Biomedical subjects

D Desai

Publications and source records attributed to D Desai.

At least 73 records · Page 4Linked to original sources

PubMed1995

Ipomeanol analogs as chemopreventive agents: effect on the in vitro metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific, powerful, organospecific lung carcinogen. 4-Ipomeanol (IPO) is an investigational chemotherapeutic drug with specific toxicity towards the lung. We hypothesized that non-toxic analogs of IPO could be competitive inhibitors of the metabolic activation of NNK. We had shown previously that 4-hydroxy-1-phenyl-1-pentanone (HPP) and 7-hydroxy-1-phenyl-1-octanone (4-HPO) are effectively inhibiting the lung tumor activity of NNK in A/J mice. In these extended studies we have synthesized 11 new analogs of HPP and tested them for their in vitro activities as inhibitors of the metabolism of NNK. The present study demonstrated that the lipophilicity in the molecule is playing an important role for the inhibition of NNK metabolism with pulmonary and hepatic microsomes of A/J mice.

Animals↗

PubMed1995

Chemoprevention of colon carcinogenesis by phenylethyl-3-methylcaffeate.

Previous studies from this laboratory have established that caffeic acid esters present in propolis, a natural resin produced by honey bees, are potent inhibitors of human colon adenocarcinoma cell growth, carcinogen-induced biochemical changes, and preneoplastic lesions in the rat colon. The present study was designed to investigate the chemopreventive action of dietary phenylethyl-3-methylcaffeate (PEMC) on azoxymethane-induced colon carcinogenesis and to examine the modulating effect of PEMC on phosphatidylinositol-specific phospholipase C (PI-PLC), phospholipase A2, lipoxygenase (LOX), and cyclooxygenase activities in the colonic mucosa and tumor tissues in male F344 rats. At 5 weeks of age, groups of rats were fed the control (modified AIN-76A) diet, or a diet containing 750 ppm of PEMC. At 7 weeks of age, all animals except those in the vehicle (normal saline)-treated groups were given 2 weekly s.c. injections of azoxymethane at a dose rate of 15 mg/kg body weight/week. All groups were maintained on their respective dietary regimen until the termination of the experiment 52 weeks after the carcinogen treatment. Colonic tumors were evaluated histopathologically. Both colonic mucosa and tumors were analyzed for PI-PLC, phospholipase A2, cyclooxygenase, and LOX activities. The results indicate that dietary administration of PEMC significantly inhibited the incidence and multiplicity of invasive, noninvasive, and total (invasive plus noninvasive) adenocarcinomas of the colon (P < 0.05-0.004). Dietary PEMC also suppressed the colon tumor volume by 43% compared to the control diet. Animals fed the PEMC diet showed significantly decreased activities of colonic mucosal and tumor PI-PLC (about 50%), but PEMC diet had no effect on phospholipase A2. The production of 5(S)-, 8(S)-, 12(S)-, and 15(S)-hydroxyeicosatetraenoic acids via the LOX pathway from arachidonic acid was reduced in colonic mucosa and tumors (30-60%) of animals fed the PEMC diet as compared to control diet. PEMC had no effect on the formation of colonic mucosal cyclooxygenase metabolites but inhibited the formation in colonic tumors by 15-30%. The precise mechanism by which PEMC inhibits colon tumorigenesis remains to be elucidated. It is likely that the chemopreventive action may be related, at least in part, to the modulation of PI-PLC-dependent signal transduction and LOX-mediated arachidonic acid metabolism.

Animals↗

PubMed1995

Photoperiod, early post-natal eye growth, and visual deprivation.

