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Biomedical subjects

J Irving

Publications and source records attributed to J Irving.

At least 19 recordsLinked to original sources

Immunoprofile of cervical and endometrial adenocarcinomas using a tissue microarray.

Adenocarcinomas of the uterine cervix show a wide range of morphological features, and can be confused with endometrial adenocarcinoma in biopsy or curetting specimens. The objective of this study was to use tissue microarray technology to evaluate the immunoprofile of a large set of uterine adenocarcinomas with an extended panel of antibodies, comparing the profile of primary cervical and endometrial adenocarcinomas. A tissue microarray was constructed using paraffin-embedded, formalin-fixed tissues from 141 hysterectomy specimens. Duplicate 0.6-mm cores were obtained from 57 cervical adenocarcinomas (16 in situ and 41 invasive) and 84 endometrial adenocarcinomas. Tissue array sections were immunostained with 21 commercially available antibodies [B72.3, CD 99, carcinoembryonic antigen (CEA), c-kit, pancytokeratin, CK 5/6, CK 7, CK8/18, CK19, CK 20, CK 22, EMA, estrogen receptor (ER), KP-1, melan-A, p53, PLAP, S-100, synaptophysin, TTF-1, and vimentin] utilizing the avidin-biotin (ABC) technique. Hierarchical clustering analysis of the tumors was done based on the immunostaining results. Only ER ( P<0.001), CEA ( P=0.04), vimentin ( P<0.001), and CK 8/18 ( P=0.002) showed a significantly different frequency of positivity in endometrial relative to cervical adenocarcinomas. ER, vimentin, and CK 8/18 were more likely to be expressed in endometrial adenocarcinomas, while cervical adenocarcinomas more frequently expressed CEA. We were able to identify immunoprofiles that were highly specific for endocervical adenocarcinoma (ER(-), vimentin(-), CK 8/18(-), CEA(+)) or endometrial adenocarcinoma (ER(+), vimentin(+), CK 8/18(+), CEA(-)), but most tumors showed an intermediate, non-specific immunophenotype. Hierarchical clustering analysis was useful in the interpretation of these intermediate immunophenotypes. Papillary serous adenocarcinoma of the endometrium was less likely to express vimentin ( P=0.002) than endometrioid carcinoma of the endometrium.

Adenocarcinoma↗

Failure of resting echocardiography and cardiac catheterization to identify pulmonary hypertension in two patients with type I Gaucher disease.

Pulmonary hypertension (PHT) is a complication of Gaucher disease. Screening with echocardiography is recommended for Gaucher patients. Two patients naive to enzyme replacement therapy are presented in whom resting echocardiography revealed no evidence of PHT. One of the patients also had normal pulmonary artery pressures at cardiac catheterization. The diagnosis of PHT was made with open lung biopsy in one patient and dobutamine echocardiography in the other. In both cases, diagnosis of PHT altered patient management. Resting echocardiographic assessment may fail to identify PHT in patients with Gaucher disease.

Adult↗

Regulation and localization of the Bloom syndrome protein in response to DNA damage.

Bloom syndrome (BS) is an autosomal recessive disorder characterized by a high incidence of cancer and genomic instability. BLM, the protein defective in BS, is a RecQ-like helicase, presumed to function in DNA replication, recombination, or repair. BLM localizes to promyelocytic leukemia protein (PML) nuclear bodies and is expressed during late S and G2. We show, in normal human cells, that the recombination/repair proteins hRAD51 and replication protein (RP)-A assembled with BLM into a fraction of PML bodies during late S/G2. Biochemical experiments suggested that BLM resides in a nuclear matrix-bound complex in which association with hRAD51 may be direct. DNA-damaging agents that cause double strand breaks and a G2 delay induced BLM by a p53- and ataxia-telangiectasia mutated independent mechanism. This induction depended on the G2 delay, because it failed to occur when G2 was prevented or bypassed. It coincided with the appearance of foci containing BLM, PML, hRAD51 and RP-A, which resembled ionizing radiation-induced foci. After radiation, foci containing BLM and PML formed at sites of single-stranded DNA and presumptive repair in normal cells, but not in cells with defective PML. Our findings suggest that BLM is part of a dynamic nuclear matrix-based complex that requires PML and functions during G2 in undamaged cells and recombinational repair after DNA damage.

Adenosine Triphosphatases↗

Capillary zone electrophoresis of a recombinant adenovirus.

