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P Diamond

Publications and source records attributed to P Diamond.

At least 19 recordsLinked to original sources
PubMed1996

Cold shock domain proteins repress transcription from the GM-CSF promoter.

The human granulocyte-macrophage colony stimulating factor (GM-CSF) gene promoter binds a sequence-specific single-strand DNA binding protein termed NF-GMb. We previously demonstrated that the NF-GMb binding sites were required for repression of tumor necrosis factor-alpha (TNF-alpha) induction of the proximal GM-CSF promoter sequences in fibroblasts. We now describe the isolation of two different cDNA clones that encode cold shock domain (CSD) proteins with NF-GMb binding characteristics. One is identical to the previously reported CSD protein dbpB and the other is a previously unreported variant of the dbpA CSD factor. This is the first report of CSD factors binding to a cytokine gene. Nuclear NF-GMb and expressed CSD proteins have the same binding specificity for the GM-CSF promoter and other CSD binding sites. We present evidence that CSD factors are components of the nuclear NF-GMb complex. We also demonstrate that overexpression of the CSD proteins leads to complete repression of the proximal GM-CSF promoter containing the NF-GMb/CSD binding sites. Surprisingly, we show that CSD overexpression can also directly repress a region of the promoter which apparently lacks NF-GMb/CSD binding sites. NF-GMb/CSD factors may hence be acting by two different mechanisms. We discuss the potential importance of CSD factors in maintaining strict regulation of the GM-CSF gene.

Amino Acid Sequence↗
PubMed1996

Androgen receptor modulation in benign human prostatic tissue and prostatic adenocarcinoma during neoadjuvant endocrine combination therapy.

Modulation of androgen receptor (AR) expression during neoadjuvant endocrine therapy in human prostates of patients with localized prostate cancer was investigated by immunohistochemistry. In 8 of 15 untreated prostatectomy specimens, the majority of prostatic glandular cells displayed nuclear immunostaining for AR, whereas only 1 of 26 pretreated cases displayed a similar glandular AR expression. Expression of AR in the prostatic stromal compartment of nontreated cases proved to be quite heterogeneous, since 4 of the 15 (27%) examined specimens did not show stromal AR expression. After preoperative neoadjuvant therapy, this value was 68%, although this difference did not reach statistical significance. Prostatectomy specimens of the treated patients contained carcinomas with a higher Gleason score than those of untreated patients. AR expression in carcinomas of treated patients was diminished (P= 0.05), which may be attributed to their relatively lower differentiation grade. The data strongly suggest that neoadjuvant hormone therapy reduces AR expression by nonneoplastic prostatic glandular cells and carcinoma cells by a selective, but incomplete, elimination of AR-positive cells.

Adenocarcinoma↗
PubMed1996

Diagnosis of advanced or noncurable prostate cancer can be practically eliminated by prostate-specific antigen.

OBJECTIVES: To determine the percentage of localized and potentially curable prostate cancers diagnosed at follow-up screening visits compared with the first screening visit. METHODS: Within the context of a prospective screening study performed in randomly chosen men aged between 45 and 80 years, up to 6-year follow-up screening visits have been performed with serum prostate-specific antigen (PSA) measurement and digital rectal examination (DRE) followed by transrectal ultrasonography of the prostate when PSA or DRE is abnormal. RESULTS: Of the 117 prostate cancers diagnosed at 14,554 annual follow-up visits, only 1 cancer (0.9%) was metastatic compared with 8% (26/322) at 8029 first visits. Moreover, 97% of the cancers detected at follow-up visits could be identified by PSA alone compared with 86% at first visit. The incidence of 0.8% per year during 15 years of screening between the ages of 55 and 70 years would diagnose localized prostate cancer in 12% of the population, a value not too different from the 10% diagnosed with prostate cancer during life-time in the absence of screening. CONCLUSIONS: The present data show that annual screening with PSA diagnoses clinically localized prostate cancer in more than 95% of cases, thus almost completely eliminating the diagnosis of metastatic prostate cancer. Moreover, the number of prostate cancers diagnosed is not significantly increased by screening.

