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Biomedical subjects

S Lai

Publications and source records attributed to S Lai.

At least 73 records · Page 4Linked to original sources
PubMed1999

Expression of p16, Rb, and cyclin D1 gene products in oral and laryngeal squamous carcinoma: biological and clinical implications.

Cyclin D1, p16, and Rb genes play a critical role in the regulation of the G1-S transition of the cell cycle and are frequently altered in several neoplastic entities. Analysis of the protein products of these genes by molecular and immunohistochemical methods provides information on their functional status and allows for the phenotypic evaluation of tumor cells. We performed Western blotting and immunohistochemical analysis on tissues from 35 primary oral and laryngeal squamous carcinoma specimens with previous molecular analysis of the p16 gene and correlated the results with relevant clinicopathologic factors. Our study shows significant concordance between Western blotting and immunostaining results for cyclin D1 (P = .01), p16 proteins (P = .01), and Rb (P = .04). Heterogeneous staining of tumor cells and the positivity of non-neoplastic host elements for Rb by immunohistochemistry contributed to the discrepancy noted in some tumors by Western blotting. Significant reciprocal relationship between p16 and Rb proteins was observed (P < .001); in most tumors, absence of p16 (89%) and detectable Rb (94%) proteins were found. Two tumors had negative cyclin D1 expression, and one third overexpressed this protein. There was a lack of correlation between cyclin D1 overexpression and the clinicopathologic factors studied. Our results indicate that the absence of p16 in most of these tumors may constitute an early tumorigenic event and that the loss of the Rb function plays a minor role in HNSC.

Adult↗
PubMed1999

Age as a prognostic factor for disease recurrence after radical prostatectomy.

OBJECTIVES: To assess whether age has an impact on biochemical recurrence after radical prostatectomy for localized adenocarcinoma of the prostate. METHODS: Four hundred eighty-nine consecutive patients who underwent radical retropubic prostatectomy and did not have metastases to the lymph nodes were retrospectively analyzed. Disease recurrence was defined as a serum prostate-specific antigen greater than 0.2 ng/mL and rising on at least two postoperative measurements. Biochemical progression was compared in patients 70 years old or younger and older than age 70. The Kaplan-Meier estimator and Cox's proportional hazards model were employed to investigate the impact of age on time to recurrence. Neoadjuvant androgen deprivation was treated as a stratification variable in the Cox models. RESULTS: The mean follow-up was 25.4 +/- 20.8 months. The Gleason score and extent of cancer in the pathologic analyses of the prostatectomy specimen was not significantly different between the two groups. Biochemical recurrence was detected in 12% of patients 70 years old or younger and in 25% of those older than 70 (P = 0.01). In multivariate analyses, after adjusting for all prognostic factors, younger age (70 years or younger) was independently associated with a longer time to recurrence (P <0.02). CONCLUSIONS: Our results suggest that age per se may be an independent prognostic factor for disease recurrence after radical prostatectomy. This implies that patients 70 years old or younger are more likely to benefit from surgery. This information may be useful when counseling patients with clinically localized carcinoma of the prostate.

Adenocarcinoma↗
PubMed1999

Positive surgical margins with radical retropubic prostatectomy: anatomic site-specific pathologic analysis and impact on prognosis.

OBJECTIVES: To correlate the extent and location of positive surgical margins after radical prostatectomy with disease progression. METHODS: Data on 495 patients who underwent radical prostatectomy by one surgeon were analyzed. All radical prostatectomy specimens were sectioned entirely using 2 to 3-mm step sections by one pathologist. One hundred fifty-one patients (30.5%) had one or more positive surgical margins and were subjected to further detailed analysis. Recurrence was defined as a serum prostate-specific antigen (PSA) level of 0.2 ng/mL and rising on at least two postoperative measurements. RESULTS: The mean follow-up was 25.3 months (range 3 to 73). The overall recurrence rate was 13.3%. Neoadjuvant hormonal treatment was given to 37 (25%) of those with a positive margin. Patients with positive surgical margins had a significantly higher incidence of recurrence compared with those with negative margins (27.8% versus 6.9%, P = 0.001). The recurrence rate for various locations was 29% apex/urethra, 30% posterior, 33% anterior, 36% lateral, 48% posterolateral, and 57% bladder neck. Time to recurrence was shorter in patients older than 70 years (P<0.055); with a preoperative PSA greater than 10 ng/mL (P<0.0001); with a biopsy Gleason score greater than 7 (P = 0.02); with a prostatectomy Gleason score greater than 7 (P<0.001); with seminal vesicle invasion (P = 0.0001); having more than 1 location of a positive margin (P = 0.002); or having a positive margin at the bladder neck (P = 0.0003) or the posterolateral surface of the prostate (P = 0.02) compared with other locations. Multivariate proportional hazards analyses indicated that age older than 70 (P = 0.005), a prostatectomy Gleason score of 7 (P = 0.015) or 8 to 10 (P = 0.003), and positive margin(s) at the bladder neck (P = 0.003) were independently associated with a shorter time to recurrence among patients with a positive margin. CONCLUSIONS: In our study, among patients with positive surgical margins, those with multiple positive margins, or a margin involving the bladder neck or the posterolateral surface of the specimen carried a higher risk of progression. A positive margin at the bladder neck appears to be the most significant adverse prognostic indicator. This information may help in decisions regarding additional therapy.

