Search PubMed⌕ Search

Biomedical subjects

R Shah

Publications and source records attributed to R Shah.

At least 37 records · Page 2Linked to original sources
PubMed2001

General practice consultation rates for psychiatric disorders in patients aged 65 and over: prospective cohort study.

OBJECTIVE: To examine consultation rates for psychiatric disorder in general practice among patients aged 65 years and over; and to examine the effect of sociodemographic factors (gender, age, social class and accommodation) on consultation rates. DESIGN: Prospective cohort study. The fourth national survey of morbidity in general practice carried out between September 1991 and August 1992. Sixty volunteer practices in England and Wales took part; study population comprised a 1% sample of the population (502,493 patients). GPs recorded the reasons for all consultations and these were converted into an ICD9 code. Trained fieldworkers collected sociodemographic data on the patients in the survey. METHOD: Psychiatric disorders were categorised by compiling the appropriate ICD9 codes. Annual consultation rates (per 1000 patients) according to psychiatric disorder and sociodemographic factors were calculated after adjustment for differing length of follow-up. RESULTS: Only 4.4% of all consultations were for psychiatric disorders. Women had consultation rates 75% higher than men. Social class had no effects on rates. Consultation rates were highest for neurotic disorders and depression. Those living alone had highest rates for depression, whilst those living in residential and nursing homes had substantially higher consultation rates for dementia and bipolar affective disorder. CONCLUSION: Consultation rates were significantly lower than expected from previous epidemiological studies. This indicates that there is considerable hidden morbidity that is being untreated in primary care. Social class appears to have no effect on consultations for psychiatric disorder in the elderly. The increasing age of the population may result in a significant increase in consultations for dementia, but not for depression or neurosis.

Aged↗
PubMed2001

Application of excimer laser angioplasty in acute myocardial infarction.

BACKGROUND AND OBJECTIVE: Patients presenting with acute myocardial infarction who fail to respond to standard therapy with thrombolytics or have contraindications for their use oftentimes need revascularization with a mechanical device for removal of an occlusive coronary thrombus and its underlying atherosclerotic plaque. As both thrombi and plaques absorb laser energy in the ultraviolet wavelength (308 nm), we studied the feasibility and safety of excimer laser angioplasty in selective patients with complicated acute myocardial infarction. STUDY DESIGN/MATERIALS AND METHODS: Fifty patients with acute myocardial infarction complicated by continuous chest pain and/or ischemia who had a total of 54 obstructive lesions were treated with percutaneous excimer coronary laser angioplasty (ELCA). A Q-wave myocardial infarction was documented in 56% and a non-Q-wave myocardial infarction in 44%. The baseline left ventricular ejection fraction was reduced at 43 +/- 13% and six patients (12%) presented to the cardiac catheterization laboratory in cardiogenic shock. Twenty-nine patients failed to respond to thrombolytic therapy and 16 had contraindications for thrombolytics and IIb/IIIa receptor antagonists. Following laser debulking, all patients received adjunct balloon dilation and then stents were deployed in 83% of the target lesions. Quantitative coronary arteriography (QCA) was performed at an independent core laboratory. RESULTS: Ninety-eight percent laser success and 100% procedural success were achieved. By QCA the minimal luminal diameter increased from baseline of 0.7 +/- 0.5 to 1.3 +/- 0.5 mm post-lasing and then to 2.0 +/- 0.6 with balloon dilation to a final of 3.0 +/- 0.5 mm. Pre-laser percent stenosis diameter of 77 +/- 17% was reduced to 51 +/- 22% post-laser to 3.0 +/- 17% post-balloon and to a final of 15 +/- 25%. An 83% laser-induced reduction of thrombus burden area was achieved as well as an increase in TIMI flow from baseline of 1.7 +/- 1.1 to 2.8 +/- 0.4 by laser to a 2.9 +/- 0.4 final. There were no deaths, emergency bypass surgery, cerebral vascular accident, neurologic injury, or major perforation. In one case, a laser-induced major dissection was successfully treated by stenting. All 50 patients survived the procedure, improved clinically, and were discharged. CONCLUSION: Application of excimer laser coronary angioplasty is feasible and safe in selected patients with acute myocardial infarction who either fail to respond to thrombolytics or have contraindications to these agents. Intracoronary thrombus at the target lesion can be successfully dissolved with this wavelength laser energy without adverse effect on the procedure results.

