Biomedical subjects

M R Freeman

Publications and source records attributed to M R Freeman.

At least 55 records · Page 3Linked to original sources

PubMed1997

Heparin-binding EGF-like growth factor is an autocrine growth factor for human urothelial cells and is synthesized by epithelial and smooth muscle cells in the human bladder.

The epidermal growth factor receptor (HER1) has been implicated in regenerative growth and proliferative diseases of the human bladder epithelium (urothelium), however a cognate HER1 ligand that can act as a growth factor for normal human urothelial cells (HUC) has not been identified. Here we show that heparin-binding EGF-like growth factor (HB-EGF), an activating HER1 ligand, is an autocrine regulator of HUC growth. This conclusion is based on demonstration of HB-EGF synthesis and secretion by primary culture HUC, identification of HER1 as an activatable HB-EGF receptor on HUC surfaces, stimulation of HUC clonal growth by HB-EGF, inhibition of HB-EGF-stimulated growth by heparin and of log-phase growth by CRM 197, a specific inhibitor of HB-EGF/HER1 interaction, and identification of human urothelium as a site of HB-EGF precursor (proHB-EGF) synthesis in vivo. ProHB-EGF expression was also detected in the vascular and detrusor smooth muscle of the human bladder. These data suggest a physiologic role for HB-EGF in the regulation of urothelial proliferation and regeneration subsequent to mucosal injury. Expression of proHB-EGF is also a feature of differentiated vascular and detrusor smooth muscle in the bladder. Because proHB-EGF is known to be the high affinity diphtheria toxin (DT) receptor in human cells, synthesis of the HB-EGF precursor by human urothelium also suggests the possibility of using the DT-binding sites of proHB-EGF as an in vivo target for the intraluminal treatment of urothelial diseases.

Bacterial Proteins↗

PubMed1997

The Neurobehavioral Cognitive Status Examination: accuracy of the "screen-metric" approach in a clinical sample.

This study assessed the accuracy of the "screen" versus "metric" portions of eight subtests of the Neurobehavioral Cognitive Status Examination (NCSE). As part of a routine hospital assessment, 95 male patients were administered both portions of the instrument regardless of outcome on the screen. Results indicate that the screen items of some of the NCSE subtests produced a relatively high false negative rate, where the screen was passed, but the metric was failed. It is recommended that all items of the subtests be administered to more fully assess each domain and, therefore, reduce the probability of overlooking significant deficits.

Aged↗

PubMed1997

Dysregulated proteolytic balance as the basis of excess extracellular matrix in fibrotic disease.

To investigate mechanisms of tissue fibrosis, we developed a model of ovine fetal bladder fibrosis due to surgically induced obstruction. Tissues were analyzed for matrix metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Active MMP-2 was not detected in obstructed bladders, while latent and active forms were detected in normal bladders. MMP-1 (interstitial collagenase) activity was lower in obstructed bladders. MMP inhibitory activity was increased with obstruction, as were levels of TIMP mRNA and protein. These results indicate that the proteins responsible for collagen degradation are present in the developing bladder, and a shift in the proteolytic balance favoring inhibition of degradation occurs in a model of obstruction-induced fibrosis. This altered proteolytic balance favors accumulation of extracellular matrix and decreased tissue compliance characteristic of this and perhaps other fibrotic conditions.

Animals↗

PubMed1996

Temperature-controlled laser photocoagulation of soft tissue: in vivo evaluation using a tissue welding model.

