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Biomedical subjects

W R Lee

Publications and source records attributed to W R Lee.

At least 109 records · Page 6Linked to original sources
PubMed1996

Do the results of systematic biopsies predict outcome in patients with T1-T2 prostate cancer treated with radiation therapy alone?

OBJECTIVES: The present study examines whether findings from systematic biopsies add any prognostic information in men with clinical Stage T1-T2 prostate cancer treated with external beam radiation therapy alone. METHODS: Seventy-two men with clinical T1-T2 prostate cancer had ultrasound-guided quadrant or sextant prostate biopsies prior to treatment with external beam radiotherapy alone between January 1, 1988 and December 31, 1993. The median follow-up is 23 months (range, 11 to 65). Biochemical failure after irradiation was defined as a prostate-specific antigen (PSA) greater than 1.5 ng/mL (Hybritech assay) and rising. RESULTS: The biochemical relapse-free survival was 90% at 36 months. The percentage of biopsies involved by cancer was not predictive of biochemical relapse-free survival on univariate analysis. Patients with less than 50% positive biopsies had similar biochemical relapse-free survival at 36 months compared to patients with 50% or more positive biopsies (93% versus 89%; P = 0.80). After stratifying according to pretreatment PSA level, the percentage of positive biopsies was not prognostic. A multivariate analysis demonstrated that pretreatment PSA level was the only variable that predicted relapse-free survival (P = 0.01). CONCLUSIONS: At present, the results of ultrasound-guided quadrant or sextant biopsies do not add further prognostic information, beyond that provided by the pretreatment PSA level, in patients with T1-T2 prostate cancer treated with radiation therapy alone. Further follow-up will be required to confirm these results.

Actuarial Analysis↗
PubMed1996

Urinary incontinence following external-beam radiotherapy for clinically localized prostate cancer.

OBJECTIVES: To determine the incidence of urinary incontinence in men with prostate cancer treated with definitive external-beam radiation therapy and to analyze the impact of various patient and treatment variables on the development of urinary incontinence. METHODS: The records of all 758 men who received definitive external-beam radiation therapy at our institution between October 1986 and December 1994 were reviewed. The development of incontinence was recorded and graded according to the Late Effects Normal Tissues/Radiation Therapy Oncology Group (LENT/RTOG) scoring system. RESULTS: Late grade 2 or higher urinary incontinence developed in 4 of 758 patients (0.5%) (3 grade 2; 1 grade 3). The actuarial urinary incontinence rate was 1.3% at 5 years. Patients with a history of prior transurethral resection of the prostate (TURP) had higher rates of urinary incontinence than patients without prior TURP (prior TURP 3 of 132 [2%] versus 1 of 626 [0.2%]; P = 0.02). CONCLUSIONS: Urinary incontinence following definitive external-beam radiation therapy for clinically localized prostate cancer is a rare event. Previous TURP increases the risk of incontinence, although the risk remains low. There is no evidence that higher doses to the prostate using conformal techniques are associated with an increased risk of urinary incontinence.

Aged↗
PubMed1996

Amebic keratitis in a wearer of disposable contact lenses due to a mixed Vahlkampfia and Hartmannella infection.

