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K Wood

Publications and source records attributed to K Wood.

At least 19 recordsLinked to original sources

The FOXP1 winged helix transcription factor is a novel candidate tumor suppressor gene on chromosome 3p.

The JC12 monoclonal antibody recognizes a previously unknown nuclear protein that showed a restricted distribution in normal tonsil and was also overexpressed in a subset of diffuse large B-cell lymphomas. Using this reagent, we expression cloned cDNAs encoding its antigenic target and identified this protein as a novel putative transcription factor, FOXP1. The FOXP1 protein sequence contains predicted domains characteristic of transcription factors, including a winged helix DNA-binding motif, a second potential DNA-binding motif, a C(2)H(2) zinc finger, nuclear localization signals, coiled-coil regions, PEST sequences, and potential transactivation domains. The FOXP1 gene has been mapped to chromosome 3p14.1, a region that commonly shows loss of heterozygosity in a wide range of tumors and which is reported to contain a tumor suppressor gene(s). Using tissue arrays and immunohistochemistry, we demonstrate that both the FOXP1 mRNA and protein are widely expressed in normal tissues. The levels of FOXP1 mRNA were compared in paired normal and tumor tissues (from the same patient) using a tissue array containing cDNAs extracted from 68 samples taken from kidney, breast, prostate, uterus, ovary, cervix, colon, lung, stomach, rectum, small intestine, and from nine cancer cell lines. Differences in FOXP1 mRNA expression between normal and tumor samples were observed in 51% of cases. Most striking was the comparative loss of expression in 73% of colon tumors and comparative overexpression of FOXP1 mRNA in 75% of stomach tumors. Analysis of the FOXP1 mRNA expression in normal tissues (not taken from cancer patients) indicated that loss of FOXP1 expression may occur in some histologically normal tissues adjacent to tumors. Immunohistochemical analysis of FOXP1 protein expression was performed on 128 solid tumors, including 16 renal, 9 breast, 12 lung, 20 colon, 21 stomach, 10 head and neck, 35 prostate, and 5 pancreatic cases. Complete loss of expression, increased expression, and cytoplasmic mislocalization of the predominantly nuclear FOXP1 protein were frequently observed in neoplastic cells. Our study identifies FOXP1 as a new candidate tumor suppressor gene localized to the chromosome 3p14.1 region.

Amino Acid Sequence↗

Use of human menopausal gonadotropins in the treatment of endometrial defects associated with recurrent miscarriage: preliminary report.

OBJECTIVE: To test the hypothesis that controlled ovarian stimulation by gonadotropins, which enhances estrogen priming, is of beneficial value in the treatment of endometrial defects associated with recurrent miscarriage. DESIGN: A retrospective, observational, nonrandomized study. SETTING: A regional recurrent miscarriage clinic in a teaching hospital. PATIENT(S): Twenty-one subjects with otherwise unexplained recurrent miscarriage who had retarded endometrial development in the mid-luteal phase. Endometrial biopsies were timed by the luteinizing hormone surge. INTERVENTION(S): Controlled ovarian stimulation using human menopausal gonadotropins and repeat endometrial biopsy in the treatment cycle in 13 subjects. MAIN OUTCOME MEASURE(S): Histological dating of endometrial biopsy in treatment cycles and miscarriage rate in treatment and nontreatment cycles. RESULT(S): Eleven (85%) of the 13 biopsies in the treatment cycle were found to be normal. The miscarriage rate in the treatment group, 2 of 13, was significantly lower than that in the nontreatment group (7/12) (chi2 5.0, P<.05). CONCLUSION(S): In this small series, preliminary experience suggests that controlled ovarian stimulation by human menopausal gonadotropins in the follicular phase is an effective treatment for luteal phase defect associated with recurrent pregnancy loss. There is now a case for a prospective, controlled study to confirm the value of such a treatment.

Abortion, Habitual↗

Paper alert. Immunology.

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in immunology.

Allergy and Immunology↗

Childhood outcome after early high-frequency oscillatory ventilation for neonatal respiratory distress syndrome.

