Biomedical subjects

S C Jacobs

Publications and source records attributed to S C Jacobs.

At least 55 records · Page 3Linked to original sources

PubMed1998

The influence of marital quality and attachment styles on traumatic grief and depressive symptoms.

Few studies have examined the relationship between marital quality and adjustment to the impending loss of a terminally ill spouse. Most studies of marital quality and grief have been based on retrospective reports of the marriage rather than pre-loss assessments. Here, we tested the pre-loss cross-sectional effects of having a security-enhancing marriage on traumatic grief and depressive symptoms among 59 caregivers aged 50 and over of terminally ill spouses. We also examined whether insecure attachment styles were associated with traumatic grief and depressive symptoms. Findings suggest that security-increasing marriages and insecure attachment styles put spouses at risk for elevated traumatic grief symptoms. Results also indicate that marital quality and attachment style did not interact and that neither was significantly associated with depressive symptoms. The differences in the relationship of marital quality and attachment styles to the two outcomes suggest that the etiology of traumatic grief and depressive symptoms may be distinct.

Adult↗

PubMed1998

Expression of African swine fever virus envelope protein j13L inhibits vaccinia virus morphogenesis.

The African swine fever virus (ASFV) strain Malawi LIL20/1 open reading frame (ORF) j13L was expressed in vaccinia virus (VV) from a strong synthetic late promoter as either a complete ORF (vSJ1) or lacking codons 1-31 (vSJ2). Each recombinant VV produced a small plaque which rapidly reverted to a normal size upon passage. The yield of infectious virus from a single cycle infection with vSJ1 or vSJ2 was reduced 50- to 100-fold compared to wild-type (wt) and a revertant virus (vSJ5) in which the j13L ORF was removed and the VV thymidine kinase gene restored. PCR analysis of nine spontaneous large plaque revertant viruses, recovered after passage of vSJ1 in BSC-40 cells, showed that six had lost the j13L ORF and the co-inserted beta-galactosidase gene. Three viruses retained the j13L and beta-galactosidase genes, but in each case the j13L protein was not expressed due to a different single base deletion near the 5' end of the j13L coding region which introduced a stop codon a short distance downstream. The formation of intracellular mature virus (IMV) and extracellular enveloped virus was reduced 50- to 75-fold in cells infected with vSJ1 compared to wt VV and revertant vSJ5. Electron microscopy showed aberrant IMV precursor structures in vSJ1-infected cells, and immunoelectron microscopy demonstrated that these structures contained j13L protein. These results indicate that expression of the j13L protein is toxic for VV replication due to interference with VV morphogenesis prior to IMV formation.

African Swine Fever Virus↗

PubMed1998

The use of bladder for total transplant ureteral reconstruction.

PURPOSE: Although complete necrosis of a transplanted renal allograft ureter is uncommon, it is a difficult complication to manage. Long or multisegment ureteral strictures, most commonly ischemic in nature, are formidable problems for the reconstructive surgeon. We reviewed 655 consecutive renal allografts to determine the incidence of these complex ureteral complications, and the effectiveness and morbidity of complete ureteral reconstruction using bladder alone. MATERIALS AND METHODS: Of 20 patients (3.0%) who required ureteral reconstruction 9 had complete ureteral necrosis and 11 had long (4) or multisegment (7) ureteral strictures. Total ureteral reconstruction was performed using a modified Boari flap in 15 patients and direct pyelovesicostomy in 5. All patients were followed postoperatively with renal ultrasound as well as 99mtechnetium mercaptoacetyltriglycine-3 diuretic renal scans. Mean followup was 28 months. RESULTS: All 20 patients had successful reconstruction of the transplant ureter using bladder for substitution. Four patients had persistent dilatation of the renal collecting system without evidence of obstruction as measured by diuretic renal scan (half-time less than 20 minutes). Reflux into the transplant renal pelvis occurred in 6 patients. Two patients had reversible deterioration in renal function secondary to rejection episodes. Of the group reconstructed via Boari bladder flap prolonged stenting (mean 27 days) and prolonged high volume drain output (mean 22 days) were not uncommon. CONCLUSIONS: Complete ureteral reconstruction is a complex problem in the renal allograft recipient. Using the bladder for reconstruction via Boari flap or direct pyelovesicostomy is an effective technique with minimal morbidity.