Adenovirus preparations are used as vectors in a number of gene therapy clinical development programs. The success of commercial production of adenovirus will strongly depend on the development of methods to define the recombinant virus product by analysis as opposed to being defined by the manufacturing process. While most analytical techniques examine portions of the virus, e.g. proteins or DNA, ion-exchange chromatography has been used to separate intact virus at low efficiency. A free zone capillary electrophoretic method was developed for high-efficiency separations of adenovirus 5. Experimental conditions such as buffer pH and concentration were explored which produced a high-efficiency separation in less than 20 min. The virus band was identified by collection of CE fractions and examination using a cell based assay. Initially, a single virus peak is found in fresh virus samples. After as little as one freeze-thaw in 1 x phosphate-buffered saline with 2% sucrose, the active virus migrates as a regular series of peaks. The nature of the virus modification leading to the differing electrophoretic mobilities is presently under investigation.

Adenoviridae↗

Delay in the application of the cover glass is a potential source of error with the Makler Counting Chamber.

OBJECTIVE: To determine the effect of delaying the application of the cover glass of a Makler Counting Chamber (Sefi Medical Instruments, Haifa, Israel) on the apparent concentration of sperm or Dynabeads (Dynal Pty Ltd, Carlton, Victoria, Australia). DESIGN: Systematic alteration of the time taken to apply the cover glass. SETTING: Comprehensive infertility service. PATIENT(S): Fresh semen from a patient or washed sperm from a donor. INTERVENTION(S): For the Makler Counting Chamber, a 5-microL drop of the sperm or bead suspension was placed in the center of the lower platform and the cover glass was applied either immediately (0 seconds) or after a delay of 5, 10, or 30 seconds. MAIN OUTCOME MEASURE(S): The concentration of beads or sperm counted using an Improved Neubauer Hemocytometer or a Makler Counting Chamber. RESULT(S): There was a progressive increase in sperm concentration with a longer delay in applying the cover glass when sperm was suspended in either seminal plasma or culture medium. Repeating the experiments with Dynabeads resuspended in phosphate-buffered saline, serum, or seminal plasma showed the same trend, although the suspension of beads in serum seemed to settle the least over the first 10 seconds. CONCLUSION(S): Delay in the application of the cover glass is a potential source of error with the Makler Counting Chamber and should be avoided.

Female↗

The ratio of X- and Y-bearing sperm in ejaculates of men with three or more children of the same sex.

PURPOSE: The present study evaluated the proportions of X-bearing and Y-bearing sperm within the semen of donors who were the declared fathers of three or more sons or daughters. METHODS: The proportions of sperm were determined using dual-color fluorescence in situ hybridization to identify the X and Y chromosomes. RESULTS: The only difference observed was in semen volume. There was no increase in the proportion of Y-bearing sperm for men with only sons (49.7 +/- 1.3%) or of X-bearing sperm for men with only daughters (44.8 +/- 2.6%). CONCLUSIONS: A preponderance of either sons or daughters in a family cannot be explained simply by an altered ratio of X-bearing and Y-bearing sperm in the father's semen.

Humans↗

Does temporomandibular disorder pain dysfunction syndrome affect dietary intake?

Temporomandibular disorder pain dysfunction syndrome (TDPDS) is the most common cause of facial pain after toothache. The symptoms are varied but are likely to affect the choice, intake and enjoyment of food. This has not been previously investigated. In this paper a preliminary study of 35 patients attending a department of oral and maxillofacial surgery at a general hospital is presented. Thirty-one subjects reported that eating was a problem; 15 prepared food differently and 24 considered that their choice of food was limited. Four of the five foods most often reported to be difficult to eat are valuable in the diet: meat (22), apples (20), bread (13), toast (7) and toffees (6). Twenty-three subjects reported eating a softer diet. Most (25) reported pain when eating. Such circumstances make it harder for TDPDS sufferers to meet current nutritional guidelines, especially, perhaps, for some to achieve an adequate intake of iron.

Adolescent↗

An altered repertoire of fos/jun (AP-1) at the onset of replicative senescence.

With multiple divisions in culture, normal diploid cells suffer a loss of growth potential that leads to replicative senescence and a finite replicative capacity. Using quantitative RT-PCR, we have monitored mRNA expression levels of c-fos, c-jun, JunB, c-myc, p53, H-ras, and histone H4 during the replicative senescence of human fibroblasts. The earliest and the largest changes in gene expression occurred in c-fos and junB at mid-senescence prior to the first slowing in cell growth rates. The basal level of c-fos mRNA decreased to one-ninth that of the early-passage levels, while junB declined to one-third and c-jun expression remained constant. The decline in the basal c-fos mRNA level in mid-senescence should lead to an increase in Jun/Jun AP-1 homodimers at the expense of Fos/Jun heterodimers and may trigger a cascade of further changes in c-myc, p53, and H-ras expression in late-passage senescent fibroblasts.