Angioplasty, Balloon, Laser-Assisted↗
PubMed2001

Red cell distribution width in the diagnosis of iron deficiency anemia.

OBJECTIVE: 1. To compare peripheral smear (PS) and Red cell distribution width (RDW) in diagnosis of Iron deficiency anemia (IDA) in various grades. 2. To study the changes in RDW and PS after therapy. METHODS: Children in the age group of six months to five years with microcytic (MCV<80fl) anemia (Hemoglobin <11 g%) were evaluated. Those who had received blood transfusion and /or were already on iron therapy were excluded. Evaluation included clinical examination, complete blood count (CBC), RDW estimation microscopic examination of peripheral smear, measurement of serum iron and transferrin saturation. Children with IDA were treated with oral iron for 8 weeks and PS, CBC including RDW were repeated. RESULT: Of the 100 children evaluated, 89 had IDA. 48% had mild, 42% had moderate and 10% had severe anemia. Transferrin saturation correlated with severity of anemia. Peripheral smear showed microcytosis and hypochromia in all cases with severe anemia, 61.5% and 22.5% of those with moderate and mild anemia respectively. RDW was suggestive of iron deficiency in 100%, 82.05% and 100% of patient with mild, moderate and severe anemia respectively. CONCLUSION: In the diagnosis of mild and moderate iron deficiency anemia, RDW had a higher sensitivity than PS. Red cell morphology, Hb, PCV and RDW showed significant improvement after iron-therapy.

Anemia, Iron-Deficiency↗
PubMed2001

Postatrophic hyperplasia of the prostate gland: neoplastic precursor or innocent bystander?

Postatrophic hyperplasia (PAH) of the prostate gland often demonstrates overlapping histological features with prostatic adenocarcinoma (PCA). These features include small acinar growth and enlarged nuclei with prominent nucleoli. Recent work has demonstrated that PAH is a proliferative, noninvoluting lesion. PAH is also histologically distinct from simple atrophy (SA), which has intermediate- to large-sized glands, minimal cytoplasm, and inconspicuous nuclei. However, despite overlapping features between PAH and PCA, high-grade prostatic intraepithelial neoplasm (HGPIN) is still considered the only direct neoplastic precursor to PCA. HGPIN resembles PCA in its topographic distribution, cytological appearance, and molecular alterations including chromosome 8p loss and chromosome 8 centromeric gain. To examine the hypothesis that PAH is the earliest histologically distinct precursor to HGPIN or PCA, the frequency, distribution, proliferative state, and chromosome 8 gain of benign prostate, SA, PAH, HGPIN, and PCA were analyzed. Forty radical prostatectomy specimens from men with clinically localized PCA were systematically analyzed. Proliferation was determined by Ki-67 immunohistochemistry (MIB-1) on formalin-fixed, paraffin-embedded tissue and quantified by digital image analysis from a total of 5,510 sample areas with benign, SA, PAH, HGPIN, and PCA. A tissue microarray was constructed to evaluate 8c gain using interphase fluorescence in situ hybridization. SA foci (n = 129) and PAH foci (n = 114) were identified in the 40 cases of which 74% (95 of 129) and 88% (100 of 114) were seen in the peripheral zone, respectively (P = 0.006). PAH and SA were identified adjacent to PCA in 28% (32 of 114) and 14% (18 of 129) of foci examined, respectively (P = 0.007). The median number of proliferating nuclei increased significantly from benign (1.20%), SA (2.67%), PAH (3.62%), HGPIN (6.14%), to PCA (12.00%) (P < 0.001). The median percentage of nuclei with more than three centromeric probe signals (chromosome 8c gain) for SA, HGPIN, PAH, and PCA were 2.1, 2.8, 4.0, and 6.0%, respectively, as compared to benign prostate with 1.3% (P = 0.006). In conclusion, the present study identified a strong topographic association between PAH and PCA. PAH is also seen often to be closely associated with chronic inflammation. Proliferation of PAH is significantly greater than benign prostatic epithelium and SA but less than HGPIN or PCA. Gain of 8c is significantly greater in PAH than benign prostate, SA, and even HGPIN. These findings demonstrate a strong association between PAH and PCA, supporting its role as a neoplastic precursor.

