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Biomedical subjects

S Myint

Publications and source records attributed to S Myint.

At least 37 records · Page 2Linked to original sources

Evaluation of nested polymerase chain methods for the detection of human coronaviruses 229E and OC43.

Currently, the diagnosis of human respiratory coronavirus infection is either slow or insensitive. This paper describes nested polymerase chain reaction assays for the detection of human coronaviruses OC43 and 229E. The specificity and sensitivity of the assays have been determined and they have been applied to the detection of the viruses in nasal aspirates. These assays are more rapid and sensitive than cell culture and may replace the latter as the diagnostic method of choice.

Animals↗

Non-uniform dwell times in line source high dose rate brachytherapy: physical and radiobiological considerations.

The ability to vary source dwell times in high dose rate (HDR) brachytherapy allows for the use of non-uniform dwell times along a line source. This may have advantages in the radical treatment of tumours depending on individual tumour geometry. This study investigates the potential improvements in local tumour control relative to adjacent normal tissue isoeffects when intratumour source dwell times are increased along the central portion of a line source (technique A) in radiotherapy schedules which include a relatively small component of HDR brachytherapy. Such a technique is predicted to increase the local control for tumours of diameters ranging between 2 cm and 4 cm by up to 11% compared with a technique in which there are uniform dwell times along the line source (technique B). There is no difference in the local control rates for the two techniques when used to treat smaller tumours. Normal tissue doses are also modified by the technique used. Technique A produces higher normal tissue doses at points perpendicular to the centre of the line source and lower doses at points nearer the ends of the line source if the prescription point is not in the central plane of the line source. Alternatively, if the dose is prescribed at a point in the central plane of the line source, the dose at all the normal tissue points are lower when technique A is used.

Brachytherapy↗

Characterization of a nested polymerase chain reaction assay for detection of parvovirus B19.

The characterization and application of a nested polymerase chain reaction (PCR) assay for the detection of human parvovirus B19 DNA is described. The assay was evaluated with 149 diagnostic serum samples (collected up to 150 days after the onset of symptoms) previously tested by dot blot hybridization for B19 DNA and by class-specific capture radioimmunoassays for the detection of B19 immunoglobulin M (IgM) and IgG. B19 DNA was detectable by the PCR in 70% of the sera. There was a statistically significant association between the detection of B19 DNA by PCR and high B19 IgM values (P < 0.005), low B19 IgG values (P < 0.05), and a short interval between onset of symptoms and serum collection (P < 0.005). Serial serum samples, throat swabs, and peripheral blood mononuclear cells collected from 10 individuals during an outbreak of parvovirus B19 were also tested by the nested PCR. B19 DNA was detectable in the throat swabs at the time of the clinical illness and in the peripheral blood mononuclear cell fraction up to the end point of the study 6 months after infection. The location of the B19 DNA could not be determined in cytocentrifuge preparations of peripheral blood mononuclear cells with nonisotopic in situ hybridization and immunolabelling.

Antibodies, Viral↗

Some characteristics of hospitalized HIV seropositive patients in Myanmar.

Twenty-two hospitalized HIV seropositive patients were studied prospectively between July 1991 and January 1992. The majority of the patients were intravenous drug users (IVDUs). Their age ranged from 20 to 38 years with a male preponderance of 12 to 1. Anemia, lymphopenia and thrombocytopenia were observed in 100%, 36% and 41%, respectively. The common pathogens like malaria parasites, Mycobacterium tuberculosis, Entamoeba histolytica, Streptococcus and Salmonella were isolated/identified rather than opportunistic organisms.

Adult↗

In vitro culture for the detection of infectious human parvovirus B19 and B19-specific antibodies using foetal haematopoietic precursor cells.

The inability to culture human parvovirus B19 in standard cell lines has rendered investigation of clinical samples for the presence of infectious virus problematic. Using haematopoietic precursors derived from first trimester foetal liver as targets for infection, and non-isotopic in situ hybridization to detect intracellular viral DNA, we have assessed infectivity in stored serum samples taken from nine volunteers at different stages following intranasal inoculation with parvovirus B19. Infectious virus was detected as early as 3 days after inoculation, the cessation of infectivity correlating with the rise in specific IgM. In all but two samples, infectivity correlated with the detection of B19 DNA by dot-blot hybridization, although in vitro culture was 10-fold more sensitive than dot-blot hybridization. B19 DNA was detected by the polymerase chain reaction in serum from one volunteer up to 36 days after inoculation, although samples containing specific antibody were non-infectious. Infection of erythroid precursors was completely inhibited by preincubation of virus with serum containing high titre B19-specific IgM and IgG. Unexpectedly, this was associated with a strong B19 DNA hybridization signal within the cytoplasm of phagocytic macrophages. This culture and detection system is a rapid and sensitive means of detecting infectious virus in serum samples, and of assessing the neutralizing ability of B19-specific antibodies.

