Biomedical subjects

M Blake

Publications and source records attributed to M Blake.

At least 73 records · Page 4Linked to original sources

PubMed1991

Management of odontogenic sinusitis with persistent oro-antral fistula.

Sixteen patients were treated for odontogenic sinusitis secondary to persistent oro-antral fistula. Males outnumbered females 12 to 4. Frequency of presentation increased directly with age. Chronic signs and symptoms included facial pain, swelling, tenderness and nasal and oral discharge. The clinical diagnosis of chronic sinusitis was confirmed in all cases by radiographic findings. An opacified maxillary sinus with or without ethmoid involvement was observed in all 16 patients. Surgical pathology revealed chronic mucosal thickening and/or antral polyps in 69% of the cases. Surgical treatment of the sinusitis consisted of antrostomy alone or in combination with Caldwell-Luc procedure. The oro-antral fistula was repaired with mucosal flaps from the buccal and/or palatal region. No postoperative recurrences have been noted during a follow-up period of six months to seven years. Bacterial cultures grew out pure aerobes (44%) or mixed aerobic-anaerobic bacteria (44%). None yielded pure anaerobes. The bacteriologic spectrum was notably lacking in S. pneumoniae and H. influenzae and differed from organisms commonly found in sinusitis of rhinogenous origin.

Adolescent↗

PubMed1991

Synergistic antiproliferative effect of interferon alpha and azidothymidine in chronic myelogenous leukemia.

The possible synergistic interaction between azidothymidine (AZT) and interferon alpha (rIFN-alpha 2a) in the treatment of chronic myelogenous leukemia (CML) was studied in vitro using marrow or peripheral blood hematopoietic progenitors from 10 patients with CML in the mixed (CFU-GEMM) colony culture assay. Used singly, either agent inhibited erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) CML hematopoietic progenitor proliferation in a dose-dependent fashion, with the inhibitory effect being more pronounced on BFU-E than on CFU-GM colony-forming cells. The combination of both drugs in therapeutic concentrations exerted a significant synergistic inhibition on CML stem cells as assessed by the median-effect principle and isobologram equation analysis. A suboptimal dose of AZT (0.5 mumol/l) synergistically augmented the effect of rIFN-alpha 2a whereas an inactive dose of 10 U/ml rIFN-alpha 2a similarly enhanced the CML stem cell growth inhibition exerted by AZT. Our data indicate that AZT may augment the already established therapeutic benefits of IFN-alpha in CML.

Adult↗

PubMed1990

Significance of blasts in low-cell-count cerebrospinal fluid specimens from children with acute lymphoblastic leukemia.

The purpose of this study was to determine whether the presence of more than 5% blasts in a differential count of cytocentrifuged cerebrospinal fluid (CSF) with less than 6 leukocytes/microliter was predictive of central nervous system (CNS) relapse in children with acute lymphoblastic leukemia (ALL). A double concentrate method of cytocentrifuge preparation was used to analyze 4543 consecutive CSF specimens from 349 children with ALL between January 1, 1982, and September 30, 1988. One hundred nine CSF specimens from 58 evaluable children had less than 6 leukocytes/microliter and more than 5% blasts on cytocentrifuge differential count (low-cell-count specimen with blasts [LCB]). During the study period, 25 of 332 evaluable children (7.5%) had CNS leukemic recurrence. In 22 of 25 (88%), the CNS relapse was preceded by at least one abnormal low-cell-count CSF specimen. One of 34 patients with a single LCB at diagnosis (3%) had subsequent CNS relapse compared with five of eight patients (62.5%) with a single LCB during remission (P = 0.0002). Of 16 children with two or more LCB during remission, nine (56%) had CNS relapse defined by standard criteria, whereas six additional patients in this group were declared to be in CNS relapse on the basis of their repetitive LCB. Whether diagnosing CNS recurrence earlier in its course based on a modification of the definition of CNS leukemia will change the frequency of subsequent adverse events or make possible decreased intensity of CNS retreatment remains to be determined.

Adolescent↗

PubMed1990

Hematological and biochemical changes during a short triathlon competition in novice triathletes.