Constriction, Pathologic↗

PubMed1997

Down-regulation of protein and mRNA expression for transforming growth factor-beta (TGF-beta1) type I and type II receptors in human prostate cancer.

Transforming growth factor-beta (TGF-beta1) is a potent negative regulator of cell growth that transduces signals through interactions with type I and II receptors. Abnormal expression and mutational alterations of these receptors have been observed in several human malignancies. In this study, we investigated the expression of the two types of TGF-beta1 receptors, R-I and R-II, in a normal human prostate, primary prostate adenocarcinoma and lymph nodes with metastatic deposits. Expression of receptor proteins was examined by immunohistochemical analysis in paraffin-embedded prostatic tissue sections, and mRNA expression was determined by Northern blot and RT-PCR analysis. Uniformly strong immunoreactivity for both TGF-beta receptor proteins, R-I and R-II, was exclusively localized to the prostatic glandular epithelium of normal prostates. In contrast, tumor epithelial cells in primary and metastatic prostatic cancer specimens exhibited a weak heterogeneous immunoreactivity for both R-I and R-II receptors; 25% of primary prostatic tumors and 45% of the lymph nodes with metastases were totally negative for R-I and R-II expression, while the rest exhibited a significantly reduced immunoreactivity for both types of receptors compared to the normal prostate (p < 0.05). Moreover, there was a significant decrease in the expression of R-I and R-II mRNA, in all 20 primary prostatic tumors and 4 lymph nodes positive for metastases, indicating that the decreased protein expression was due to down-regulation of gene expression for the two receptors. Our findings imply that decreased expression of TGF-beta1 type I and type II receptors might be involved in prostate tumorigenesis.

Activin Receptors, Type I↗

PubMed1997

Concentrations of specific epithelial growth factors in the urine of interstitial cystitis patients and controls.

PURPOSE: Interstitial cystitis (IC) is a chronic bladder disease for which the etiology is unknown. Because the bladder epithelium is often abnormal in IC, we determined whether the levels of specific urine growth factors postulated to be important for bladder epithelial proliferation are altered in IC. MATERIALS AND METHODS: ELISAs were used to determine levels of epidermal growth factor (EGF), insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), and heparin binding epidermal growth factor-like growth factor (HB-EGF) in urine specimens from women with IC, asymptomatic women without bladder disease, and women with bacterial cystitis. RESULTS: Urine HB-EGF levels were specifically and significantly decreased in IC patients as compared to asymptomatic controls or patients with bacterial cystitis, whether expressed as concentration (amount per volume of urine) or the amount relative to urine creatinine in each specimen. In contrast, urine EGF, IGF1, and IGFBP3 levels were all significantly elevated in IC patients compared to asymptomatic controls. Further, the amounts of urine EGF and IGF1 were also elevated in IC patients as compared to patients with bacterial cystitis, and urine IGFBP3 levels were significantly elevated when expressed per milligram of urine creatinine. CONCLUSIONS: These findings indicate that complex changes in the levels of urine epithelial cell growth factors (EGF, IGF1, and HB-EGF) and a growth factor binding protein (IGFBP3) are associated with IC. While EGF, IGF1, and IGFBP3 levels are either the same or increased in the urine of IC patients as compared to patients with bacterial cystitis or asymptomatic controls, HB-EGF levels are significantly decreased in the urine of IC patients. Understanding the reasons for these changes may lead to understanding the pathogenesis of this disorder.

Adult↗

PubMed1997

Influence of maternal grooming, sex and age on Fos immunoreactivity in the preoptic area of neonatal rats: implications for sexual differentiation.