OBJECTIVE: In a previous multicenter controlled clinical trial, we randomly assigned surfactant-treated premature newborns with moderate to severe respiratory distress syndrome to early treatment with high-frequency oscillatory ventilation (HFOV) or to conventional ventilation (CV). Compared with control infants who were treated with CV, neonates who were treated with HFOV using a strategy designed to recruit and maintain lung volume and minimize oxygen exposure had clinical evidence of improved pulmonary outcome and less lung injury. We report a follow-up study designed to determine whether clinical differences persisted between these study groups. METHODS: Patients were recruited from 81 survivors at 1 center (Provo, Utah) and evaluated for sociodemographic and health history, growth, mental development, motor proficiency, and pulmonary function. RESULTS: Eighty-seven percent of the cohort who originally were assigned to treatment with HFOV (n = 36) or CV (n = 33) were seen in follow-up at a mean age of 77 months (6.4 years). There were no differences in the frequency of hospitalization, pulmonary illness, asthma, or disabilities. Growth, verbal IQ, and motor development were appropriate for age and not different between groups. Patients who initially were randomized to treatment with CV showed pulmonary function evidence of decreased peak expiratory flow, increased residual lung volume, and maldistribution of ventilation. CONCLUSION: Neurodevelopmental childhood outcome after early intervention HFOV was normal and not different compared with patients who were treated with CV. Surfactant replacement combined with early HFOV using a lung recruitment strategy ameliorates the acute lung injury in respiratory distress syndrome that predisposes some preterm infants to develop chronic lung disease.

Child↗

High-dose ifosfamide in combination with etoposide and epirubicin (IVE) in the treatment of relapsed/refractory Hodgkin's disease and non-Hodgkin's lymphoma: a report on toxicity and efficacy.

One hundred and seven patients (61 with diffuse large B-cell non-Hodgkin's lymphomas and 46 with Hodgkin's disease) in relapse or following of primary therapy received ifosfamide 3 g/m2 i.v. daily for 3 days in combination with epirubicin 50 mg/m2 i.v. day 1 and etoposide 200 mg/m2 i.v. days 1-3. Of the 46 patients with Hodgkin's disease (28 male, 18 female, and a median age of 28 years) 85% of patients had a response to treatment, with 17 achieving complete remission and 11 good partial remission. Twenty-eight proceeded to autologous bone marrow or peripheral blood stem cell transplantation. Twenty-three patients remain alive in continuous remission with a follow-up of 12-61 months. The median overall survival time for all patients in this group is 36 months. Haematological toxicity, particularly WHO Grade IV neutropenia, occurred in all patients but improved over the three courses of treatment. There was no major non-haematological toxicity. Further trials of this regimen in this clinical situation are indicated. The patients with non-Hodgkin's lymphomas in this study had diffuse large B-cell lymphomas and had only received first-line treatment. Twenty had primarily refractory disease, 15 had only achieved partial remissions (PR), and 26 had developed relapse following primary treatment. The overall response rate was 43%; it was 60% for those who had achieved initial PR, 58% for those in relapse after an initial CR or very good PR following initial therapy, but only 10% for those with primarily refractory disease. Tolerance to the regimen was similar to that observed in treatment of the patients with Hodgkin's disease and many were able to undergo stem cell collection, following mobilization with this regimen. The 2-year overall survival result was 22% for patients with some response to first-line treatment but 0% for primary refractory patients.

Adolescent↗

Continued lamivudine versus delavirdine in combination with indinavir and zidovudine or stavudine in lamivudine-experienced patients: results of Adult AIDS Clinical Trials Group protocol 370.

OBJECTIVE: To compare the virologic activity of continued lamivudine (3TC) versus a switch to delavirdine (DLV) when initiating protease inhibitor therapy in nucleoside-experienced patients. DESIGN: Randomized, open-label, multi-center study. SETTING: Adult AIDS clinical trials units. PATIENTS: Protease and non-nucleoside reverse transcriptase inhibitor-naive patients who had received 3TC plus zidovudine (ZDV), stavudine (d4T), or didanosine (ddl) for at least 24 weeks. INTERVENTIONS: Patients with plasma HIV-1 RNA levels > 500 copies/ml who previously received d4T + 3TC or ddI + 3TC were randomized to ZDV + 3TC + indinavir (IDV) or ZDV + DLV + IDV. MAIN OUTCOME MEASURES: Primary endpoints were the proportion of patients with plasma HIV-1 RNA levels < or = 200 copies/ml at 24 weeks, and occurrence of serious adverse events. The proportion of patients with plasma HIV-1 RNA levels < or = 200 copies/ml at week 48 was a secondary endpoint. RESULTS: At week 24, 58% of subjects in the ZDV + 3TC + IDV arm and 73% in the ZDV + DLV + IDV arm had plasma HIV-1 RNA levels < or = 200 copies/ml (P = 0.29). At week 48, plasma HIV-1 RNA levels were < or = 200 copies/ml in 48% and 83%, respectively (P = 0.007). Rash and hyperbilirubinemia occurred more frequently in the DLV arm than in the 3TC arm. Steady-state plasma IDV levels were higher among patients in the DLV arm as compared with the 3TC arm. CONCLUSIONS: Substituting DLV for 3TC when adding IDV improved virologic outcome in nucleoside-experienced patients. This result might be explained, in part, by the positive effect of DLV on IDV pharmacokinetics.