Adenocarcinoma↗
PubMed1999

HLA-DRB1*01 and DRB1*04 alleles in Sardinian rheumatoid arthritis patients.

In Sardinia, like in other Caucasoid populations, rheumatoid arthritis (RA) is significantly associated with HLA-DR4 and DR1 antigens. To discover which DR4 and DR1 alleles were associated with the disease we selected 22 Sardinian patients affected by RA. Fifty DR4+ and 28 DR1+ healthy individuals coming from the same geographical area were used as controls. In the Sardinian patients only two DRB1*04 alleles were observed: DRB1*0405 in 11 and DRB1*0403 in three patients. The DRB1*0102 allele was observed in two patients and DRB1*0101 in six patients. Hereditary predisposition to RA in Sardinia therefore seems to be almost exclusively associated with the DRB1*0405 and DRB1*0101 alleles which share the 67LLEQRRAA74-85VG86 epitope in the peptide binding groove.

Alleles↗
PubMed1999

HLA-DMA alleles are possible new markers of rheumatoid arthritis: study of a Corsican group.

The HLA-DMA gene, along with the HLA-DMB gene, encodes the not classical class II molecule. This molecule catalyzes the class-II-associated invariant-chain peptide (CLIP)-antigen peptide exchange in classical class II molecule peptide-binding groove. As such, the DM heterodimer is an antigen presentation regulator and may be linked to immune system deficiencies such as those observed in autoimmune diseases. The study of DMA gene polymorphism seems be a reasonable approach to provide an answer to this question. Thanks to PCR-derived methods, the relationship between DMA gene polymorphism and rheumatoid arthritis (RA) was demonstrated in the present study. The DMA*0101 allele was observed to confer a significant predisposition to RA while the DMA*0102 allele significantly protected from this disease. Polymorphism experiments with the HLA-DRB1 gene revealed that this relationship between DMA polymorphism and RA is not a consequence of a linkage disequilibrium with the HLA-DRB1 alleles implicated in this pathology. The study of the DMA gene could therefore prove to be very useful in the early diagnosis of RA.

Alleles↗
PubMed1999

The effect of marital status on survival in late-stage cancer patients: an analysis based on surveillance, epidemiology, and end results (SEER) data, in the United States.

Recently findings that marital status is associated with survival in patients with late-stage prostate cancer led to an examination of the generalizability of this association for all cancers. We restricted the investigation to patients with late-stage cancer using population-based data collected from 261,070 patients with late-stage cancer at multiple sites in the United States to determine relations between marital status and survival. After controlling for age, race, and treatment, married patients with cancers of all major primary sites had significantly better survival than single, separated, divorced, or widowed patients. Although single and widowed patients had the poorest prognosis in general, single patients appeared to show the most consistently poor survival across the different types of cancers. Survival differences by marital status were more pronounced in men than in women. This observation raises the possibility that some characteristics associated with being married delay death from cancer. These findings require investigators to ask new questions about the effect of being married and its possible correlates, such as general health status, access to health care, and socioeconomic status. Known correlates of marital status, such as available social support and social isolation also merit attention in relation to these findings.

Journal Article↗
PubMed1999

Differential expression of key cell cycle genes (p16/cyclin D1/pRb) in head and neck squamous carcinomas.

Cyclin D1, p16, and Rb are key genes that play critical roles in the control of G1/S cell cycle progression and cellular homeostasis. To assess the differential expression of these genes in the biologic evaluation of head and neck squamous carcinoma (HNSC), we analyzed their protein expression in 11 cell lines and 46 primary tumors by Western blotting and correlated the results with clinicopathologic factors. In all cell lines, reciprocal expression between p16 and cyclin-D1 and Rb proteins was noted; p16 protein was detected in one (9%) cell line that lacked Rb and cyclin D1 and was absent in 10 of the cell lines (91%) that expressed both cyclin D1 and Rb proteins. Similar, albeit less striking, results were obtained in primary tumors: 30 tumors (65%) lacked p16 expression, and 33 tumors (72%) and 38 tumors (83%) expressed Rb and cyclin D1 proteins, respectively. p16 and Rb proteins were inversely expressed in 72% of tumors and in all cell lines. Except for gender and age, no significant correlation between protein expression and the clinicopathologic factors was found. Our results indicate that (1) loss of the p16 protein may constitute an early event in the development of these HNSC, (2) the reciprocal expression of p16 and Rb suggests a tight regulatory interaction between these genes in HNSC tumorigenesis, and (3) alteration in at least one of these genes might be required for HNSC development and progression.

