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Biomedical subjects

J M Carter

Publications and source records attributed to J M Carter.

At least 91 records · Page 5Linked to original sources
PubMed1990

Sequence comparison of allelic forms of the Plasmodium falciparum merozoite surface antigen MSA2.

MSA2 is a strain variable blood-stage merozoite surface antigen of Plasmodium falciparum. We have derived the MSA2 nucleotide sequence for four cloned parasite isolates. Comparison with three other published sequences suggests that variation may be limited, and that the architecture of the gene can be conveniently described by segregation into four distinct regions. The N and C terminal regions (Regions 1 and 4) are highly conserved in all seven genes. Six of these seven MSA2 genes can be grouped in a single family, within which variation is largely limited to a region characterized by the presence of tandem repeats (Region 2). We have observed two new forms of repeat in a Gly, Ser, Ala-rich block, and noted the absence of repeat in this block of the CAMP strain. The region downstream of the repeat region (Region 3) is highly conserved within this family. Immunochemical analysis reveals that MSA2 is one of the antigens recognized by immune antibodies eluted from intact merozoites. Regions 2 and 3, expressed as recombinant proteins, are recognized by these antibodies, suggesting that these regions are exposed at the surface of the intact merozoite.

Alleles↗
PubMed1990

Effects of procainamide hydroxylamine on generation of reactive oxygen species by macrophages and production of cytokines.

A series of experiments was conducted to examine the effects of the N-oxidized metabolite of procainamide, procainamide hydroxylamine (PAHA), on reactive oxygen species (ROS) production by macrophages in vitro, as well as on the release of the cytokine interleukin-1 (IL-1). Results with PAHA were compared with those from the parent compound, procainamide, and in some cases with other procainamide metabolites such as N-acetylprocainamide or nitrosoprocainamide. The effects of PAHA on ROS production by mouse and rat macrophages were complex, resulting in both stimulatory and inhibitory activity depending upon the PAHA concentration and whether macrophages were resting or elicited. The primary effect of PAHA appeared to be a stimulation of ROS production. Monocytes pretreated with PAHA (20 microM) depressed the responsiveness of lymphocytes in co-culture to a T-cell mitogen (conconavalin A) but not a B-cell mitogen (lipopolysaccharide). This effect was inhibited when monocyte pretreatment with PAHA was accompanied by the antioxidants, catalase or superoxide dismutase. IL-1 production by rat adherent splenocytes was unaffected by PAHA in concentrations that were not cytotoxic. These observations suggest that the oxidative metabolism of procainamide to PAHA may result in enhanced production of ROS by macrophages contributing its toxicity to lymphocytes.

Animals↗
PubMed1990

Primary structure of the 175K Plasmodium falciparum erythrocyte binding antigen and identification of a peptide which elicits antibodies that inhibit malaria merozoite invasion.

The Plasmodium falciparum gene encoding erythrocyte binding antigen-175 (EBA-175), a putative receptor for red cell invasion (Camus, D., and T. J. Hadley. 1985. Science (Wash. DC). 230:553-556.), has been isolated and characterized. DNA sequencing demonstrated a single open reading frame encoding a translation product of 1,435 amino acid residues. Peptides corresponding to regions on the deduced amino acid sequence predicted to be B cell epitopes were assessed for immunogenicity. Immunization of mice and rabbits with EBA-peptide 4, a synthetic peptide encompassing amino acid residues 1,062-1,103, produced antibodies that recognized P. falciparum merozoites in an indirect fluorescent antibody assay. When compared to sera from rabbits immunized with the same adjuvant and carrier protein, sera from rabbits immunized with EBA-peptide 4 inhibited merozoite invasion of erythrocytes in vitro by 80% at a 1:5 dilution. Furthermore, these sera inhibited the binding of purified, authentic EBA-175 to erythrocytes, suggesting that their activity in inhibiting merozoite invasion of erythrocytes is mediated by blocking the binding of EBA-175 to erythrocytes. Since the nucleotide sequence of EBA-peptide 4 is conserved among seven strains of P. falciparum from throughout the world (Sim, B. K. L. 1990. Mol. Biochem. Parasitol. 41:293-296.), these data identify a region of the protein that should be a focus of vaccine development efforts.

Amino Acid Sequence↗
PubMed1990

Interrelationship between platelet count, red cell count, white cell count and weight in men.

