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Biomedical subjects

C Nilsson

Publications and source records attributed to C Nilsson.

At least 73 records · Page 4Linked to original sources

A mechanism-based pharmacokinetic-enzyme model for cyclophosphamide autoinduction in breast cancer patients.

AIMS: This study investigated the pharmacokinetics of cyclophosphamide (CP) and its main metabolite 4-hydroxycyclophosphamide (4-OH-CP) in patients with breast cancer undergoing high dose chemotherapy prior to autologous stem cell transplantation. An enzyme turn-over model was also developed to study the time course of cyclophosphamide induction. METHODS: Fourteen patients received a combination of CP (6 g m-2 ), thiotepum (500 mg m-2 ) and carboplatin (800 mg m-2 ) as a 96 h infusion. Plasma concentrations of CP and 4-OH-CP were determined with h.p.l.c. and a pharmacokinetic and enzyme turn-over model applied to data using NONMEM. RESULTS: CP plasma concentrations were described by a two-compartment model with a noninducible and an inducible pathway, the latter forming 4-OH-CP. In the final enzyme model, CP affects the amount of enzymes by increasing the enzyme production rate. CP concentrations decreased during the infusion with no subsequent change in 4-OH-CP concentrations. CP inducible and noninducible clearance were estimated to 1.76 l h-1 (90% C.I. 0.92-2.58) and 1.14 l h-1 (0.31-1.85), respectively. The induction resulted in an approximately doubled CP clearance through the inducible pathway at the end of treatment. The model predicted the enzyme turn-over half-life to be 24 h. CONCLUSIONS: The presented mechanism-based enzyme induction model where the pharmacokinetics of the inducer and the enzyme pool counterbalance each other successfully described CP autoinduction. It is reasonable to believe that CP affects its own elimination by increasing the enzyme production rate and thereby increasing the amount of enzyme by which CP is eliminated.

Adult↗

Beta-chemokine production in macaques vaccinated with live attenuated virus correlates with protection against simian immunodeficiency virus (SIVsm) challenge.

Simian immunodeficiency virus (SIV) uses the CCR5 chemokine receptor as the main co-receptor to enter CD4+ cells. RANTES, MIP-1alpha and MIP-1beta have been suggested as the major human immunodeficiency virus-suppressor factors produced by CD8+ T-cells. The aim of this study was to investigate the CD8+ T-cell production of anti-viral factors and of beta-chemokines in six cynomolgus macaques vaccinated with live attenuated SIVmacC8 in relation to protection against infectious intrarectal SIVsm challenge. Three of the vaccinated animals were completely protected and one was partially protected against the challenge virus. Interestingly, these monkeys showed higher in vitro anti-viral CD8+ cell suppressor activity and beta-chemokine production both before and after vaccination as compared to the infected monkeys. The results indicate that beta-chemokines may play a role in protective immunity but also that genetic and/or environmental factors may influence their production.

Animals↗

The influence of interferon-alpha on the pharmacokinetics of cyclophosphamide and its 4-hydroxy metabolite in patients with multiple myeloma.