BACKGROUND AND OBJECTIVES: Laser surgical procedures involving photocoagulation of soft tissue have relied on subjective visual endpoints. The thermal damage to the denatured tissue in these procedures is highly dependent on the tissue temperatures achieved during laser irradiation. Therefore, a system capable of real time temperature monitoring and closed loop feedback was used to provide temperature controlled photocoagulation (TCPC). STUDY DESIGN/MATERIALS AND METHODS: The TCPC system consisted of a 1.32 microns Nd:YAG laser, an infrared thermometer, and a microprocessor for data acquisition and feedback control. A porcine skin model was used. Tissue welds were completed to evaluate the photocoagulation effects at different predetermined temperatures. A quantitative measurement of tissue photocoagulation was obtained by tensile strength measurements of the laser repairs. Histology of the irradiated tissue was used to determine the extent of thermal injury associated with different photocoagulation temperatures. RESULTS: The TCPC system was capable of maintaining a relatively constant temperatures (+/- 4 degrees C) during laser irradiation. The tensile strengths of acute repairs increased with temperature over the range studied (65-95 degrees C). Tensile measurements made after several days of healing showed that higher temperature (95 degrees C) welds had lower strengths than repairs completed at lower (65 degrees C or 75 degrees C) temperatures and were significantly lower at 3 days. Acute histology showed that the amount thermal damage was strongly dependent on the tissue temperature and increased both in tissue depth and lateral to the repair with temperature. The histologic results suggest that the increase in the acute repair tensile strength as the weld temperature increased was due to an increase in the depth of tissue photocoagulation. The increase in the lateral tissue injury measured histologically for higher temperature welds likely resulted in the decreased chronic tensile strengths, as a healing response to excessive thermal damage. CONCLUSION: Tissue temperatures can be controlled during laser photocoagulation of skin. The degree of acute and chronic tissue damage is highly dependent on the temperature during welding. By controlling the tissue temperature during laser procedures, the surgical outcome can be more reliably predicted and reproduced, as compared to the conventional open loop methods. In addition, the use of a TCPC system should significantly reduce the learning curve for photothermal surgical procedures.

Animals↗

PubMed1996

Human albumin solder supplemented with TGF-beta 1 accelerates healing following laser welded wound closure.

BACKGROUND AND OBJECTIVE: We examined the possibility that human albumin solder can be used as a vehicle for site specific delivery of growth factors for the purpose of accelerating tissue repair following laser welded wound closure. Certain human recombinant growth factors have been shown to accelerate wound healing in model systems. Pilot in vitro studies have established that several growth factors, including TGF-beta 1, maintain bioactivity following exposure to temperatures achieved during laser tissue welding. Using a temperature controlled laser delivery system (TCL) to precisely maintain welding temperatures, it is now possible to avoid thermal denaturation of exogenous bioactive molecules such as growth factors. STUDY DESIGN/MATERIALS AND METHODS: HB-EGF, bFGF, and TGF-beta 1 were tested in vitro for maintenance of bioactivity after exposure to 80 degrees C. In vivo experiments using porcine skin determined the efficacy of solders augmented with growth factors. Incisions were repaired using human albumin alone or supplemented with HB-EGF (2 micrograms), bFGF (10 micrograms), or TGF-beta 1 (1 microgram). Wounds were excised at 3, 5, and 7 days post-operatively. Tensile strength, total collagen content, and histology were performed. RESULTS: At 3 days, tensile strength (TS) of TGF-beta 1 wounds were 36% (P < 0.05) and 20% (n.s.) stronger than laser alone and suture closures, respectively. By 5 days the TS of the TGF-beta 1 group increased by 50% (P < 0.05) and 59% (P < 0.02) over laser alone and suture groups, respectively. At 7 days the TGF-beta 1 group was 50% (P < 0.05) and 79% (P < 0.01) stronger than laser solder alone or suture, respectively. The HB-EGF and bFGF groups were equivalent to the laser solder group at all time points. Total collagen TGF-beta 1 Accelerates Healing Following Laser Welding content at 7 days increased in the TGF-beta 1 group by 7% (n.s.) over the suture group and 21% (P < 0.05) in the laser group. CONCLUSION: Human albumin solder supplemented with TGF-beta 1 increases the early post-operative strength of laser welded wounds. This novel application of laser tissue soldering augmented with a growth factor has the potential to bring about immediate fluid tight seals while providing site specific delivery of biological modifiers. This may lead to an overall improvement in post-operative convalescence, wound infections, and hospital costs.

Albumins↗

PubMed1996

Autologous granulosa cell coculture demonstrates zygote suppression of granulosa cell steroidogenesis.

