of platelet activating factor. 6. Mono- and bis-aryl phosphate antagonists of platelet activating factor.

A series of aryl phosphoglyceride (3, 19-61) and bis-aryl phosphate (67-135) antagonists of platelet activating factor (PAF) were prepared. A group of four bifunctional phosphorus reagents (5a-c and 7) were developed that allowed the preparation of these aryl phosphates in which the position of aromatic substitution can be varied. These compounds were examined for their ability to inhibit PAF-induced platelet aggregation of rabbit platelets.

Novel agents that promote bone regeneration.

Regulation of bone growth is controlled partly by local growth factors, which have effects on bone including the differentiation of precursor cells, osteoblast proliferation, the stimulation of matrix synthesis and angiogenesis. These factors are hypothesized to have a role in augmenting bone repair. In the past year, recombinant technology has provided sufficient material to allow extensive in vivo evaluation of this hypothesis.

Correlation of leukocyte interleukin-1 production with the stimulation of prostaglandin and tissue factor synthesis by human umbilical vein endothelial cells.

Human leukocyte suspensions (neutrophils 80-85%, monocyte 15-20%) were incubated alone or with cultured human umbilical vein endothelial cells. Leukocytes were either directly added to the endothelial cell cultures or separated from them by a 0.4 micron insert filter.

Proliferative and lipid metabolism response to balloon angioplasty in canine renal arteries.

The mechanisms responsible for reocclusion after percutaneous transluminal angioplasty are still poorly understood. The effects of angioplasty on arterial morphology, deoxyribonucleic acid (DNA) synthesis (3H-thymidine incorporation) and lipid metabolism (14C-oleate incorporation) were studied in renal arteries of 24 male mongrel dogs. Balloon-dilated (identified by Evans blue dye accumulation) and adjacent normal arterial segments were collected 90 min and 2, 5 and 14 days after the procedure.

1,4-Dihydronaphthoquinones as water-soluble inhibitors of 5-lipoxygenase.

The acetate derivatives of 1,4-dihydronaphthoquinones showed significant inhibition of 5-lipoxygenase. Among them, 1-acetyl-2-n-butyl-4-methoxy-naphthalene and 1-acetyl-2, 3-diethyl- 4- methoxy-naphthalene were found to be the best inhibitors. A series of HCl salts of the amino acid esters and other derivatives of the two parent molecules, 1-hydroxy-2-n-butyl-4-methoxy-naphthalene and 1-hydroxy-2, 3-diethyl-4-methoxynaphthalene, were synthesized as water-soluble potential inhibitors of 5-lipoxygenase to improve the formulation characteristics of this class of compounds.

In vivo demonstration of enhanced arterial constrictor response to serotonin following focal endothelial cell loss.

Arterial sensitivity to vasospasm was assessed prior to and 2 weeks following a 15-min period of external compression of the superficial femoral artery in dogs. Compression was achieved by placing a plastic cuff around the artery to produce a 40-60% reduction in the artery cross-sectional area. An additional six dogs were used to assess morphologic changes produced in the artery immediately and at 2 weeks after compression.

Suppression of aortic atherosclerosis in cholesterol-fed rabbits by purified rabbit interferon.

The effectiveness of rabbit interferon in suppressing atherosclerosis was evaluated in rabbits fed a diet containing 1% cholesterol. Ten male New Zealand White rabbits received intramuscular injections of 1 million units of interferon twice a week, while a control group of 10 rabbits received injections of buffer. Both groups had average serum cholesterol levels of over 2000 mg/dl during the 8-week experimental period.

1,4-Dihydronaphthoquinones, hydroindoloquinones, benzofurans, and benzothiophenes as inhibitors of 5-lipoxygenase. Synthesis and structure-activity studies.