(1) We studied the influence of photoperiod and unilateral lid suture on post-natal ocular growth in two types of White Leghorn chicks previously reported to respond differently to visual deprivation, Truslow and Cornell K chicks. We analyzed the chicks after 2 weeks of rearing, a time period commonly used in neuropharmacological studies of eye growth but much shorter than in most prior studies of photoperiod effects on the chick eye. (2) Altering the photoperiod length significantly influenced the refraction and growth of both open and sutured eyes even at this early time, with differences between the two types of chicks. (3) The most prominent effect on the open eyes was the development of hyperopia with rearing under constant light, a response especially prominent in the Cornell K chicks. In the open eyes under this condition, the anterior chamber shallowed and the vitreous chamber elongated in the axial dimension only, reciprocal changes that resulted in no net alteration of axial length at 2 weeks. A high variability in refraction of open eyes reared with constant illumination suggests the need for a dark period in the regulation of eye growth. (4) Compared to contralateral open eyes, the lid-sutured eyes of both types of chicks developed longer total axial lengths and enlarged vitreous chambers in both axial and equatorial dimensions under each photoperiod. The effects on anterior chamber depth and refraction were complex and differed between the two types of chicks. (5) The responses in open eyes support the notion that growth of the vitrious chamber of the chick eye is differentially regulated in the axial and equatorial dimensions, previously indicated by pharmacological studies. The responses in both open and sutured eyes indicate different control mechanisms for anterior chamber and vitreous cavity growth.

Animals↗

PubMed1995

Tumorigenicity in newborn mice of fjord region and other sterically hindered diol epoxides of benzo[g]chrysene, dibenzo[a,l]pyrene (dibenzo[def,p]chrysene), 4H-cyclopenta[def]chrysene and fluoranthene.

Diol epoxides of benzo[g]chrysene, dibenzo[a,l]pyrene (dibenzo[def,p]chrysene), 4H-cyclopenta[def]chrysene and fluoranthene were tested for tumorigenicity in newborn mice. The compounds tested were racemic trans-11,12-dihydroxy-anti-13,14-epoxy-11,12,13, 14-tetrahydrobenzo[g]-chrysene (BgCDE), trans-11, 12-dihydroxy-anti-13,14-epoxy-11,12,13,14-tetrahydrodibenzo [a,l]pyrene (DB[a,l]PDE), trans-1,2-dihydroxy-anti-3, 3a-epoxy,1,2,3,3a-tetrahydro-4H-cyclopenta[def]chrysene (C[def]C-1,3a-DE), trans-6,7-dihydroxy-anti-8,9-epoxy-10b,1, 2,3-tetrahydrofluoranthene (FDE). BgCDE and DB[a,l]PDE are fjord region diol epoxides and their tumorigenic activities were compared to those of trans-3,4-dihydroxy-anti-1, 2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene (BcPDE), a fjord region diol epoxide with known high tumorigenicity and trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9, 10-tetrahydrobenzo[a]-pyrene (BPDE), a highly tumorigenic bay region diol epoxide. The protocol called for testing of each compound at a total dose of 25 nmol per mouse, administered on days 1, 7 and 15 of life, with killing at age 35 weeks. BgCDE had similar activity as BcPDE for induction of lung tumors and was more active than BcPDE for induction of liver tumors in male mice. Both compounds were significantly more tumorigenic than BPDE. DB[a,l]PDE was highly toxic. All mice died within 1 week of the first dose. It was then tested in a second study using total doses of 5 and 1 nmol per mouse. Only the first dose of the intended 5 nmol total dose was given due to toxicity. The full course of doses with a total of 1 nmol per mouse was administered; DB[a,l]PDE induced a significant incidence and multiplicity of lung tumors and, in male mice, liver tumors at both doses. These results demonstrate that fjord diol epoxides are highly active tumorigens in newborn mice, with activity greater than that of the most active unsubstituted bay region diol epoxide, BPDE. C[def]C-1-3a-DE and C[def]-6-9-DE were compared to trans-1,2-dihydroxy-anti-3, 4-epoxy-1,2,3,4-tetrahydrochrysene (CDE), at a total dose of 500 nmol per mouse. FDE was also tested at this dose. The most active compound among the chrysene derivatives was C[def]C-1-3a-DE, followed by C[def]C-6-9-DE and CDE. C[def]C-1-3a-DE has a sterically constrained bay region, in which the benzylic carbon of the tri-substituted epoxide ring is part of a fused ring system. This feature is also present in FDE, which and considerable tumorigenic activity, greater than that of CDE in lung and greater than any of the chrysene derivatives in liver.(ABSTRACT TRUNCATED AT 400 WORDS)

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1995

Effects of phosphorylation by CAK on cyclin binding by CDC2 and CDK2.