OBJECTIVE: To determine if embryos can modulate steroid hormone production by luteinized granulosa cells. DESIGN: Granulosa cells obtained from follicular aspirates were cultured alone or in the presence of a two-pronuclear zygote. The production of E2 and P by these cultures was evaluated by RIA. SETTING: In Vitro Fertilization Unit in an academic research environment. PATIENTS: Sixteen women undergoing IVF. INTERVENTIONS: Standard IVF-ET treatment cycle using leuprolide acetate for pituitary desensitization before hMG or urofollitropin for ovarian stimulation. MAIN OUTCOME MEASURES: Estradiol and P concentration in culture media of luteinized granulosa cells alone or granulosa cells cocultured with a two-pronuclear embryo. RESULTS: Both E2 and P production by luteinized granulosa cells was reduced when cultured in the presence of an embryo. CONCLUSIONS: Human embryos secrete a factor that regulates granulosa cell steroidogenesis.

Adult↗

PubMed1995

Peripheral blood T lymphocytes and lymphocytes infiltrating human cancers express vascular endothelial growth factor: a potential role for T cells in angiogenesis.

CD3+ peripheral blood T lymphocytes were evaluated for expression of vascular endothelial growth factor (VEGF), an endothelial cell mitogen and potent angiogenic factor. VEGF mRNA expression was confirmed in CD3+ cells and Jurkat cells, a human T-cell line, by reverse transcription-PCR and in CD4+ and CD8+ T cell subtypes by Northern blot hybridization. Steady-state levels of VEGF mRNA were inducible in CD3+ T cells by hypoxia, a known inducer of VEGF mRNA accumulation. Secreted VEGF was detected in CD4+ and CD8+ T cell- and Jurkat cell-conditioned medium, indicating that T lymphocytes are capable of exporting bioactive concentrations of VEGF into the extracellular space. Human prostate and bladder cancers (prostatic adenocarcinoma and transitional cell carcinomas) were evaluated for VEGF mRNA expression by in situ hybridization. Tumor-infiltrating lymphocytes (TIL), identifiable immunocytochemically as T cells, along with tumor cells in these cancers, expressed VEGF mRNA. TIL in bladder cancers could be labeled with a specific anti-VEGF mAb, indicating that TIL are likely to be able to secrete VEGF protein in situ at bioactive concentrations. The finding that peripheral T cells and TIL in human tumors synthesize a factor known to be a specific mediator of neovascularization suggests a role for T lymphocytes as cellular effectors of angiogenesis.

Base Sequence↗

PubMed1995

T lymphocytes that infiltrate tumors and atherosclerotic plaques produce heparin-binding epidermal growth factor-like growth factor and basic fibroblast growth factor: a potential pathologic role.

Despite significant infiltration into tumors and atherosclerotic plaques, the role of T lymphocytes in these pathological conditions is still unclear. We have demonstrated that tumor-infiltrating lymphocytes (TILs) and plaque-infiltrating lymphocytes (PILs) produce heparin-binding epidermal growth factor-like growth factor (HB-EGF) and basic fibroblast growth factor (bFGF) in vitro under nonspecific conditions and in vivo in tumors by immunohistochemical staining. HB-EGF and bFGF derived from TILs and PILs directly stimulated tumor cells and vascular smooth muscle cells (SMCs) in vitro, respectively, while bFGF displayed angiogenic properties. Therefore, T cells may play a critical role in the SMC hyperplasia of atherosclerosis and support tumor progression by direct stimulation and angiogenesis.

3T3 Cells↗

PubMed1995

Usefulness of ischemic response to mental stress in predicting silent myocardial ischemia during ambulatory monitoring.

To evaluate the relation of mental stress-induced ischemia to silent ischemia on ambulatory monitoring, 46 patients with stable coronary artery disease underwent standardized laboratory mental stress and exercise treadmill testing according to National Institutes of Health protocol during which left ventricular ejection fraction (EF) was determined using the nuclear VEST. Life stress, type A behavior, and hostility were determined using standard interviews. Subsequently, 48-hour ambulatory electrocardiographic monitoring was performed. Twenty-three patients (50%) had an ischemic response (left ventricular EF decrease > or = 5%) to mental stress, which was associated with ambulatory ischemia (13 of 19 with ambulatory ischemia had mental stress-induced ischemia vs 10 of 27 without ambulatory ischemia, p = 0.04). Left ventricular EF response to mental stress was a significant predictor of ambulatory ischemia independent of EF response to exercise (F = 4.8, p = 0.03). Patients with mental stress-induced ischemia had longer total duration (31.4 +/- 57.0 vs 8.3 +/- 18 minutes, p = 0.06) and more frequent episodes of ambulatory ischemia (3.1 +/- 4.6 vs 0.9 +/- 1.9 episodes, p = 0.03). Life stress, type A behavior, and hostility were not associated with prevalence or severity of ambulatory ischemia. In conclusion, an ischemic response to mental stress is significantly associated with higher prevalence, longer duration, and more frequent episodes of ambulatory ischemia.