Acquired Immunodeficiency Syndrome↗

Rehabilitative placement of poststroke patients: reliability of the Clinical Practice Guideline of the Agency for Health Care Policy and Research.

OBJECTIVE: To determine the interrater reliability of the United States Agency for Health Care Policy and Research (AHCPR) Clinical Practice Guideline Number 16 for rehabilitative placement of poststroke patients. DESIGN: Pairs of rehabilitation professionals, highly trained in the Guideline, rated the appropriateness of rehabilitative placements. SETTING: Acute care hospitals in three regions of the country. PATIENTS: Sixty patients with moderate-to-severe stroke. MEASURES: Numerous factors affecting appropriate placement according to the Guideline were abstracted from medical records or obtained by direct evaluation of patients. RESULTS: Good reliability was attained for home and nursing facility placement with rehabilitation services but with no multidisciplinary rehabilitation program (intraclass correlation coefficient = .73 and .60, respectively). Serious reliability problems were found for placements in low-intensity outpatient rehabilitation and high-intensity inpatient rehabilitation programs. Chief sources of unreliability were ambiguous or missing data in hospital medical records, complexities in the Guideline, and raters' tendencies to follow their own clinical judgments. More than one type of placement was appropriate for 65% of patients. CONCLUSIONS: Reliable placement guidelines are possible, but aspects of the Guideline require additional development. Evidence of demonstrated reliability and validity will be required to resolve disputes between rehabilitation professionals and payers regarding appropriate levels and types of rehabilitation and to guide patients and their families.

Adult↗

The impairment of health-related quality of life in patients with intermittent atrial fibrillation: implications for the assessment of investigational therapy.

OBJECTIVES: We sought to assess the impact of intermittent atrial fibrillation (AF) on health-related quality of life (QoL). BACKGROUND: Intermittent AF is a common condition with little data on health-related QoL questionnaires to guide investigational therapies. METHODS: Outpatients from four centers, with documented AF (n = 152), completed validated QoL questionnaires (Medical Outcomes Study Short Form 36 [SF-36], Specific Activity, Symptom Checklist, Illness Intrusiveness and University of Toronto AF Severity Scales). Comparison groups were made up of healthy individuals (n = 47) and four cardiac control groups: published (n = 78) and created for study (n = 69) percutaneous transluminal coronary angioplasty (PTCA); published heart failure (n = 216) and published postmyocardial infarction (MI) (n = 107). RESULTS: Across all domains of the SF-36, AF patients reported substantially worse QoL than healthy controls (1.3 to 2.0 standard deviation units), with scores of 24%, 23%, 16% and 30% lower than healthy individuals on measures of physical and social functioning, mental and general health, respectively (all p < 0.001). Patients with AF were either significantly worse (p < 0.05, published controls) or as impaired (study controls) as either PTCA or post-MI patients on all domains of the SF-36 and the same as heart failure controls on SF-36 psychological subscales. Patients with AF were as impaired or worse than study PTCA controls on measures of illness intrusiveness, activity limitations and symptoms. Associations between objective disease indexes and subjective QoL measures had poor correlations and accounted for <6% of the total variability in QoL scores. CONCLUSIONS: Quality of life is as impaired in patients with intermittent AF as in patients with significant structural heart disease. Patients' perception of QoL is not dependent on the objective measures of disease severity that are usually employed.

Anti-Arrhythmia Agents↗

A comparative evaluation of three accelerometry-based physical activity monitors.