Adenocarcinoma↗
PubMed2001

Echocardiography, nuclear scintigraphy, and stress testing in the emergency department evaluation of acute coronary syndrome.

There are between 3 and 5 million visits to EDs each year for complaints of chest pain. Of these, about one half of the patients have a noncardiac cause for their chest pain. Of the remainder, about 30% to 50% have significant coronary disease. It is quite clear that patients who are at high risk for a coronary event should be admitted to the hospital. For the low-to-moderate risk patients, the decision to admit or discharge the patient from the ED is not quite so easy. The emergency physician has to decide which tests can be helpful in the decision-making process, this can be undertaken in conjunction with a consultative cardiologist. It can be argued that if a patient does not have a normal test result whichever that evaluatory test is), then the patient should be admitted for further work-up and evaluation. The easiest test to perform in the ED setting is an echocardiogram. The images can be sent by telecommunication to a qualified echocardiogram reader for interpretation. This also has a reasonable NPV, although not necessarily as good as some of the other modalities available, unless interpreted in light of cardiac enzyme test results. If the index of suspicion is still high, then a stress echocardiogram can be considered. This has an excellent NPV and can be easily performed in [table: see text] most patients. This should not be undertaken in the face of an evolving MI, and patients should be observed for at least 8 hours after their initial presentation to the ED prior to undergoing a provocative test. Nuclear scintigraphy, another modality available for cardiac risk stratification, can be a logistical nightmare. The nuclear isotopes are strictly regulated by the Nuclear Regulatory Commission. The emergency physician may inject the isotopes, provided that he or she has undergone the necessary radiation training. Also, the patient must be removed from the ED to a radioisotope-approved area for the duration of the scan. One of the most difficult questions left open after review of all these analytical modalities is the duration of time these test results remain valid; when does an individual patient need to be reevaluated as to their specific pretest probability? The answer to this question lies in the presenting clinical scenario. If the patient presents with a similar inciting trigger for his or her symptoms, and the cardiac risk profile has not changed appreciably, then the previous study (whether a provocative stress test or even a cardiac catheterization) probably can be reliably counted. If the patient's risk profile has changed or the symptoms are new or more intense, the physician is compelled to pursue this encounter as a new, acute event. This can be true even in the setting of a previous cardiac catheterization that showed nonobstructive coronary disease, because plaque rupture can be acute and unpredictable. Ultimately, optimal care calls for each institution to develop a specific approach, in conjunction with their consultative cardiologist or critical care specialist, to enhance patient care, safety, and diagnostic outcome, while maintaining cost efficiency.

Coronary Disease↗
PubMed2001

Cardiopulmonary endoscopy: an effective and low risk method of examining the cardiopulmonary system during cardiac surgery.

OBJECTIVES: During cardiac surgery it is sometimes necessary to examine heart chambers remote from the site of surgery. Similarly visualization of the pulmonary arterial tree will enable assessment for the completeness of pulmonary embolectomy. There are no standard adjunctive procedures to accomplish this. Left ventriculotomy used to examine the left ventricle, and maneuvers used to ensure complete pulmonary embolectomy can have serious complications. Impelled by the need to obviate the complications, we adopted and, herein describe a simple method of examining the cardiopulmonary system with an endoscope. Our early experience is also presented. METHOD: Transmitral cardioscopy was performed in two patients, and pulmonary angioscopy in one. One patient had the combined procedure. The indications for transmitral cardioscopy were; suspected left ventricular thrombus and a right atrial thrombus propagating into the left atrium through a patent foramen ovale. The indications for pulmonary angioscopy were pulmonary embolectomy and right atrial thrombus. SSURGICAL TECHNIQUE Cardiopulmonary endoscopy was performed on cardiopulmonary bypass, at an appropriate stage of the primary procedure. For transmitral cardioscopy, a flexible fibreoptic endoscope was passed into the left ventricle through the right superior pulmonary vein, or the right atrium. For pulmonary endoscopy, the flexible endoscope was introduced through a pulmonary arteriotomy. At the end of the procedure, the port of entry of the endoscope was closed and cardiopulmonary bypass terminated. RESULTS: A good visualization of the cardiac chambers and the pulmonary artery was obtained in all the patients. One patient was found to have an endocardial scarring, and a left ventricular thrombus was excluded in another. Visual guidance facilitated pulmonary emboli retrieval. There were no complications in these patients. CONCLUSION: Cardiopulmonary endoscopy is simple, safe and effective in examining the cardiac chambers and the pulmonary arterial system. It can be performed with a sterilized flexible fibreoptic endoscope. It facilitates pulmonary embolectomy, and precludes procedures and maneuvers that can cause serious complications. It adds a visual advantage to pulmonary embolectomy, which is otherwise blind. Cardiopulmonary endoscopy has the potential for a wider applicability, possibly in minimally invasive and robotic cardiac surgery.