In 83 healthy normotensive males aged 20-55 years the platelet count is positively correlated with the red cell count (r = 0.371; P = 0.0006), the white cell count (r = 0.358; P = 0.0009), and with weight (r = 0.252; P = 0.0269). The red cell count is also positively related with the white cell count (r = 0.242; P = 0.0278) and with weight (r = 0.326; P = 0.0039); while the white cell count is slightly correlated with weight (r = 0.210; P = 0.067). These findings provide further indirect evidential support for a haemopoetic growth factor acting on a single pluripotent stem cell.

Adult↗
PubMed1990

The 56-kilodalton major protein antigen of Rickettsia tsutsugamushi: molecular cloning and sequence analysis of the sta56 gene and precise identification of a strain-specific epitope.

Lasting immunity against Rickettsia tsutsugamushi, the causative agent of scrub typhus fever, has been demonstrated to be strain specific. Two protein antigens of 110 and 56 kilodaltons (kDa) have been shown to exhibit strain-specific epitopes. The 56-kDa scrub typhus antigen (Sta56) is an abundant outer membrane protein of R. tsutsugamushi and is an antigen often recognized by humans infected with this obligate intracellular bacterium. In this study the complete gene encoding Sta56 (strain Karp) was cloned into pBR322 on a 2.3-kilobase genomic HindIII DNA fragment and the complete 56-kDa polypeptide was expressed in Escherichia coli. DNA sequence analysis of the 2.3-kilobase HindIII fragment revealed an open reading frame large enough to encode a 56-kDa polypeptide. A putative signal sequence was identified at the deduced amino terminus of the Sta56 polypeptide, and pulse-chase analysis of maxicells labeled with [35S]methionine demonstrated that a higher-molecular-weight precursor matures into the 56-kDa polypeptide. Epitope scanning analysis with synthetic peptides derived from the deduced amino acid sequence identified an octapeptide (located from amino acid residues 117 to 124) that was reactive with a Karp strain-specific monoclonal antibody (K13F88A). Other epitopes recognized by different monoclonal antibodies, including another Karp strain-specific monoclone (K1E106), were localized to different regions of the protein based on their reactivities with lambda gt11 recombinants expressing various portions of the sta56 gene.

Amino Acid Sequence↗
PubMed1990

Haemostasis in hypothyroidism.

Abnormalities that have been reported for platelet indices and function, coagulation factors and tests, and the fibrinolytic system in hypothyroidism are reviewed. These abnormalities, although usually of limited importance clinically, may occasionally lead to major bleeding episodes and to diagnostic confusion.

Blood Coagulation Disorders↗
PubMed1990

Pulmonary cavitation with Nocardia and Aspergillus in a renal transplant patient.

We present an autopsy case of concomitant pulmonary aspergillosis and nocardiosis undiagnosed during life in a long-term surviving renal transplant recipient. The patient had fever and a newly developed cavitary lesion on a chest x-ray. The working diagnosis was pulmonary tuberculosis with possible colonization by Aspergillus species. Cultures of bronchial washings became positive for Aspergillus fumigatus 1 day after death. The study of tissue from the lung cavity at autopsy revealed Aspergillus fumigatus (confirmed by postmortem culture) and the filaments of Nocardia species. Increased numbers of surviving immunosuppressed patients will require aggressive, comprehensive diagnostic techniques for the detection of polymicrobial infections.

Aspergillosis↗
PubMed1990

Panoramic zonography of the midface: a clinician's guide to vertical magnification.

Surgical procedures involving the maxilla require details regarding the topography of the nasal floor and that of the maxillary sinus. Panoramic zonography can provide this information with a minimum of radiation exposure and may be used in certain instances when other imaging modalities cannot. Spatially dependent variations in vertical magnification inherent to panoramic zonography using the midface program were determined. Radiographic lengths of marker wires attached at seven locations along the maxillary arch of dry skulls were measured. Radiographs were obtained at 0, -10 and -20 mm shifts. Analysis of variance and ranking did not reveal any significant differences in magnification between skulls. However, a dichotomy between the anterior and posterior portions of the maxillary arch in terms of vertical magnification was found at all three shift positions. In addition, at all marker locations, the magnification diminished as a function of decreasing shift position. These variations are due to the fact that teeth within the arch are not all located at the central plane of the focal trough generated by the unit. The results provide the clinician with vertical magnification factors from which actual measurements can be derived from zonographs.

Alveolar Process↗
PubMed1990

High-frequency oscillatory ventilation and extracorporeal membrane oxygenation for the treatment of acute neonatal respiratory failure.