Aged↗
PubMed1996

Effect of neoadjuvant endocrine therapy (combined androgen blockade) on normal prostate and prostatic carcinoma. A randomized study.

The morphologic changes induced by neoadjuvant combination endocrine therapy were evaluated in prostatectomy specimens from patients diagnosed with localized prostate cancer. These patients participated in a prospective, randomized clinical trial investigating the effect of 3 months of combination therapy with flutamide and an LHRH agonist prior to radical prostatectomy versus radical prostatectomy alone. Ninety-six radical prostatectomy specimens processed according to the same protocol were evaluated without knowledge of prior treatment. Forty-seven patients were randomly assigned to the neoadjuvant combination therapy group and 49 to the control arm. Compared with the control group, several changes were strongly and significantly associated with exposure to neoadjuvant combination therapy. The nonmalignant prostatic tissue showed strong prominence and hyperplasia of the basal cell layer, accompanied by epithelial cell vacuolization and markedly reduced occurrence of prostatic intraepithelial neoplasia (p < 0.001) after combination therapy. Prostate cancer tissue, on the other hand, showed smaller nucleoli (p < 0.001), cell vacuolization (p < 0.001), rare intraluminal crystalloids (p < 0.001), higher Gleason grade (p < 0.001), lower prevalence of capsular penetration (p < 0.001), and less frequent invasion of the perineural spaces (p < 0.001) and surgical margins (p = 0.002). Tumor volume, was also reduced by more than 40% in the treated group (p = 0.007). The present findings show that preoperative endocrine combination therapy induces highly characteristic changes in both nonmalignant and cancerous prostatic tissue. Furthermore, following endocrine treatment, the surgical margins are less likely to be involved by cancer and capsular penetration is reduced.

Adult↗
PubMed1996

The relationship between parental communication deviance and relapse in schizophrenic patients in the 1-year period after hospital discharge. A pilot study.

The present pilot study examined the ability of parental communication deviance (CD) to predict relapse in schizophrenic patients in the 1-year period after hospital discharge. Measures of CD were obtained from verbatim transcripts of family problem-solving discussions for 20 schizophrenic patients and their parents at an initial assessment and before the patients' hospital discharge. Relapse was assessed using the Brief Psychiatric Rating Scale at 3-month intervals after discharge. Findings indicated that parental CD measured at an assessment immediately before the patient's release from the hospital was moderately correlated (r = .49, p < .05) with relapse in the 1-year follow-up period. Results are discussed with respect to the possible role of parental CD as an environmental stressor in the period after discharge. Potential contributors to parental CD, including genetically transmitted cognitive deficits and stress resulting from resuming the care-giver role, are also discussed.

Adult↗
PubMed1996

[Validation of a French adaptation of the international prostatic symptom score].

OBJECTIVE: To evaluate the reliability and the validity of a French Canadian version of the International Prostatic Symptom Score. DESIGN: Between November 23, 1993 and April 8, 1994, a self-administered questionnaire was submitted to a group of men on two occasions at an interval of at least one week. This questionnaire was composed of seven questions designed to score the severity of prostatic symptoms and two questions designed to score quality of life. CONTEXT: Family medicine unit and prostatic cancer screening programme of the hormonal treatment clinic of the Laval University hospital centre. PARTICIPANTS: Men between the ages of 50 and 80 years presenting for prostatic cancer screening or for a family medicine visit were invited to participate. A total of 207 men answered the questionnaire on the first occasion and all but two answered the questionnaire on the second occasion. MAIN ASSESSMENT CRITERIA: The internal consistency of the scale, its test-retest stability, the correlation between the prostatic symptom index of the scale and the quality of life index and the urine output were estimated. RESULTS: The internal consistency of the scale has found to be good, with Cronbach's coefficient alpha equal to 0.82. Each question of the scale displayed a good test-retest stability, with coefficient Kappa varying between 0.41 and 0.66 according to the question. The correlation coefficient between the prostatic symptom index of the scale and the quality of life index was 0.75 (P < 0.001). An inverse linear relationship was observed between urine output and the prostatic symptom index, with a correlation coefficient of -0.289 (p < 0.001). CONCLUSION: The psychometric qualities of the adapted scale, evaluated during the present study, are similar to the qualities of the original English language I-PSS scale. The present French version of the scale constitutes a reliable and valid tool to assess the severity of prostatic symptoms in the Quebec male population.