PURPOSE: To support the hypothesis that Acanthamoeba is not a unique cause of amebic keratitis, we report a case of amebic keratitis in which viable Acanthamoeba could not be isolated from corneal tissue. Vahlkampfia and Hartmannella, two other genera of free-living ameba, were isolated, however, using prolonged culture. METHODS: A 24-year-old wearer of soft contact lenses had keratitis. Extensive histologic and microbiologic investigations were performed on corneal scrape, biopsy, and keratoplasty tissue. Contact lenses, storage case, and the home water supply, where contact lens hygiene was practiced, were examined for the presence of micro-organisms. RESULTS: No viruses, pathogenic bacteria, or fungi were detected from corneal tissue samples. Amebae were observed using light and electron microscopy, but these could not be unequivocally classified using immunocytochemical staining. Viable Vahlkampfia and Hartmannella, but no Acanthamoeba, were isolated from the corneal biopsy sample. Indirect immunofluorescence with a range of polyclonal rabbit antisera raised against axenically cultivated stains of the three amebal genera was unhelpful because of cross-reactivity. A diverse range of micro-organisms was present within the storage case, including the three amebal species. Amebic cysts also were associated with the contact lens. CONCLUSION: A mixed non-Acanthamoeba amebic keratitis has been identified in a wearer of soft contact lenses where lack of storage case hygiene provided the opportunity for the free-living protozoa Vahlkampfia and Hartmannella to be introduced to the ocular surface. When Acanthamoeba-like keratitis occurs, but where Acanthamoeba cannot be isolated using conventional laboratory culture methods, alternate means should be used to identify other amebae that may be present. Polyclonal immunofluorescent antibody staining was unreliable for generic identification of pathogenic free-living amebae in corneal tissue.

Adult↗
PubMed1996

Prostate specific antigen nadir following external beam radiation therapy for clinically localized prostate cancer: the relationship between nadir level and disease-free survival.

PURPOSE: We determined whether the prostate specific antigen (PSA) nadir achieved following external beam radiation therapy alone predicts biochemical disease-free survival in a large cohort of men with clinically localized prostate cancer. MATERIALS AND METHODS: Between January 1986 and October 1993, 364 men with clinically localized, stages T1 to T3 adenocarcinoma of the prostate received definitive external beam radiation therapy with no prior, concomitant or adjuvant endocrine therapy. PSA was measured before treatment in 326 men (90%) and serial PSA was measured following treatment in all patients. All men were followed continuously for at least 24 months (median 44 months, range 24 to 90, mean 46). Biochemical failure after irradiation was defined as PSA of 1.5 ng./ml. or more and 2 consecutive serum PSA elevations. RESULTS: The 5-year overall biochemical disease-free survival rate for the entire group was 56%. PSA nadir was predictive of subsequent biochemical disease-free survival. The biochemical disease-free survival rate at 3 years was 93, 49 and 16% for PSA nadirs of 0 to 0.99, 1 to 1.99 and 2 or more ng./ml., respectively (p = 0.0001). In a multivariate analysis PSA nadir (0 to 0.99 versus 1.0 to 1.99 versus 2 or more ng./ml.) was an independent predictor of biochemical disease-free survival along with pretreatment PSA, central axis dose, Gleason grade and T stage. CONCLUSIONS: PSA nadir after radiation therapy is an indicator of subsequent biochemical disease-free survival. Patients who achieve a nadir of less than 1 ng./ml. following external beam radiation therapy have a favorable biochemical disease-free survival rate, while those with a nadir of greater than 1 ng./ml. have a high subsequent failure rate. Strategies to improve results should focus on techniques to increase the likelihood of achieving a PSA nadir of less than 1 ng./ml.

Actuarial Analysis↗
PubMed1996

Multidrug resistance in ocular melanoma.

AIMS/BACKGROUND: Metastatic disease in patients with ocular melanoma is resistant to chemotherapy. One of the main mechanisms of modulating multidrug resistance is the expression of the multidrug resistance gene 1 (MDR1) product (p-glycoprotein) by tumour cells. The purpose of this study was to evaluate the frequency of expression of the MDR1 gene in ocular melanoma whose primary treatment was surgical excision or enucleation. METHODS: Twelve recent ocular melanomas were received fresh, snap frozen and cryostat sections of tumour were analysed for expression of MDR1 by immunohistochemistry using a well characterised monoclonal antibody to MDR1. Tumour explants were established in short term tissue culture from four tumours and cell blocks were examined by immunohistochemistry. RESULTS: MDR1 expression was present in five of 12 ocular melanomas. Upregulation of protein expression was found in four cell lines established in short term culture from tumour explants. A recurrent tumour, initially treated by local excision and radioactive plaque, showed overexpression of MDR1 mRNA. CONCLUSIONS: These results suggest that significant level of MDR1 may be intrinsically present in ocular melanomas before exposure to drugs involved in multidrug resistance, and indicate the possible importance of MDR1 in modulating chemoresistance in ocular melanoma. Chemosensitisation may be of potential value in planning adjuvant chemotherapy for patients with metastatic disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Systematic biopsies: do they add prognostic information in men with clinically localized prostate cancer treated with radiation therapy alone?