PURPOSE: Accelerometry-based activity monitors offer promise for the assessment of free-living physical activity. They provide an objective record of frequency, intensity, and duration of physical activity with minimal burden on participants. The purpose of this study was to evaluate the absolute and relative validity of three contemporary activity monitors (Computer Science and Applications, Inc. [CSA], Tritrac, and Biotrainer) under both laboratory and field conditions. METHODS: Fifty-two participants completed two 30-min choreographed routines designed to simulate a variety of lifestyle physical activities. Three different treadmill paces were completed in both routines to evaluate reliability and validity under laboratory conditions. Six different lifestyle activities were also examined to evaluate the validity of the monitors under field conditions. During each routine, the activity levels of participants were monitored with the three activity monitors as well as by indirect calorimetry systems. RESULTS: The correlations between the monitors and measured VO2 were higher for treadmill activity (mean r = 0.86) compared with lifestyle activity (mean r = 0.55). Correlations among the different monitors were high for both treadmill (r = 0.86) and lifestyle activities (r = 0.70), suggesting that the monitors provide similar information under both conditions. Under laboratory conditions, the CSA yielded accurate predictions of energy expenditure (EE), whereas the Tritrac and Biotrainer tended to overestimate the EE (101-136% of measured value). The Tritrac, however, was found to have less error in individual estimates of EE. Under field conditions, all of the monitors underestimated EE (range: 42-67% of measured value). CONCLUSION: The observed differences among the monitors were attributed primarily to differences in the accuracy of the calibration equations rather than to the monitors themselves. Further research is needed to better understand how to use these devices for field-based assessments of physical activity.

Activities of Daily Living↗

Developmental regulation of methyl benzoate biosynthesis and emission in snapdragon flowers.

In snapdragon flowers, the volatile ester methyl benzoate is the most abundant scent compound. It is synthesized by and emitted from only the upper and lower lobes of petals, where pollinators (bumblebees) come in contact with the flower. Emission of methyl benzoate occurs in a rhythmic manner, with maximum emission during the day, which correlates with pollinator activity. A novel S-adenosyl-l-methionine:benzoic acid carboxyl methyl transferase (BAMT), the final enzyme in the biosynthesis of methyl benzoate, and its corresponding cDNA have been isolated and characterized. The complete amino acid sequence of the BAMT protein has only low levels of sequence similarity to other previously characterized proteins, including plant O-methyl transferases. During the life span of the flower, the levels of methyl benzoate emission, BAMT activity, BAMT gene expression, and the amounts of BAMT protein and benzoic acid are developmentally and differentially regulated. Linear regression analysis revealed that production of methyl benzoate is regulated by the amount of benzoic acid and the amount of BAMT protein, which in turn is regulated at the transcriptional level.

Amino Acid Sequence↗

Coma from fat embolism syndrome after hemiarthroplasty of the hip for metastatic breast cancer to the proximal femur: a case report.

We present a case report of fat embolism syndrome (FES) that resulted in prolonged coma after cemented hemiarthroplasty in a patient with metastatic breast cancer. After the cemented hip prosthesis was placed, the patient developed decreased sensorium that progressed to coma in association with hypoxemia and tachypnea. Pulmonary compromise was mild, and the patient required only supplemental oxygen for support. The patient demonstrated no petechiae. Magnetic imaging results were consistent with FES. While the pulmonary symptoms resolved quickly, the patient remained unresponsive for 11 days without purposeful motor function. After waking she recovered rapidly, and at her 2-month follow-up appointment, demonstrated no adverse orthopedic, pulmonary, or neurologic sequelae.

Aged↗

Pet travel scheme.

Explore the source record for details and available documents.

Animal Diseases↗

Lamivudine in combination with zidovudine, stavudine, or didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group Protocol 306 Investigators.

OBJECTIVE: To study the antiviral activity of lamivudine (3TC) plus zidovudine (ZDV), didanosine (ddl), or stavudine (d4T). DESIGN: Randomized, placebo-controlled, partially double-blinded multicenter study. SETTING: Adult AIDS Clinical Trials Units. PATIENTS: Treatment-naive HIV-infected adults with 200-600x10(6) CD4 T lymphocytes/l. INTERVENTIONS: Patients were openly randomized to a d4T or a ddl limb, then randomized in a blinded manner to receive: d4T (80 mg/day), d4T plus 3TC (300 mg/day), or ZDV (600 mg/day) plus 3TC, with matching placebos; or ddl (400 mg/day), ddl plus 3TC (300 mg/day), or ZDV (600 mg/day) plus 3TC, with matching placebos. After 24 weeks 3TC was added for patients assigned to the monotherapy arms. MAIN OUTCOME MEASURE: The reduction in plasma HIV-1 RNA level at weeks 24 and 48. RESULTS: Two hundred ninety-nine patients were enrolled. After 24 weeks the mean reduction in plasma HIV-1 RNA copies/ml from baseline was 0.49 log10 (d4T monotherapy) versus 1.03 log10 (d4T plus 3TC; P = 0.001), and 0.68 log10 (ddl monotherapy) versus 0.82 log10 (ddl plus 3TC; P>0.22). After 48 weeks the mean reduction was 1.08 log10 (d4T plus 3TC) versus 1.01 log10 (ZDV plus 3TC) in the d4T limb (P = 0.66), and 0.94 log10 (ddl plus 3TC) versus 0.88 log10 (ZDV plus 3TC; P = 0.70) in the ddl limb. CONCLUSIONS: 3TC added significantly to the virologic effects of d4T, but not ddl, in treatment-naive patients. 3TC plus d4T produced virologic changes comparable to those of 3TC plus ZDV. These results support the use of 3TC with either ZDV or d4 as a component of initial combination antiretroviral therapy.