Base Sequence↗

Decline in histone H5 phosphorylation during erythroid senescence in chick embryos.

Previous studies have implicated histone H5 dephosphorylation as a causal factor in genetic inactivation and chromatin condensation during erythroid senescence in adult chickens. We show that histone H5 phosphorylation declines in two stages as various cohorts of erythroid cells senesce in chick embryos. The first decline occurs between 5 and 6 days and coincides with the senescence of primitive erythrocytes. The second decline in H5 phosphorylation occurs between 17 and 19 days of chicken development, when the definitive erythrocytes undergo senescence and chromatin condensation. These results point to a role for histone dephosphorylation during the programmed senescence of erythroid cells.

Animals↗

A phosphatase inhibitor enhances the DNase I sensitivity of active chromatin.

Although it is well-known that active domains of chromatin have elevated DNase I sensitivity, it can be difficult to observe preferential sensitivity in many cell types. We show that the DNase I sensitivity of active chromatin is enhanced some 10-fold by treating nuclei with the phosphatase inhibitor p-(chloromercuri)benzenesulfonic acid (CMBS) whereas DNase I sensitivity in inactive domains is only 3-fold higher. We further show that CMBS-enhanced DNase I sensitivity is associated with at least two histone modifications. First, the negatively charged CMBS molecule becomes covalently attached to the thiol groups on histone H3. Second, histone H2A phosphorylation is significantly elevated in treated nuclei. The phosphorylation data along with other results point to the possibility that H2A phosphorylation plays a role in enhancing preferential DNase I sensitivity. Whatever the mechanism, CMBS treatment of nuclei followed by DNase I digestion provides a novel and reproducible assay for probing the chromatin structure of active domains.

4-Chloromercuribenzenesulfonate↗

Relaxation distribution function of intracellular dielectric zones as an indicator of tumorous transition of living cells.

The response decay data of living cells subject to electric polarization is associated with their relaxation distribution function (RDF) and can be determined using the inverse Laplace transform method. A new polynomial, involving a series of associated Laguerre polynomials, has been used as the approximating function for evaluating the RDF, with the advantage of avoiding the usual arbitrary trial values of a particular parameter in the numerical computations. Some numerical examples are given, followed by an application to cervical tissue. It is found that the average relaxation time and the peak amplitude of the RDF exhibit higher values for tumorous cells than normal cells and might be used as parameters to differentiate them and their associated tissues.

Animals↗

Histologic and magnetic resonance imaging correlations in Kienböck's disease.

Nine patients had magnetic resonance imaging studies to aid in the diagnosis of wrist pain in the midcarpal region. Six had positive magnetic resonance imaging studies with a decrease in signal intensity from the area of the lunate, one had an occult ganglion, and two had negative studies. Among the six patients with a diagnosis of Kienböck's disease by magnetic resonance imaging, four patients had collapse of the lunate on plain radiographs, and the other two patients had normal wrist radiographs. Magnetic resonance imaging studies showed a substantial decrease in the signal intensity on T1- and T2-weighted images of the entire lunate in three patients, and three patients had focal areas of decreased signal intensity. All of the patients had a biopsy of the lunate at the time of surgery. The histology of the biopsies of the lunate appeared to correspond to the magnetic resonance imaging studies. Undecalcified bone specimens from the patients with Kienböck's disease showed marked osteonecrosis in three patients, focal areas of osteonecrosis in two patients, and alternating areas of osteonecrosis with dramatic areas of new bone formation in one patient. Although in four patients the diagnosis was obvious by plain radiographs, magnetic resonance imaging studies were essential in confirming the diagnosis in two patients and were helpful in ruling out the diagnosis in three patients.

Adult↗

Can general practitioners counsel?

It has been suggested that general practitioners are in a prime position to counsel patients presenting with psychosocial problems. While many doctors use counselling skills in their consultations few have received training in counselling and the difference between the use of counselling skills and the process of counselling is not always understood. This paper examines the differences between counselling and counselling skills and compares the role of doctors and counsellors. It is concluded that there is a need for trained counsellors to work alongside general practitioners and that this is of benefit to patients and all members of the primary care team.

Counseling↗

Drug testing in the military--technical and legal problems.

The Armed Forces drug-testing program has been in operation since 1971. Since that time, its goals, capabilities, and methods of operation have undergone extensive evolution and change. As these laboratories developed, they helped to establish many of the currently accepted operating standards for drug screening. For laboratories considering entry into the business of drug screening, an examination of the evolution and current operation of the military laboratories will be of benefit. It will help to define the currently accepted standards and NIDA guidelines and assist them to avoid the types of problems that were encountered by the military laboratories.

Gas Chromatography-Mass Spectrometry↗