PURPOSE: To determine whether systematic biopsy can help predict treatment outcome in men with clinically localized prostate cancer treated with external-beam radiation therapy alone. MATERIALS AND METHODS: Two hundred twenty-four men with clinically localized prostate cancer underwent ultrasound-guided systematic biopsies before undergoing external-beam radiation therapy. Median follow-up was 25 (range, 4-80) months. Treatment failure after irradiation was defined as a prostate-specific antigen (PSA) level greater than 1.5 ng/mL and rising. RESULTS: Univariate analysis demonstrated that the percentage of biopsy specimens involved by cancer was predictive of relapse-free survival. Patients in whom more than 50% of biopsy specimens were positive had significantly lower relapse-free survival rates at 36 months than patients with 50% or fewer positive biopsy specimens. After stratifying patients according to pretreatment PSA level, however, the percentage of positive biopsy specimens was no longer prognostic. Multivariate analysis demonstrated that pretreatment PSA level was the only variable that enabled prediction of relapse-free survival. CONCLUSION: Systematic biopsy added little further prognostic information beyond that provided by pretreatment PSA level. A larger series with longer follow-up is necessary to verify these results.

Adenocarcinoma↗
PubMed1996

Patterns-of-failure analysis of patients with high pretreatment prostate-specific antigen levels treated by radiation therapy: the need for improved systemic and locoregional treatment.

PURPOSE: The patterns of failure (local and/or regional v metastatic) have been determined for patients with prostate cancer and pretreatment prostate-specific antigen (PSA) levels > or = 20 ng/mL treated with radiation alone with the purpose to design appropriate multimodal treatments. MATERIALS AND METHODS: One hundred twenty patients with pretreatment PSA levels > or = 20 ng/mL were treated with external-beam radiation alone between February 1988 and October 1993. They were arbitrarily divided by PSA levels, 20 to 29.9 ng/mL, 30 to 49.9 ng/mL, and > or = 50 ng/mL, and analyzed in terms of freedom from any failure (no evidence of biochemical disease [bNED], and PSA level < 1.5 ngm/mL and not increasing), as well as freedom from imaging evidence of distant metastasis (fdm). RESULTS: There was no significant difference in short-term outcome by pretreatment PSA level, and thus all patients were pooled for analysis. At 4 years, 81% were fdm and 28% were free of any failure. This suggests that approximately 50% have recurred with local and/or regional disease or undetectable metastatic disease. Multivariate analysis indicated that low palpation stage and higher center of prostate dose were associated with better bNED survival. Multivariate analysis indicated that increasing stage and younger age are significantly associated with increasing distant metastasis. CONCLUSION: Patients with pretreatment PSA levels > or = 20 ng/mL are not optimally treated by irradiation alone. The pattern of failure suggests improvement may come from systemic treatment of metastatic disease and high-dose radiation to improve locoregional disease. To evaluate this, we have begun a multimodal trial of chemohormonal therapy followed by extended-field irradiation.

Analysis of Variance↗
PubMed1996

Short communication: CT-MRI image fusion for 3D conformal prostate radiotherapy: use in patients with altered pelvic anatomy.

We describe the application of CT-MRI fusion software for 3D conformal radiotherapy in two patients with localized prostate cancer who had significantly altered pelvic anatomy due to prior surgery. Patient A had a hemipelvectomy for fibrosarcoma and Patient B had an abdominoperineal resection (APR) for rectal carcinoma. Using the Picker AcQSIM 3D treatment planning software equipped with CT-MRI fusion capabilities, we were able to construct 3D conformal treatment plans for the two patients. The CT-MRI fusion was invaluable in the 3D conformal treatment planning of these cases with distorted pelvic anatomy. It allowed for accurate identification of the clinical target volume (CTV) and was also able to better visualize normal structures so that the radiation beams could be placed to minimize toxicity to the normal tissues.