Short-course 'sprint' triathlons have become popular in recent years, often as a precursor to the longer full-course triathlons. We undertook a study investigating the haematological and biochemical changes that occur in novice triathletes between the start and finish and after each of the three legs of a short sprint triathlon involving swimming, cycling and running. The changes that occurred in the triathlon included a significant (P less than 0.003) decrease in weight from 71.7 kg, SD 7.9 to 70.3 kg, SD 7.6. Throughout the time span of the triathlon, the white blood cell count increased significantly (P less than 0.001), as did the platelet count (P less than 0.005) and plateletcrit (P less than 0.001). There were no significant changes during the period of the race in any of the other haematological variables measured. The biochemical variables measured were glucose, triglycerides, sodium, potassium, calcium, lactate dehydrogenase, creatinine and aspartate aminotransferase. Triglyceride, calcium and potassium values did not change between the pre- and post-race samplings. All other biochemical parameters showed a significant change (P less than 0.05 or better). Changes that occurred in the haematological and biochemical parameters between stages were many and varied. There was also a significant change in plasma volume during the swimming event (P less than 0.001), but this returned to normal during the later stages of the triathlon. In conclusion the changes that occurred during the triathlon were many and were similar to those reported elsewhere in the literature for longer events.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspartate Aminotransferases↗

PubMed1990

Community-acquired pseudomonas pneumonia in a normal host complicated by metastatic panophthalmitis and cutaneous pustules.

Pseudomonas aeruginosa is a frequent pathogen of patients with chronic underlying disease in the hospital environment. This organism is, however, an extremely rare cause of either community-acquired pneumonia in a normal host, metastatic bacterial endophthalmitis or metastatic cutaneous pustules. We report here a case combining these three rare manifestations in a previously well young woman, to highlight the serious disease that may result from this pathogen and the difficulties of treatment.

Adult↗

PubMed1989

Aggregation by fragilis and non-fragilis Bacteroides strains in vitro.

Bacteroides fragilis is associated with the formation of intra-abdominal abscesses, whereas other Bacteroides species are rarely involved. Since bacterial clumping may contribute to the survival of bacteria in the face of host defence mechanisms, the hypothesis has been put forward that differences in aggregation between fragilis and non-fragilis strains of Bacteroides may account for their differences in survival in vivo. All seven B. fragilis strains tested formed aggregates within 4 h, but strains not associated with intra-abdominal sepsis--B. vulgatus, B. thetaiotaomicron and B. distasonis--did not form aggregates in vitro. Aggregation occurred at 37 degrees C, but not at 4 degrees C or 20 degrees C. Treatment with pronase partially inhibited aggregation. Periodate treatment killed the cells and caused them to form clumps which were distinguishable from the control aggregates. Heat-killed B. fragilis cells formed similar distinct clumps, but cells killed by glutaraldehyde and formaldehyde did so to a lesser degree. No inhibition was found upon addition of carbohydrates, ethylenediaminetetraacetic acid or after treatment with trypsin. These results demonstrate that aggregate formation occurs with B. fragilis strains alone, and that surface proteins probably mediate this interaction.

Bacteroides↗

PubMed1988

Immunogenicity of liposome-bound hyaluronate in mice. At least two different antigenic sites on hyaluronate are identified by mouse monoclonal antibodies.

Hyaluronate (HA) was previously demonstrated to be immunogenic in rabbits. The immunogenicity of HA in mice was studied. Hyaluronidase-digested streptococcal HA (IA1) covalently linked to liposomes (IA1-liposomes) were produced for immunization. Mice immunized with IA1-liposomes developed measurable serum antibodies to IA1, while mice immunized with IA1 in Freund's adjuvant did not. mAbs produced by two stable hybridomas (10G6 and 5F11) from mice immunized with IA1-liposomes produced IgG antibody reactive with HA in ELISA. 10G6 had a much higher avidity for liposome-bound IA1 than free IA1, while 5F11 did not, suggesting that the mode of presentation of IA1 is important in HA immunogenicity and antigenicity. Both mAbs recognized terminal HA immunodeterminants exposed by hyaluronidase treatment. Sonication had no effect on HA reactivity for either mAb. However, ascorbic acid treatment significantly reduced the antigenicity of HA for mAb 5F11, but not 10G6. Only 10G6 was inhibited by glucuronic acid. Electrostatic forces appear to play a role in the binding site of 5F11, but not 10G6. 5F11 crossreacts with heparan sulfate and phosphorylcholine, while 10G6 did not crossreact with any glycosaminoglycans or phosphorylated compounds tested. These results confirm that HA is immunogenic. They suggest that the mode of presentation of HA is important for the induction of the immune response, and in HA antigenicity. At least two different antigenic sites on HA were demonstrated. 10G6 recognizes a terminal HA antigenic site expressed on IA1-liposomes that contains glucuronic acid in its immunodominant site. 5F11 recognizes an HA antigenic site in which electrostatic forces appear to play a role, is sensitive to ascorbic acid treatment, and is crossreactive with heparan sulfate. The use of mAbs should facilitate immunologic studies of HA.