The medial preoptic area (mPOA) of the hypothalamus contains a sexually dimorphic nucleus (SDN-POA) that is 5-7 times larger in males than females and which contributes to the development and expression of male-specific sex behaviors in adulthood. Aside from a critical role for estrogen, the mechanisms that establish and maintain this sex difference are largely unknown. Differences in the size of the SDN-POA are thought to be related to estrogen-associated effects on programmed cell death (apoptosis) during early neonatal development. The expression of male sex behavior is also influenced by maternal behavior during development. During the postnatal period, the dam grooms the anogenital region of the pups to stimulate urination and defecation; however, male pups are groomed significantly more often than females and this maternal attention influences the expression of normal male sexual behavior in adulthood. Based on these observations, we hypothesized that different amounts of anogenital sensory stimulation might contribute to the sexually dimorphic development of the SDN-POA, specifically by providing for different levels of neuronal activation in the SDN-POA resulting in different degrees of cell death. Two experiments were conducted to test this hypothesis. In the first experiment, male and female rat pups on postnatal day 3 (PN 3) received simulated anogenital grooming with a stiff bristle paint brush. One hour later, the brains were removed and sections through the POA were cut and processed for the immunocytochemical detection of Fos-like immunoreactivity (IR) as an indicator of neuronal activation. In the second experiment, male and female littermates were killed on PN 3, 5, 7 and 12 and the number of Fos-immunoreactive cells and pyknotic cells detected in the SDN-POA were counted and compared. Our data demonstrate that anogenital stimulation on PN 3 results in a rapid induction of Fos-immunoreactive in the POA of both males and females. However, the majority of Fos-immunoreactive cells were located in the ventral POA and were distinctly lacking in the SDN-POA. In experiment 2, again no Fos-immunoreactive cells were detected in the SDN-POA of animals examined on PN 5-12. However, there was an increase in the number of pyknotic cells in the area surrounding and including the SDN-POA of females relative to males at PN 5, 7 and 12. Collectively, the data suggest that (1) anogenital grooming during early postnatal development induces a rapid activation of cells in the ventral mPOA, but not in the SDN-POA of rats, (2) there is a greater incidence of cell death in and around the SDN-POA of females vs. males during neonatal development, particularly toward the end of the hormone-sensitive critical period, and (3) Fos expression does not appear to be correlated with the sexually dimorphic development of, and/or programmed cell death within, the developing SDN-POA.

Aging↗

PubMed1997

Subjective ratings of emotional health as a risk factor for major depression in a community sample.

BACKGROUND: Although subjective ratings of health have been shown to be accurate predictors of physical health outcomes, there is little research on the association between subjective emotional health (SEH) and psychiatric outcomes. METHOD: This paper utilises data from the Epidemiologic Catchment Area study to explore the relationship between baseline SEH and the risk for major depression in the next year. Both recurrent and incident episodes of depression are outcomes of interest. RESULTS: The age- and gender-adjusted relationship between SEH and depression is quite significant, and remains so after adjusting for other factors associated with major depression. The more positive the SEH rating, the lower the risk of an episode of depression in the next year. CONCLUSIONS: Some possible explanations for this association are explored, including possible confounders that were not accounted for and the possibility that SEH ratings pose an independent risk for major depression.

Affective Symptoms↗

PubMed1997

Urine autoantibodies in interstitial cystitis.

Interstitial cystitis is a chronic bladder disease with certain features that suggest autoimmunity may play a role in initiating or maintaining the disease process. We therefore determined whether immunoglobulin fractions from 14 IC patient and 19 control urine specimens bound in vitro to primary cultures of human bladder epithelial cells, as well as epithelial cells from a variety of other tissues. Urine autoantibodies that bound to normal human bladder epithelial cells were present in 8 of 14 IC specimens (from 6 of 9 IC patients) as compared to 3 of 23 control specimens (from 2 of 17 control patients). These antibodies, which were usually also present at low titers in sera from these persons, bound to at least four nuclear or cytoplasmic antigens, with the specificity of autoantibodies from a given individual varying over time. The autoantibodies were not specific for normal or malignant bladder epithelial cells, but bound to epithelial cells from a variety of tissues. These data show that anti-epithelial cell autoantibodies are present in the urine of IC patients, but suggest that these antibodies are not likely to be a primary cause of this disease.

Adult↗

PubMed1996

Incidence of apoptosis and cell proliferation in prostate cancer: relationship with TGF-beta1 and bcl-2 expression.