Adenocarcinoma↗
PubMed1996

Keratokyphosis in rabbits: a functional and morphologic study.

Keratokyphosis, a "nonfreeze keratomileusis" procedure, was applied in rabbits. The refractive changes were -6.5 +/- 0.7 (SD), -9.5 +/- 2.6, and -13.0 +/- 3.2 D for convex applanation surfaces with a vertex of +100 microns, +125 microns, and +150 microns in the microkeratome and +1.5 +/- 2.0 and +2.5 +/- 2.6 D for concave applanation surfaces with a vertex of -100 microns and -125 microns. The pachymetric corneal changes were +43 +/- 24 microns, +39 +/- 32 microns, and +71 +/- 24 microns for the convex applanation surfaces and -21 +/- 40 microns and -17 +/- 24 microns for the concave. Wound healing was uncomplicated. The scar at the interface was 0-5 microns wide. The mean central density of nerve endings was 1,255 +/- 532/mm2. The endothelial cell size was 25.1% (p < 0.01) greater as measured by specular microscopy than by vital preparation technique; this difference was greater with higher (33.4%) than with lower (18.02%) corneal refraction (p = 0.02). In addition, there was a method-independent correlation (correlation coefficient, -0.63) between endothelial cell count and corneal thickness. This may indicate an increased demand on corneal endothelium in thickened corneas.

Animals↗
PubMed1995

Management of extremity soft tissue sarcomas with limb-sparing surgery and postoperative irradiation: do total dose, overall treatment time, and the surgery-radiotherapy interval impact on local control?

PURPOSE: To evaluate potential prognostic factors in the treatment of extremity soft tissue sarcomas that may influence local control, distant metastases, and overall survival. METHODS AND MATERIALS: Sixty-seven patients with extremity soft tissue sarcomas were treated with curative intent by limb-sparing surgery and postoperative radiation therapy at the Fox Chase Cancer Center or the Hospital of the University of Pennsylvania, between October 1970 and March 1991. Follow-up ranged from 4-218 months. The median external beam dose was 60.4 Gy. In 13 patients, interstitial brachytherapy was used as a component of treatment. RESULTS: The 5-year local control rate for all patients was 87%. The 5-year local control rate for patients who received < or = 62.5 Gy was 78% compared to 95% for patients who received > 62.5 Gy had larger tumors (p = 0.008) and a higher percentage of Grade 3 tumors and positive margins than patients who received < or = 62.5 Gy. The 5-year local control rate for patients with negative or close margins was 100% vs. 56% in patients with positive margins (p = 0.002). Cox proportional hazards regression analysis was performed using the following variables as covariates: tumor dose, overall treatment time, interval from surgery to initiation of radiation therapy, margin status, grade, and tumor size. Total dose (p = 0.04) and margin status (p = 0.02) were found to significantly influence local control. Only tumor size significantly influenced distant metastasis (p = 0.01) or survival (p = 0.03). CONCLUSION: Postoperative radiation therapy doses > 62.5 Gy were noted to significantly improve local control in patients with extremity soft tissue sarcomas. This is the first analysis in the literature to demonstrate the independent influence of total dose on local control of extremity soft tissue sarcomas treated with adjuvant postoperative irradiation.

Adolescent↗
PubMed1995

Incidence of and factors related to late complications in conformal and conventional radiation treatment of cancer of the prostate.