The cyclin-dependent protein kinases (CDKs) are activated by association with cyclins and by phosphorylation at a conserved threonine residue by the CDK-activating kinase (CAK). We have studied the binding of various human CDK and cyclin subunits in vitro, using purified proteins derived from baculovirus-infected insect cells. We find that most CDK-cyclin complexes known to exist in human cells (CDC2-cyclin B, CDK2-cyclin A, and CDK2-cyclin E) form with high affinity in the absence of phosphorylation or other cellular components. One complex (CDC2-cyclin A) forms with high affinity only after CAK-mediated phosphorylation of CDC2 at the activating threonine residue. CDC2 does not bind with high affinity to cyclin E in vitro, even after phosphorylation of the CDC2 subunit. Thus, phosphorylation is of varying importance in the formation of high-affinity CDK-cyclin complexes.

CDC2 Protein Kinase↗

PubMed1995

Peripartum cardiomyopathy: experiences at King Edward VIII Hospital, Durban, South Africa and a review of the literature.

The clinical profile of patients with peripartum cardiomyopathy (PP-CMO) seen in the patient population in Durban, South Africa, is documented. Parameters such as age, multiparity, time of presentation and the role of hypertension in PP-CMO were evaluated. The study comprised 97 patients seen over a 4 year period. Group 1 (n = 63), had a good outcome at follow-up and group II (n = 34), had an adverse outcome, namely: persistently severe symptoms New York Hospital Association, Class III/IV; major thromboembolic complications; or a fatal outcome. These results confirm that PP-CMO is more likely to occur in the older and multiparous female. Increasing age and multiparity did not adversely affect outcome. Eighteen per cent of the study group were primiparous, and a third of these had an adverse outcome. Late presentation of symptoms (after 1 month postpartum) tended to favour an adverse outcome (P = 0.06). Fifteen of the 19 patients with complete obstetric records had antenatal hypertension: in nine blood pressure levels were > or = 160/110 mmHg. We were unable to ascertain the prognostic value of hypertension in PP-CMO. In conclusion, this study showed a high incidence of PP-CMO in the local African population (1:1000 deliveries), and a high complication rate (35%): it suggests that early diagnosis and appropriate therapy may avert an adverse outcome.

Adult↗

PubMed1994

Distinct sub-populations of the retinoblastoma protein show a distinct pattern of phosphorylation.

Phosphorylation of the retinoblastoma protein (pRB) is assumed to regulate its growth-controlling function. Moreover, hypophosphorylated and hyperphosphorylated forms of pRB can be distinguished by virtue of the distinct affinities with which they bind to the cell nucleus. This property allows the identification of individual cell nuclei that contain pRB in one or the other form. We show here that after cells emerge from a quiescent (G0) state, conversion of their complement of pRB into a hyperphosphorylated form occurs in late G1, preceding entry into S phase by several hours. Thus, contrary to earlier reports, pRB phosphorylation is not co-ordinated with the G1-S transition and may not directly regulate it. A distinct set of phosphopeptides is found exclusively in those forms of pRB that show the loose nuclear association characteristic of the hyperphosphorylated form of pRB. Another set of phosphopeptides is found with both hypophosphorylated and hyperphosphorylated forms. This suggests the existence of distinct patterns of phosphorylation that are associated with different subsets of pRB molecules. We conclude that substantial phosphorylation of pRB exists in G1 even prior to the hyperphosphorylation point. Cyclin-dependent kinases can cause a liberation of pRB from cell nuclei in vitro. Phosphorylation by members of this kinase family is therefore likely to be directly involved in the change in nuclear affinity in vivo and the associated changes in pRB functioning.

Adenovirus E1A Proteins↗

PubMed1993

Inhibitory effect of caffeic acid esters on azoxymethane-induced biochemical changes and aberrant crypt foci formation in rat colon.

