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C Fletcher

Publications and source records attributed to C Fletcher.

At least 73 records · Page 4Linked to original sources
PubMed1988

Transcription factor OTF-1 is functionally identical to the DNA replication factor NF-III.

Octamer transcription factor-1 (OTF-1) and nuclear factor III (NF-III) are sequence-specific DNA binding proteins that activate transcription and DNA replication, respectively. It is shown here that OTF-1 is physically and biologically indistinguishable from NF-III. This conclusion is based on the following observations. First, the two proteins have identical mobilities by SDS-polyacrylamide gel electrophoresis. Second, OTF-1 binds to the adenovirus origin of DNA replication at the same site and with the same affinity as NF-III. Third, OTF-1 can substitute for NF-III in activating the initiation of adenovirus DNA replication in vitro. Fourth, the ability of OTF-1 to stimulate viral DNA replication is dependent on the presence of an intact NF-III binding site within the origin of replication. Fifth, NF-III can substitute for OTF-1 in activating in vitro transcription from the human histone H2b promoter. These data suggest the possibility that NF-III/OTF-1 is a protein that functions in both cellular DNA replication and transcription.

Adenoviridae↗
PubMed1988

Concerted contractions of tumour fragments derived from a pure mucoid carcinoma of the breast in vitro.

Organized tissue fragments obtained by dissociation of a pure mucoid carcinoma of the breast were cultured in vitro. The cellular organization of the fragments appears similar to that observed in vivo, and consist of mucous-filled spherules surrounded by a single layer of tumour cells. Time-lapse video recordings revealed that the cells surrounding these fragments undergo a concerted contraction and relaxation over the time span of several hours. The presence of cytokeratin and oestrogen receptors in the cells suggests an epithelial derivation. Movement of tumour fragments of the type described here could potentially influence the metastatic process of some breast cancers.

Adenocarcinoma, Mucinous↗
PubMed1988

Estrogen receptor distribution in the peripheral, intermediate and central regions of breast cancers.

The central, intermediate and peripheral regions of 25 breast tumors were analyzed for estrogen receptors (ER) using a combined biochemical (BC)/immunohistochemical (IHC) micromethod. To optimize the regional comparison, the percentage carcinoma per sample (PCS) was evaluated and incorporated into the quantification of the ER. Correction of the measured ER for the PCS eliminated differences in receptor levels between the central and peripheral regions but not the intermediate region. Although the corrected BC-ER level in this region was found to be about 20% higher, the IHC method did not detect such a difference. Determination of the ER status at the actual growth front of a tumor, rather than in the intermediate region where ER levels appear to be highest, may be of greater clinical relevance. Intra-regional ER heterogeneity appears, however, to be particularly pronounced in this area of a tumor.

Aged↗
PubMed1988

The effect of cigarette smoke, nicotine, and carbon monoxide on the permeability of the arterial wall.

The association between cigarette smoking and the development of atherosclerosis is well established, but the mechanism that makes cigarettes such a potent "risk factor" is not understood. There is normally a constant insudation of plasma macromolecules into the arterial wall. Fibrinogen and lipids are two of the large molecules involved in atherosclerosis. Therefore we studied the effect of cigarette smoke, nicotine, and carbon monoxide on the permeability of the canine arterial wall to 125I-labeled fibrinogen. The results show that inhaled cigarette smoke significantly and rapidly increases the permeability of the arterial wall to fibrinogen and that this effect can be produced with carbon monoxide alone but not with intravenous nicotine.

Animals↗
PubMed1987

Purification and characterization of OTF-1, a transcription factor regulating cell cycle expression of a human histone H2b gene.

An octamer-binding transcription factor, OTF-1, which stimulates transcription of a human histone H2b gene, has been purified from HeLa nuclear extracts. This purification was achieved through the use of DNA affinity chromatography, and the factor was unambiguously identified by renaturation of activity following SDS-polyacrylamide gel electrophoresis. The purified factor retained the ability to efficiently stimulate H2b transcription in a reconstituted in vitro system. This effect was dependent upon an intact octamer element and was observed in the absence of the other H2b promoter elements (except the TATA motif). Furthermore, this activity was not detected in nuclear extracts prepared from cells synchronized in G2, in agreement with the in vivo data showing S-phase-specific utilization of the octamer element. From these data, we conclude that we have purified the bona fide H2b transcriptional regulatory factor.

Cell Cycle↗
PubMed1987

Ganciclovir treatment of cytomegalovirus disease in transplant recipients and other immunocompromised hosts.