PURPOSE: The fundament hypothesis of conformal radiation therapy is that tumor control can be increased by using conformal treatment techniques that allow a higher tumor dose while maintaining an acceptable level of complications. To test this hypothesis, it is necessary first to estimate the incidence of morbidity for both standard and conformal fields. In this study, we examine factors that influence the incidence of late Grade 3 and 4 morbidity in patients treated with conformal and standard radiation treatment for prostate cancer. METHODS AND MATERIALS: Six hundred sixteen consecutive patients treated with conformal or standard techniques between 1986 and 1994 to doses greater than 65 Gy and with more than 3 months follow-up were analyzed. No patients treated with prostatectomies were included in the analysis. The conformal technique includes special immobilization by a cast, careful identification of the target volume in three dimensions, localization of the inferior border of the prostate using a retrograde urethrogram, and individually shaped portals that conform to the Planning Target Volume (PTV). Multivariate analysis using a proportional hazards model compares differences in the incidence of Radiation Therapy Oncology Group/European Organization for Research and Center Treatment (RTOG/EORTC) Grade 3 and 4 late gastrointestinal (GI) and genitourinary (GU) morbidity by technique, T-stage, grade, age, hormonal treatment, irradiated volume, dose, and comorbid conditions. Grade 3 rectal bleeding was defined as requiring three or more cautery procedures. RESULTS: The overall actuarial incidence of genitourinary (GU) toxicities at 5 years was 3.4%, with the crude incidence being six cases in 616 patients satisfying the selection criteria; for gastrointestinal (GI) toxicities, the overall actuarial incidence was 2.7%, with the crude incidence being 13 cases out of 616 patients. The average time to complication for our patients was 12.8 months for GI toxicity and 32.9 months for GU toxicity (p < 0.001). No factors were found that were predictive for GU morbidity. The only factors significantly related to incidence of late GI morbidity on multivariate analysis of our data were dose and age. The central axis dose was a more significant variable than the dose prescribed to the Treated Volume. Age was negatively correlated with late GI morbidity, with older patients having a reduced incidence of toxicity. The median tolerance dose for GI complications was estimated to be 92.8 Gy, and the dose for 10% incidence was estimated to be 80.2 Gy. Treating the pelvis to 45 Gy did not increase the incidence of late morbidity. Late GI and GU toxicities were not correlated. CONCLUSION: The conformal technique has been associated with fewer acute Grade 2 toxicities (6). The use of conformal fields did not decrease the incidence of late GI morbidity; however, patients with this technique invariably had higher doses. Because of the dose response for this complication and the correlation between the dose and the use of conformal fields, one would not expect to demonstrate an advantage to conformal fields in this data set. On the other hand, no dose effect was observed for late GU morbidity. In this case, there appears to be an advantage for conformal treatment that has not reached statistical significance because the follow-up time is shorter than for the patients treated with conventional fields and the latency for GU morbidity is long.

Aged↗
PubMed1995

Amino acids important in enzyme activity and dimer stability for Drosophila alcohol dehydrogenase.

We have determined the nucleotide sequences of eight ethyl methanesulphonate-induced mutants in Drosophila alcohol dehydrogenase (ADH), of which six were previously characterized by Hollocher and Place [(1988) Genetics 116, 253-263 and 265-274]. Four of these ADH mutants contain a single amino acid change: glycine-17 to arginine, glycine-93 to glutamic acid, alanine-159 to threonine, and glycine-184 to aspartic acid. Although these mutants are inactive, three mutants (Gly17Arg, Gly93Glu and Gly184Asp) form stable homodimers, as well as heterodimers with wild-type ADH, in which the wild-type ADH subunit retains full enzyme activity [Hollocher and Place (1988) Genetics 116, 265-274]. Interestingly, the Ala159Thr mutant does not form either stable homodimers or heterodimers with wild-type ADH, suggesting that alanine-159 is important in stabilizing ADH dimers. The mutations were analysed in terms of a three-dimensional model of ADH using bacterial 20 beta-hydroxysteroid dehydrogenase and rat dihydropteridine reductase as templates. The model indicates that mutations in glycine-17 and glycine-93 affect the binding of NAD+. It also shows that alanine-159 is part of a hydrophobic anchor on the dimer interface of ADH. Replacement of alanine-159 with threonine, which has a larger side chain and can hydrogen bond with water, is likely to reduce the strength of the hydrophobic interaction. The three-dimensional model shows that glycine-184 is close to the substrate binding site. Replacement of glycine-184 with aspartic acid is likely to alter the position of threonine-186, which we propose hydrogen bonds to the carboxamide moiety of NAD+. Also, the negative charge on the aspartic acid side chain may interact with the substrate and/or residues in the substrate binding site. These mutations provide information about ADH catalysis and the stability of dimers, which may also be useful in understanding homologous dehydrogenases, which include the human 17 beta-hydroxysteroid, 11 beta-hydroxysteroid and 15-hydroxyprostaglandin dehydrogenases.