Adult↗

NCL-CD10-270: a new monoclonal antibody recognizing CD10 in paraffin-embedded tissue.

CD10 (CALLA) antigen is expressed in a wide variety of epithelial and nonepithelial tissues, but its most significant application is in the diagnosis and classification of certain types of malignant lymphoma and leukemia. CD10 is expressed in a high percentage of cases of acute lymphoblastic leukemia (ALL), follicular lymphoma, Burkitt's lymphoma, and some hematopoietic tumors. Although the antigen is not lineage specific, CD10 expression is widely used to define subgroups within B-ALL and is a useful tool for detecting the presence of leukemic blasts in the bloodstream. Currently available monoclonal antibodies to CD10 have been found to be effective only in fresh-frozen tissue and for techniques such as flow cytometry. We have used a recombinant protein corresponding to the whole of CD10 to generate a monoclonal antibody that is effective in paraffin-embedded tissue sections. We have used this antibody to assay for the presence of CD10 on a range of normal and pathological tissues. Strong staining was seen in lymphoid germinal centers, renal tubules, glomeruli, syncytiotrophoblast, hepatic parenchymal canaliculi, B-lineage ALL, follicle center cell lymphoma, and a proportion of cases of large-B-cell lymphoma. We believe that this antibody will be of value in the characterization of malignant lymphoma, in particular the differential diagnosis of small-B-cell lymphoma and subtyping of lymphoblastic leukemia, as well as the investigation of the significance of expression of CD10 in other normal and pathological tissues.

Animals↗

Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure.

BACKGROUND: Patients with acute renal failure (ARF) have high morbidity and mortality rates, particularly if they have serious comorbid conditions. Several studies indicate that in rats with ARF caused by ischemia or certain nephrotoxins, insulin-like growth factor-I (IGF-I) enhances the recovery of renal function and suppresses protein catabolism. METHODS: Our objective was to determine whether injections of recombinant human IGF-I (rhIGF-I) would enhance the recovery of renal function and is safe in patients with ARF. The study was designed as a randomized, double-blind, placebo-controlled trial in intensive care units in 20 teaching hospitals. Seventy-two patients with ARF were randomized to receive rhIGF-I (35 patients) or placebo (37 patients). The most common causes of ARF in the rhIGF-I and placebo groups were, respectively, sepsis (37 and 35% of patients) and hypotension or hemodynamic shock (42 and 27% of patients). At baseline, the mean (+/- SD) APACHE II scores in the rhIGF-I and placebo-treated groups were 24 +/- 5 and 25 +/- 8, respectively. In the rhIGF-I and placebo groups, the mean (median) urine volume and urinary iothalamate clearances (glomerular filtration rate) were 1116 +/- 1037 (887) and 1402 +/- 1183 (1430) ml/24 hr and 6.4 +/- 5.9 (4.3) and 8.7 +/- 7.2 (4.4) ml/min and did not differ between the two groups. Patients were injected subcutaneously every 12 hours with rhIGF-I, 100 microgram/kg desirable body weight, or placebo for up to 14 days. Injections were started within six days of the onset of ARF. The primary end-point was a change in glomerular filtration rate from baseline. Other end points included changes from baseline in urine volume, creatinine clearance and serum urea, creatinine, albumin and transferrin, frequency of hemodialysis or ultrafiltration, and mortality rate. RESULTS: During the treatment period, which averaged 10.7 +/- 4.1 and 10.6 +/- 4.5 days in the rhIGF-I and placebo groups, there were no differences in the changes from baseline values of the glomerular filtration rate, creatinine clearance, daily urine volume, or serum urea nitrogen, creatinine, albumin or transferrin. In patients who did not receive renal replacement therapy, there was also no significant difference in serum creatinine and urea between the two groups. Twenty patients in the rhIGF-I group and 17 placebo-treated patients underwent dialysis or ultrafiltration. Twelve rhIGF-I-treated patients and 12 placebo-treated patients died during the 28 days after the onset of treatment. CONCLUSIONS: rhIGF-I does not accelerate the recovery of renal function in ARF patients with substantial comorbidity.

Acute Kidney Injury↗