Angioscopy↗
PubMed2001

Deaths from antidepressants in England and Wales 1993-1997: analysis of a new national database.

BACKGROUND: The prescription of antidepressants has increased substantially over the last 10 years. It is therefore timely to examine trends in mortality associated with overdoses of antidepressants and to compare the relative mortality associated with different antidepressants. METHODS: Data were derived from a newly developed national database of deaths from overdose and poisoning in England and Wales between 1993 and 1997. Age and sex specific death rates associated with overdose and poisoning with antidepressants were calculated together with numbers of deaths per 100,000 prescriptions of individual antidepressants. RESULTS: Twenty per cent (2,503) of all deaths from overdose or poisoning were antidepressant related. The number of deaths increased by 18% between 1993 and 1997. Ninety-five per cent of deaths from antidepressants were associated with tricyclic antidepressants, particularly dothiepin and amitriptyline. Tricyclic antidepressants were associated with 5.3 deaths per 100,000 prescriptions, 4.4 for monoamine oxidase inhibitors and 0.4 for selective serotonin reuptake inhibitors. Annual death rates were highest in men aged 30-44 years (18.2 per million) and women aged 45-59 years (14.8). Death rates from antidepressants were 2.5 times higher in the most deprived fifth than in the least deprived fifth of enumeration districts. CONCLUSIONS: Antidepressants are an important cause of death from poisoning and overdose. SSRIs and newer antidepressants are associated with <10% of the risk of death than the older antidepressants. There is a strong association between area deprivation and deaths from antidepressants.

Aged↗
PubMed2001

Dacryocystorhinostomy for epiphora in the presence of a patent lacrimal system.

PURPOSE: To evaluate the success rate of dacryocystorhinostomy (DCR) for epiphora in patients with a clinically patent lacrmal drainage system. METHODS: A series of 51 patients, 12 men and 39 women, who underwent DCR surgery for epiphora with a clinically patent lacrimal drainage system in the background of normal eyelid examination, were evaluated. All patients underwent fluorescein dye disappearance testing and Jones 1 and 2 testing with dacryocystograms in borderline cases. A standard DCR was performed with bicanalicular silicone tubing inserted in all cases. The average time for the removal of the silicone tubes was 9.6 weeks. RESULTS: In 48 cases (94%) there was improvement in symptoms with minimal or no significant epiphora postoperatively. CONCLUSIONS: Epiphora with a patent lacrimal drainage system obstruction can be successfully treated by DCR based on fluorescein dye disappearance tests and Jones 1 and 2 tests, with dacryocystography in borderline cases.

Adolescent↗
PubMed2001

Population-based survey and analysis of trends in the prevalence of diabetic nephropathy in Type 1 diabetes.

AIMS: To determine the prevalence of the various stages of diabetic nephropathy in Type 1 diabetes in a population-based survey. To make direct comparison with results from previous published studies to assess current trends. METHODS: Identification of all Type 1 patients using a population-based diabetes register. Urine samples for albumin assay were obtained at clinic visit and by postal request. Prevalence rates were calculated specifically for direct comparisons with previously published surveys. RESULTS: This study and European data from the 1990s show a clear reduction in the cumulative prevalence of microalbuminuria and established nephropathy compared with surveys from Copenhagen (1985), Pittsburgh (1986-8) and Boston (1992). In North Wales in 1999 the overall cumulative prevalence of microalbuminuria was 27.2% (95% confidence interval (CI) 24.3-30.1%) and established nephropathy was 9.6% (7.7-11.5%). Comparisons with data from EURODIAB and from Spain indicated similar results, although the prevalence of microalbuminuria was lower in North Wales than in the EURODIAB study. Significantly lower rates of nephropathy were seen in more recent Swedish cohorts. Diabetic nephropathy remains more common in males. Microalbuminuria before 10 years duration of diabetes was seen at all post-pubertal ages. CONCLUSIONS: Rates of nephropathy in Europe in the 1990s are lower than a decade ago. Modern methods of management are therefore associated with demonstrable benefit at the population level. The lowest rates of nephropathy are associated with optimum glycaemic control in Swedish data, indicating the importance of metabolic in addition to haemodynamic factors.