Aged↗

PubMed1995

Metaiodobenzylguanidine imaging in diabetes mellitus: assessment of cardiac sympathetic denervation and its relation to autonomic dysfunction and silent myocardial ischemia.

OBJECTIVES: This study in patients with diabetes mellitus was undertaken 1) to evaluate cardiac sympathetic innervation in diabetic patients using metaiodobenzylguanidine (MIBG) imaging; 2) to study the relation between autonomic function assessed by clinical maneuvers and abnormalities in MIBG uptake; and 3) to examine the basis for our previous observation of an association between abnormalities in autonomic nervous system dysfunction and silent myocardial ischemia. BACKGROUND: The clinical detection of autonomic dysfunction in diabetes mellitus has been linked to both abnormal perception of pain, including angina, and poor prognosis. METHODS: Uptake of MIBG was measured by dual-isotope imaging in 23 normal subjects and 65 asymptomatic diabetic patients. Silent myocardial ischemia was defined as the presence of a reversible perfusion defect in patients with ST segment depression. RESULTS: The MIBG uptake in the diabetic patients was significantly lower than that in normal subjects in the apex (67 +/- 17% vs. 82 +/- 7%, p = 0.0001), distal third (77 +/- 11% vs. 85 +/- 3%, p = 0.0001), proximal third (77 +/- 9% vs. 84 +/- 3%, p = 0.0001) and base (71 +/- 9% vs. 80 +/- 4%, p = 0.0001) of the left ventricle. Similarly, MIBG uptake was variable across different vascular territories. When MIBG uptake was corrected for perfusion abnormalities, diabetic patients had a greater MIBG uptake defect than normal subjects on visual score assessment (16 +/- 13 vs. 8 +/- 7%, p = 0.0002) and on quantitative MIBG mismatch assessment (13 +/- 15% vs. 2 +/- 2%, p = 0.0001). Diabetic patients with versus without autonomic dysfunction had more extensive MIBG uptake mismatch (17 +/- 17% vs. 4 +/- 6%, p = 0.0001). There was a greater diffuse abnormality in diabetic patients with versus without silent myocardial ischemia detected by sestamibi/MIBG uptake ratio (68 +/- 35% vs. 19 +/- 33%, p = 0.001). CONCLUSIONS: Sympathetic cardiac innervation in normal subjects is inhomogeneous. In contrast to normal subjects, diabetic patients have evidence of a significant reduction in MIBG uptake, most likely on the basis of autonomic dysfunction. Furthermore, diabetic patients with silent myocardial ischemia have evidence of a diffuse abnormality in MIBG uptake, suggesting that abnormalities in pain perception may be linked to sympathetic denervation.

3-Iodobenzylguanidine↗

PubMed1995

Granulosa cell co-culture enhances human embryo development and pregnancy rate following in-vitro fertilization.

A preliminary study and related clinical trial were performed to evaluate the effects of granulosa-lutein cell co-culture on human embryo development and pregnancy rates for in-vitro fertilization (IVF). In the study, sibling two-pronuclear zygotes were randomly allocated to culture with (co-culture) or without (control) autologous granulosa-lutein cells. After 24 h, embryos were examined for blastomere number and degree of fragmentation. Co-culture had no effect on the average number of blastomeres per embryo at 24 h; however, fragmentation was significantly decreased in co-cultured embryos (0.7 +/- 0.1) compared with controls (1.3 +/- 0.2; P < 0.05). In the subsequent clinical trial, all two-pronuclear zygotes were co-cultured for 48 h prior to embryo transfer. The live birth rate per embryo transfer was 43.4% with an implantation rate per embryo of 17.6%. Of the untransferred embryos, 68% developed to the blastocyst stage and were cryopreserved. We conclude that the simple system of autologous granulosa-lutein cell co-culture improves embryo development, implantation and subsequent pregnancy rates for IVF.