The pharmacokinetics of cyclophosphamide (CP) and its cytotoxic metabolite 4-hydroxycyclophosphamide (4-OHCP) have been studied in multiple myeloma patients treated with the CIB (CP, interferon-alpha (IFN-alpha) and betamethasone) regimen. In the present investigation we aimed to determine whether exposure to CP and its cytotoxic metabolite 4-OHCP is influenced by the concomitant administration of IFN-alpha. Ten patients with previously untreated multiple myeloma entered the study. Each patient received two courses of CIB in randomized order. Interferon was administered either 2 h before the CP infusion in one course or 24 h after the CP infusion in the other course. A cyclophosphamide dose of 750-900 mg/m2 was given as a 2 h constant infusion. Interferon-alpha (10-15 x 10(6) IE) was given subcutaneously. All patients received betamethasone 24 h after CP or later. The elimination of CP was described by monoexponential decay. The administration of IFN-alpha before CP caused a decrease in CP clearance to 63% (P=0.004), a 137% longer half-life (P = 0.004) and a 137% higher peak plasma concentration (P = 0.006) compared to the results obtained when IFN-alpha was administered 24 h after CP. The formation of 4-OHCP was also affected by the administration of IFN-alpha prior to CP, 45% less exposure to 4-OHCP expressed as AUC (P = 0.002) and a 61% lower peak plasma concentration (P = 0.002) compared with that observed when IFN-alpha was administered 24 h after CP. The administration of IFN-alpha after CP resulted in a greater (45%, P = 0.02) decrease in leukocyte count compared with results when IFN-alpha was given before CP. This study demonstrates that the administration of IFN-alpha prior to CP significantly impairs pharmacokinetics of CP and 4-OHCP. When IFN-alpha was administered after CP, a higher exposure to the cytotoxic metabolite 4-OHCP was observed and reflected by a significant decrease in leukocyte count compared to that when IFN-alpha was given before CP. In conclusion, the time of administration of IFN-alpha in relation to concomitant chemotherapy (CP) has to be considered to obtain a higher efficacy of IFN-alpha/alkylating agent combining regimens for induction in multiple myeloma and related disorders.

Aged↗

Induction of insulin resistance by glucosamine reduces blood flow but not interstitial levels of either glucose or insulin.

To study the effects of a glucosamine infusion on skeletal muscle metabolism, microdialysis was performed in the medial femoral muscle in Sprague-Dawley rats during a euglycemic-hyperinsulinemic clamp (insulin infusion 18 mU x kg(-1) x min(-1)). During steady-state clamping conditions (70 min), an infusion of glucosamine (30 micromol x kg(-1) x min(-1)) or saline was given for 240 min. Blood flow was measured by the microsphere technique at the end of the clamp. An approximately 36% (P < 0.001) reduction in the glucose infusion rate was seen after 170 min in the glucosamine-treated rats compared with control rats. There were no significant differences in interstitial or plasma levels of either insulin or glucose between the two groups. Both interstitial (2.31 +/- 0.18 vs. 1.71 +/- 0.24 mmol/l, P < 0.05) and arterial plasma lactate concentrations (1.29 +/- 0.09 vs. 0.79 +/- 0.09 mmol/l, P < 0.01) were significantly higher in control rats compared with glucosamine-treated rats. Blood flow was significantly reduced in hind limb femoral muscles in the glucosamine-treated rats compared with control rats. The most pronounced reduction in blood flow was seen in the Soleus muscle (27.6 +/- 3.4 vs. 14.7 +/- 2.0 ml x 100 g(-1) x min(-1), P < 0.01). These results demonstrate that induction of insulin resistance by glucosamine results in a reduction of the blood flow rate as well as the uptake of glucose and the production of lactate in skeletal muscle. As a result of the inhibited glucose metabolism, the interstitial glucose concentration was unchanged despite the reduced blood flow after glucosamine administration. The data suggest the importance of regulation of blood flow by nonoxidative metabolism of glucose in resting muscle.

Animals↗

Live attenuated simian immunodeficiency virus (SIV)mac in macaques can induce protection against mucosal infection with SIVsm.