Antibodies, Viral↗

Measurement of phosphoinositide-specific phospholipase C activity in mononuclear leucocytes from atopic and normal subjects.

The intracellular inositol pathway is an important route for cell activation and relies on the stimulation of membrane-bound phosphoinositide-specific phospholipase C (PLC). Previously we have shown abnormalities of inositol metabolism in mononuclear cells (MNL) in atopic dermatitis (AD) using an indirect method. We now describe a direct method of measuring PLC activity in membrane and cytosol preparations of MNL in AD. We compare PLC activity in AD with that in normal controls and examine the effect of substrate concentration and nucleotide stimulation on the system. Our findings show increased membrane-bound PLC activity in AD compared with normal controls. Non-specific stimulation of AD PLC activity by nucleotides suggests that the enzyme of atopics is more sensitive to substrate-driven activity than that of non-atopics.

Adenosine Triphosphate↗

Accelerated fast neutron therapy: a pilot study.

The clinical role of fast neutron therapy has been limited by excessive late normal tissue damage. A pilot study of accelerated fractionation of fast neutron therapy was performed, based on the rationale that this should result in an increase in the response in acute reacting tissues (normal and malignant), with no change in late damage and a consequent increase in the therapeutic ratio. Further accelerated fractionation should improve the local control of rapidly proliferating tumour, without the potential problem of inadequate reoxygenation inherent in accelerated photon schedules. 6 or 12 fractions of 62 MeV (p-Be) neutrons were given over 12 days to 27 sites in 23 patients with locally advanced tumours. With a dose reduction of 12% (18 Gy), acceptable skin and oral mucosa early reactions were obtained. A larger dose reduction (15%) was required at pelvic sites. The incidence of late EORTC/RTOG grade 4 toxicity was 46%. The overall response rate was 76% with a complete response rate of 16%. For locally advanced breast cancer, the complete response rate was 9%, which compares unfavourably with previous results with conventional neutron fractionation schedules. The combination of a low overall complete response rate and excessive late normal tissue toxicity suggests that accelerated fractionation of fast neutrons does not lead to an improvement in the therapeutic ratio, and that late normal tissue damage will continue to be dose limiting.

Adult↗

High energy neutron treatment for pelvic cancers: study stopped because of increased mortality.

OBJECTIVE: To compare high energy fast neutron treatment with conventional megavoltage x ray treatment in the management of locally advanced pelvic carcinomas (of the cervix, bladder, prostate, and rectum). DESIGN: Randomised study from February 1986; randomisation to neutron treatment or photon treatment was unstratified and in the ratio of 3 to 1 until January 1988, when randomisation was in the ratio 1 to 1 and stratified by site of tumour. SETTING: Mersey regional radiotherapy centre at Clatterbridge Hospital, Wirral. PATIENTS: 151 patients with locally advanced, non-metastatic pelvic cancer (27 cervical, 69 of the bladder, seven prostatic, and 48 of the rectum). INTERVENTION: Randomisation to neutron treatment was stopped in February 1990. MAIN OUTCOME MEASURES: Patient survival and causes of death in relation to the development of metastatic disease and treatment related morbidity. RESULTS: In the first phase of the trial 42 patients were randomised to neutron treatment and 14 to photon treatment, and in the second phase 48 to neutron treatment and 47 to photon treatment. The relative risk of mortality for photons compared with neutrons was 0.66 (95% confidence interval 0.40 to 1.10) after adjustment for site of tumour and other important prognostic factors. Short term and long term complications were similar in both groups. CONCLUSIONS: The trial was stopped because of the increased mortality in patients with cancer of the cervix, bladder, or rectum treated with neutrons.

Fast Neutrons↗

Human papilloma virus and carcinoma of the laryngopharynx.

The presence of human papillomavirus (HPV) genomes 6, 11, 16 and 33 in 16 patients with laryngopharyngeal carcinomas was examined by means of a polymerase chain reaction. HPV genomes were detected in 75 per cent of cases. In hypopharyngeal carcinoma, HPV 6 and 11 were present in adjacent tissue but absent from the tumour. HPV 16 and 33 were present in 40 per cent of laryngeal tumours and adjacent tissue. These results suggest that HPV 16 and 33 may be closely associated with the development of some laryngopharyngeal carcinomas.

Aged↗

Characterization of a nucleic acid probe for the diagnosis of human coronavirus 229E infections.

A cDNA copy of the HCV229E nucleocapsid protein gene was isolated and characterized. Sequence analysis predicts a nucleocapsid polypeptide of 389 amino acids with a molecular weight (mol. wt.) of 43,450. Single strand RNA probes derived from the cDNA copy hybridize specifically to HCV229E RNA and approximately 50 pg of intracellular viral RNA can be readily detected. The application of nucleic acid hybridization as a routine procedure for the diagnosis of HCV229E infection is discussed.