Thirty-one immunocompromised patients with severe cytomegalovirus (CMV) disease were treated with intravenous ganciclovir. Twenty-one patients had received transplants--15 bone marrow recipients, five renal allograft recipients, and one liver transplant recipient--while the other ten were immunocompromised due to acquired immunodeficiency syndrome (six), hematologic malignancies (three), and systemic lupus erythematosus (one). They presented with one or more of the following syndromes: CMV pneumonitis (19), CMV of the gastrointestinal tract (six), CMV retinitis (seven), and CMV hepatitis (three). Seventeen (55%) of 31 patients demonstrated clinical improvement during ganciclovir therapy, with the best response seen in the transplant recipients. Viremia ceased in 14 (93.3%) of 15 patients after a mean of 4.7 days of therapy; viruria ceased in eight (53.3%) of 15 patients after a mean of 11 days of therapy. Ganciclovir plasma concentrations at a dosage of 2.5 mg/kg/three times a day were as follows: mean peak, 16.04 mumol/L; mean trough, 2.38 mumol/L. Neutropenia occurred in 11 (35%) of 31 patients and in nine (60%) of 15 bone marrow transplant recipients. We conclude that ganciclovir exerted an antiviral effect against CMV and may play a role in the treatment of CMV disease in patients with depressed immunity, especially bone marrow and organ transplant recipients.

Acyclovir↗
PubMed1987

Use of intravitreal ganciclovir (dihydroxy propoxymethyl guanine) for cytomegalovirus retinitis in a patient with AIDS.

A patient with acquired immune deficiency syndrome with bilateral cytomegalovirus retinitis was treated with intravitreal 200-micrograms/0.1-ml doses of ganciclovir (9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl]guanine). The ganciclovir serum and intravitreal concentrations were measured with an enzyme-linked immunosorbent assay and pharmacokinetic factors were determined. There was no evidence of systemic absorption of ganciclovir from the eye. The elimination half-life of ganciclovir from the vitreous was estimated to be 13.3 hours. The intravitreal concentration remained above the ID50 of cytomegalovirus for approximately 62 hours after a single injection. Clinically, the patient retained useful vision in his right eye for three months. A total of 28 intravitreal injections were given on an outpatient basis under topical anesthesia and were well tolerated. There was no evidence of retinal toxicity from the drug.

Acquired Immunodeficiency Syndrome↗
PubMed1987

The cat infected with Brugia pahangi as a model of human filariasis.

The responses of cats to Brugia pahangi, which parasitizes them in nature, mimic those of humans to Brugia malayi and Wuchereria bancrofti in many important respects. It is likely that many of the features of the relationship between host and parasite that can be studied in cats infected with B. pahangi also apply to humans, but for a variety of practical reasons cannot be demonstrated in humans. Both immunologically and parasitologically there is a profound difference between B. pahangi-infected cats that have microfilariae in their blood and those that either do not become microfilaraemic or clear their blood of microfilariae and become post-microfilaraemic. Microfilaraemic cats are susceptible to reinfection and fail to recognize the surface of the sheath of microfilariae. They also do not produce antibodies against several components recognized by post-microfilaraemic cats. Cats that have destroyed their microfilariae also destroy their adult worms and are very resistant to challenge with infective larvae. Apart from the unique ability to recognize the sheath of microfilariae in fluorescent antibody tests, sera from these cats react with microfilarial antigens at 61-81 kDa, antigens of infective larvae at 22 and 18.5 kDa and adult antigens at 34, 18, 16, 13 and 11.5 kDa. None of these antigens are recognized by microfilaraemic cats.

Animals↗
PubMed1987

The clinical significance of exercise-induced left ventricular wall motion abnormality occurring at a low heart rate.

We studied the relationship between the heart rate at the time of onset of exercise-induced wall motion abnormality and the severity of coronary artery disease in 89 patients who underwent exercise equilibrium radionuclide ventriculography as part of their evaluation for coronary artery disease. Segmental wall motion was scored with a five-point system (3 = normal; -1 = dyskinesis); a decrease of one score defined the onset of wall motion abnormality. The onset of wall motion abnormality at less than or equal to 70% of maximal predicted heart rate had 100% predictive accuracy for coronary artery disease and higher sensitivity than the onset of ischemic ST segment depression at similar heart rate during exercise: 36% (25 of 69 patients with coronary disease) vs 19% (13 of 69 patients), p = 0.01. Wall motion abnormality occurring at less than or equal to 70% of maximal predicted heart rate was present in 49% of patients (23 of 47) with critical stenosis (greater than or equal to 90% luminal diameter narrowing), and in only 5% of patients (2 of 42) without such severe stenosis, p less than 0.001. The sensitivity of exercise-induced wall motion abnormality occurring at a low heart rate for the presence of severe coronary artery disease was similar to that of a deterioration in wall motion by more than two scores during exercise (49% vs 53%) or an absolute decrease of greater than or equal to 5% in exercise left ventricular ejection fraction (49% vs 45%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Evidence for an immune-dependent action of praziquantel on Schistosoma mansoni in mice.

Effective schistosomicidal action of praziquantel against Schistosoma mansoni infections in mice appears to be dependent to some extent on appropriate immunological stimulation. Indirect evidence consistent with this hypothesis was obtained by demonstrating a positive relationship between drug efficacy and both the intensity and the age of the parasitic infection. More directly, it has previously been shown that praziquantel kills fewer S. mansoni worms in immunosuppressed T cell-deprived mice than in immunologically intact controls; and we show here that infections 5 weeks old, against which the drug alone is sub-optimally active, are more effectively killed by a combination of drug and a rabbit antiserum raised against adult worm antigens.