Blastomeres↗

PubMed1995

Pathophysiology and time course of silent myocardial ischaemia during mental stress: clinical, anatomical, and physiological correlates.

OBJECTIVE: To define the prevalence and pathophysiology of myocardial ischaemia induced by mental stress in patients with coronary artery disease and exercise inducible ischaemia, and to determine the correlation between the severity of coronary artery disease and ischaemia induced by speech. DESIGN: Prospective cohort study. SETTING: Tertiary care academic institution. PATIENTS AND PROTOCOL: 47 patients with coronary artery disease and 20 normal controls were studied using standardised exercise and mental stress. The ambulatory nuclear vest provided continuous measures of left ventricular ejection fraction and relative volume changes: an ischaemic response to mental stress was defined as a decrease in ejection fraction of > or = 5% for > or = 60 s. Severity of coronary artery disease was assessed by the extent of thallium reversibility on exercise testing and the severity of angiographic disease. RESULTS: 23 (49%) of 47 patients with coronary artery disease had an ischaemic response to mental stress which occurred early, was sustained throughout the task and associated with an increase in end systolic volume. In contrast, the pattern of left ventricular response in the remaining 24 patients (51%) resembled that in the normal controls. Patients with mental stress induced ischaemia tended to have greater severity of coronary disease (mean (SD) total number of diseased vessels 1.9 (0.8) v 1.4 (0.9), P = 0.07), more frequent exercise induced angina (17/23 v 7/24, P = 0.003) and lower increases in heart rate (36 (11) v 49 (23) beats per min, P = 0.023) and systolic blood pressure (32 (19) v 45 (18) mm Hg, P = 0.03) during exercise. Left ventricular responses to speech and exercise were compared in the 23 patients with mental stress induced ischaemia: mental stress was associated with a greater decrease in ejection fraction at comparable increases in rate pressure product (-6.5 (6.3)% v 4.7 (11.2)%, P = 0.0001). CONCLUSIONS: These findings suggest that mental stress induction of myocardial ischaemia is common in patients with stable coronary artery disease. Susceptible patients may have more functionally severe coronary disease. The time course, pattern, and haemodynamic features of mental stress induced ischaemia suggest a dynamic decrease in coronary supply.

Adult↗

PubMed1995

Cognitive estimation in traumatic brain injury: relationships with measures of intelligence, memory, and affect.

Brain injury is associated with a reduced capcity to engage in effective cognitive estimation. The current study utilized two measures of this construct, the Cognitive Estimation Test (CET) and Luria Memory Test (Luria), to investigate the relationships between cognitive estimation and intelligence, memory, and affect in a sample of 30 traumatically brain-injured individuals. Results demonstrated significant correlations between cognitive estimation and tests of intelligence and memory. However, measures of depression and state anxiety were not meaningfully associated with cognitive estimation. The ability to recall stories accounted for the greatest portion of the variance for both the CET and Luria. Specifically, the 30-minute Logical Memory subtest from the Wechsler Memory Scale-Revised accounted for 38% of the variance in the CET, while the Logical Memory 30-minute savings score accounted for 47% of the variance in the Luria. Intellectual and affective variables explained only negligible amounts of variance on cognitive estimation tasks.

Adult↗

PubMed1995

Expression of cell growth regulated genes in the fetal kidney: relevance to in utero obstruction.