Previous work from this laboratory established that caffeic acid esters, present in the propolis of honey bee hives, are potent inhibitors of human colon tumor cell growth, suggesting that these compounds may possess antitumor activity against colon carcinogenesis. The present study was designed to investigate (a) the inhibitory effects of methyl caffeate (MC) and phenylethyl caffeate (PEC) on azoxymethane (AOM)-induced ornithine decarboxylase (ODC), tyrosine protein kinase (TPK), and arachidonic acid metabolism in liver and colonic mucosa of male F344 rats, (b) the effects of caffeic acid, MC, PEC, phenylethyl-3-methylcaffeate (PEMC), and phenylethyl dimethylcaffeate (PEDMC) on in vitro arachidonic acid metabolism in liver and colonic mucosa, and (c) the effects of PEC, PEMC, and PEDMC on AOM-induced aberrant crypt foci (ACF) formation in the colon of F344 rats. At 5 weeks of age, groups of animals were fed diets containing 600 ppm MC or PEC (biochemical study) or 500 ppm PEC, PEMC, or PEDMC (ACF study). Two weeks later, all animals except the vehicle-treated groups were given s.c. injections of AOM, once weekly for 2 weeks. The animals intended for the biochemical study were sacrificed 5 days later and colonic mucosa and liver were analyzed for ODC, TPK, lipoxygenase, and cyclooxygenase metabolites. The animals intended for the ACF study were sacrificed 9 weeks later and analyzed for ACF in the colon. The results indicate that the PEC diet significantly inhibited AOM-induced ODC (P < 0.05) and TPK (P < 0.001) activities in liver and colon. The PEC diet significantly (P < 0.001) suppressed the AOM-induced lipoxygenase metabolites 8(S)- and 12(S)-hydroxyeicosatetraenoic acid (HETE). The animals fed the MC diet exhibited a moderate inhibitory effect on ODC and 5(S)-, 8(S)-, 12(S)-, and 15(S)-HETEs and a significant (P < 0.001) effect on colonic TPK activity. However, the MC and PEC diets showed no significant inhibitory effects on cyclooxygenase metabolism. In an in vitro study, caffeic acid and MC showed inhibitory effects on HETE formation only at a 100 microM concentration, whereas PEC, PEMC, and PEDMC suppressed in vitro HETE formation in a dose-dependent manner. AOM-induced colonic ACF were significantly inhibited in the animals fed PEC (55%), PEMC (82%), or PEDMC (81%). The results of the present study indicate that PEC, PEMC, and PEDMC, present in honey, inhibit AOM-induced colonic preneoplastic lesions, ODC, TPK, and lipoxygenase activity, which are relevant to colon carcinogenesis.

Animals↗

PubMed1993

A study of tobacco carcinogenesis. LI. Relative potencies of tobacco-specific N-nitrosamines as inducers of lung tumours in A/J mice.

Tobacco-specific N-nitrosamines (TSNA) are formed from nicotine and the minor Nicotiana tabacum alkaloids during tobacco processing and tobacco smoking. The TSNA are the most abundant strong carcinogens in smokeless tobacco and in smoke. In this comparative study six TSNA and two major volatile N-nitrosamines of cigarette smoke are assayed for their relative tumorigenicities in strain A/J female mice and for their potential to induce lung tumors. N-nitrosodimethylamine was the most potent inducer of lung adenoma in the A/J mouse model followed in order of decreasing potencies by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, N-nitrosopyrrolidine, N'-nitrosonornicotine and N'-nitrosoanabasine. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol and 4-(methylnitrosamino)-4-(3-pyridyl)butyric acid were inactive. The relative tumorigenic activities of the tobacco-specific nitrosamines in strain A/J mice compare well with the available data for their relative tumorigenic activities in F344 rats and Syrian golden hamsters.

Adenoma↗

PubMed1993

Early versus late replacement of autotransfused blood in elective spinal surgery. A prospective randomized study.