Animals↗
PubMed1987

Progressive mucocutaneous herpes simplex infection due to acyclovir-resistant virus in an immunocompromised patient: correlation of viral susceptibilities and plasma levels with response to therapy.

Rapidly progressive disease due to acyclovir-resistant herpes simplex has not been described. We report such a case and detail successful patient management using viral sensitivities and plasma acyclovir levels to guide therapy. Response was correlated with plasma levels above those inhibiting viral growth by 50% (ID50) in vitro.

Acyclovir↗
PubMed1987

Remediation for subgroups of retarded readers using a modified oral spelling procedure.

The effectiveness of Bradley's modification of the method of Simultaneous Oral Spelling (SOS) remedial training for both spelling and reading was assessed in this study. Subgroups of disabled readers, 'Chinese' (dysphonetic) and 'Phonecians' (dyseidetic), received six remedial sessions and were assessed immediately after treatment and then two months later on spelling of the training words and on general reading measures. Compared with a non-treated group, the two experimental groups showed significant but different general gains in reading. SOS training appears to be more effective for the teaching of regular words, as opposed to exceptional ones.

Adolescent↗
PubMed1986

Consultation skills of young doctors: I--Benefits of feedback training in interviewing as students persist.

Thirty six young doctors who as medical students had been randomly allocated to either video feedback training or conventional teaching in interviewing skills during a psychiatry clerkship were reassessed five years later. Each doctor interviewed one patient with a psychiatric illness and two with a physical illness. Each interview was rated independently. Both groups had improved since the fourth year clerkship, but those given feedback training had maintained their superiority in the skills associated with accurate diagnosis. This superiority was as evident in their interviews with physically ill patients as it was with psychiatric patients. Both groups, however, still used "closed" questions and were more reluctant to cover psychosocial problems in physically ill patients. Those trained conventionally were clinically inadequate in both these aspects and in clarifying their patients' statements. Given these lasting benefits, all medical students should have feedback training in interviewing skills.

Education, Medical, Undergraduate↗
PubMed1986

Consultation skills of young doctors: II--Most young doctors are bad at giving information.

Forty young doctors, half of whom had had feedback training in interviewing as students, were assessed five years later. Each interviewed three patients and after being given results of examination, investigations, and diagnosis and prognosis returned to discuss them with each patient for 10 minutes. These discussions were filmed on videotape and evaluated. There was no difference between the scores of interview trained and control doctors. Though most gave simple information on diagnosis and treatment, few mentioned investigations, aetiology, or prognosis. Very few obtained and took any account of patients' views or expectations of these matters. Some young doctors do discover for themselves how best to give patients information and advice, but most remain extremely incompetent. This is presumably because they get no training as students in this important aspect of clinical practice. This deficiency should be corrected, and competence tested before qualification to practise.

Communication↗
PubMed1986

Schistosoma mansoni: chemotherapy of infections of different ages.

Mice were treated with potassium antimony tartrate, hycanthone, oxamniquine, niridazole, or praziquantel at different times after infection with Schistosoma mansoni. The rate of cure was assessed by perfusion of surviving worms approximately 4 weeks after treatment, and the percentage reduction in worm burden was estimated relative to the number of adult worms perfused from control mice, comparably infected but untreated. All six drugs were relatively inactive against S. mansoni between 3 and 4 weeks after infection when compared with treatment at 5 to 6 weeks. However, the drugs differed in the patterns of cure they achieved in the 2-week period after administration of cercariae and in the period around the onset of patency. Worms that had been subjected to amoscanate or hycanthone in the third week after infection showed evidence of this as adults in having a reduced fecundity. Factors such as worm or host physiology, or host immune status may have had roles in the outcome of chemotherapy at different stages of maturation of S. mansoni.

Animals↗
PubMed1986

Human pharmacokinetics of the antiviral drug DHPG.

The pharmacokinetics of the antiviral drug 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl]guanine (DHPG) were examined in six patients receiving 2.5 or 5.0 mg/kg every 8 or 12 hours for human cytomegalovirus (HCMV) pneumonitis or retinitis. Biexponential decay with a mean distribution t1/2 of 0.23 hours and terminal t1/2 of 2.53 hours was observed. Total clearance correlated well with and exceeded creatinine clearance by a factor of 2.4. Mean volume of the central compartment was 15.26 L/1.73 m2 and the volume of distribution at steady state was 32.8 L/1.73 m2. Peak (model predicted) and trough plasma concentrations were 4.75 to 6.20 micrograms/ml and less than 0.25 to 0.63 microgram/ml, respectively, in patients receiving 2.5 mg/kg. Peak concentrations are well above those needed to inhibit HCMV at the 50% level (ID50) and troughs are near this ID50. Cerebrospinal fluid concentrations of DHPG indicate a penetration of 24% to 67%. No accumulation of DHPG was apparent in these patients. However, dosage reduction is necessary in renal insufficiency. Neutropenia occurred in one patient. The plasma concentration profile of DHPG suggests potential beneficial activity against HCMV.

Acyclovir↗