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Biomedical subjects

G Newman

Publications and source records attributed to G Newman.

At least 19 recordsLinked to original sources
PubMed2000

DnaA, the initiator of Escherichia coli chromosomal replication, is located at the cell membrane.

Given the lack of a nucleus in prokaryotic cells, the significance of spatial organization in bacterial chromosome replication is only beginning to be fully appreciated. DnaA protein, the initiator of chromosomal replication in Escherichia coli, is purified as a soluble protein, and in vitro it efficiently initiates replication of minichromosomes in membrane-free DNA synthesis reactions. However, its conversion from a replicatively inactive to an active form in vitro occurs through its association with acidic phospholipids in a lipid bilayer. To determine whether the in situ residence of DnaA protein is cytoplasmic, membrane associated, or both, we examined the cellular location of DnaA using immunogold cryothin-section electron microscopy and immunofluorescence. Both of these methods revealed that DnaA is localized at the cell membrane, further suggesting that initiation of chromosomal replication in E. coli is a membrane-affiliated event.

Animals↗
PubMed1999

Ligase-based detection of mononucleotide repeat sequences.

Up to 15% of all colorectal cancers are considered to be replication error positive (RER(+)) and contain mutations at hundreds of thousands of microsatellite repeat sequences. Recently, a number of intragenic mononucleotide repeat sequences have been demonstrated to be targets for inactivating genes in RER(+)colorectal tumors. In this study, thermostable DNA ligases were tested for the ability to detect alterations in microsatellite sequences in colon tumor samples. Ligation profiles on mononucleotide repeat sequences were determined for four related thermostable DNA ligases, Thermus thermophilus ( Tth ) ligase, Thermus sp. AK16D ligase, Aquifex aeolicus ligase and the K294R mutant of the Tth ligase. While the limit of detection for point mutations was one mutation in 1000 wild-type sequences, the ability to detect a single base deletion in a 10 base mononucleotide repeat was one mutation in 100 wild-type sequences. Furthermore, the misligation error increased exponentially as the length of the mono-nucleotide repeat increased, and was 10% of the correct signal for a 19 base mononucleotide repeat. A fluorescent ligase-based assay [polymerase chain reaction/ligase detection reaction (PCR/LDR)] correlated with results obtained using a radioactive assay to detect instability within the TGF-beta Type II receptor gene. PCR/LDR was also used to detect the APCI1307K mononucleotide repeat allele which has a carrier frequency of 6.1% in Ashkenazi Jewish individuals. In a blind study, 30 samples that had been typed for the presence of the APCI1307K allele were tested. The PCR/LDR results correlated with those obtained using sequencing and allele-specific oligonucleotide hybridization for 16 samples carrying the mutation and 13 wild-type samples. Ligation assays that characterize mononucleotide repeats can be used to rapidly detect somatic mutations in tumors, and to screen for individuals who have a hereditary predisposition to develop colon cancer.

Adenomatous Polyposis Coli↗
PubMed1999

The expression of TGF-beta receptors in human atherosclerosis: evidence for acquired resistance to apoptosis due to receptor imbalance.

The degree of cellularity in vascular lesions is determined by the balance between the migration and proliferation of cells relative to their rate of egress and apoptosis. Transforming growth factor-beta(1) can act as a potent antiproliferative and apoptotic factor for proliferating vascular cells. Our laboratory has previously identified cells cultured from human vascular lesions that are resistant to the antiproliferative effect of TGF-beta(1) due to an acquired mutation in the Type II receptor for TGF-beta(1). In the present studies, the expression of the Type I and II receptors in coronary and carotid atherosclerotic lesions was analysed by immunostaining, RT-PCR, and in situ RT-PCR. Levels of the Type I and Type II receptors varied widely within lesions, with the highest levels in the fibrous cap and at discrete foci within the lesion. Regions of smooth muscle-like cells (SMC) were commonly found that were Type I positive but Type II receptor negative. In 43 cell lines cultured from 126 human lesions, 84% of the lesion-derived cell (LDC) cultures exhibited functional resistance to the antiproliferative effect of TGF-beta(1). This resistance was conferred against TGF-beta(1), TGF-beta(2), and TGF- beta(3), but not interferon-gamma or mimosine. While normal SMC exhibited a four-fold increase in the rate of apoptosis after TGF- beta(1) treatment, most LDC were resistant to apoptosis in response to TGF-beta(1). Resistant cells exhibited selective loss of Type II receptor expression, and retroviral transfection of Type II receptor cDNA partially corrected the functional deficit. Thus, resistance to apoptosis may lead to the slow proliferation of resistant cell subsets, thereby contributing to the progression of atherosclerotic and restenotic lesions.