Albuminuria↗
PubMed2001

The Spo12 protein of Saccharomyces cerevisiae: a regulator of mitotic exit whose cell cycle-dependent degradation is mediated by the anaphase-promoting complex.

The Spo12 protein plays a regulatory role in two of the most fundamental processes of biology, mitosis and meiosis, and yet its biochemical function remains elusive. In this study we concentrate on the genetic and biochemical analysis of its mitotic function. Since high-copy SPO12 is able to suppress a wide variety of mitotic exit mutants, all of which arrest with high Clb-Cdc28 activity, we speculated whether SPO12 is able to facilitate exit from mitosis when overexpressed by antagonizing mitotic kinase activity. We show, however, that Spo12 is not a potent regulator of Clb-Cdc28 activity and can function independently of either the cyclin-dependent kinase inhibitor (CDKi), Sic1, or the anaphase-promoting complex (APC) regulator, Hct1. Spo12 protein level is regulated by the APC and the protein is degraded in G1 by an Hct1-dependent mechanism. We also demonstrate that in addition to localizing to the nucleus Spo12 is a nucleolar protein. We propose a model where overexpression of Spo12 may lead to the delocalization of a small amount of Cdc14 from the nucleolus, resulting in a sufficient lowering of mitotic kinase levels to facilitate mitotic exit. Finally, site-directed mutagenesis of highly conserved residues in the Spo12 protein sequence abolishes both its mitotic suppressor activity as well as its meiotic function. This result is the first indication that Spo12 may carry out the same biochemical function in mitosis as it does in meiosis.

Amino Acid Sequence↗
PubMed2001

Trends in deaths from drug overdose and poisoning in England and Wales 1993-1998.

BACKGROUND: The study examines time trends and sociodemographic aspects of drug poisoning deaths in England and Wales. METHODS: Socio-demographic data from the four drug groups most commonly used in poisoning were extracted, and annual age- and sex-specific mortality rates calculated. Enumeration districts were ranked into five groups on the basis of their Carstairs scores, and the number of deaths in each of the five groups was calculated. RESULTS: There were 15720 deaths from drug poisoning between 1993 and 1998. More deaths occurred in men than in women (10 223 versus 5497). Opiates were the most commonly used drugs in deaths from drug poisoning (32 per cent of deaths); mortality rates increased twofold for these drugs. Males had higher number of deaths from opiate poisoning than females (4523 versus 1221). Highest mortality rates from opiate poisoning (77.4 per million) occurred in men aged 24-35 years. Deaths from drug poisoning were strongly associated with deprivation. CONCLUSION: There are substantial socio-demographic differences in mortality rates from drug poisoning.

Acetaminophen↗
PubMed2001

Prevention of diabetes in the NOD mouse by intra-muscular injection of recombinant adeno-associated virus containing the preproinsulin II gene.

Using the Adeno-associated virus (AAV) as a gene delivery vehicle, we have constructed a recombinant vector containing the full length rat preproinsulin gene (vLP-1). Utilizing the well described non-obese diabetic (NOD) mouse model, an experimental group (n = 10) of animals were intramuscularly (i.m.) injected with 10(7) rAAV virions containing the insulin gene and compared to a mock-injected control group (n = 10). Blood glucose (glc) was then measured weekly for 16 weeks. Data showed that the experimental group contained 70% euglycemic animals (defined as glc<200 mg/dL) versus 10% of the control animals (P < .05) at 14 weeks. Mean weight in the treated group was greater than the untreated group. Insulin mRNA was detected at the injection site of all of the treated animals, but not controls. Complete destruction of islets was confirmed by histology ruling out the possibility of spontaneous reversal of insulinitis. We conclude that i.m. delivery of the insulin gene in the NOD mouse was able to prevent clinical DM up to 14 weeks in a majority of treated animals. Our experimental data suggests that gene therapy may be an alternative treatment for IDDM in the future.