Carcinoma, Squamous Cell↗
PubMed1999

Neoadjuvant Hormonal Therapy Prior to Radical Prostatectomy.

The US T(2b) study of 3 months of neoadjuvant hormonal therapy (NHT) showed a reduction in the likelihood of positive margins from 48% (control group) to 18% in the treated patients. Follow-up at 42 months shows that the cumulative relapse rate (prostate specific antigen) for 129 patients having NHT was not statistically different from that of the 126 control patients. Because the T(2b) study has been criticized for lacking central pathology review, we present a review of a series involving only one surgeon (MS) and one pathologist (FC) of NHT plus prostatectomy (109 patients) v prostatectomy alone (145 patients) with 24 months' follow-up. Positive margins were decreased from 38% in the untreated to 28% in the treated group, the only statistically significant difference in the results. Biochemical recurrence (PSA >0.2 ng/mL) was higher in the treated group, reflecting selection of more aggressive tumors for NHT, but the difference was not statistically significantly. The incidence of extracapsular extension, seminal vesicle invasion, and lymph node metastasis was similar in the two groups. The largest nonrandomized experience with NHT shows a decrease in the incidence of positive surgical margins when used in high-risk patients with clinically localized carcinoma of the prostate. However, it does not have an impact on disease-free survival at a mean 24-month follow-up.

Journal Article↗
PubMed1998

Association of antibody reactivity to ELDKWA, a glycoprotein 41 neutralization epitope, with disease progression in children perinatally infected with HIV type 1.

The association between antibody reactivity to the neutralizing epitope ELDKWA in the transmembrane glycoprotein gp41 and disease progression was investigated in 29 children perinatally infected with HIV-1. Levels of antibody reactivity to this epitope, measured over time, were associated with absolute CD4+ lymphocyte numbers and disease status, and inversely associated with the levels of acid-dissociated p24 antigen in the plasma. Early virus isolates from 10 of 12 children with no detectable antibody reactivity to this epitope were sequenced. Only three contained sequences that differed from the consensus, indicating that this epitope is well conserved in this population. None of these three children developed antibodies to the autologous sequences, indicating that at least 80% of children with negative antibody reactivity to this epitope were true nonresponders. Together, these results indicate that the ELDKWA determinant could be an important component in the formulation of a vaccine or for immunotherapeutic approaches to HIV-1 infection.

Amino Acid Sequence↗
PubMed1998

Three-dimensional spiral fMRI technique: a comparison with 2D spiral acquisition.

A comparison study was performed of 3D and 2D spiral k-space fMRI techniques using BOLD contrast with a 4.25-min finger-tapping task paradigm. The 3D sequence uses the conventional 2D spiral technique in conjunction with Fourier phase encoding in the slice select direction. Characteristics that were compared included image appearances, signal-to-noise ratio (SNR), fluctuation noise, functional contrast-to-noise ratio (fCNR), detected activation areas, inflow effect, and large vessel involvement. The results showed that, with constant total scan time, the 3D spiral acquisition has higher SNR and fCNR despite its slightly higher fluctuation noise. The capability for thin-slice incoherent averaging is a further advantage of 3D over 2D. With these advantages as well as its intrinsic ability for contiguous slices and image reformatting, the 3D spiral fMRI technique may be superior to its 2D counterpart.

Brain Mapping↗
PubMed1998

In vivo measurement of changes in venous blood-oxygenation with high resolution functional MRI at 0.95 tesla by measuring changes in susceptibility and velocity.

High-resolution functional imaging experiments at 0.95 Tesla have been performed to determine the changes in oxygen saturation in pial veins during motor activation by measuring both flow and susceptibility changes in the blood. Averaging across subjects, mean values for the change of the oxygenation level, deltaY = 0.16 +/- 0.08 (n = 7) and deltaY = 0.13 +/- 0.09 (n = 4), were obtained from the susceptibility sensitive and the flow sensitive acquisitions, respectively. The results suggest that the increase in blood flow is largely uncoupled from the oxygen consumption. The quoted errors reflect mainly the intersubject variability. In addition, low-resolution echo planar imaging (EPI) measurements were performed on the same volunteers to quantify signal intensity changes. Using the measured change in oxygenation, the observed signal changes in the EPI experiments can be attributed to a 5% venous blood volume.