Activin Receptors, Type I↗
PubMed1998

Fantastic issue!

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Child↗
PubMed1996

Increased morbidity following the introduction of remote afterloading, with increased dose rate, for cancer of the cervix.

A retrospective review of the treatment of cancer of the cervix compared the 3-year period before and after the introduction of remote afterloading using a "low dose rate' Selectron. Data was collected on 270 patients. Compared to manually loaded caesium the dose rate to point A was doubled with Selectron and a dose reduction of 20% was adopted to compensate for the expected increased effectiveness. The combined grade 2 and 3 complication rates were 12% with manually loaded caesium and 32% with Selectron at the higher dose rate. Survival and local control rates were similar.

Adenocarcinoma↗
PubMed1993

TNF-alpha response of human monocyte-derived macrophages to Mycobacterium avium, serovar 4, is of brief duration and protein kinase C dependent.

Human monocyte-derived macrophages (M phi) from the majority of normal donors respond to inoculation with Mycobacterium avium, serotype 4, (MAI) by elaboration of the inflammatory monokines TNF-alpha, IL-1 beta, and IL-6, which are of central importance for the protection against bacterial and parasitic infections. Peak TNF-alpha mRNA levels were of brief duration, being maximal at 1.5 h, and were only slightly higher than background levels at 4 h. Increases of IL-1 beta and IL-6 mRNA levels, on the other hand, persisted for 48 to 72 h. In contrast to LPS, MAI induced the production of only small amounts of TNF-alpha protein in the first 12 h and of large amounts of IL-1 beta and IL-6 protein between 3 and 72 h. MAI-induced TNF-alpha transcripts, in contrast to LPS induced TNF-alpha transcripts, were highly unstable. Their accumulation was blocked and their t 1/2 significantly decreased by the protein kinase C inhibitor staurosporine. In contrast, LPS-induced increases of TNF-alpha mRNA levels and MAI-induced increases of IL-1 beta and IL-6 mRNA levels were PKC independent. The cAMP- and cGMP-dependent protein kinase inhibitors, KT5720 and KT5823, respectively, and the tyrosine kinase inhibitors herbimycin and erbstatin had no effect on the MAI-dependent mRNA accumulation of TNF-alpha, IL-1 beta, and IL-6. W7, a calmodulin-dependent protein kinase inhibitor, was inhibitory in all cases. Thus, MAI-induced TNF-alpha mRNA accumulation is of short duration and PKC dependent. MAI-induced TNF-alpha protein production is low, possibly resulting in a mitigated antimicrobial effect.

Alkaloids↗
PubMed1992

The management of carcinoma of the anal canal by external beam radiotherapy, experience in Vancouver 1971-1988.

From 1971 to 1988 72 cases of carcinoma of the anal canal were treated by external beam radiotherapy, most commonly by 5000 cGy in 20 fractions given over 4 weeks. The actuarial survival at 5 years was 66% and the disease specific survival 78%. Nine patients had inguinal node metastases at diagnosis; their 5-year disease specific survival was 75%. 63 patients were inguinal node negative at presentation; their 5-year disease specific survival was 78%, by UICC 1987 staging: T1 71%, T2 88%, T3 41%, T4 42%. 17 patients developed local recurrence; 10 were suitable for abdominoperineal (AP) resection which was successful in 7. The probability of local control was related to T stage. 13 patients were left with a colostomy because of recurrence, 2 had a colostomy for radiation damage and 4 had their local recurrence managed palliatively, without a colostomy. As a result, 53 of the 72 patients (74%) were left with a functional anus. Severe late complications occurred in 6 (8%).

Aged↗
PubMed1992

Suicide in psychiatric institutions.

In 14 years of operation, there have been seven suicides among patients at the North Florida Evaluation and Treatment Center in Gainesville, a rate comparable to the experience at other psychiatric institutions. Suicides do occur among patients who have been carefully diagnosed, are receiving appropriate treatment and are monitored by a professionally trained staff. Even though the "occasional occurrence of in-hospital suicide is inevitable," psychiatrists have the responsibility to carry out all measures to prevent it.

Adult↗
PubMed1991

Inhibition of interleukin-1 by an interleukin-1 receptor antagonist prevents graft-versus-host disease.

