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Biomedical subjects

C Paul

Publications and source records attributed to C Paul.

At least 271 records · Page 15Linked to original sources

Sequence relationships of three human satellite DNAs.

The simple sequence components of three human classical satellite DNAs have been defined, and some segments of each satellite have been sequenced. Each of the classical satellites I, II and III was found to contain, as a major component, a single family of simple repeated sequences. The three simple-sequence families have been called satellites 1, 2 and 3, to indicate the enrichment of each in one of the classical satellites I, II and III, and to differentiate them from these classical satellites, which also contain other repeated components. Satellite 3, the simple sequence component of classical satellite III, when digested with the restriction endonuclease HinfI, forms a ladder based on a repeat of five base-pairs, 5' A-T-T-C-C. The HinfI ladder was shown to be composed of repeated elements with the general sequence 5' (A-T-T-C-C)n-A-TC-T-C-G-G-G-T-T-G. Satellite 2, the simple sequence component of classical satellite II, is digested by HinfI into a large number of very small fragments, of length 10 to 80 base-pairs. These were found to contain the simple repeat 5' A-T-T-C-C, in a highly diverged form. Analysis of satellite 2 sequences suggested that the five base-pair repeat was originally amplified as a higher-order repeat like that of satellite 3. However, the main tandemly repeated segments of satellite 2 in the human genome are much longer, and the simple sequence elements on which they are based are quite degenerate. Satellite 1, the simple sequence component of classical satellite I, is digested by the restriction endonuclease RsaI into a ladder of fragments less than 150 base-pairs in length. These ladder fragments were found to be formed by the loss of RsaI sites from two related A + T-rich sequences, A (17 base-pairs) and B (25 base-pairs), arranged in alternating arrays, -A-B-A-B-A-. Analysis of a large number of cloned fragments from the RsaI ladder of satellite 1 showed that the tandem arrays, -A-B-A-B-A, have a more complex arrangement, with apparent amplification of segments containing particular sequence variants of the repeat units, A and B. No sequence relationship was evident between the repeat elements of satellite 1 and those of satellites 2 and 3.

Base Sequence↗

Effect of antibodies to recombinant and synthetic peptides on P. falciparum sporozoites in vitro.

Antibodies were raised in mice immunized with several recombinant and synthetic peptides of the circumsporozoite protein of Plasmodium falciparum. The antibodies were evaluated for protective activity in a human hepatocyte culture system. They exerted their protective effect against the parasite at three points: sporozoite attachment to the hepatocyte surface, entry, and subsequent intracellular development. Inhibition of attachment and entry were found to be related to the antibody titer against the authentic circumsporozoite protein on the sporozoite surface, especially when peptides were administered with alum or complete Freund's adjuvant. Even when invasion was not totally inhibited, the presence of abnormal trophozoites and a frequent inhibition of schizont development in long-term cultures suggested continued activity of antibodies at the intracellular level after sporozoite penetration had been completed.

Animals↗

Recommendations for routine cervical screening.

Because of concern about the rising incidence of cervical cancer in young women, the Department of Health and the Cancer Society invited a working group to make recommendations on cervical screening. There is now compelling evidence that cytological screening is an effective preventive measure. All women who have had sexual intercourse should be offered screening. They should be screened as soon as possible after commencing sexual activity, or when first receiving contraceptive advice, antenatal care, or treatment of a sexually transmitted disease. If the first smear is negative, it should thereafter be repeated at least every three years. A special effort must be made to reach women who have never been screened, including those who are middle-aged, or elderly. The cervical smear test should be part of the assessment of women with gynaecological symptoms regardless of whether there has been a negative smear within the previous three years. The three-yearly schedule also does not apply to women who have had an abnormal smear.

Adult↗

Complete development of hepatic stages of Plasmodium falciparum in vitro.

An in vitro model was developed to study the hepatic phase of Plasmodium falciparum, the only malaria parasite lethal to man. Primary cultures of human hepatocytes were inoculated with sporozoites of Brazilian and African strains of P. falciparum. On days 1 through 7 after inoculation examination of fluorescence-labeled and Giemsa-stained preparations demonstrated the presence of many intracellular parasites. In three separate sets of experiments all cultures were found to be infected with as many as 650 liver schizonts measuring up to 40 micrometers. After the addition of red blood cells, intraerythrocytic forms of P. falciparum were detected on days 12 and 13 by an immunofluorescence assay, indicating that the hepatic cycle had been completed in vitro.

Animals↗

Folding patterns of porin and bacteriorhodopsin.

Porin spans the outer membrane of Escherichia coli with most of the protein embedded within the membrane. It lacks pronounced hydrophobic domains and consists predominantly of beta-pleated sheet. These observations require the accommodation of polar and ionizable residues in an environment that has a low dielectric constant. Owing to a currently limited understanding of the constraints governing membrane protein structure, a minimal approach to structure prediction is proposed that identifies segments causing polypeptides to reverse their direction (turn identification). The application of this procedure avoids hydrophobicity parameters and yields a model of porin which is in good agreement with all experimental data available. The presence of polar and ionizable residues within membrane boundaries implies a dense (saturating) network of hydrogen bond donor and acceptor groups. Application to a paradigm of hydrophobic membrane proteins, bacteriorhodopsin, reveals a pattern consistent with its alpha-helical folding. The postulated structure includes significantly more polar residues in the membrane domain than have been assumed previously, suggesting that there are also hydrogen bonding networks in bacteriorhodopsin. Extensive networks permeating protein interior and surfaces would explain the extraordinary stability and the tight interactions between functional units in the formation of crystalline arrays of both proteins.