Previous studies of fetal urinary tract obstruction (bladder outlet obstruction and ureteral obstruction) in lambs have shown that obstructions created relatively early in gestation (4/10 to 6/10 term) can significantly affect growth of the developing kidney. This suggests that urinary tract obstruction in utero can alter normal mechanisms of kidney growth. However, a mechanism for these effects has not yet been proposed. In this study we have used mRNA expression analysis to characterize the temporal sequence of expression of several growth-regulated genes during normal ovine kidney development. The purpose of this study was to test the hypothesis that early obstructions, such as those believed to arise in congenital obstructive uropathy in humans, might have a disproportionate effect on hyperplastic growth if the cellular growth fraction (percent of cells in the organ undergoing DNA synthesis) was greater in the second trimester than in the last. Northern blot analysis of the cell cycle-dependent genes histone H3, c-myc and ornithine decarboxylase (ODC) indicated a progressive, gradual decline in cellular proliferation in the kidney from approximately 60 to 135 days (4/10 term to term) gestation, as evidenced by decreases in the respective mRNA levels. The greatest levels of cell proliferation occurred near the midpoint of gestation. This indirect measurement of decline in cellular growth fraction was reflected in direct measurements of change in relative kidney weight. To test whether this decline in mRNA levels occurs widely among genes expressed in the fetal kidney during this period, relative expression levels of more than 300 anonymous mRNA transcripts were evaluated by differential display analysis. This method showed that genes whose expression patterns resembled the growth-regulated genes constituted less than 5% of the expressed mRNAs identified. These data indicate that intrauterine urinary tract obstructions that arise at or near the midpoint of gestation coincide with the highest rates of cell proliferation occurring in the second and third trimesters and, therefore, might adversely affect mechanisms of cell proliferation.

Animals↗

PubMed1995

Detection of silent ischemia adds to the prognostic value of coronary anatomy and left ventricular function in predicting outcome in unstable angina patients.

BACKGROUND: Patients with unstable angina are at increased risk of unfavourable outcomes such as myocardial infarction, death and urgent revascularization. Early risk stratification may improve subsequent outcome. Recently the presence and duration (at least 60 mins) of silent ischemia as measured by Holter monitoring has been shown to be of prognostic value. The incremental value of this information over that provided by coronary angiography and assessment of left ventricular function is not known. OBJECTIVE: To determine whether detection of silent ischemia is of independent and additional prognostic significance beyond that provided by the angiographic extent of coronary artery disease and left ventricular dysfunction. METHODS: One hundred and thirty-five unstable angina patients with 24 h of ST segment monitoring in addition to early cardiac catheterization (4 +/- 3 days) were assessed. Eighty-nine patients (66%) had ST segment shift for a total of 593 episodes (mean duration of 18 +/- 30 mins per episode) of which 92% were asymptomatic. Ten patients had a myocardial infarction and six patients died during the hospitalization. In addition, there were 33 urgent revascularization procedures. RESULTS: With the generalized additive logistic model, various clinical variables were assessed for predicting unfavourable outcomes. Duration of ST shift (P = 0.02) was second only to angiographic severity of coronary artery disease (P = 0.004) as a predictor. In the presence of these two variables left ventricular function did not have independent prognostic significance (P = 0.16). Event-free survival curves show that duration of ST shift of at least 60 mins was of incremental value in predicting unfavourable in-hospital outcomes compared with both the extent of coronary artery disease and left ventricular dysfunction. CONCLUSION: In patients with unstable angina, further stratification can be achieved early with Holter monitoring in addition to coronary angiography and assessment of left ventricular function.

Angina, Unstable↗

PubMed1994

Frequency of transient reductions in left ventricular ejection fraction at rest in coronary artery disease.

To determine the prevalence of decreases in left ventricular (LV) ejection fraction (EF) at rest in patients with coronary artery disease (CAD), including those with stable angina (n = 21), unstable angina (n = 13), and recent myocardial infarction (n = 11), continuous assessment of LV function for 162 +/- 136 minutes was performed using a new nuclear device. The results were compared with those of a group of normal subjects (n = 10) monitored for 80 +/- 28 minutes. Episodes of EF reduction of > 7% from baseline for a total duration of > 5% monitored time occurred in 0 of 10 normal subjects; episodes were more frequent in patients with stable angina (10 of 21, 48%; p = 0.01), with recent myocardial infarction (7 of 11, 64%; p = 0.004), and with unstable angina (11 of 13, 85%; p = 0.0001). The number of EF decreases per hour in patients after myocardial infarction (1.7 +/- 2.5 [SD]) and unstable angina (1.2 +/- 0.7) was significantly more frequent than in normal subjects (0.3 +/- 0.4), but was not different from that in patients with stable angina (0.8 +/- 1.0). The duration of the decrease in EF, expressed as minutes per hour of monitored time in normal subjects (0.7 +/- 1.0%), was significantly less than in patients with unstable angina (10 +/- 8%). Patients with stable angina (6 +/- 9%) and recent myocardial infarction (6 +/- 6%) were not significantly different from normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Does ambulatory monitoring contribute to exercise testing and myocardial perfusion scintigraphy in the prediction of the extent of coronary artery disease in stable angina?