Aged↗
PubMed1995

Combination of screening and preoperative endocrine therapy: the potential for an important decrease in prostate cancer mortality.

Prostate cancer is the second cause of cancer death in men in the Western world; its medical and social impact is comparable to that of breast cancer in women. Although it is well recognized that early treatment is the only possibility for reducing the high rate of death from prostate cancer, screening and even early treatment are controversial issues due mainly to arguments based upon old literature and lack of awareness of the significant advances recently made in this field. As it is well known that surgical removal of organ-confined prostate cancer cures the disease, and it has been demonstrated that annual screening with prostate-specific antigen coupled with digital rectal examination followed, when indicated, by transrectal ultrasonography of the prostate more than doubles the proportion of organ-confined disease, screening alone offers the possibility of at least doubling the number of patients curable from prostate cancer or the potential for a cure to an estimated 45% of prostate cancer patients compared to a maximum of 20% in the absence of screening. It is important to mention that screening does not detect small and insignificant cancers, especially when random biopsies are not performed routinely. The critical volume of prostate cancer is estimated at 0.3 cm or a tumor 7.5 mm in diameter, if spherical. Such a tumor should increase serum prostate-specific antigen by 0.5 ng/mL. Contrary to the belief that screening detects cancers that are too small, the fact is that screening detects prostate cancer too late or nonorgan- or nonspecimen-confined cancer in 35-50% of cases. There is, thus, a narrow window when prostate cancer can be detected at a curable stage, and even the best available screening techniques cannot succeed in all cases. It should be mentioned that the recent improvements of the technique of radical prostatectomy have markedly improved the acceptability of surgery. Concerning the recent publicity related to watchful waiting, it is essential to indicate that all such reports support the notion that prostate cancer grows slowly, but steadily and irremediably, with increasing malignancy and risk of distant metastases and death if sufficient time is allowed. Another serious limitation of watchful waiting is that the available prognostic factors have a large margin of error and cannot predict with certainty the rate of progression of the tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgen Antagonists↗
PubMed1995

Downstaging by combination therapy with flutamide and an LHRH agonist before radical prostatectomy.

A total of 161 patients diagnosed as having stage B (134 patients) or C (27 patients) prostate cancer were randomly assigned to radical prostatectomy alone or to 3 months of neoadjuvant combination therapy with the anti-androgen flutamide and an LHRH agonist before radical prostatectomy. Neoadjuvant combination therapy before radical prostatectomy decreased cancer positive surgical margins from 33.8% in the control group to only 7.8%, thus leaving 92.2% of patients with negative margins at surgery for a 39.2% increase in specimen confined disease. Although on average the final stage determined at histopathological examination of the surgical specimen was more advanced than predicted at initial diagnosis in 33.8% of control patients, an opposite observation was made in the group of men who received the 3 month neoadjuvant combination therapy where the final stage, instead of being more advanced, was less advanced than at diagnosis in an average of 21.1% of men for a net 54.9% improvement of staging in favour of combination therapy. On the other hand, organ confined disease increased from 49.3% to 77.8% of patients after 3 months of combination therapy, for a 57.9% increase in the incidence of organ confined disease. Although long term follow up of these patients is required to determine the impact on survival, the marked influence of neoadjuvant combination therapy on the stage of the disease suggests the possibility of a major improvement in the morbidity and mortality from prostate cancer.

Aged↗
PubMed1994

Metastatic prostate cancer pulmonary nodules: beneficial effects of combination therapy and subsequent withdrawal of flutamide.

