Polyacetylene analogs, isolated from hairy roots of Panax ginseng, inhibit Acyl-CoA : cholesterol acyltransferase

In the course of our screening program for acyl-CoA : cholesterol acyltransferase (ACAT) inhibitors from Korean herbal medicines, ACAT inhibitors were isolated from the hairy roots of Panax ginseng (Araliaceae) and identified as panaxynol, panaxydol, panaxydiol, and panaxytriol. These active compounds inhibit rat liver ACAT with IC50 values of 94, 80, 45 and 79 microM, respectively.     

Transcriptional activation of the tobacco retrotransposon Tto1 by wounding and methyl jasmonate

Health visitors and Clinical Medical Officers (CMOs) were trained in parent counselling and worked at home in a highly deprived area with parents of pre-school children with multiple psychosocial problems. Their basic aims were to establish a mutually respectful partnership and to support parents in managing their diverse problems. Detailed evaluation indicated that the Service was highly valued by both parents and referrers, and suggested significant changes, including: improvements in the severity of problems; increased parental self-esteem; decreased levels of parental stress and emotional difficulties; more positive constructions of their children; improvements in the home environment; and decreased child behavioural problems.     

The development of congestive cardiac failure in a patient with hairy cell leukemia treated with 2-chlorodeoxyadenosine

Deoxyadenosines are closely related to adenosine and as such, may interfere with the cardiac adenylate cyclase pathway resulting in cardiac dysfunction. We report a rare case of a 42 year old man who developed transient cardiac failure following treatment with 2-CDA for hairy cell leukemia.     

Fracture resistance of endodontically treated roots after restoration

This study evaluated the shear strength resistance of endodontically treated roots that were restored by two different techniques. Twenty-seven recently extracted single-rooted teeth with similar anatomic characteristics were sectioned to obtain the same length for all specimens. Group I (GI) consisted of 14 roots restored with cast post-core (nickel-chromium alloy) and cemented using zinc phosphate cement; group II (GII) consisted of 13 roots restored with steel prefabricated posts (FKG) cemented with zinc phosphate cement and rotated with caution for anchorage. The crown portion of this group was made using a hybrid composite resin (Prisma APH). Results showed that on all specimens of GI the fracture occurred in the cervical root structure while in GII the composite resin fractured in all specimens. Statistical analysis showed a significantly higher resistance to fracture for GI than GII. The specimens were sectioned longitudinally for stereoscopic microscope analysis (63x) and did not show fracture lines in the dentin anchorage post area for any of the specimens.     

Activation of macrophages by crude polysaccharide fractions obtained from shoots of Glycyrrhiza glabra and hairy roots of Glycyrrhiza uralensis in vitro

Many plant polysaccharide fractions have been reported as immunomodulatory agents. However, sometimes the possibility of contamination with bacterial lipopolysaccharide (LPS), a potent B cell mitogen and immune modulator, is discussed. In the present paper, we investigated the effects of crude polysaccharide fractions obtained from the shoot and hairy root of Glycyrrhizae sp. on murine peritoneal macrophage function, in order to clarify whether plants grown under aseptic conditions produce immunomodulatory polysaccharides. All crude polysaccharide fractions induced nitric oxide production by murine peritoneal macrophages in vitro. Chemical analysis revealed that LPS-like molecules were not present in all preparations. These results suggested that shoot and hairy root biosynthesized polysaccharides that could stimulate macrophages de novo.     

Long-lasting complete remission in patients with hairy cell leukemia treated with 2-CdA: a 5-year survey