OBJECTIVE: To investigate whether vaccination of macaques with attenuated simian immunodeficiency virus (SIV)macC8 could induce long-term protective immunity against rectal exposure to SIVsm and intravenous exposure to the more divergent HIV-2. DESIGN AND METHODS: Eight months after vaccination with live attenuated SIVmacC8, four cynomolgus monkeys were challenged with SIVsm intrarectally and another four vaccinated monkeys were challenged with HIV-2 intravenously. Sixteen months after SIVmacC8 vaccination, another two monkeys were challenged with SIVsm across the rectal mucosa. Two vaccinees shown to be protected against SIVsm were rechallenged 8 months after the first challenge. Ten naive animals were used as controls. Serum antigenaemia, virus isolation, antibody responses, cell-mediated immunity and CD4+ and CD8+ T-cell subpopulations were monitored. PCR-based assays were used to distinguish between virus populations. RESULTS: At the time of challenge, eight out of 10 vaccinees were PCR-positive for SIVmacC8 DNA but no virus could be isolated from peripheral blood mononuclear cells. After SIVsm challenge, three out of six vaccinees were repeatedly SIVsm PCR-negative. In one of the three infected monkeys, the challenge virus was initially suppressed but the monkey ultimately developed AIDS after increased replication of the pathogenic virus. Rechallenged monkeys remained protected. All HIV-2-challenged vaccinees became superinfected. All controls became infected with either SIVsm or HIV-2. At the time of challenge the vaccinees had neutralizing antibodies to SIVmac but no demonstrable cross-neutralizing antibodies to SIVsm or HIV-2. Titres of antigen-binding or neutralizing antibodies did not correlate with protection. Cytotoxic T-cell responses to SIV Gag/Pol and virus-specific T-cell proliferative responses were low. CONCLUSION: The live attenuated SIVmacC8 vaccine was able to induce long-term protection against heterologous intrarectal SIVsm challenge in a proportion of macaques but not against the more divergent HIV-2, which was given intravenously.

Animals↗

Correct targeting of a vacuolar tobacco chitinase in Saccharomyces cerevisiae--post-translational modifications are dependent on the host strain.

The chitinase gene FB7-1 of Nicotiana tabacum cv. samsun line 5 was expressed in the two Saccharomyces cerevisiae strains, INVSC2 and H4, under the control of the GAL1 promoter from S. cerevisiae and a multicopy plasmid vector. Both yeast strains express the plant gene as enzymatic active proteins. In transformants of the strain INVSC2, 94% of the total plant chitinase is contained inside the cells, probably within the vacuole which has been confirmed by subcellular fractionation as well as immunohistochemical experiments. This retention inside the cells is due to the C-terminally located 7 amino acids long vacuolar targeting peptide of the prochitinase. When this sequence was removed, chitinase was transported into the culture medium. Pulse-chase experiments revealed that during translation in transformants of both yeast strains one chitinase polypeptide can be immunoadsorbed with specific antibodies. In the case of INVSC2-transformants, newly formed chitinase is modified in a 60 min chase to slightly increase its molecular mass, whereas in H4-transformants the molecular mass constantly remained 32 kDa. By Western blot analysis two chitinase corresponding polypeptides of 32 and 37 kDa were accumulated in the culture medium of both transformants carrying the chitinase gene without the vacuolar targeting sequence. The larger one was very likely O-glycosylated. Whereas, both polypepitdes were also detected in cell extracts of the H4-transformant, only the smaller one was found in the INVSC2-transformant. The plant chitinase passed through the endoplasmic reticulum on its way to the vacuole. The N-terminal signal peptide responsible for the uptake into the endoplasmic reticulum is cleaved correctly. However, cleavage of the vacuolar targeting peptide located at the C-terminus, to give the mature chitinase is obviously influenced by the genetic background of the host strain. In INVSC2-transformants chitinase accumulates in its mature form whereas both the polypeptides of H4-transformants retain their vacuolar targeting peptide. Our results demonstrate that in the case of plant class I chitinase, the plant sorting signal is recognized in yeast cells but post-translational modifications are influenced by the host strain.

Amino Acid Sequence↗

Imprinting of female offspring with testosterone results in insulin resistance and changes in body fat distribution at adult age in rats.