The incidence of programmed cell death (apoptosis) and cell proliferation was investigated in the normal and malignant human prostate to define the significance of their potential deregulation in human prostate cancer. The incidence of "spontaneous" apoptosis was analyzed using an in situ end-labeling procedure for detection of nucleosomal DNA fragmentation, as well as the pattern and topological localization of expression of the 2 proteins regulating apoptosis, TGF-beta1, and bcl-2, in 40 primary prostatic adenocarcinomas with varying tumor grades, 17 lymph nodes positive for metastatic prostate cancer and 9 normal prostate specimens. The basal level of cell proliferation of the different prostatic cell populations in the same specimens was determined, utilizing the Ki-67 nuclear antigen. Localized prostate cancer cells exhibited a relatively low rate of apoptosis, which was significantly lower than the apoptotic index of normal prostate glandular epithelial cells. Metastatic prostate tumor cells, however, exhibited a significantly higher apoptotic index compared with localized prostate cancer cells. A significant increase in the proliferative index was detected in prostatic tumors compared with the normal gland (5-fold), and there was an even more marked elevation in the proliferative index of the metastatic prostate tumor cells compared to the normal prostate epithelial cells (approximately 24-fold). Immunohistochemical analysis of normal and malignant prostate specimens revealed a predominant TGF-beta immunoreactivity in the glandular epithelial cells, while the stromal component was totally negative. There was a significant increase in the levels of TGF-beta in primary prostatic tumors compared to the normal prostate. Bcl-2 expression was detected among certain populations of tumor epithelial cells in a mutually exclusive topological distribution pattern for apoptosis. In marked contrast, neither TGF-beta1 nor bcl-2 immunoreactivity was detected in metastatic prostate tumor cells, despite their high proliferative and apoptotic rates. Balancing the prostatic growth equation for the prostatic tumor epithelial cell populations revealed a substantial net increase in cell number in both primary and metastatic prostate cancers. This loss of apoptotic control in favor of cell proliferation may be responsible for prostate cancer initiation and progression.

Adenocarcinoma↗

PubMed1996

Prednisone can protect against exercise-induced muscle damage.

In an experimental animal exercise model we tested whether daily administration of prednisone prevents the development of mechanically induced muscle fibre damage. Six-week-old rats were treated with different doses of prednisone ranging from 1 to 50 mg/kg body weight per day or with placebo, for 8 days. On day 6 of treatment the rats were forced to run for 2 h on a level treadmill. Two days after exercise morphological damage in the soleus muscles was quantified using light microscopy and a semi-automatic image analysis system. Creatine kinase (CK) activity was measured before exercise (day 5) and directly after exercise (day 6). The expression of dystrophin in a placebo group and in a group that received 5 mg prednisone/kg body weight per day with and without performing exercise was studied with Western blotting. The effect of prednisone on fibre type distribution was determined with an antibody against fast myosin and the effect of prednisone on the proliferative activity of muscle satellite cells was studied using bromodeoxyuridine (BrdU) immunohistochemistry. Exercise-induced muscle fibre damage varied in a dose-dependent way. In the placebo group the mean (SEM) damaged muscle fibre area was 4% (1%). The groups that received low doses of prednisone, 1 or 2.5 mg/kg per day, showed a similar level of muscle damage. However, with 5 mg prednisone/kg per day the amount of muscle fibre damage [mean (SEM)] was significantly reduced to 1.4% (0.5%) (P <or= 0.05, Student's t-test). High doses of prednisone had no protective effect. Directly after exercise the CK activity was increased two-fold, except in the group that received 50 mg prednisone/kg body weight per day. No changes in the amount of dystrophin were found after densitometric analysis of the Western blots. Prednisone did not affect the fibre distribution or the labelling index of satellite cells. We conclude that prednisone, given in an appropriate dose, protects muscle fibres against the development of mechanically induced damage, possibly by stabilizing the muscle fibre membranes. This action may explain the beneficial effect of prednisone observed in Duchenne muscular dystrophy patients.

Animals↗

PubMed1996

Effect of hypothyroidism on satellite cells and postnatal fiber development in the soleus muscle of rat.

The effect of hypothyroidism, induced by 4-propyl-2-thiouracil, on muscle satellite cells in vivo and in vitro, and on postnatal muscle fiber development in the soleus muscle of rats during the first 40 days of postnatal life was analyzed. The proliferative activity of satellite cells was determined by means of bromodeoxyuridine incorporation. Creatine kinase activity was used as a marker for differentiation. In vivo, hypothyroidism resulted in smaller fibers in which the amount of sarcoplasm remained in balance with the number of myonuclei. The in vivo labeling data of satellite cells did not indicate a decreased proliferative activity, but the in vitro experiments showed that the hypothyroid rat muscles contained fewer satellite cells that were less active in proliferation and differentiation at the start of culture. Despite this, the bromodeoxyuridine signal increased in time at a similar rate as that in control cultures. From this and because the cells resembled control cells in their response to bFGF, we conclude that hypothyroid satellite cells remain responsive to proliferation stimuli. However, in hypothyroid cultures, the activity of creatine kinase is lower, even at longer culture times. We therefore conclude that hypothyroid status affects muscle precursor cells mainly by depressing their ability to differentiate and fuse with existing myofibers.