The use of autologous blood is a well established and extremely popular technique to decrease the necessity for homologous transfusions and the attendant risks of hepatitis, HIV, and HTLV--I/II infections. The most beneficial timing for autologous reinfusion of predonated blood remains unknown. The present study was undertaken to determine the optimal timing of autologous blood reinfusion in elective spinal surgery. Fifty-seven patients were prospectively individually randomly allocated into early versus delayed reinfusion groups prior to undergoing elective spinal surgery by a single surgeon. Three surgical subgroups were entered into the study: anterior/posterior (A/P) spinal fusion patients, posterior thoracolumbar scoliosis fusion patients (PSF), and degenerative posterior lumbar fusion patients (LF). Randomization was successful in that three was no significant difference in male to female ratio, age, preoperative hemoglobin, or number of units predonated between the early and delayed reinfusion groups. Likewise, there was no significant difference in the details of the operative procedure when compared as a group for the early versus delayed reinfusion groups. A significant increase in the postoperative day #1, 2 and 3 hemoglobin was seen in the early reinfusion group, while there was no significant difference seen in the postoperative day #7 hemoglobin between the early versus delayed reinfusion group. There was no effect of surgical grouping on these significant comparisons. Earlier patient mobilization was also seen in the early reinfusion groups for the A/P and PSF groups. There was no difference in patients' subjective evaluation of satisfaction and discomfort between the early or delayed reinfusion groups as determined by blinded interview on days 1, 3, 5, and 7 postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Epidural anaesthesia and analgesia do not affect energy expenditure after major abdominal surgery.

Our objective was to determine the effect of perioperative epidural anaesthesia and analgesia on the increase in energy expenditure which accompanies major elective abdominal surgery in a prospective, randomized study. Eight patients undergoing elective resections of the colon and/or rectum received general anaesthesia alone (nitrous oxide, oxygen, and isoflurane, supplemented with intravenous fentanyl to a maximum of 10 micrograms.kg-1), and 12 patients received perioperative epidural anaesthesia and analgesia using lidocaine (carbonated lidocaine 2% with epinephrine 1:200,000, 20 ml over 30 min) and morphine (preservative-free morphine 0.10 mg.kg-1 after catheter insertion and 0.05 to 0.10 mg.kg-1 every 12 hr as needed until the morning following surgery) via a lower lumbar catheter in addition to general anaesthesia. Respiratory gas exchange was measured using a metabolic cart and canopy system early on the morning of surgery, six hours postoperatively, and on the first and second postoperative mornings. Parenteral analgesic administration (P < 0.001) and visual analogue pain scores (P < 0.05) were lower in the patients receiving epidural anaesthesia and time to first parenteral analgesia was longer (P < 0.005). Oxygen consumption, carbon dioxide production, and energy expenditure increased after surgery (all P < 0.001) but were very similar in the two groups (all P > or = 0.8) before and after surgery. Despite substantial effects on postoperative pain, we conclude that oxygen consumption and energy expenditure following major abdominal surgery are not diminished by perioperative epidural anaesthesia and analgesia.

Aged↗

PubMed1993

Tumor-initiating activity on mouse skin of bay region diol-epoxides of 5,6-dimethylchrysene and benzo[c]phenanthrene.