In women, a relative hyperandrogenicity is statistically associated with insulin resistance and centralization of body fat, which are predictors for the development of non-insulin-dependent diabetes mellitus. The aim of this study was to evaluate the effect of androgenization of newborn female rats on insulin sensitivity at adult age. To mimic the neonatal androgen peak normally observed in male rats, female pups were administered one high dose of testosterone (T) subcutaneously within 3 h after birth. They were then given back to their mothers and followed to adult age. At the end of the week 9, tail samples were taken, showing no differences in fasting plasma concentrations of glucose, lactate, insulin, or free fatty acids between T-treated rats and controls. Plasma concentrations of T and progesterone were significantly lower in the T-treated rats, whereas no differences were found in the levels of corticosterone, estradiol, insulin-like growth factor I, or ACTH. After 10 wk, insulin sensitivity was studied with hyperglycemic and euglycemic hyperinsulinemic (5 mU insulin/kg/min) clamp techniques. The T-treated rats showed insulin resistance with both techniques, which was overcome with time and increasing insulin concentrations during the clamp measurements. The T-treated rats were also heavier and had increased relative weights of skeletal muscles and the spleen. Parametrial, retroperitoneal, and inguinal adipose tissues decreased in weight while mesenteric adipose tissue tended to increase, resulting in an approximately 30-50% larger mesenteric than other adipose tissues. It is concluded that neonatal T imprinting of female rats is followed by insulin resistance, changes in adipose tissue distribution, and an enlarged lean mass, without elevation of circulating T. Similar changes are seen in adult female rats or women receiving T.

Adipose Tissue↗

Pharmacokinetics and distribution of liposomal busulfan in the rat: a new formulation for intravenous administration.

The plasma pharmacokinetics and tissue distribution of busulfan (Bu) were investigated after intravenous injection of free Bu (D-Bu) and freshly prepared liposomal Bu (L-Bu). Liposomal Bu was prepared using L-alpha-phosphatidylcholine, 1,2-dioleolyl-sn-glycero-3-phosphate, and cholesterol. The liposomes formed were unilamellar vesicles measuring 220 +/- 14 nm in diameter and containing a Bu concentration of 0.31 +/- 0.03 mg/ml. The half-life of Bu in the present formulation was determined to be 8.7 +/- 2.7 days at 4 degrees C. The liposomes in the new formulation were stable for 20 days at 4 degrees C. After the intravenous administration of L-Bu or D-Bu (dissolved in a mixture of DMSO, ethanol, and propylene glycol) to the rats a higher bone marrow exposure to Bu as expressed in AUC marrow/AUC blood was achieved using L-Bu as compared with D-Bu (1.59 and 0.83, respectively). A higher distribution volume was observed for L-Bu as compared with D-Bu (1.39 versus 0.67 l/kg, respectively). The elimination half-lives were significantly longer in both blood and marrow after the administration of L-Bu as compared with D-Bu (2.52 and 3.08 versus 1.53 and 1.75 h, respectively). The new liposomal Bu showed linear pharmacokinetics within the range of 0.5-3.5 mg/kg, which is comparable with that obtained for D-Bu. A slight difference was observed in systemic exposure to L-Bu as compared with D-Bu as expressed in AUC (9.93 and 11.82 microg h ml(-1), respectively). The distribution study using 14C-labeled Bu showed that the radioactivity was significantly higher over 18 h in the bone marrow (3-fold) and spleen (2-fold; P < 0.01) in a comparison of L-Bu with D-Bu. However in the brain, lungs, and heart the distribution of radioactivity after the administration of L-Bu was significantly lower (P < 0.05) than that obtained using D-Bu. On the basis of the present study, the new formulation of liposomal Bu seems to be a promising preparation for clinical trials, since it appears to target bone marrow and spleen with no accumulation in the liver or other organs known for Bu toxicity.

Animals↗

Processing of neuropeptide Y and somatostatin in human cerebrospinal fluid as monitored by radioimmunoassay and mass spectrometry.