Forty-six (92%) outborn and four (8%) inborn term or near-term neonates were admitted for extracorporeal membrane oxygenation (ECMO) treatment to a neonatal intensive care unit between July 1, 1985, and November 1, 1987. All infants had PAO2-PaO2 greater than or equal to 600 mm Hg in spite of aggressive conventional ventilatory and pharmacologic therapy. All patients were offered rescue treatment with high-frequency oscillatory ventilation (HFOV), and only if there was no improvement in PAO2-PaO2 with HFOV were infants treated using ECMO. Four patients died before receiving an adequate trial of HFOV and before emergency ECMO support could be initiated; 21 patients, all of whom survived to hospital discharge, responded to HFOV; 25 patients ultimately required ECMO therapy for cardiopulmonary support, with 22 (88%) surviving to discharge. Neonates responding to HFOV were of slightly younger gestational age (38 +/- 2 weeks vs 40 +/- 2 weeks, mean +/- SD; P less than .001) and more frequently had clinical evidence of pneumonia (11 of 21 vs 2 of 25; P less than .002). There was no statistically significant difference in outcome with respect to the number of ventilator days, hospital days, or survival between patients responding to HFOV and patients who required ECMO. Morbidity was increased in ECMO patients, with bleeding abnormalities, seizures, and renal failure occurring more frequently than in HFOV-treated infants. Overall, 92% (46 of 50) of the patients were treated with a staged protocol using HFOV before ECMO. A total of 46% (21 of 46) responded to HFOV treatment alone and did not require ECMO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracorporeal Membrane Oxygenation↗
PubMed1989

Racial differences in platelet counts in New Zealand men.

Healthy Maori males were found to have higher platelet counts (mean 295 x 10(9)/L: SD 46) compared to healthy nonMaori males (mean 253 x 10(9)/L; SD 50). Maori males had higher weights (mean 88.4 kg; SD 12.5) than nonMaori males (mean 81.0 kg; SD 9.0); and the platelet count was significantly correlated with weight (r = 0.30; p = 0.003). After weight adjustment significant differences between Maori and nonMaori males for platelet counts remained. These findings have implications for laboratory reference ranges, and may be of epidemiological significance in cardiovascular disease.

Adult↗
PubMed1989

Treatment of hairy cell leukaemia with recombinant alpha interferon.

Eleven patients with progressive hairy cell leukaemia (three nonsplenectomised) were treated with recombinant alpha-2 interferon (Intron-A or Roferon-A) subcutaneously three times per week at a dosage of 3 x 10(6) units. Ten patients completed at least ten weeks of therapy and could be evaluated; one patient died of haemorrhage from severe thrombocytopenia after only three weeks treatment. Nine of the ten patients responded and all of these are regarded as good partial remissions (normalisation of all blood parameters but still discernible hairy cells in the marrow). Responding patients have all been followed for a median of two years and in one case 3 1/2 years since commencement of therapy. The patients are all transfusion independent and free of infection. We conclude that alpha-2 interferon therapy for progressive hairy cell leukaemia is effective therapy in both splenectomised and nonsplenectomised patients.

Adult↗
PubMed1989

Serum and red cell folate and serum vitamin B12 levels in hyperthyroidism.

Serum and red blood cell folate levels and serum B12 concentration were determined by radioassay in 20 hyperthyroid patients and compared with values obtained when the same patients had been euthyroid for at least 4 months. In hyperthyroidism, the levels of serum and red blood cell folate were significantly (P less than .01) higher than when euthyroidism was achieved. There was no significant change in serum B12 concentration. Declines in serum and red blood cell folate levels between hyperthyroidism and euthyroidism occurred in 15 and 16 of the 20 patients, respectively. Although the explanation for the relative elevations of serum and red blood cell folate levels in hyperthyroid patients is unclear at present, our findings do not support the view that hyperthyroidism in man is associated with depletion of folate stores or subclinical deficiency of the vitamin.

Adult↗
PubMed1989

Counting reticulocytes by flow cytometry: use of thiazole orange.

Thiazole orange is a new fluorescent dye which will bind to the residual RNA in the cytoplasm of reticulocytes and allow their enumeration by FACS analysis. We have evaluated the use of this dye in the routine haematology laboratory. There is an excellent correlation between manual and FACS reticulocyte counts (r = 0.98) but FACS counting showed significantly higher precision (CV = 3.1) than the manual method (CV = 11.9) for single observer, 20.8% for multiple observers). Clinical specimens showed stable reticulocyte counts for 6 h if stored at 4 degrees C allowing efficient batching of samples. There was a significant fall in reticulocyte counts stored for 24 h at both 4 degrees C and 21 degrees C. Evaluation of 78 male and 76 female blood donors by FACS analysis gave normal ranges (mean % +/- 2 SD) of 0.74 +/- 0.48 and 0.84 +/- 0.56 respectively (P less than 0.005). When corrected to absolute values there was no sex difference (36 +/- 24 x 10(9)/l). Thiazole orange is an effective stain for the automated counting of reticulocytes by FACS analysis.