A case is presented of a middle-aged man suffering from stage D2 prostate cancer with pulmonary metastases who responded favorably, first, to endocrine combination therapy with the antiandrogen flutamide and an LHRH agonist for 5.5 years, and, second, to the subsequent withdrawal of Flutamide at the time of the progression of the disease. This case has several exceptional features: absence of bone metastases, pulmonary metastatic nodules characterized as focal neuroendocrine differentiation, and a positive response to antiandrogen withdrawal upon relapse of metastases after initial positive response. The concept of escape to androgen blockade and development of androgenic hypersensitivity is discussed.

Acid Phosphatase↗
PubMed1994

Child abuse presenting as a thoracolumbar spinal fracture dislocation: a case report.

A child sustained a traumatic thoracolumbar spinal fracture--dislocation with cord compression. A court confirmed the diagnosis of child abuse. There was no history of trauma, and the diagnosis of child abuse was missed by the physicians who first saw the child. Spinal injuries in child abuse are uncommon. They may be symptomatic or asymptomatic, stable or unstable, or occur with or without bony changes on the x-rays. Injuries without a history of trauma may be overlooked if asymptomatic. Radiologic skeletal surveys in suspected abuse should include a minimum of two views of the spine even if the child has no symptoms referrable to the spine. Conversely, a traumatic cause should be considered whenever there is spinal cord injury without vertebral injury. Having a high index of suspicion for abuse while remembering that pediatric spinal injuries may occur in the context of normal x-rays will decrease the likelihood of missed diagnosis, repeated abuse, or complications from delayed immobilization of unstable injuries.

Child Abuse↗
PubMed1994

Changes in serum concentrations of conjugated and unconjugated steroids in 40- to 80-year-old men.

It is well recognized that aging in men is accompanied by a decline in the serum levels of some adrenal and testicular steroids, but little or no attention has focused on the multiple steroid metabolites that are formed by steroid-converting enzymes in target tissues. In the present study, we have examined in detail the serum concentrations of a large series of adrenal and testicular steroids and their most significant metabolites produced in intracrine peripheral tissues. The serum concentrations of 26 conjugated and unconjugated C21-, C19-, and C18-steroids were measured in 2423 men aged 40-80 yr. The serum concentrations of the major circulating adrenal C19-steroids, namely dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), androst-5-ene-3 beta, 17 beta-diol and its sulfate, and androstenedione, decreased by about 60% between the ages of 40-80 yr. The small decrease in the serum concentrations of progesterone and pregnenolone in the presence of increased levels of cortisol and markedly decreased levels of DHEA, androst-5-ene-3 beta, 17 beta-diol, and their polar metabolites suggests that adrenal 17,20-lyase is particularly affected by aging. In addition to a marked decline in the serum concentrations of adrenal C19-steroids, a smaller, but significant, decrease occurred in serum testosterone. However, serum dihydrotestosterone levels remained constant, but the glucuronidated derivatives of dihydrotestosterone metabolites (androstane-3 alpha, 17 beta-diol glucuronide, androstane-3 beta, 17 beta-diol glucuronide, and androsterone glucuronide) were reduced by 45-50%, suggesting that 5 alpha-reductase activity in peripheral tissues may show a compensatory increase during aging. Analysis of the fatty acid esters of DHEA (DHEA-FA) also revealed that these nonpolar steroids markedly decrease between 40-80 yr of age, although such a decrease in DHEA-FA levels was smaller than that in DHEA and DHEA-S, suggesting that the formation of DHEA-FA may be specifically increased during aging. In summary, the present study suggests that in contrast to the marked decline in activity of steroidogenic enzymes in the adrenals and the small decrease in the testis, the activity of the steroid-converting enzymes present in peripheral tissues does not decrease during aging. In fact, the marked decrease in DHEA formation by the adrenals leads to a decrease of about 50% in total androgens in men between the ages of 40-80 yr. Such a decrease probably affects many physiological processes during aging.