The processing of four neuropeptides, neuropeptide Y (NPY) 1-36, NPY (18-36), somatostatin (SOM) 1-28, and SOM (15-28) was studied in human cerebrospinal fluid (CSF) by using a novel combination of methods that included radioimmunoassay (RIA) and mass spectrometry. Untreated CSF samples were chromatographed using reversed-phase high pressure liquid chromatography (RP-HPLC) followed by NPY-RIA or SOM-RIA. These results were compared with those obtained by incubating CSF with exogenous synthetic peptides and directly detecting peptide fragments by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-MS). Using this combination of methods, we were able to determine the probable identities of peptides/peptide fragments recognized in radioimmunoassays. The most important NPY-immunoreactive components in CSF were found to be NPY (1-36) and NPY (3-36). Metabolic products of SOM (15-28) were found to contribute to SOM-like immunoreactivity (SOM-LI) in CSF, but SOM (1-28) only to a lesser degree. Differences in the rate of neuropeptide processing were observed. These differences depended more on the length of the peptide than its sequence. NPY (18-36) and SOM (15-28) were rapidly and extensively processed, whereas NPV (1-36) and SOM (1-28) were processed much more slowly in CSF. The production of SOM (15-28) from SOM (1-28) by enzymes in CSF was not observed. Also, the presence of a disulfide bond in the somatostatins appeared to stabilize them against enzymatic digestion of the ring structure. The results detailed in this report confirm MALDI-MS important role in studies of neuropeptide processing in CSF.

Amino Acids↗

Liposomal busulphan: bioavailability and effect on bone marrow in mice.

High-dose busulphan is an important component of many BMT conditioning regimens. High-dose busulphan therapy is associated with an increased risk of acute toxicity such as CNS toxicity and veno-occlusive disease (VOD). The toxicity was reported to correlate with a high AUC (area under the curve) during therapy. An intravenous form of busulphan would overcome the problems caused by inter-individual variability and bioavailability of busulphan and most probably minimize the problems with dose adjustment during therapy. The liposomal form of busulphan is an attractive alternative for intravenous administration of busulphan. In the present study, we compared the myeloablative effect of liposomal busulphan (LB) with that of the oral administration form and busulphan dissolved in organic solvent (Bus/DMSO) in mice. The pharmacokinetics of LB and Bus/DMSO were described by one compartment model while the oral data were fitted to one compartment model with first order absorption. The bioavailability of LB was 0.86+/-0.02 compared to that obtained after the oral administration (0.40-0.74). Myelosuppression was determined using the colony-forming unit granulocyte-macrophage assay (CFU-GM) on days 1, 3, 6 and 9 after the conditioning regimen. LB resulted in significant myelosuppression from day 1 to day 9. The decrease in CFU-GM after conditioning regimen with LB was not significantly different from that observed after oral busulphan. Moreover, the administration of liposomes only to the mice did not affect the bone marrow. No side-effects of the liposomal formulation were observed. We suggest that the novel form of busulphan is a promising drug for clinical use.

Administration, Oral↗

Determination of a common genetic variant of luteinizing hormone using DNA hybridization and immunoassays.

OBJECTIVE: An immunologically anomalous form of LH, due to two point mutations in codons 8 and 15 of the LH beta gene, has previously been described. LH status, i.e. the discrimination between wild-type (WT) and variant (V) LH, is usually determined by immunoassays, which can be unreliable at low serum concentrations of LH. A DNA hybridization assay was therefore developed to score the LH genotype in all subjects, independent of their serum LH concentrations. To evaluate the performance of the hybridization method, and to expand our observations of the worldwide occurrence of the V-LH, we determined its frequency in additional populations. To confirm the connection between the anomalous immunoreactivity and the V-LH beta gene, we also sequenced the LH beta subunit gene of a homozygous person. DESIGN: According to the ratio of two immunoassays, one detecting only WT-LH and the other detecting equally WT and V-LH, individuals can be classified as homozygotes for the V-LH beta allele, heterozygotes or WT. DNA samples from persons with known LH status, according to the immunoassays, were used for the development and evaluation of a new allele-specific DNA hybridization assay. This assay, and PCR and restriction fragment length polymorphism analysis, were used to determine the frequency of the V-LH beta allele in DNA samples obtained from eight populations. PATIENTS: Ambulatory adult men and women, apparently healthy and with no endocrine disorders. RESULTS: The LH genotyping by immunoassays and by the new hybridization method gave identical results with all samples analysed (n = 25). The V-LH beta subunit was observed to always have the two point mutations, and to be identical with the ones previously reported. The V-LH beta carrier frequency in the DNA samples collected from various populations varied between 0 and 53.5%. CONCLUSIONS: The immunoassay technique and the hybridization assay can be used as alternatives to determine the LH status. A great variation in carrier frequency of the V-LH beta allele is observed in different populations.