A series of substituted 1,4-dihydronaphthoquinones, hydroindoloquinones, benzofuran-4,7-dihydroquinones, and benzothiophene-4,7-dihydroquinones were synthesized and evaluated for inhibitory activity against 5-lipoxygenase. These compounds were found to be active in vitro for LTC4/D4 inhibition with the potencies (IC50's) ranging from 0.2 to 85 microM.

Interleukin-1 induced vascular pathology "in vivo": a scanning electron-microscopy study.

Ethylene vinyl acetate (EVA) discs containing either 50 U interleukin-1 (IL-1) or 250 mg bovine serum albumin as control were implanted around the exposed jugular veins of rabbits. After 24 hr, the veins were examined by scanning electron-microscopy. Compared with minor changes in control vein lumena, those of EVA-IL-1 treated veins showed extensive endothelial cell denudation and exposure of basement membrane associated with platelet accumulation and adherence/subendothelial migration of leucocytes.

Perception and significance of dental appearance: the case of missing teeth.

The perception and significance of dental appearance was investigated in three groups of patients. One group had a missing front tooth replaced by partial dentures, which were taken out during the tests. A second group had some missing (pre-)molars.

Comparison of lipid accumulation and metabolism in carrageenan-induced granulomas to aorta and blood monocytes of normal and cholesterol-fed rabbits.

New Zealand rabbits (six each) were either maintained on a standard chow diet (ND) or the chow diet supplemented with cholesterol/peanut oil (HD) for 2 weeks. After 2 weeks, each animal had 15 ml of a 1% carrageenan gel injected subcutaneously into the midabdominal area. Rabbits were maintained on the diets for an additional 4 weeks.

Dental hygienists' influence on the patients' knowledge, motivation, self-care, and perception of change.

The purpose of this study was to assess the success of the dental hygienist in the dental health education of dental patients in general dental practice. Special emphasis was laid on health education in the field of periodontics. The answers on a questionnaire of 159 dental patients who visited a dental hygienist were compared with the answers of 302 dental patients who had never visited a dental hygienist.

Attitudes of two groups of dentists towards dental hygienists.

The purpose of the study was to assess whether cooperation with a dental hygienist was based on pursuit of financial gain or on aspirations to improve patient care. To this end a questionnaire was sent to 972 dentists. 412 dentists replied, of whom 178 had patients treated by a dental hygienist.

Significance of dental problems to the public and their comparability with general health problems.

A group of 109 subjects received a short questionnaire concerning their general health status. The subjects were invited to recall all the (health) problems experienced in the foregoing 6 months. Every participant in this study had visited the dentist, in the 6 months preceding the investigation, because of a dental problem.

Social and psychologic implications of missing teeth for chewing ability.

The impact of loss of teeth on chewing ability was investigated in three groups of patients. One group already had missing teeth replaced by partial dentures, which were taken out during the tests. This group was taken as not being adapted to chew without a complete dentition.

Ciprostene, a stable prostacyclin analog, produces peripheral vasodilation, platelet inhibition and increased clot dissolution in the cat.

The effect of the stable prostacyclin analog ciprostene on hemodynamic parameters, platelet aggregation and clot dissolution was examined in the sodium pentobarbital anesthetized cat. Hemodynamic and platelet aggregation effects were measured in 5 cats following infusion of 5, 10, 20, 40 and 80 micrograms/kg/min of ciprostene. Drug was dissolved in Tyrode's buffer (pH 7.

Pathways to full mouth extraction.

The process of not attending the dentist is a vicious cycle in which anxiety plays a crucial role. A research project concerning the disease and non-disease reasons for full mouth extraction provided an opportunity to describe the dental histories in terms of dental attendance pattern and related factors which resulted in full dentures. Three profiles of dental histories could be outlined: 1) The regular attenders (19%).

Spontaneous recall as an indicator of the impact of dental complaints.

A hypothesis was developed that the impact or importance of oral health problems may be reflected in a person's ability to remember these problems occurring in a given period spontaneously. That means that the recollection should occur on a nonspecific stimulant, i.e.