Adrenal Glands↗
PubMed1993

Fasciclin I and II have distinct roles in the development of grasshopper pioneer neurons.

We have used a new technique, micro-CALI (chromophore-assisted laser inactivation), to investigate the function of the neural cell adhesion molecules fasciclin I and II in the development of the grasshopper Ti1 neurons. Micro-CALI of fasciclin I results in defasciculation of the Ti1 axons similar to that achieved using large scale CALI (Jay and Keshishian, 1990). The initial point of axon separation corresponds to the site of laser irradiation, and defasciculation always continues distal to this point. Micro-CALI of fasciclin II prevents the initiation of Ti1 axon outgrowth but has no effect on fasciculation. This effect is restricted to a 3 hr interval between cytokinesis and growth cone emergence.

Animals↗
PubMed1993

Optimized strategy for detection of early stage, curable prostate cancer: role of prescreening with prostate-specific antigen.

In 1,002 men aged 45-80 y, 81% of the cancers detectable by serum prostate-specific antigen (PSA), digital rectal examination (DRE), and transrectal ultrasonography (TRUS) were present in a subpopulation (19% of total) identified by serum PSA above the threshold value of 3.0 micrograms/L. This study was extended to 7,350 men using serum PSA and DRE as first approach, followed by TRUS only when 1 of these 2 tests was abnormal. Because the aim of prostate cancer detection is to find cancers at an early, potentially curable stage, it is of major interest that 71.8% of evaluable cancers were clinical stage B; 8.4% and 10.7% were stages C1 and C2, respectively; only 9.2% were stage D (metastatic) at first visit while none was at stage D at follow-up visits. This study, the first performed in an unselected, unscreened population, shows that serum PSA is the most sensitive technique to identify men at high risk of having prostate cancer and that 12% more cancers can be found at first visit by doing DRE in addition to PSA. Follow-ups can be done every second year using serum PSA alone, as 97% of the cancers detected at annual follow-up by DRE + PSA were PSA+. Cancers are discovered by the present approach at an estimated cost of $2,665 per cancer. Such cancers are potentially curable in at least 80% of cases detected at first visit and in 97% of cases at follow-up. This strategy offers the possibility to improve markedly morbidity and mortality from prostate cancer, presently the second leading cause of cancer death in North American men.

Aged↗
PubMed1993

Major advantages of "early" administration of endocrine combination therapy in advanced prostate cancer.

Combination therapy with the antiandrogen flutamide and the luteinizing hormone-releasing hormone (LHRH) agonist [D-Trp6, des-Gly-NH2(10)] LHRH ethylamide or orchiectomy was administered to 268 patients with previously untreated metastatic stage D2 prostate cancer for an average of 1,191 d (3.26 y). Only 17 of the 268 evaluable patients (6.5%) showed no objective positive response to the combination therapy assessed according to the National Prostatic Cancer Project objective criteria of response. The median duration of the disease-free response was 2.23 y and median overall survival was 3.58 y. The median survival for patients with only 1-5 bone metastases was not yet reached at 8 y, but for patients with 6-10 bone lesions, 11-40 bone lesions, and multiple bone metastases (superscan), median survival was markedly reduced to 3.56, 2.36, and 1.76 y, respectively. Analysis of patients according to general symptomatology, pain, and performance status showed median survivals of 5.47, 2.71, and 2.1 y for minimal, moderate, and severe symptoms, respectively. The present data demonstrate that administration of combination therapy to stage D2 prostate cancer patients having 1-5 bone metastases adds a minimum of 4.4 y of good quality life compared with patients whose disease is slightly more advanced. Our findings clearly demonstrate the major importance of starting combination therapy as soon as possible after diagnosis of metastatic prostatic cancer.

Androgen Antagonists↗
PubMed1993

Downstaging of localized prostate cancer by neoadjuvant therapy with flutamide and lupron: the first controlled and randomized trial.