Animals↗

PubMed1988

Long-term survival of children with acute non-lymphoblastic leukemia.

Results of a pilot protocol employing chemoimmunotherapy for treatment of 23 children with acute non-lymphoblastic leukemia consecutively diagnosed between 1975 and 1979 are reported. Twenty-two children achieved remission, ten of whom are surviving 6.5-9.5 years after completion of primary systemic therapy (median 7.8 years). Treatment consisted of intermittent courses of Daunomycin, Cytosine Arabinoside, 6-Thioguanine, VP-16, with or without Decadron, Connaught BCG applied between courses of chemotherapy for the first 8 months of treatment, and cranial irradiation/intrathecal Cytosine Arabinoside in early first remission. Five patients with leukemic cells in spinal fluid at diagnosis had myelomonoblastic or monoblastic subtypes and a median diagnostic white blood cell count (WBC) of 149,000/mm3 compared with a median WBC of 12,000/mm3 for the other 18 patients (P = .007).

Acute Disease↗

PubMed1988

Voltage gating of conductance in lipid bilayers induced by porin from outer membrane of Neisseria gonorrhoeae.

Porins, polypeptides of approximately 35 kDa, are present as integral membrane proteins in the outer membranes of a variety of Gram-negative bacteria. As reported previously for a purified porin from Escherichia coli, voltage gating of conductance was found to be induced in a lipid bilayer by the solubilized purified porin, protein I, from Neisseria gonorrhoeae. The unitary response to an applied potential showed a cascade of current from an initial level through at least three levels, more or less equal, to a persisting lower level. The initial level of current corresponded to 1.0-1.3 nS for 0.2 M NaCl on either side of the bilayer. Briefly reducing the potential to zero restored the current to its initial level. Interpretation of the unitary response is suggested by electron microscopic data obtained on negatively stained outer membranes of E. coli indicating the presence of "pores" appearing in triplets. Moreover, low-resolution x-ray and neutron diffraction studies on crystals obtained with an E. coli porin show that three polypeptides associate to form a unit. Combining such structural data with the present electrical data lends support for the hypothesis that the unitary response results from three pores acting as a unit in response to an applied potential. Evidence obtained with the patch-clamp technique is mounting for a similar mechanism of many channels operating as a unit in a variety of cell membranes. The porin channel holds promise as a concrete model for the analysis of voltage gating of ionic conductance.

Bacterial Outer Membrane Proteins↗

PubMed1988

Fetal development, and placental and maternal plasma concentrations of progesterone in the little brown bat (Myotis lucifugus).

Progesterone concentrations measured in plasma samples from 280 bats captured during pregnancy or early lactation were related to fetal attributes indicative of stage of pregnancy. Fetal weight increased exponentially from 40 mg at crown-rump length of 6 mm to 2000 mg at 23 mm (term). Fetal weights at term accounted for up to 35% of the weight of intact pregnant animals. Progesterone concentrations increased from less than 5 ng/ml at 2 mm estimated crown-rump length to plateau values of approximately 65 ng/ml (geometric means) from 16 mm crown-rump length until the most advanced stages of pregnancy. Mean concentration in 8 post-partum bats, most of which were actively lactating, was 8.4 ng/ml; 11.6 ng/ml was measured in one animal that was carrying a wet neonate when sampled yet was still pregnant when captured 5 h earlier. Placental concentrations of progesterone ranged from 43 to 964 ng/g wet weight of tissue and mean values increased in a similar fashion though were about 4-fold greater than changes in plasma concentrations of the steroid. The concentrations in placental tissue were at least 15- to 20-fold higher than could be expected from blood contamination, indicating that placental steroidogenesis is likely to occur in this species.