Benzothiazoles↗
PubMed1989

Long-term intra-individual variation of platelet parameters.

Mean platelet volume, platelet count and platelet distribution width were determined in eight male subjects at monthly intervals over a 4-6 month period. Measurements were made on a Coulter S Plus VTM exactly 15 min and 2 h after blood collection. Long-term intra-individual variability for mean platelet volume showed a mean coefficient of variation (CV) of 1.60% at 15 min and 2.01% at 2 h after blood collection; for platelet count a mean CV of 3.18% at 15 min and 2.40% at 2 h; and for platelet distribution width a mean CV of 7.3% at 15 min and 6.5% at 2 h. Platelet parameters are stable over time in the normal male individual.

Adult↗
PubMed1988

Management of Pneumocystis carinii pneumonia in the immunocompromised host.

From 1982 to 1987, 22 patients with proven Pneumocystis carinii pneumonia were diagnosed at Wellington Hospital. Patients comprised 15 males and 7 females aged 15-76 years and included seven with AIDS, eight with haematological malignancy and seven with renal disease. Two distinct clinical prodromes occurred. In renal patients a classic fulminating pneumonitis developed over 24 to 72 hours. In patients with AIDS a more indolent illness occurred lasting 3 or more weeks and was characterised by fever, dry cough and breathlessness. Haematology patients showed no specific duration of prodrome. At the time of diagnosis all had an abnormal chest radiograph and the arterial PO2 was reduced in all but one case. An invasive diagnostic procedure was performed in all except one case where the diagnosis was made at post mortem. Two patients required a second procedure to establish the diagnosis. Procedures performed included bronchoalveolar lavage [14], open lung biopsy [7] and transbronchial lung biopsy [2]. All patients were treated with high dose cotrimoxazole and 18 survived to leave hospital. A review of the approach to the diagnosis and treatment of Pneumocystis carinii pneumonia is presented.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Mean platelet volume is increased in hyperthyroidism.

In 28 unselected patients with hyperthyroidism, platelet count, platelet hematocrit, mean platelet volume, and platelet distribution width were measured at the time of presentation and again when the patients were euthyroid. On return to the euthyroid state, there were highly significant falls in the mean values of the mean platelet volume (16% decline, P less than 0.001) and the platelet hematocrit (16% decline, P less than 0.001) and a slight but highly significant increase in the mean value of the platelet distribution width (2% increase, P less than 0.01). A decline in mean platelet volume was observed in 24 of 28 patients (86%); three patients showed no change. There was no significant change in the mean value of the platelet count. The observed effects of thyrotoxicosis on platelets appeared to be largely independent of the well-known effects on erythrocytes and white blood cells. An increase in mean platelet volume is a regular feature of hyperthyroidism that has not previously been described.

Adult↗
PubMed1988

Quantitative analysis of early in vivo tissue response to synthetic apatite implants.

Studies have shown synthetic calcium phosphates such as hydroxyapatite and beta tricalcium phosphate to be biocompatible in vivo. However, few studies have quantitated histological responses to the implants. The aim of this study was to develop a method for the quantitative assessment of tissue biocompatibility to ceramic materials in vivo and to use this method to compare noncarbonated and carbonated apatite implants. Synthetic sintered apatites of 0, 3, and 6% carbonate by weight were prepared and cut into implants 4 X 4 X 1 mm. These were placed 2 mm into the medial aspect of rat femurs. Following sacrifice at 4 weeks, the femurs were fixed in formalin, demineralized in formic acid, and embedded in glycol methacrylate. Sections were cut on an ultramicrotome set at 1.5 micron and stained with toluidine blue. A point counting technique using standard stereological grids and a low-power microscope was used to measure areas of new bone formation. The width of the connective tissue zone adjacent to muscle was measured using an image analyzer. All implants were well accepted by the host tissues judging from criteria of minimal inflammation and degree of fixation. Results showed an increase in new bone formed in the marrow cavity with increasing carbonate content. This may improve stability of the implant in the host bone, particularly during the initial healing period. A technique which should enable quantitative histological evaluation of different ceramic materials has been developed. The use of this method indicates that further studies are warranted to investigate carbonated apatite as an implant material.

Animals↗