Alcohol Dehydrogenase↗
PubMed1995

Conformal treatment of prostate cancer with improved targeting: superior prostate-specific antigen response compared to standard treatment.

PURPOSE: Conformal radiation therapy (CRT) decreases the morbidity of prostate cancer treatment, but no published data attest to the improved ability of CRT to control disease. Therefore, we compared Prostate-Specific Antigen (PSA) response at 1 year among similarly staged patients treated by conformal techniques to those treated with conventional approaches, looking for an early indicator of tumor response. METHOD AND MATERIALS: Patients with locally advanced disease were treated by pelvic field followed by prostate field conedowns; those with early stage/low grade disease received only prostate field irradiation. Between October, 1987 and November, 1991, conventional treatments used rectangular beams with or without corner blocks. Neither urethrography nor immobilization casts were used for conventionally treated patients. Between April, 1989 and December, 1992, conformal treatments have used rigid immobilization and Computed Tomography-based, beams-eye-view field design. As such, our conformal approach allowed improved targeting. Median prescribed doses (minimal doses to the Planning Target Volume) were 70 Gy (66-73 Gy) and 70.2 Gy (64.8-75 Gy) for conventionally and conformally treated patients, respectively. Median daily fraction size was 1.8 Gy for conventional treatment and 2.0 Gy for conformal therapy. Baseline PSA data were available on 170 consecutive patients treated conformally and 90 consecutive patients treated conventionally. RESULTS: Among those receiving only prostatic field irradiation, 12-month PSA values returned to normal in 96% and 85% of conformally and conventionally treated patients, respectively, when normalization was defined as < or = 4 ng/ml (p < 0.03) and in 76% vs. 55% of patients when PSA normalization was defined as < or = 1.5 ng/ml (p < 0.02). Among those receiving pelvic irradiation prior to prostatic conedown, PSA normalization (< or = 4 ng/ml) occurred in 82% and 61% (p < 0.01) of conformally and conventionally treated patients, respectively, and in 56% vs. 38% of patients when normalization was defined as < or = 1.5 ng/ml (p < 0.05). In a multivariate analysis, pretreatment PSA level (< or = 15 vs. > 15), and the use of conformal irradiation were statistically significant prognostic discriminants of PSA normalization at 1 year while total irradiation dose, clinical stage, and the addition of pelvic fields were not significant. CONCLUSIONS: As measured by PSA normalization, conformal techniques with improved targeting produced responses that were significantly better than conventional techniques among patients treated with definitive irradiation. These results, coupled with our previously documented reduction of acute and chronic sequelae, support the continued use of CRT as a more effective method of treatment for prostate cancer.

Humans↗
PubMed1995

Observations of pretreatment prostate-specific antigen doubling time in 107 patients referred for definitive radiotherapy.

PURPOSE: To determine pretreatment prostate-specific antigen doubling times (PSADT) in patients referred for definitive radiotherapy. METHODS AND MATERIALS: One hundred and seven patients with histologically proven nonmetastatic prostate cancer and an elevated prostate-specific antigen (PSA) who were referred for radiation therapy had three serum PSA values obtained prior to the start of definitive therapy. Prostate-specific antigen doubling times were calculated by linear regression. RESULTS: Prostate-specific antigen values increased during the period of observation in 78 patients (73%). Forty-three patients (40%) had calculated PSADT of less than 2 years and of those patients with pretreatment serum PSA values of greater than 10 ng/mL more than 50% has calculated PSADT of less than 2 years. CONCLUSIONS: A significant minority of patients referred for radiotherapy have calculated PSADT of less than 2 years. The significance of this relatively fast growth rate is as yet undetermined, but suggests that patients referred for radiotherapy may have aggressive disease prior to treatment.