Animals↗

PubMed1996

Apoptotic versus proliferative activities in human benign prostatic hyperplasia.

Cell growth in the normal prostate is regulated by a delicate balance between cell death and cell proliferation (ie, apoptotic v proliferative activity). Disruption of the molecular mechanisms that regulate these two processes may underline the abnormal growth of the gland leading to benign prostatic hyperplasia (BPH). In this study, the incidence of programmed cell death (apoptosis) and cell proliferation was comparatively analyzed among the various cell subpopulations in the normal and benign hyperplastic human prostate. The authors also examined the relative expression of two proteins involved in the regulation of prostate apoptosis: (1) transforming growth factor (TGF)-beta1, a negative growth factor able to induce prostate apoptosis under physiological conditions; and (2) bcl-2, a potent apoptosis suppressor. Analysis of the incidence of "spontaneous" apoptosis in situ, using the end-labeling terminal transferase staining technique for the detection of nucleosomal DNA fragmentation, revealed infrequent apoptotic staining in isolated basal and secretory prostate epithelial cells. The basal level of cell proliferation was determined on the basis of the Ki-67 nuclear antigen staining, a nuclear protein that appears primarily during the proliferative phases of the cell cycle. The Ki-67-positive nuclei were equally distributed among the basal and secretory epithelial cells of the hyperplastic prostatic acini. The apoptotic index of the secretory and basal cells of the prostate epithelium was higher in the normal prostate compared with BPH tissue, whereas there was a significant increase in the proliferative index of the respective cell populations in the hyperplastic prostate. Balancing the apoptotic versus the proliferative activities revealed a substantial net decrease (fourfold) in the total number of cells dying via apoptosis in both the glandular and basal epithelial cell compartments of the hypertrophic prostate (BPH) when compared with the normal gland. TGF-beta staining was exclusively identified in the secretory epithelial cells, lining the prostatic lumen with minimal involvement of the basal cells and total lack of immunoreactivity among the stroma elements. Statistical analysis revealed a significant elevation in TGF-beta expression in the epithelial cells of BPH tissue compared with the normal prostate (P < .001). Expression of bcl-2 was topologically restricted to the glandular epithelium of the prostate. In the normal prostate, bcl-2 immunoreactivity was predominantly identified in the basal cell layer. An increase in both the intensity of immunoreactivity for bcl-2 and the number of positive epithelial cells (basal and secretory) was detected in BPH specimens relative to the normal prostate (P < .02). These results suggest a potential involvement of enhanced expression of this antiapoptosis protein in deregulation of the normal apoptotic cell death mechanisms in the human prostate, thus resulting in a growth imbalance in favor of cell proliferation that might ultimately promote prostatic hyperplasia.

Adult↗

PubMed1996

Transforming growth factor-alpha expression in human renal cell carcinoma: TGF-alpha expression in renal cell carcinoma.

OBJECTIVES: To characterize the expression of transforming growth factor-alpha (TGF-alpha) in various histologic types of renal cell carcinomas. METHODS: Immunohistochemistry of renal cell carcinoma and adjacent normal tissue was performed on formalin-fixed tissue using a specific monoclonal antibody to TGF-alpha. RESULTS: Clear and distinct staining was present in normal distal convoluted tubules and collecting ducts. The growth factor was not observed in the glomerulus or the proximal tubule. In tumors composed of clear cells, staining was evident only in endothelial cells but not in the tumor cells themselves. In granular cell type tumors, the tumor cells as well as endothelial cells stained for TGF-alpha. When mixed cell type tumors were studied, a heterogenous pattern of growth factor expression was found. Endothelial cells and granular cells but not clear cells demonstrated positive staining. CONCLUSIONS: These studies suggest that TGF-alpha is likely to play a major role in neovascularization of clear cell carcinomas and that the growth factor may be more important in supporting proliferation of granular cell type tumors.