Graft-versus-host disease (GVHD) is the major complication of allogeneic bone marrow transplantation (BMT). Dysregulation of inflammatory monokines such as tumor necrosis factor alpha (TNF alpha) has been noted in both clinical and experimental GVHD. We present evidence that interleukin-1 (IL-1), another inflammatory monokine, is an important mediator of GVHD. Expression of the gene for IL-1 alpha as well as the gene for TNF alpha is increased in the skin of mice with GVHD. Inhibition of IL-1 function by the in vivo administration of IL-1 receptor antagonist (IL-1ra) reduces the immunosuppression and mortality of GVHD without impairing the engraftment of hematopoietic stem cells. GVHD thus appears to be a systemic inflammatory process in which monokines, especially IL-1, appear to be important mediators. Inhibition of IL-1 by IL-1ra represents a novel approach to the understanding and control of GVHD.

Animals↗
PubMed1991

You Can Control Asthma: evaluation of an asthma education program for hospitalized inner-city children.

A self-management education program was designed for staff nurses to offer children while they received medical care for asthma in the hospital. The program uses videotapes, written activity books and nurse discussion with the patient. Evaluation was conducted to assess program feasibility and impact. Pre- and post-tests of 40 children age 6-12 years revealed that the children had statistically significant increases in knowledge of and expected response to early warning signs of acute asthma, and in their sense of personal control (Health Locus of Control). Parents reported an increased use of asthma self-management techniques for acute episodes of asthma. Medical record review for a 15 month pre- and post-period indicated reductions in emergency room use. Inpatient hospital based education offers a critical opportunity to introduce asthma management skills, especially to children not reached by more traditional programs.

Asthma↗
PubMed1989

Pulmonary changes in breast cancer patients treated by three different radiotherapy techniques.

Twenty eight patients with breast cancer were studied by CT, perfusion scans and pulmonary function tests to assess the extent of post-irradiation changes. The patients had been treated by three treatment techniques using either two, three or four fields with different amounts of lung included in the target volume. The most extensive changes were seen in those patients who received treatment to the mediastinum.

Breast Neoplasms↗
PubMed1989

Thyroid function in survivors of cancer.

Thyroid function was assessed in three selected groups of children who had survived cancer. Children in group 1 had received radiotherapy to the thyroid area, group 2 had radiotherapy to the thyroid area and adjuvant chemotherapy, and group 3 had chemotherapy with or without radiotherapy away from the thyroid area. There were 75 survivors and 63 (40 boys, 23 girls) were available for study. Eighteen (29%) were found to have thyroid dysfunction, and these included all those who had had lymphangiograms or received a radiation dose greater than 40 Gy to the thyroid area. Only nine of the 18 children were already known to have thyroid dysfunction, and only 15 of 44 children who had had irradiation to the thyroid area had had their thyroid function examined. This study shows that children who have received radiotherapy to the thyroid area should have their thyroid function assessed regularly. Chemotherapy does not appear to be a risk factor but longer follow up of these children is necessary.

Adolescent↗
PubMed1987

Pyoderma gangrenosum and hairy cell leukemia.

Hairy cell leukemia (HCL) is an uncommon hematologic malignancy in which simultaneous cutaneous disturbances of various types have been reported. We report a case of a 62-year-old man with HCL who developed pyoderma gangrenosum (PG) at the site of incision for splenectomy. PG has been reported previously in a patient with HCL. Since splenectomy is important in the treatment of HCL, it is important for the clinician to know that surgical wound dehiscence may not be due to poor technique nor infection, but rather to pathergy.

Humans↗
PubMed1987

Development of a computerized sexual assessment laboratory.

Computer-assisted psychological assessment has been operational for 25 years. It has been well received by patients and shows a degree of reliability that is comparable to that of conventional testing. The authors report on the development of a computerized psychosexual assessment laboratory in a forensic facility housing convicted sex offenders who volunteered for treatment. The development of the laboratory was in response to the need for uniform psychosocial data on each resident that can be used for making better diagnoses, developing personalized treatment programs, and assessing treatment outcome. The process of selecting the psychological tests and programming them for interactive administration is described, as are the testing procedures using the penile plethysmograph with stimuli based on the Tanner developmental stages. A computer-assisted psychosocial assessment that produces a psychosocial history was developed. The laboratory's overall value in the treatment program is assessed.

Arousal↗