Amino Acid Sequence↗

Influence of substrate carbon on the metabolism of Clostridium thermohydrosulfuricum.

The concentration of carbon sources has a significant influence on the growth, carbohydrate uptake and metabolite distribution in Clostridium thermohydrosulfuricum. The growing concentrations of glucose or starch increase the production of ethanol and lactate, the intracellular fructose-1,6-diphosphate (FDP) and the specific activity of lactate dehydrogenase (LDH), but decrease the ethanol/lactate ratio.

Clostridium↗

Phosphate transport across the basolateral membrane of chick kidney proximal tubule cells.

Characterization of the phosphate transport system across the basolateral membrane of renal proximal tubule has been attempted using isolated proximal tubule cells prepared from chicks. The Pi efflux system is independent of Na+ ions and is not influenced by the nature of the chief anion present in the bathing medium. Pi efflux is not sensitive to DIDS and it is concluded that a generalized anion transporter of band III type is not the chief agent for facilitating Pi exit from the cell across the basolateral membrane. Inhibition of efflux by vanadate is evidence for a specific carrier protein in the membrane. The carrier probably possesses thiol group(s) that are essential for activity. The carrier may effect electroneutral transport of Pi possibly in exchange for OH- ions. The activity of the transport process is not stimulated by depleting the cells of phosphate or inhibited by rearing the chicks on a vitamin D-deficient diet. The system is unlikely to be of great importance for the expression of various regulatory mechanisms that act on the kidney to control the excretion of Pi. The activity declines as the chicks mature however.

Age Factors↗

Detection of human coronavirus 229E in nasal washings using RNA:RNA hybridisation.

A method is described for the detection of human coronavirus 229E (HCV 229E) in nasal washings using RNA:RNA filter hybridisation. Volunteers were inoculated with HCV 229E, and daily nasal washings were collected. These washings were then examined for the presence of viral RNA using a single-stranded RNA probe. Nucleic acid hybridisation is shown to be a sensitive technique for the diagnosis of HCV 229E infections.

Coronaviridae↗

Treatment of small cell lung cancer with induction chemotherapy followed by late intensification.

Seventy-seven patients with small cell lung cancer were entered on a protocol comprising induction chemotherapy with cyclophosphamide 1 g m-2, adriamycin 40 mg m-2 and vincristine 1.4 mg m-2 (CAV) every 21 days for four to six cycles. The overall response rate was 72.8%. Twenty-six patients achieving complete remission received intensification with two further cycles of ifosfamide 5 g m-2, mesna 8 g m-2, methotrexate 30 mg m-2 and etoposide 100 mg m-2 per day for 3 days (IME). Six of the 15 patients in partial remission following CAV achieved a further remission on IME (response rate 40%). Median survival in the limited disease group was 11 months compared with 7 months in the extensive disease patients and four patients are alive at more than 2 yr follow up. There was no significant prolongation of the median survival (11 months) seen in those patients in complete remission who had negative second bronchoscopy examination. This sequential six drug regime produces high response rates in small cell lung cancer, and there is evidence of lack of cross-resistance between CAV and IME.

Adult↗

Sequential chemotherapy, surgery and radiotherapy in locally advanced breast cancer.

Thirty-seven patients with locally advanced breast cancer, 86% of whom had skin involvement, were treated with three to six cycles of vincristine 1.4 mg m-2, doxorubicin 40 mg m-2 and cyclophosphamide 600 mg m-2. A complete response rate of 19%, and overall response rate of 61% were achieved. Fourteen patients had received a trial of hormone therapy, but no patient had been given prior cytotoxic chemotherapy or radiation therapy. In no case was chemotherapy discontinued on account of toxicity. In patients with partial remission where gross disease more than 3 cm remained, mastectomy (10 patients) or local excision (five patients), was carried out increasing the complete remission rate to 49%. Thirty-two patients then received 45 Gy in 24 days to the breast and regional lymphatics with a further 12 Gy boost to the tumour site. The overall response rate achieved was 86% of the 37 patients, with a total, complete response rate of 76%. The median time to relapse in the 28 complete responders was 17 months. Local palliation, defined as absence of pain, ulceration or an enlarging mass was achieved in 92% of the total number of patients, and the projected local palliation rate at 2 years by life table analysis was 60%. Only 50% of the 10 N3 patients were alive at 1 year, compared to 93% of the 27 N0-N2 patients (P less than 0.05). The overall survival in the entire group at 2 years was 50%. This is an effective and tolerable combined modality approach for the control of local disease in a subgroup of breast cancer patients with complex management problems.

Adult↗