Animals↗
PubMed2001

Bite the bullet: lead poisoning after ingestion of 206 lead bullets.

A 45-y-o male with a history of schizophrenia was admitted to a local VA psychiatric unit. Five days later, endoscopy due to abdominal pain, gastrointestinal bleeding and blood hemoglobin of 5.6 g/dL revealed bullets in the stomach. On subsequent radiograph, > 50 bullets were visualized in the stomach and intestines. Poison Center recommendations included whole bowel irrigation and a blood lead level. After poor results with gastrointestinal decontamination and a repeat radiograph showing > 100 cartridges, surgical intervention was considered but not performed due to perceived risk of bullet detonation from electrocautery. The blood lead was reported as 391 mcg/dL. Calcium EDTA therapy was initiated, followed by aggressive gastrointestinal decontamination. Four days of whole bowel irrigation facilitated passage of 206 cartridges over the next 10 days. The patient was discharged on a 14-day course of 600 mg Succimer tid to treat the bone lead deposits and blood lead level of 49 mcg/dl. An outpatient visit 6 w later showed the blood lead level had dropped to 24 mcg/dl. Aggressive gastrointestinal decontamination and calcium EDTA and Succimer administration successfully treated an ingestion lead bullets and the resulting lead poisoning.

Antidotes↗
PubMed2001

Lack of association of prostate carcinoma nuclear grading with prostate specific antigen recurrence after radical prostatectomy.

PURPOSE: Grading prostate cancer using the Gleason system relies only on architectural tumor growth, in contrast to other systems, such as the WHO system, which grade prostate carcinoma based on nuclear features as well as architectural patterns. The prognostic significance of nuclear grading remains controversial since most studies were performed before prostate specific antigen (PSA) screening became widely available. We evaluated the significance of nuclear grade for predicting PSA recurrence in a contemporary cohort of patients treated with radical prostatectomy for clinically localized prostate carcinoma. MATERIALS AND METHODS: Nuclear grades 1 to 3 were determined in 141 consecutive radical prostatectomies in 1995. Predominant and worst nuclear grade was determined by a consensus of 3 pathologists. Statistical analysis compared nuclear grade with Gleason score using the chi-square test. The Cox proportional hazards analysis was performed to calculate the ability of nuclear grade, Gleason score and other variables to predict PSA recurrence. RESULTS: We identified a significant association of Gleason score with worst nuclear grade (p = 0.007). All 6 cases with a Gleason score of 8 or greater had a worst nuclear grade of 3, in contrast to 36 of 60 (60%) with a score 6 or less, in which the worst nuclear grade was 3. Of the 141 patients 31 (21.9%) had PSA recurrence at a median followup of 3.7 years. The univariate Cox model revealed significant associations of PSA recurrence with Gleason score 8 or greater (hazards ratio 5.5, p = 0.005), extraprostatic extension (hazards ratio 3.4, p = 0.001), positive surgical margin (hazards ratio 2.6, p = 0.009), seminal vesicle involvement (hazards ratio 7.3, p <0.001), preoperative serum PSA (hazards ratio 1.03, p = 0.007), tumor stage (hazards ratio 3.6, p = 0.001) and maximal tumor dimension (hazards ratio 2.4, p <0.001). However, overall and worst nuclear grade did not predict PSA recurrence (p = 0.89 and 0.13, respectively). Nuclear grade did not fit any multivariate model tested, which otherwise included Gleason score, log(PSA), surgical margin status, extraprostatic extension, seminal vesicle status, tumor size and pathological stage. By varying sample fixation time we also showed that benign prostate tissue in the same section as prostate carcinoma had grade 2 or 3 nuclear changes, that is moderate to marked anaplasia. CONCLUSIONS: High nuclear grade is associated with high Gleason score. However, prostate carcinoma with a Gleason score of 6 or less shows extreme variability. Nuclear grade determined by light microscopy failed to predict PSA recurrence in a contemporary series of men with clinically localized prostate cancer treated with radical prostatectomy. Nuclear morphology is subject to tissue fixation and processing artifact. Any nuclear morphometric study must consider this artifact.