Between January 1991 and January 1994, 40 patients with hairy-cell leukemia (HCL), 30 males and 10 females, with a median age of 54 years, were treated with a single course of 2-chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg/kg/day continuous infusion for 7 days. Thirteen patients were untreated and 27 had previously received alpha-interferon. Thirty out of 40 patients (75%) achieved complete remission (CR) and 10 (25%) partial remission (PR). The median follow-up duration for patients in CR has been 48 months (range 30-66). Five of the complete responders (17%) relapsed at 12, 24, 26, 30 and 36 months after treatment as documented by the increase of hairy cells (Hc) in the bone marrow and two of them, who were retreated with 2-CdA after showing an initial impairment of peripheral blood values, obtained a second CR. The remaining three relapsed patients were never retreated and still show normal peripheral counts after 30, 38 and 40 months. Twelve of the continuous complete responder patients are still in CR after more than 5 years. In contrast, 8 out of 10 partial responders progressed after 8-36 months and all of them were retreated with 2-CdA at a dose of 0.15 mg/kg/day for 5 days i.v. Four of them (50%) achieved a CR, three a better PR and one patient died 6 months after the second 2-CdA course because of infectious complications. Two additional patients, both in CR, died after 28 and 37 months because of a second neoplasm. Toxic side-effects consisted of febrile episodes recorded in 16 patients: in seven of them, fever lasted only 24-48 h after the end of treatment and was apparently not infection-related. In the remaining nine patients, showing in addition severe neutropenia (neutrophils less than 1.0 x 10(9)/l), fever was related to bacterial infection requiring systemic antibiotics in all of them and G-CSF in three cases. In conclusion, 2-CdA induces a very high proportion of complete and long-lasting remissions in patients with HCL. In a number of cases relapse at bone marrow level may not affect peripheral blood values for prolonged time. However, in those patients with initial pancytopenia a retreatment with 2-CdA is still effective in inducing a durable second CR.     

Development of essential thrombocythemia in a patient treated with interferon alfa and pentostatin for hairy cell leukemia

A patient is reported who developed essential thrombocythemia after successful treatment for hairy cell leukemia. He was initially treated with interferon alfa and subsequently relapsed within one year of treatment. His diagnosis was reconfirmed and then treated with Pentostatin. Six years after treatment he had a progressive increase in the platelet count and was diagnosed as essential thrombocythemia. Second cancers including various types of hematological malignancy have been reported in patients with hairy cell leukemia treated with chemotherapy or interferon alfa. These malignancies may represent either a new clonal disorder or a complication of drug treatment. This is the first report of a chronic myeloproliferative disorder following successful treatment of hairy cell leukemia.     

The promoter of the plant defensin gene PDF1.2 from Arabidopsis is systemically activated by fungal pathogens and responds to methyl jasmonate but not to salicylic acid

OBJECTIVES: Hemoglobin-based oxygen carriers are designed to replace blood volume and to increase oxygen delivery to tissues after blood loss. The goals of the present study were two-fold: a) to determine the systemic and regional vascular effects of resuscitation with recombinant human hemoglobin (rHb1.1) in rats during controlled hemorrhage; and b) to determine whether nitric oxide (NO) or prostaglandins were involved in the observed responses. DESIGN: Paralyzed, ventilated rats were hemorrhaged (18 mL blood/kg body weight) during halothane anesthesia and allowed to stabilize for 30 mins. Systemic and regional hemodynamics and oxygen delivery were monitored at three time points, using the radioactive microsphere method. Microspheres were first infused at the end of the hemorrhage stabilization period (t=0 min). rHb1.1 (1 g/kg body weight) or rHb1.1 diluent (phosphate buffered saline, 36 mL/kg body weight) were infused over 20 mins and microspheres were administered again, 30 mins later (t=50 mins). Saline (0.5 mL), indomethacin (5 mg/kg to inhibit cyclooxygenase), or NG-monomethyl-L-arginine (L-NMMA, 100 mg/kg, to inhibit NO synthase) were then infused in rHb1.1-treated rats and microspheres injected once more (t=80 mins). SETTING: Research laboratory. SUBJECTS: Male Wistar rats (n=37). INTERVENTIONS: Recombinant human hemoglobin (rHb1.1), rHb1.1 diluent (phosphate buffered saline) resuscitation of hemorrhaged rats. Saline, L-NMMA, or indomethacin treatment after resuscitation. MEASUREMENTS AND MAIN RESULTS: Resuscitation with rHb1.1 increased mean arterial pressure (MAP), cardiac output, and systemic oxygen delivery significantly when compared with diluent. After rHb1.1 resuscitation, regional blood flows were significantly increased in skin, kidney, spleen, and heart compared with diluent resuscitation. Compared with saline treatment after rHb1.1 resuscitation, L-NMMA increased MAP and regional resistances in virtually all tissues; indomethacin did not alter MAP, but increased resistance in the brain. CONCLUSIONS: These data indicate that rHb1.1 resuscitation was more effective than diluent in improving systemic and regional hemodynamics and oxygen delivery, suggesting that rHb1.1 may be of benefit in the treatment of acute blood loss. Increased resistance after L-NMMA in the presence of rHb1.1 indicated that rHb1.1 resuscitation did not eliminate NO dependent circulatory control. Increased resistance after indomethacin in brain indicated that vasodilator prostanoids were important in regulating vascular resistance in these tissues after rHb1.1 resuscitation.     