Adenocarcinoma↗
PubMed1995

Abnormal extracellular material in the levator palpebrae superioris complex in congenital ptosis.

OBJECTIVE: To determine the pathologic abnormalities of the levator palpebrae superioris in congenital ptosis. METHODS: By means of light and electron microscopy and immunohistochemistry, anterior levator tissue specimen from 15 patients with congenital ptosis excised during routine levator resections were examined. RESULTS: All specimens showed lack of muscle fibers with endomysial and perimysial fibrosis and thickening of the aponeurosis. In addition, in four of the 15 patients, an abnormal extracellular material was present. By light microscopy this appeared as an unusual amorphous material arranged in clumps and bands, and electron microscopy showed it to consist of parallel coarse bundles of fibrillogranular material. Collagen type III and fibronectin were identified within this material by immunohistochemistry. There was no detectable collagen types I, II, IV, V, VI, or VII or laminin, and the material did not stain for actin, myosin, myoglobin, amyloid P component, or amyloid A. CONCLUSIONS: In four of 15 samples of levator palpebrae superioris from patients with congenital ptosis, we identified an unusual amorphous extracellular material that stained positively for collagen type III and fibronectin on immunohistochemistry. This novel material, which we call "amorphocollagenoid," may represent a product of dysgenesis of the levator tissues. The source and full composition of this material merit further study.

Adolescent↗
PubMed1995

Biological basis of germline mutation: comparisons of spontaneous germline mutation rates among drosophila, mouse, and human.

Spontaneous mutation rates per generation are similar among the three species considered here--Drosophila, mouse, and human--and are not related to time, as is often assumed. Spontaneous germline mutation rates per generation averaged among loci are less variable among species than they are among loci and tests and between gender. Mutation rates are highly variable over time in diverse lineages. Recent estimates of the number of germ cell divisions per generation are: for humans, 401 (30-year generation) in males and 31 in females; for mice, 62 (9-month generation) in males and 25 in females; and for Drosophila melanogaster, 35.5 (18-day generation) in males and 36.5 (25-day generation) in females. The relationships between germ cell division estimates of the two sexes in the three species closely reflect those between mutation rates in the sexes, although mutation rates per cell division vary among species. Whereas the overall rate per generation is constant among species, this consistency must be achieved by diverse mechanisms. Modifiers of mutation rates, on which selection might act, include germline characteristics that contribute disproportionately to the total mutation rates. The germline mutation rates between the sexes within a species are largely influenced by germ cell divisions per generation. Also, a large portion of the total mutations occur during the interval between the beginning of meiosis and differentiation of the soma from the germline. Significant genetic events contributing to mutations during this time may include meiosis, lack of DNA repair in sperm cells, methylation of CpG dinucleotides in mammalian sperm and early embryo, gonomeric fertilization, and rapid cleavage divisions.

Animals↗
PubMed1995

Hydrogen peroxide induces microvilli on human retinal pigment epithelial cells in culture.

We have found that hydrogen peroxide (10(-4)-10(-2) M) rapidly induces microvilli on separate cells and confluent sheets of human retinal pigment epithelium in culture. t-butyl hydroperoxide and sodium arsenite do not induce microvilli. A role for hydrogen peroxide as an intercellular messenger has previously been proposed in the inflammatory response, in which hydrogen peroxide from phagocytes may signal to vascular endothelial cells. Our observations thus provide a second example of the induction of what may be a physiological response by this potentially toxic agent. In the retina, hydrogen peroxide released from illuminated photoreceptors may elongate the microvilli which extend into the spaces between them. Increased numbers of microvilli and their protrusion further into the photoreceptor layer may enhance various interactions between the two cell types, including the antioxidant functions of the epithelium.

Aged↗