Adult↗

The frequency of an inactivating point mutation (566C-->T) of the human follicle-stimulating hormone receptor gene in four populations using allele-specific hybridization and time-resolved fluorometry.

We have described previously in the Finnish population an inactivating point mutation (566C-->T) in the human FSH receptor (FSHR) gene. In women, this mutation causes hypergonadotropic ovarian failure with arrest of follicular maturation and infertility, whereas in men, there is variable suppression of spermatogenesis, but no absolute infertility. To determine whether the same FSHR mutation occurs in other populations, its frequency was determined in Finland, Switzerland, Denmark, and the Chinese population of Singapore. The mutation was screened for using genomic DNA extracted from whole blood or dried blood spots. Exon 7 of the FSHR gene was first amplified using a pair of biotinylated primers. The PCR products were then immobilized on streptavidin-coated microtitration wells and hybridized using short allele-specific oligonucleotide probes labeled with europium. Time-resolved fluorometry was used for europium signal detection. To test the reliability of this method, 40 isolated DNA samples and 35 dried blood spot samples were blindly tested for the 566C-->T FSHR mutation. The analyses yielded identical results with denaturing gradient gel electrophoresis and allele-specific restriction enzyme digestion of the same samples, thus demonstrating the reliability of the tested method. Automation of this procedure allows the screening of large numbers of samples, which was subsequently carried out to investigate the frequency of the 566C-->T mutation in the study populations. A total of 4981 samples from the above-mentioned 4 countries were analyzed. The frequency of the 566C-->T mutation was 0.96% for all Finnish samples (n=1976), with a strong enrichment of the mutant allele in the northeastern part of the country. Only 1 mutation carrier was identified in the samples from Switzerland (n=1162), whereas none was found in samples from Denmark (n=1094) and the Singapore Chinese (n=540). These results suggest that the 566C-->T mutation of the FSHR gene is enriched in Finland, but is uncommon in other populations.

Alleles↗

Long-Term Responses of River-Margin Vegetation to Water-Level Regulation

The long-term effect of water-level regulation on riparian plant communities was assessed for storage reservoirs and run-of-river impoundments. Soon after the onset of regulation, there were few species and sparse vegetation cover, regardless of whether the new water level intersected former upland or riparian vegetation. In the longer term, an impoverished vegetation was maintained by storage reservoirs, whereas in run-of-river impoundments, some community characteristics deteriorated and others recovered compared to adjacent free-flowing rivers.

Journal Article↗

The effect of selective sympathetic denervation on pancreatic exocrine secretion.

The purpose of this study was to investigate the influence of selective sympathetic denervation of the rat pancreas on exocrine secretion and to study whether the observed effects were due to pancreatic trophism. Sprague-Dawley rats were divided into two groups. One group underwent selective sympathetic denervation by skeletonizing the superior and inferior pancreaticoduodenal and splenic arteries. The other group underwent simple laparotomy and served as controls. One week after the operation a catheter was introduced into the bile-pancreatic duct and pancreatic juice was collected at 30-min intervals for 4 h. The output of bicarbonate, total protein, amylase, trypsin, chymotrypsin, lipase, colipase and carboxyesterlipase were determined. Following denervation secretion of pancreatic enzymes was significantly enhanced compared with sham-operated animals. We did not find any signs of pancreatic trophism 1 week after denervation.