Animals↗

PubMed1987

Gonococcal pilin variants in experimental gonorrhea.

When pilus+ Gc were introduced into a male subject's urethra, they gave rise to pilus+ variants whose pilin mRNAs differed from that of input Gc. The differences stemmed from the Gc genome's single complete pilin gene having undergone gene conversion by different partial pilin genes' sequences and by different length stretches of a single partial pilin gene. In some instances, the variant's pilin mRNA appeared to reflect two independent gene-conversion events that used sequences from two different partial pilin genes. The resulting variants' pilins exhibited antigenic differences compared with the pilin polypeptide of input Gc; these differences were discernible by immunoblotting with mAbs. Amino acid and antigenic changes occurred in a segment of the variants' pilin polypeptides that previously was thought to be conserved or constant in sequence.

Amino Acid Sequence↗

PubMed1987

Methodology of premature chromosome condensation and its potential for relapse prediction in acute leukemia of children and adolescents.

Premature chromosome condensation has been examined as a method for measuring the proliferative potential of bone marrow cells derived from children with acute leukemia with the intention of finding a predictor of relapse. A proliferative potential index (PPI) has been determined for patients with active disease at diagnosis and relapse, as well as at onset of remission and at extramedullary relapse. A modification of the technique established by Hittelman is described, which can be easily performed by the leukemia cytogeneticist. A PPI of 35% or greater is usually obtained for patients at diagnosis or in relapse. At the onset of remission, the PPI declines to values significantly below 35% and during extramedullary relapse the value of the PPI is near normal (12%). The method for the determination of the PPI is given in detail.

Acute Disease↗

PubMed1987

Premature chromosome condensation as a predictive indicator of relapse in children and adolescents with acute leukemia: initial observations.

Premature chromosome condensation has been used to determine a proliferative potential index (PPI) in a study of children in leukemia remission at varying times during the disease. Values 35% and greater were considered predictive of relapse. Such values preceded relapse with a mean of 5 months in acute lymphoblastic leukemia (ALL) patients who had previously relapsed and in myeloid leukemia patients. ALL patients followed from diagnosis and children off therapy had fluctuating and false predictive PPI values preceding long courses of continued remission. This study suggests that the PPI as a predictive indicator for relapse may be useful for patients with ALL who have previously relapsed and for patients with myeloid leukemias. Future exploration to further evaluate this mechanism of prediction is to be attempted by investigating the ability to obtain similar and more detailed information through the use of peripheral blood rather than bone marrow samples.

Acute Disease↗

PubMed1986

Induction of antibodies to hyaluronic acid by immunization of rabbits with encapsulated streptococci.

The immunogenicity of hyaluronic acid was investigated. Rabbits were immunized with encapsulated group A and C streptococci. Intact long-chain hyaluronate was conjugated to BSA for use as antigen in an ELISA. Antibodies to the hyaluronate-BSA conjugate were detected in peak immune sera. The specificity of the antibodies for both mammalian and streptococcal hyaluronate was shown by inhibition studies. To further confirm the presence of antihyaluronate antibodies, hyaluronidase-digested streptococcal hyaluronate was conjugated to biotin and used as an antigen in the ELISA. A clear immunization effect was shown for each rabbit by the study of preimmune and postimmunization bleedings. Titers for each rabbit increased by greater than 32 - 256 - fold. Inhibition studies using hyaluronidase-digested hyaluronate and periodate-treated hyaluronate showed that the immunodominant site of antibody reactivity was a terminal glucuronic acid residue. Further studies showed that the carboxyl group of the terminal glucuronide was the major immunoreactive site. Both mammalian and streptococcal hyaluronate inhibited the immune rabbit sera reaction to streptococcal hyaluronate, demonstrating crossreactivity of these molecules. Thus, hyaluronate was shown to be immunogenic in rabbits.