Previous metabolism and DNA-binding studies indicated that 5,6-dimethylchrysene (5,6-diMeC) is metabolically activated in mouse skin through formation of its 1,2-dihydrodiol (5,6-diMeC-1,2-diol) and bay region diol-epoxide (anti-5,6-diMeC-1,2-diol-3,4-epoxide). These metabolites were tested as tumor initiators on mouse skin. Included for comparison were syn-5,6-diMeC-1,2-diol-3,4-epoxide and anti-4,3-dihydroxy-2,1-epoxy- 4,3,2,1-tetrahydrobenzo[c]phenanthrene (anti-B[c]Ph-4,3-diol-2,1-epoxide). At an initiating dose of 100 nmol/mouse, 5,6-diMeC-1,2-diol and anti-5,6-diMeC-1,2-diol-3,4-epoxide were significantly more tumorigenic than 5,6-diMeC, inducing 7.1 and 3.9 skin tumors per mouse respectively compared to 1.1 induced by 5,6-diMeC. Similar results were obtained at an initiating dose of 33 nmol/mouse. This is the first example of a methylated polynuclear aromatic hydrocarbon bay region diol-epoxide which is more tumorigenic than its parent hydrocarbon on mouse skin. syn-5,6-diMeC-1,2-diol-3,4-epoxide was only weakly tumorigenic. Comparisons of anti-5,6-diMeC-1,2-diol-3,4-epoxide and anti-B[c]Ph-4,3-diol-2,1-epoxide demonstrated that the latter was a stronger tumor initiator. The results of this study confirm the bay region diol-epoxide metabolic activation pathway of 5,6-diMeC but do not provide an explanation for the relatively weak tumorigenicity of this hydrocarbon on mouse skin.

Animals↗

PubMed1992

Effect of caffeic acid esters on carcinogen-induced mutagenicity and human colon adenocarcinoma cell growth.

Propolis, a honey bee hive product, is thought to exhibit a broad spectrum of activities including antibiotic, antiviral, anti-inflammatory and tumor growth inhibition; some of the observed biological activities may be due to caffeic acid (cinnamic acid) esters that are present in propolis. In the present study we synthesized three caffeic acid esters, namely methyl caffeate (MC), phenylethyl caffeate (PEC) and phenylethyl dimethylcaffeate (PEDMC) and tested them against the 3,2'-dimethyl-4-aminobiphenyl, (DMAB, a colon and mammary carcinogen)-induced mutagenicity in Salmonella typhimurium strains TA 98 and TA 100. Also, the effect of these agents on the growth of human colon adenocarcinoma, HT-29 cells and activities of ornithine decarboxylase (ODC) and protein tyrosine kinase (PTK) was studied. Mutagenicity was induced in Salmonella typhimurium strains TA 98 and TA 100 plus S9 activation using 5 and 10 micrograms DMAB and antimutagenic activities of 0-150 microM MC, 0-60 microM PEC and 0-80 microM PEDMC were determined. The results indicate that MC, PEC and PEDMC were not mutagenic in the Salmonella tester system. DMAB-induced mutagenicity was significantly inhibited with 150 microM MC, 40-60 microM PEC and 40-80 microM PEDMC in both tester systems. Treatment of HT-29 colon adenocarcinoma cells with > 150 microM MC, 30 microM PEC and 20 microM PEDMC significantly inhibited the cell growth and syntheses of RNA, DNA and protein. ODC and PTK activities were also inhibited in HT-29 cells treated with different concentrations of MC, PEC and PEDMC. These results demonstrate that caffeic acid esters which are present in Propolis possess chemopreventive properties when tested in short-term assay systems.

Caffeic Acids↗

PubMed1992

Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle.

Human cyclin E, originally identified on the basis of its ability to function as a G1 cyclin in budding yeast, associated with a cell cycle-regulated protein kinase in human cells. The cyclin E-associated kinase activity peaked during G1, before the appearance of cyclin A, and was diminished during exit from the cell cycle after differentiation or serum withdrawal. The major cyclin E-associated kinase in human cells was Cdk2 (cyclin-dependent kinase 2). The abundance of the cyclin E protein and the cyclin E-Cdk2 complex was maximal in G1 cells. These results provide further evidence that in all eukaryotes assembly of a cyclin-Cdk complex is an important step in the biochemical pathway that controls cell proliferation during G1.

Animals↗

PubMed1992

Activation of human cyclin-dependent kinases in vitro.