Adolescent↗
PubMed1998

Self-navigated spiral fMRI: interleaved versus single-shot.

This study compares the measured activation volumes in motor cortex as well as the fluctuation noise and off-resonance characteristics for 1-, 2-, and 4-shot spiral gradient-recalled echo blood oxygen level dependent contrast functional magnetic resonance imaging (fMRI) acquisitions, under conditions of constant resolution and scan time and with two readout durations. Reconstructions were made with and without self-navigator correction. It was found that the navigator correction provided a 50% reduction in image fluctuation noise with 4-shot acquisitions, and that multishot acquisitions perform as well as single-shot techniques when self-navigation is employed. An analysis of blurring showed that off-resonance delta f causes blurring when delta f > 1/(2*Tad), where Tad is the readout duration. Off-resonance effects were readily corrected during reconstruction with retrospective linear shim, even with the longer readout duration needed for single-shot methods. With navigator and shim correction, single-shot and multishot spiral methods are highly effective for fMRI acquisitions.

Algorithms↗
PubMed1998

Dimensions of quality of life in prostate cancer.

PURPOSE: Quality of life research in prostate cancer involves the use of many questionnaires and specific items that may be partly redundant. We examine dimensions of quality of life in prostate cancer in the hope of somewhat simplifying communication of basic information. MATERIALS AND METHODS: We analyzed cross-sectional survey data on quality of life in patients with prostate cancer belonging to a Southern California HMO. Quality of life was assessed with the University of California, Los Angeles prostate cancer index. Scree plot and parallel analysis were used to identify factors for extraction and orthogonal (varimax) rotation to examine scale loadings. RESULTS: Four extracted factors explained a cumulative variance of 86%. The 8 physical and emotional scales loaded on 1 general factor explained 41% of the cumulative variance. Urinary function and bother, sexual function and bother, and bowel function and bother scales loaded on factors explained 16, 15 and 14% of the cumulative variance, respectively. CONCLUSIONS: The observation of only 1 general quality of life factor diverges from consistent previous observations of distinct physical and emotional factors in other types of patients, and the tight interaction of emotional and physical scales supports the vulnerability hypothesis, "with age the increasing interactions across dimensions of health leave a patient vulnerable in all when any is affected." The tight interaction of physical and emotional scales in these but not other patients opens the door theoretically to better evaluation of and targeting of health services for patients with prostate cancer.

Aged↗
PubMed1998

HLA-B35 frequency variations correlate with malaria infection in Sardinia.

The hypothesis of a possible selective role of malaria in HLA allele frequency variations was investigated in Sardinia by typing completely 1,039 individuals for HLA: 536 from six lowland villages exposed to malaria until 1948, and 503 from six highland villages with no history of malaria. Another 1,928 individuals from 136 villages scattered all over the island were studied to establish if the HLA allele frequencies among villages correlated with the malaria incidence and/or altitude above sea level. Only the HLA-B35 allele yielded significantly higher frequencies in the lowland versus the highland villages (P<1 x 10(-5)). The observed B35 variance was 9.5 times higher than expected in the absence of selection, showing an adaptive origin. The highly significant positive correlation found between HLA-B35 frequency and malaria in 136 villages suggests that malaria has been the selective factor for HLA-B35 in Sardinia.

Alleles↗
PubMed1998

Uncoupling of the autonomic and cardiovascular systems in acute brain injury.

We hypothesized that acute brain injury results in decreased heart rate (HR) variability and baroreflex sensitivity indicative of uncoupling of the autonomic and cardiovascular systems and that the degree of uncoupling should be proportional to the degree of neurological injury. We used HR and blood pressure (BP) power spectral analysis to measure neuroautonomic regulation of HR and BP and the transfer function magnitude (TF) between BP and HR as a measure of baroreflex modulation of HR. In 24 brain-injured patients [anoxic/ischemic injury (n = 7), multiple trauma (n = 6), head trauma (n = 5), central nervous system infection (n = 4), and intracranial hemorrhage (n = 2)], neurological injury and survival was associated with low-frequency (0.01-0.15 Hz) HR and BP power and TF. Brain-dead patients showed decreased low-frequency HR power [0. 51 +/- 0.36 (SE) vs. 2.54 +/- 0.14 beats/min2, P = 0.03] and TF [0. 61 +/- 0.16 (SE) vs. 1.29 +/- 0.07 beats . min-1 . mmHg-1, P = 0.05] compared with non-brain-dead patients. We conclude that 1) severity of neurological injury and outcome are inversely associated with HR and BP variability and 2) there is direct evidence for cardiovascular and autonomic uncoupling in acute brain injury with complete uncoupling during brain death.

Acute Disease↗