Saikosaponins from roots of Bupleurum scorzonerifolium

Saikosaponin u and saikosaponin v, were isolated from the roots of Bupleurum scorzonerifolium and these saponins were identified as 3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl- (1-->3)-beta-D-fucopyranosyl]-3 beta,16 alpha,23,28-tetrahydroxy-olean- 11,13(18)-dien-30-oic acid-30-O-[pentito(1-->1)-beta-D-glucopyranosyl-(6-->)] ester and 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-fucopyranosyl]-3 beta,16 alpha,23,28-tetrahydroxy-olean-11,13(18)-dien-30-oic acid-30-O-[pentito(1-->1)-beta-D-glucopyranosyl(6-->)] ester, respectively.     

Differential induction by methyl jasmonate of genes encoding ornithine decarboxylase and other enzymes involved in nicotine biosynthesis in tobacco cell cultures

A cDNA of tobacco BY-2 cells corresponding to an mRNA species which was rapidly induced by methyl jasmonate (MeJA) in the presence of cycloheximide (CHX) was found to encode ornithine decarboxylase (ODC). Another cDNA from a MeJA-inducible mRNA encoded S-adenosylmethionine synthase (SAMS). Although these enzymes could be involved in the biosynthesis of polyamines, the level of putrescine, a reaction product of ODC, increased slowly and while the levels of spermidine and spermine did not change following treatment of cells with MeJA. However, N-methylputrescine, which is a precursor of pyrrolidine ring of nicotine, started to increase shortly after MeJA-treatment of cells and the production of nicotine occured thereafter. The levels of mRNA for arginine decarboxylase (ADC), an alternative enzyme for putrescine synthesis, and that for S-adenosylmethionine decarboxylase (SAMDC), required for polyamine synthesis, were not affected by MeJA. In addition to mRNAs for ODC and SAMS, mRNA for putrescine N-methyltransferase (PMT) was also induced by MeJA. Unlike the MeJA-induction of ODC mRNA, MeJA-induction of SAMS and PMT mRNAs were blocked by CHX. The level of ODC mRNA declined after 1 to 4 h following MeJA treatment, while the levels of mRNAs for SAMS and PMT continued to increase. Auxin significantly reduced the MeJA-inducible accumulation of mRNAs for ODC, SAMS and PMT. These results indicate that MeJA sequentially induces expression of a series of genes involved in nicotine biosynthesis by multiple regulatory mechanisms.     

Purification of peroxidase isoenzymes from turnip roots

Simple reproducible procedures for purification of the main soluble (S) and ionically bound (IB) cationic peroxidase isoenzymes from turnip roots were established. The procedures included ammonium sulfate precipitation of the isoenzymes, chromatographic separation of the main isoenzymes using cellulose phosphate columns and purification to homogeneity by hydrophobic interaction chromatography on phenyl Sepharose columns. The specific activity of the phenyl Sepharose purified S and IB isoenzymes were 2760 and 896 units/mg protein with 140 and 4.8 fold increase over the crude extract and 38 and 13% recovery. The pH maxima and K(m) for phenol and H2O2 of purified S and IB were determined.     

Differential expression of a novel gene in response to coronatine, methyl jasmonate, and wounding in the Coi1 mutant of Arabidopsis

Coronatine is a phytotoxin produced by some plant-pathogenic bacteria. It has been shown that coronatine mimics the action of methyl jasmonate (MeJA) in plants. MeJA is a plant-signaling molecule involved in stress responses such as wounding and pathogen attack. In Arabidopsis thaliana, MeJA is essential for pollen grain development. The coi1 (for coronatine-insensitive) mutant of Arabidopsis, which is insensitive to coronatine and MeJA, produces sterile male flowers and shows an altered response to wounding. When the differential display technique was used, a message that was rapidly induced by coronatine in wild-type plants but not in coi1 was identified and the corresponding cDNA was cloned. The coronatine-induced gene ATHCOR1 (for A. thaliana coronatine-induced) is expressed in seedlings, mature leaves, flowers, and siliques but was not detected in roots. The expression of this gene was dramatically reduced in coi1 plants, indicating that COI1 affects its expression. ATHCOR1 was rapidly induced by MeJA and wounding in wild-type plants. The sequence of ATHCOR1 shows no strong homology to known proteins. However, the predicted polypeptide contains a conserved amino acid sequence present in several bacterial, animal, and plant hydrolases and includes a potential ATP/GTP-binding-site motif (P-loop).     