We have analyzed the activation of human cyclin-dependent kinases in a cell-free system. Human CDC2, cyclin-dependent kinase 2 (CDK2), cyclin A, and cyclin B1 were produced in insect cells by infection with recombinant baculoviruses. CDC2 or CDK2 monomers in lysates of infected cells could be activated by the addition of lysates containing cyclin A or B1. CDC2 activation by cyclin B1, as well as CDK2 activation by cyclins A and B1, was accompanied by the formation of high molecular weight complexes. In contrast, CDC2 did not bind effectively to cyclin A. CDC2 activation by cyclin B1 was studied in detail and was found to be accompanied by phosphorylation of CDC2 on Threonine 161. The binding of CDC2 to cyclin B1 also occurred under conditions where CDC2 phosphorylation was prevented, resulting in an inactive complex that could then be phosphorylated and activated on addition of cell extract. Highly purified CDC2 and cyclin B1 also formed inactive complexes that could be activated in an ATP-dependent fashion by unidentified components in crude cell extracts. These data suggest that the CDC2 activation process begins with cyclin binding, after which CDC2 phosphorylation, catalyzed by a separate enzyme, leads to activation.

Amino Acid Sequence↗

PubMed1992

Comparative tumorigenicity of nitrochrysene isomers in newborn mice.

6-Nitrochrysene (6-NC) is a potent lung and liver carcinogen in the newborn mouse assay. In this report, we extended our studies of the structure--tumorigenicity relationships of the mononitrochrysene isomers. We synthesized 1-NC, 2-NC and 3-NC by oxidation of the corresponding aminochrysenes with mCPBA; efforts to synthesize 4-NC and 5-NC from 4- and 5-aminochrysene were not successful. The tumorigenic activities of 1-NC, 2-NC, 3-NC and 6-NC were compared. Groups of mice were treated with the appropriate compounds in dimethylsulfoxide (DMSO) by i.p. injection on the 1st, 8th and 15th day of life. At a total dose of 100 nmol/mouse, 6-NC induced significant incidences and multiplicities of lung tumors in mice in both sexes; only males were susceptible to liver tumor induction. At 100 nmol/mouse, induction of lung and liver tumors by 1-NC, 2-NC and 3-NC was not significantly different from that observed in mice treated with DMSO. The results indicate that nitro substitution at the 6-position of chrysene is critical for strong tumorigenicity in the newborn mouse assay.

Animals↗

PubMed1991

Tuberculous meningiomyeloradiculitis--a report of two cases.

Two cases of tuberculous meningitis complicated by spread to the spinal cord and nerve roots are described. Recognition of impending paraplegia by a rising cerebrospinal fluid protein content and manometric block should prompt steroid therapy as this may prevent irreversible neurological deficit.

Adolescent↗

PubMed1991

Serogrouping of halophilic bdellovibrios from chesapeake bay and environs by immunodiffusion and immunoelectrophoresis.

Little has been reported on the serological relationship of halophilic bdellovibrios (Bd). Immunodiffusion analysis performed with rabbit or mouse Bd antisera developed against eight halophilic Bd isolates and one terrestrial Bd isolate, when reacted with soluble antigen preparations of 45 isolates of halophilic Bd, allowed separation into seven serogroups, which were distinct from the terrestrial isolate. Soluble antigen preparations of prey bacteria, Vibrio parahaemolyticus P-5 (P-5) and Escherichia coli ML 35 (ML 35), exhibited no reactivity with the antisera by immunodiffusion. Immunoelectrophoresis revealed the presence of three distinct antigens in homologous reactions and one shared antigen in heterologous Bd reactions. Shared antigens were noted between halophilic and terrestrial Bd, in addition to between halophilic Bd strains, indicating the possible existence of an antigen(s) which may be shared among all Bd. Again, no shared antigen was noted when P-5 or ML 35 was allowed by immunoelectrophoresis to react with the antisera. Prey susceptibility testing of the seven distinct groups of halophilic Bd, using 20 test prey, produced essentially identical spectra for each group, indicating that this was not a useful technique in delineating the Bd. While immunoelectrophoresis was able to demonstrate an antigen common to all Bd tested, immunodiffusion was able to delineate strains on the basis of a "serogroup specific" antigen. This suggests that immunological tools may serve as important means to study the taxonomy of halophilic Bd, as well as in the formation of a clearer taxonomic picture of the genus Bdellovibrio.

Journal Article↗