Carcinoma, Renal Cell↗

PubMed1996

The efficacy of relaxation response interventions with adult patients: a review of the literature.

The relaxation response is an integrated psycho-physiologic response originating in the hypothalamus that leads to a generalized decrease in arousal of the central nervous system. As such it is the physiologic antithesis of the stress response. This hypometabolic state is the foundation of many nursing interventions. Relaxation interventions have been taught for centuries. They include many theoretic and philosophic traditions and an array of specific strategies. The possible outcomes using relaxation response strategies in nursing practice are numerous and enable the patient to use the body's own innate mechanisms for health and healing. Thirty-seven studies of the efficacy of relaxation response interventions with adult patients are reviewed. Although numerous patient populations are addressed by the studies, some of which have methodologic problems, consistencies in the results suggest the effectiveness of the relaxation response in reducing hypertension, insomnia, anxiety, pain, and medication use across multiple populations, diagnostic categories, and settings. Recommendations for the use of relaxation responses in varied clinical settings are included.

Adult↗

PubMed1996

Surgical transfer of the sartorius muscle to the groin after lymphadenectomy or debridement: CT findings.

OBJECTIVE: We describe the CT findings of medial transfer of a sartorius muscle flap, which is done to protect the femoral blood vessels after radical inguinal lymphadenectomy for cancer or surgical debridement of infected femoral vascular grafts. MATERIALS AND METHODS: We reviewed the appearances and initial interpretations of 33 CT studies in 17 patients who underwent medial sartorius flap transfer after either (1) inguinal lymphadenectomy for melanoma or penile cancer or (2) debridement of infected groin wounds complicating vascular reconstruction of the femoral arteries. Muscle flap transfer was defined by the surgical record as either complete or incomplete. In complete sartorius muscle transfer, the proximal end of the muscle is dissected from the anterior superior iliac spine, rotated along its long axis, and sutured medially to the inguinal ligament. In incomplete transfer, the muscle it mobilized and stretched medially, and its medial border is fixed to the inguinal ligament and deep tissues. Clinical correlation and follow-up examinations were done for all patients, and CT reevaluation at intervals was done in nine patients. RESULTS: Complete sartorius flap transfer resulted in a mass anterolateral or anterior to the femoral vessels on postoperative CT scans in 20 studies; five of these masses were misinterpreted initially as possible recurrent metastatic lymphadenopathy, infection, or hematoma. Incomplete sartorius flap transfer resulted in bandlike stretching of the muscle over the femoral vessels in 13 studies. CONCLUSION: Medial transfer of the sartorius muscle causes a variable appearance of the groin on CT scans. The findings on CT scans after complete sartorius flap transfer should be distinguished from recurrent lymphadenopathy and from postoperative phlegmon or hematoma.

Debridement↗

PubMed1996

Incidence of apoptosis, cell proliferation and bcl-2 expression in transitional cell carcinoma of the bladder: association with tumor progression.

PURPOSE: Apoptosis is the distinctive form of programmed cell death that complements cell proliferation in maintaining normal tissue homeostasis. The significance of constitutive apoptosis in the development and progression of transitional cell carcinoma of the bladder has yet to be investigated. In the present study, the incidence of baseline apoptosis and the expression of 2 genes regulating this molecular process, bcl-2 and TGF-beta 1, as well as the level of cell proliferation, were examined by an intensive immunohistochemical analysis in normal bladder and bladder cancer specimens. MATERIALS AND METHODS: Apoptosis was detected by in situ end-labeling of fragmented DNA using the terminal deoxynucleotidyl transferase reaction in 45 paraffin-embedded primary transitional cell carcinoma specimens, 9 metastatic lymph nodes and 5 normal bladder specimens. The proliferation status of the tumor cells among the same bladder cancer specimens was evaluated by using a monoclonal antibody that recognizes the proliferation-associated nuclear antigen, Ki-67. RESULTS: The apoptotic index of normal transitional epithelium (0.06%) was significantly lower than that of all grades of transitional bladder carcinoma (p = 0.006). Although the apoptotic index of transitional carcinomas increased with increasing grade, this difference failed to achieve statistical significance, ranging from 0.54 +/- .23% in grade I to 1.24 +/- .77% in grade III. The proliferative index, as determined by Ki-67 positivity, also increased with increasing grades of tumor (12.8 +/- 8.4% in grade I to 22.6 +/- 15.2% in grade III) and was significantly greater than in normal urothelium (0.64 +/- 0.52%, p = 0.003). Bcl-2 expression was significantly lower in the normal transitional epithelium and in the well and moderately differentiated tumors (grades I-II) when compared with poorly differentiated (grade III) tumors (p = .004). The incidence of bcl-2 expression in all bladder specimens analyzed was uniformly low (< 5.3%). Transforming growth factor-beta 1 expression was not detected in any of the normal bladder specimens, primary tumors, or metastatic lymph nodes analyzed. CONCLUSIONS: The present findings revealed that no statistically significant correlation exists between the frequency of apoptosis and the pathological stage of bladder tumors, while they clearly demonstrate a strong direct correlation between an increased rate of cell proliferation and bladder cancer progression.