Although the only opportunity to cure prostate cancer is treatment at an early stage, radical prostatectomy has remained relatively unpopular because 40-50% of prostate cancers estimated at diagnosis as confined to the prostate are found to be at a more advanced stage following histopathological analysis of the surgical specimen. This first prospective, randomized trial investigated the potential advantages of 3-month neoadjuvant combination therapy with flutamide and lupron before radical prostatectomy vs. prostatectomy alone in early stage prostate cancer. Cancer-positive margins were reduced from 38.5% (25 of 65) in control patients to only 13.0% (10 of 77) in men who received neoadjuvant combination therapy with the antiandrogen flutamide and the luteinizing hormone-releasing hormone (LHRH) super-agonist Lupron before radical prostatectomy (p = 0.006). Moreover, comparison of the final stage determined by histopathological examination of the surgical specimen with that estimated at diagnosis showed that a more advanced stage (upstaging) was found in 53.8% of controls, but patients who received combination therapy had an opposite effect: a more favorable stage than expected at diagnosis was found in 23.4% of cases (downstaging), a 77.2% advantage of neoadjuvant combination therapy. The concern about radical prostatectomy, underestimation of stage, is thus markedly improved by 3-month neoadjuvant therapy with flutamide and a LHRH superagonist. Cancer-negative margins are expected to be accompanied by a life expectancy not different from that of men of similar age with no prostate cancer; therefore, the present data, combined with efficient detection of early stage prostate cancer, offer the basis for dramatic improvement in the morbidity and mortality of prostate cancer.

Adenocarcinoma↗
PubMed1991

Thermogenic and hormonal responses to palatable protein and carbohydrate rich food.

Simultaneous variations of oxygen consumption, and plasma insulin and norepinephrine were measured during the postprandial cephalic and gastrointestinal phases of feeding in six human subjects following the ingestion of various nutrients. On alternative days the subjects were given foods (1280 kjoules) either rich in carbohydrates (sugar pie) or in proteins (fish). Both nutrients produced an initial (0-40 min) enhanced thermogenesis and an early (2 min) cephalic insulin release. During that period, elevations of plasma norepinephrine were also observed with pie feeding at 10 and 30 min and at 10 min with fish. Palatability ratings indicated that both food items were equally tasting. During the gastrointestinal phase (40 to 120 min) the variations of these same parameters including glucagon seem to be explained by the content in carbohydrates and proteins in the food rather than by its palatability. Indeed during that period the protein meal was more thermogenic and the carbohydrate meal induced the expected insulin secretion. These results suggest that the palatability of the food is responsible for the early cephalic increase in postprandial thermogenesis, and for the insulin and norepinephrine release. During the subsequent gastrointestinal phase the increased thermogenesis is related to the composition of the food which exerts its action by the biochemical processes involved in the disposal of the absorbed nutrients.

Adult↗
PubMed1989

Trait anxiety, submaximal physical exercise and blood androgens.

This study evaluates the relationship between trait anxiety and both androgen and gonadotrophic hormone levels at rest and during severe physical exercise. Twelve volunteers were selected among 160 untrained male collegial students and classified as anxious (N = 6) or non-anxious (N = 6) subjects according to their scores on three trait-anxiety tests (STAI, IPAT, 16 PF). Serum delta 4-androgen (testosterone and delta 4-androstenedione), delta 5-androgen (DHEA and DHEA-SO4) and gonadotrophin (LH and FSH) concentrations were measured by radioimmunoassay before, during and after 20 minutes of intensive bicycle exercise (80% of maximal heart rate). Results indicate significantly lower serum delta 4-androgens in anxious subjects before exercise. However, for each subject and irrespective of his anxiety level, all measured serum androgen concentrations increased significantly during exercise, although delta 4-androstene-dione remained lower in anxious subjects than in non-anxious ones. Serum LH concentrations (but not FSH) were significantly higher in anxious subjects throughout the observation periods. However, exercise induced in each subject a significant decrease in the serum level of both gonadotrophic hormones. The results suggest that trait anxiety level may constitute an important factor that affects both pre-exercise and exercise serum androgen concentrations in untrained subjects.

Adult↗