The role of ambulatory myocardial ischemia detection, in addition to exercise testing and myocardial perfusion scintigraphy, in the prediction of the angiographic severity of coronary artery disease in patients with stable angina was examined. Ninety-seven patients underwent ambulatory electrocardiographic monitoring, exercise testing with scintigraphy, and coronary angiography. In addition to the number of diseased vessels involved, proximal arterial segment and coronary artery jeopardy scores were calculated to evaluate the extent of disease and amount of myocardium at risk. Thirty patients (31%) had 1.8 +/- 1.8 episodes/24 hours of ambulatory ischemia (94% of episodes were asymptomatic) and were similar to 67 without ambulatory ischemia in regard to clinical characteristics, left ventricular function and mean number of diseased vessels involved. Proximal arterial segment and coronary artery jeopardy scores were greater in: (1) 30 patients with versus 67 without ambulatory ischemia (3.3 +/- 1.8 vs 1.9 +/- 1.5 [p = 0.0002] and 6.6 +/- 3.6 vs 5.0 +/- 3.4 [p = 0.03], respectively); (2) 78 with versus 19 without a positive exercise test (2.6 +/- 1.8 vs 1.4 +/- 0.8 [p = 0.0001] and 6.1 +/- 3.5 vs 3.0 +/- 2.5 [p = 0.0003], respectively); and (3) 69 with versus 6 without a positive perfusion scan (2.4 +/- 1.8 vs 1.0 +/- 0 [p = 0.0008] and 5.5 +/- 3.6 vs 2.3 +/- 2.0 [p = 0.03], respectively). In multivariate analysis, ambulatory ischemia was the best predictor of the proximal segment score, whereas exercise testing and myocardial perfusion imaging were predictive of the coronary jeopardy score.

Angina Pectoris↗

PubMed1994

T lymphocytes synthesize and export heparin-binding epidermal growth factor-like growth factor and basic fibroblast growth factor, mitogens for vascular cells and fibroblasts: differential production and release by CD4+ and CD8+ T cells.

T lymphocytes infiltrate wounds, tumors, and atherosclerotic plaques, pathophysiological processes characterized by the migration and proliferation of vascular cells and fibroblasts. Although T lymphocytes are known to produce cytokines for inflammatory cells, it has not been demonstrated that they synthesize growth factors that are mitogenic for vascular cells and fibroblasts. We demonstrate that cultured T lymphocytes isolated from normal human peripheral blood synthesize and export two well-characterized growth factors, heparin-binding epidermal growth factor-like growth factor (HB-EGF) and basic fibroblast growth factor (bFGF). This conclusion is based on mRNA expression analysis, heparin-affinity chromatography profiles, target-cell specificity, and functional inhibition by specific neutralizing antibodies. Atypically, a substantial amount of T-cell-derived bFGF-like activity appears to be constitutively released into conditioned medium, almost as much as is associated with T-cell lysates. bFGF is synthesized and exported by purified CD4+ and CD8+ T cells, whereas HB-EGF is synthesized and exported primarily by CD4+ T cells. The T-cell-derived HB-EGF and bFGF activities are potent mitogens for fibroblasts and smooth muscle cells, and the bFGF-like activity is also mitogenic for endothelial cells. These results suggest that T lymphocytes may play key roles in mediating smooth muscle hyperplasia associated with atherosclerosis and in angiogenesis associated with wound healing and tumor growth by acting locally to deliver vascular-cell growth factors to tissues.

CD4-Positive T-Lymphocytes↗