Amylases↗

Worldwide frequency of a common genetic variant of luteinizing hormone: an international collaborative research. International Collaborative Research Group.

OBJECTIVE: To determine the worldwide frequency of a common immunological LH variant because of two point mutations in the LH beta-subunit gene (Trp8Arg and Ile15Thr). DESIGN: Cross-sectional study on LH status (variant and wild-type) in serum (or DNA) samples from Finland (Finns and Lapps), Estonia, Poland, Sweden, The Netherlands, United Kingdom, Italy, South Africa (blacks), Thailand, China, Japan, and the United States (Hispanics and blacks). SETTING: Academic research environment. PATIENT(S): Ambulatory adult men and women (n = 2,936) with minor illnesses and no known endocrinological disorders. INTERVENTION: A single blood sample was collected from each subject. MAIN OUTCOME MEASURE(S): The LH status was determined by two immunofluorometric assays using monoclonal antibodies. One (assay 1) only recognizes the wild-type LH, the other (assay 2) recognizes equally variant and wild-type LH. The ratio of assay 1 to assay 2 indicates the LH status: wild-type, > 0.9; heterozygote, 0.2 to 0.9; and homozygote, < 0.15. One population (Lapps) was studied by DNA analysis using polymerase chain reaction and allele-specific oligonucleotide hybridization. RESULT(S): The carrier frequency of the variant LH beta allele varied from 7.1% in U.S. Hispanics to 41.9% in Lapps of northern Finland. The variant LH beta allele tended to be more common in populations from Northern Europe as compared with those from Asia. CONCLUSION(S): The high frequency of the LH beta variant worldwide makes it an important confounding factor when obtaining disproportionately low LH levels with some immunometric assays. The LH variant may contribute to some pathologies of the pituitary-gonadal function.

Adolescent↗

Microorganisms in vaginal fluid from women in prolonged pregnancy.

In order to compare the vaginal microflora of women in prolonged pregnancy with that of women who delivered at term, samples for quantitative aerobic and anaerobic microbiological culture were collected from 100 women at 42 weeks of gestation and from 60 women at term. The occurrence of lactobacilli-dominated flora was similar in women at term and women with prolonged pregnancy. However, non-hydrogen-peroxide-producing lactobacilli (p < 0.01) were significantly more common and Peptostreptococci species (p < 0.05) significantly less common in postterm women as compared with term controls. In postterm women, Candida albicans was more common (p < 0.001) in microfloras dominated by non-hydrogen-peroxide-producing lactobacilli than in floras dominated by hydrogen-peroxide-producing lactobacilli. The ecosystem of the vagina in asymptomatic postterm women was disrupted concerning the composition of lactobacilli as compared with term controls.

Adult↗

Cloning of human cDNA encoding a novel heptahelix receptor expressed in Burkitt's lymphoma and widely distributed in brain and peripheral tissues.

Using PCR with degenerate primers and screening of a human B-cell lymphoblast cDNA library, a full-length cDNA encoding a 375-amino-acid protein was isolated. It contains seven regions of hydrophobic amino acids probably representing membrane-spanning domains of a novel heptahelix receptor, tentatively named CMKRL2. It shows nearly 30% overall identity with the high-affinity IL8 receptor and similar degree of homology with other chemoattractant receptors, including the "fusin" coreceptors for HIV1. Measurements of various transduction pathways following application of a panel of chemokines to transfected cells failed to evoke any reproducible response. Although the natural ligand for CMKRL2 could, thus, not be identified, receptor expression in spleen and lymph nodes as well as in Burkitt's lymphoma (irrespective of EBV status) supports a functional role in activated B-cells. Receptor message was ubiquitously distributed in normal peripheral tissues and CNS, suggesting that CMKRL2 is expressed in widespread cell populations, such as macrophages and neuroglia.

Adenylyl Cyclases↗