Agglutination Tests↗

PubMed1985

Purification of Legionella pneumophila major outer membrane protein and demonstration that it is a porin.

We have purified the major outer membrane protein (MOMP) of Legionella pneumophila, determined that it is associated with peptidoglycan, and characterized it as a porin. To purify the MOMP, we used a simple, rapid, three-step procedure that gave us the protein in high yield. The first step of the purification procedure involved selectively extracting the MOMP from whole bacterial cells with calcium and zwitterionic detergent. The second and third steps achieved purification by ion-exchange and molecular-sieve chromatography. The dissociation of the MOMP into monomers was dependent upon the presence of a reducing agent and was enhanced by treatment at 100 degrees C. To study the relationship of the MOMP to peptidoglycan, we extracted the protein by a modification of the Rosenbusch procedure. Like the Escherichia coli porins, the MOMP was peptidoglycan associated. The MOMP was at least partially dissociated from peptidoglycan in sodium dodecyl sulfate and a high salt concentration. To study the ion channel-forming properties of the MOMP, we reconstituted the MOMP in planar lipid membranes. The MOMP formed ion-permeable channels with a single-channel conductance size of 100 picoSiemens. The MOMP channels exhibited a fourfold selectivity for cations over anions and voltage-independent gating. These findings demonstrate that the MOMP is a porin with properties similar to those of E. coli porins.

Bacterial Outer Membrane Proteins↗

PubMed1983

Antibiotic-associated diarrhoea and pseudomembranous colitis caused by Clostridium difficile. A review of 40 cases.

We found antibiotic-associated diarrhoea (AAD) and pseudomembranous colitis caused by Clostridium difficile in 19% of patients with diarrhoea related to antibiotic therapy or with diarrhoea for which no other cause could be found. Ampicillin, cephalosporins and co-trimoxazole appear to be the agents most commonly associated with this complication. The clinical presentation of AAD falls into two categories: (i) an early-onset type characterized by severe diarrhoea with watery stools which may contain mucus; and (ii) a late-onset variety characterized by chronic, persistent diarrhoea with bulky stools. A definitive diagnosis was made in all cases by the detection of the cytotoxin of Cl. difficile in patients' stools using tissue culture assay. Discontinuation of the implicated agent when possible together with a 14-day course of oral vancomycin effected a cure in 90% of patients. The remaining 10% were successfully treated with a similar course of oral bacitracin.

Adult↗

PubMed1983

Prognosis in acute lymphoblastic leukemia of childhood as determined by cytogenetic studies at diagnosis.

Fifty-one children with acute lymphoblastic leukemia on a common protocol of treatment were classified according to presence or absence of chromosomal abnormalities found at the time of diagnosis in bone marrow and/or blood. Twenty-two or 43% had normal karyotypes while 29 (57%) had clonal abnormalities using the Giemsa-trypsin banding technique. Thirteen of the 29 (45%) chromosomally abnormal patients relapsed while only three of 21 (14%) with normal karyotypes have relapsed with a median follow-up of 49.5 months (42-76 months). (One child with a normal karyotype did not respond to therapy.) Several hypotheses have been offered to attempt to explain the significantly better prognosis of patients with no observable initial chromosomal aberrations.

Adolescent↗

PubMed1983

Properties of the major outer membrane protein from Neisseria gonorrhoeae incorporated into model lipid membranes.

The major outer membrane protein from Neisseria gonorrhoeae was incorporated into artificial planar bilayer membranes by a detergent-dilution procedure. The integrated protein forms voltage-dependent aqueous pores with a minimal pore diameter estimated to be 11 A. A pore of this size suggests a role for this protein in macromolecular sieving at the level of the outer membrane. This protein self-associates preferentially in triplets of three equal unit conductance steps of 130 pS (in 0.1 M NaCl) each. The two-state model may be applied to explain the voltage-dependent conductance. The average lifetime of the open state of single channels is strongly dependent on the applied voltage, the channels shifting to the closed state at higher voltages. The pore is anion selective, differing from porins of other Gram-negative bacteria studied so far but resembling the voltage-dependent anion-selective channel of the outer membrane of mitochondria.

Bacterial Proteins↗