Midtrimester and missed abortion treated with intramuscular 15 (s)-15 methyl PGF2alpha

Abortion was successfully induced in 79 of 80 patients in midtrimester, by the serial administration of 250 microgram of 15 (S)-15 methyl PGF2alpha intramuscularly every second hour until abortion occurred. All 12 patients with missed abortion and 87% of the legal abortion patients aborted within 24 hours. The average period until abortion occurred in the missed abortion group was 8.2 hours (+/- 4.5 SD), and in the legal abortion group 16.4 hours (+/- 7.3 SD). All the patients were given prophylactic treatment for vomiting, using prochlorperazine. The average number of episodes of vomiting was 2.8 per ptient. All but 3 patients were given loperamide or diphenoxylate for "diarrhoea". The average number of episodes of diarrhoea was 2.5 per patient. The frequency of complications was low apart from a case of low uterine rupture.     

Increased frequency of chromosome abnormalities in fibroblasts from hairy cell leukemia patients

A hereditary component is implicated in many different cancers, including hairy cell leukemia (HCL), and may involve an instability of the genome. We have previously documented recurrent clonal and non-clonal chromosomal abnormalities in hairy cells. To ascertain whether this instability of the genome is restricted to the malignant cells or if it might also include normal cells we performed cytogenetic investigations on skin fibroblasts and hairy cells from eight HCL patients and skin fibroblasts from eight referents. The frequency of chromosome abnormalities, regardless of clonality, was significantly increased in the fibroblasts from patients compared to referents. Also, five patients compared to one referent showed clonal abnormalities in their fibroblasts. Immunohistochemical investigations excluded the possibility that the fibroblast cultures were contaminated with hairy cells. Two patients had constitutional abnormalities, inv(5)(p13.1q13.3) and t(13;14), and one additional patient, possibly mosaic, showed the same abnormality, inv(9)(p21-22q22), in both fibroblasts (17/30) and blood (5/21) cells. Aberrations in patient fibroblasts also included sporadic inv(5), del(6)q, inv(19), and del(20)q, abnormalities previously shown to occur in hairy cells. A clonal expansion with trisomy 7 occurred in vitro as documented by fluorescence in situ hybridization (FISH). The only clonal abnormality occurring in a referent was -Y/-Y,+15 in an elderly male. In conclusion, a constitutional chromosomal instability may precede chromosome abnormalities and be of importance in the development of hairy cell leukemia.     

A saponin from the roots of Gypsophila bermejoi

A new saponin was isolated from the methanol extract of the roots of Gypsophila bermejoi and identified by a combination of chemical degradation and spectral methods, which included negative FABMS and extensive 1D and 2D-NMR analysis (DQCOSY, TOCSY, ROESY, HMQC and HMBC), as gypsogenin 28-O-beta-D-glucopyranosyl(1-->2)-[beta-D-glucopyranosyl (1-->6)]-beta-D-glucopyranoside.     

New taxane diterpenoids from the roots of Taxus mairei

OBJECTIVE: We tested the hypothesis that nitric oxide synthesis by the kidney is increased in children with primary nephrotic syndrome. METHODS: We examined the urinary excretion of nitrite, a stable metabolite of nitric oxide, using the Griess reaction, in children with nephrotic syndrome. RESULTS: In comparison with healthy children, patients with minimal change nephrotic syndrome had increased urinary nitrite excretion regardless of whether the disease was in relapse or remission (p < 0.025). In contrast, urinary nitrite excretion was similar in control subjects and patients with focal segmental glomerulosclerosis or IgA nephropathy. CONCLUSION: These findings indicate that measurement of urinary nitrite excretion may be a useful test to help discriminate between minimal change nephrotic syndrome and focal segmental glomerulosclerosis in children with idiopathic nephrotic syndrome.