Adult↗
PubMed2001

Involvement of the nuclear matrix in the control of skeletal genes: the NMP1 (YY1), NMP2 (Cbfa1), and NMP4 (Nmp4/CIZ) transcription factors.

The functional role of the osteoblast nuclear matrix has been a matter of supposition. Its presumed function as an architectural agent of transcription derives primarily from the low solubility of nuclear matrix proteins and their typical localization into discrete subnuclear domains. In addressing how the nuclear matrix regulates skeletal genes, the authors compare Nmp4, Cbfal, and YY1 for the purpose of profiling osteoblast nuclear matrix transcription factors. All three proteins contribute to the transcription of ECM genes and partition into the osteoblast nuclear matrix via a nuclear matrix targeting domain. The authors propose that osteoblast nuclear matrix transcription factors involved in ECM regulation generally have the capacity to alter DNA geometry and reciprocally respond to DNA as an allosteric ligand. This may allow these proteins to adapt to the local nuclear architecture and generate the pattern of regulation specified by that architecture via unmasking of the appropriate transactivation domains. Osteoblast nuclear matrix transcription factors may also act as transcriptional adaptor molecules by supporting the formation of higher order protein complexes along target gene promoters. The genes encoding all three proteins considered here have trinucleotide repeat domains, although the significance of this is unclear. There is no canonical nuclear matrix binding motif, but finger-like structures may be suited for anchoring proteins to discrete subnuclear domains. Finally, the ability to leave the osteoblast nuclear matrix may be as important to the function of some nuclear matrix transcription factors as their association with this subcompartment.

Animals↗
PubMed2000

Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana.

The genome of the model plant Arabidopsis thaliana has been sequenced by an international collaboration, The Arabidopsis Genome Initiative. Here we report the complete sequence of chromosome 5. This chromosome is 26 megabases long; it is the second largest Arabidopsis chromosome and represents 21% of the sequenced regions of the genome. The sequence of chromosomes 2 and 4 have been reported previously and that of chromosomes 1 and 3, together with an analysis of the complete genome sequence, are reported in this issue. Analysis of the sequence of chromosome 5 yields further insights into centromere structure and the sequence determinants of heterochromatin condensation. The 5,874 genes encoded on chromosome 5 reveal several new functions in plants, and the patterns of gene organization provide insights into the mechanisms and extent of genome evolution in plants.

Animals↗
PubMed2000

Benign prostatic glands at surgical margins of radical prostatectomy specimens: frequency and associated risk factors.

OBJECTIVES: Elevation of serum prostate-specific antigen (PSA) after radical prostatectomy for prostate cancer is considered a surrogate marker of therapeutic failure. The most likely explanation for early PSA failure is considered to be due to local recurrent disease, provided the patient had a nondetectable PSA level after radical prostatectomy. Others have recently suggested that benign prostatic glands located on the surgical margins may often lead to detectable PSA levels. We examined the frequency of benign prostatic glands at the surgical margins of radical prostatectomy specimens and the factors associated with this finding. METHODS: One hundred nineteen consecutive radical prostatectomies were performed by two experienced oncologic surgeons. Whole-mount sectioning of the prostatectomy specimens was performed at 3-mm intervals. Bivariate and multivariate analyses were used to determine which clinical and pathologic factors were associated with benign glands on inked surgical margins. RESULTS: Of the 119 cases, 13 (11%) had benign glands on the inked surgical margins. Four of these 13 had tumor on the inked margins. The remaining 9 cases (8%) were organ confined (pT2), with negative surgical margins. Benign glands were most often seen to involve the apex focally (7 of 9 cases). On bivariate and multivariate analyses, a high Gleason score and prostate gland volume were significantly associated with finding benign glands on the surgical margins. Only 2 of 86 patients with follow-up had PSA recurrence at 59 and 67 days and neither had benign glands on the inked surgical margins. CONCLUSIONS: The presence of benign prostatic glands identified on inked surgical margins was an infrequent occurrence in this consecutive series of 119 whole-mount prostatectomy specimens. When benign glands were identified, they most often consisted of 1 to 3 glands at the apex margin. These findings suggest that benign glands on surgical margins are an unusual cause of postoperative detectable PSA.

Follow-Up Studies↗