Apoptosis↗

PubMed1996

Decreased 3H-thymidine incorporation by human bladder epithelial cells following exposure to urine from interstitial cystitis patients.

PURPOSE: Interstitial cystitis (IC) is a chronic bladder disease of unknown etiology. We sought to determine whether a cytotoxin is present in the urine of IC patients that could cause the epithelial damage seen in this disease. MATERIALS AND METHODS: Evidence for a cytotoxin was sought using both a neutral red uptake viability assay in T24 bladder epithelial cells, and a 3H-thymidine incorporation assay in primary normal adult bladder epithelial cells and FHS 738 Bl human fetal bladder cells. RESULTS: The neutral red assay in T24 cells indicated the presence of a cytotoxin in 2 of 9 IC patient urine specimens. However, the more sensitive assay of cell proliferation (3H-thymidine incorporation) in normal adult human bladder epithelial cells revealed antiproliferative activity in urine from 10 of 13 (77%) IC patients vs. 3 of 19 (16%) controls (two-way analysis of variance, p = .019). The antiproliferative activity of IC urine specimens was confirmed using FHS 738 Bl human fetal bladder cells. The antiproliferative urinary substance(s) appeared to be a low molecular weight (< 10,000 Da), heat stable, trypsin-sensitive factor(s). CONCLUSIONS: Because a denuded or damaged bladder epithelium is a central finding in IC, it is possible that the antiproliferative protein(s) contributes to the pathogenesis of this disease.

Adult↗

PubMed1995

Triggering of acute myocardial infarction onset by episodes of anger. Determinants of Myocardial Infarction Onset Study Investigators.

BACKGROUND: Many anecdotes and several uncontrolled case series have suggested that emotionally stressful events, and more specifically, anger, immediately precede and appear to trigger the onset of acute myocardial infarction. However, controlled studies to determine the relative risk of myocardial infarction after episodes of anger have not been reported. METHODS AND RESULTS: We interviewed 1623 patients (501 women) an average of 4 days after myocardial infarction. The interview identified the time, place, and quality of myocardial infarction pain and other symptoms, the estimated usual frequency of anger during the previous year, and the intensity and timing of anger and other potentially triggering factors during the 26 hours before the onset of myocardial infarction. Anger was assessed by the onset anger scale, a single-item, seven-level, self-report scale, and the state anger subscale of the State-Trait Personality Inventory. Occurrence of anger in the 2 hours preceding the onset of myocardial infarction was compared with its expected frequency using two types of self-matched control data based on the case-crossover study design. The onset anger scale identified 39 patients with episodes of anger in the 2 hours before the onset of myocardial infarction. The relative risk of myocardial infarction in the 2 hours after an episode of anger was 2.3 (95% confidence interval, 1.7 to 3.2). The state anger subscale corroborated these findings with a relative risk of 1.9 (95% confidence interval, 1.3 to 2.7). Regular users of aspirin had a significantly lower relative risk (1.4; 95% confidence interval, 0.8 to 2.6) than nonusers (2.9; 95% confidence interval, 2.0 to 4.1) (P < .05). CONCLUSIONS: Episodes of anger are capable of triggering the onset of acute myocardial infarction, but aspirin may reduce this risk. A better understanding of the manner in which external events trigger the onset of acute cardiovascular events may lead to innovative preventive strategies aimed at severing the link between these external stressors and their pathological consequences.

Adrenergic beta-Antagonists↗