Bacterial Outer Membrane Proteins↗

Factors and inhibitors of blood coagulation and fibrinolysis in acute nonlymphoblastic leukaemia.

Factors of coagulation and fibrinolysis have been evaluated in 15 patients with untreated acute nonlymphoblastic leukaemia (ANLL). 10 patients had major bleeding (MB) and 6 had laboratory signs of DIC. 5 patients went into complete remission (CR). Antithrombin III (AT III) was decreased in 7 patients, antiplasmin (AP) in 9, fibronectin (FN) in 6 and factor XIII in 4/12. The ratio between factor VIIIR:Ag and factor VIII:C was over 2.0 in 11 patients, and high values were especially seen in patients with MB and patients with DIC. Spontaneous proteolytic activity, measured with S-2288 was increased in 3 patients who all had MB, and none of whom achieved CR. 2 patients with promyelocytic leukaemia (M3) had low fibrinogen and AP, high FDP and normal AT III, speaking for primary fibrinolysis, which in addition to proteolytic enzymes in the blast cells are important contributing factors regarding MB in ANLL.

Adult↗

Adoptive transfer of murine host protection to salmonellosis with T-cell growth factor-dependent, Salmonella-specific T-cell lines.

A spent medium antigen was prepared from the avirulent RIA strain of Salmonella typhimurium. Lymph node cells isolated from female BALB/c mice injected subcutaneously with the spent medium antigen exhibited antigen-specific proliferation. By using these cells and T-cell growth factor, continuous spent medium antigen-specific, Thy 1.2-sensitive lines were generated. These cells exhibited antigen-specific proliferation in vitro and were effective in inducing significant (P less than 0.01) host protection when adoptively transferred to naive syngeneic mice.

Animals↗

An unexplained illness in West Otago.

An apparent epidemic of undiagnosed illness in a rural general practice was investigated. The aims were to describe the illness, the characteristics of the people affected, and to look for possible causes. The patients were questioned about their symptoms, and both patients and controls matched for age and sex, were questioned about possible aetiological factors. Twenty-eight cases were identified; all but three were less than 45 years of age; there were equal numbers of females and males. The most commonly experienced symptoms were tiredness, mood and sleep disturbances, headache, and joint or muscle pains. Results of the case-control study suggested that pollution of the water supply, zoonotic infections, contact with agricultural chemicals, and self-dosing with selenium were unlikely to be causes of this illness. An unidentified virus was regarded as the most likely cause.

Adolescent↗

A comparative randomized trial of low-dose versus high-dose streptokinase in deep vein thrombosis of the thigh.

Fibrinolytic treatment of acute deep vein thrombosis (DVT) of the leg with high-dose streptokinase (SK) (100,000 U/h) in 39 cases, or low-dose SK (approx 10,000 U/h) in combination with low-dose heparin in 41 cases, was studied in a prospective randomized trial. The degree of thrombolysis was similar in both groups and did not correlate with age or size of the thrombus or with fibrinogen level. The degree of late recanalization was also similar in both groups. There were however significantly more patients with postthrombotic changes in the low-dose group than in the high-dose group after a mean follow-up time of 31 and 38 months respectively. In the low-dose group 2 intracranial hemorrhages occurred (one was fatal) and one patient died of pulmonary embolism, but there were significantly less allergic side effects to SK. There were no cases of such serious side effects in the highdose group. Although low-dose SK has equal thrombolytic effect it seems inferior to high-dose SK, since it probably causes more severe hemorrhagic side-effects.

Clinical Trials as Topic↗

[Obtaining hepatic stages of Plasmodium falciparum in vitro].

Sporozoites of Plasmodium falciparum, obtained by membrane feeding of Anopheles freeborni or A. stephensi with cultured gametocytes, were used to infect monolayers of human hepatocytes. Fluorescent labelling with an African serum as well as Giemsa staining performed from day one to day 7 of cultures, demonstrated the presence of numerous hepatic schizonts measuring up to 40 micron.

Animals↗

Interferon-alpha treatment of a patient with acute lymphoblastic leukaemia and Down's syndrome. Effects on natural killer cell activity and mitogen responsiveness.

A 32-year-old female with Down's syndrome and common ALL was treated with human leucocyte interferon-alpha (IFN-alpha) at a dose of 3 X 10(6) units i.m. daily. Side-effects consisted of slight tenderness and localized haematomas at the sites of injection. During treatment the number of leukaemic cells decreased in the peripheral blood. The proportion of blast cells in the bone marrow decreased only slightly, but a large fraction of them became vacuolized. After the initial response the disease progressed and IFN was withdrawn after treatment for 67 d. Prior to initiation of IFN treatment the natural killer activity of the patient's lymphocytes, as well as the response of these cells to mitogenic stimuli, was low. During IFN therapy these functions increased. Following the withdrawal of IFN therapy the patient received vincristine/prednisone treatment and a complete remission was achieved after 5 weeks. She is still in remission and on maintenance therapy 24 months after initiation of treatment.

Adult↗

Sample-specific ratio effects in matching to sample.

In a symbolic matching-to-sample task, pigeons were trained using sample-specific, fixed-ratio "observing responses." Subsequently, in a mixed condition, each sample was presented equally often with each ratio requirement, i.e., the ratios were no longer correlated with the samples. In a second experiment, pigeons were trained initially in the mixed condition and subsequently shifted to the sample-specific condition in which the required ratios were correlated with the samples. Results of both experiments suggested joint control of choices by ratio value and by the exteroceptive stimuli. The discriminative properties of the ratios appeared to outweigh absolute ratio-size effects.

Journal Article↗