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At least 127 records · Page 7Linked to original sources
PubMed1995

Internal mammary node status: a major prognosticator in axillary node-negative breast cancer.

BACKGROUND: The internal mammary lymph nodes (IMN) have received little attention in recent years, yet are a well-documented site of metastasis and a major prognostic factor in early-stage breast cancer. METHODS/RESULTS: Ten-year follow-up of the final 195 patients treated by extended radical mastectomy (ERM) in this practice (selected largely on the basis of medial tumor location, and comprising 15% of all patients treated from 1965 to 1978) found IMN+ in 24% of all cases: 36% of AX+ versus 18% of AX- patients (p = 0.0023). In a multivariate analysis, the disease-free survival impact of IMN+ (p = 0.004) was second only to axillary node involvement (p < 0.0005), and surpassed tumor size (p = 0.077). IMN+ was equally frequent for tumors less than, or greater than, 2 cm (24%), and was not significantly related to patient age. Among AX- patients, there was a twofold greater risk of recurrence or death at 10 years for IMN+ than for IMN-. Among T1N0 patients, 19.6% were IMN+. CONCLUSIONS: Failure to consider IMN status in the steadily enlarging cohort of T1N0 breast cancers may result in the undertreatment of a significant proportion of stage I patients. Systemic adjuvant therapy should be considered for T1N0 patients with central or medial tumors.

Adult↗
PubMed1996

Molecular cloning of the mouse gene coding for carbonic anhydrase IV.

Carbonic anhydrase IV (CA IV) is expressed on apical surfaces of renal tubular epithelium and endothelium of specialized capillary beds. It plays a key role in bicarbonate reabsorption in kidney and in CO2 transport in other tissues. The human cDNA and genomic sequences have been cloned and characterized. Here we report the cloning and characterization of the entire mouse CA IV gene (contained in two overlapping lambda clones), which should enable generation of targeting constructs for disrupting the mouse CA IV gene to produce mouse models for in vivo analysis of CA IV gene function. The gene is approximately 8.2 kb long and contains eight exons ranging from 54 to 434 bp in length. The first exon (exon 1a) encodes the signal sequence. Exons 1b through 7 encode the remaining coding sequences. Exon 7 encodes the C terminus of the membrane-associated protein, as well as the 242-bp 3' untranslated sequence. The nucleotide sequence alignment between mouse and rat CA IV cDNAs reveals 84% identity. The nucleotide sequence alignment between mouse and human CA IV shows 69% identity in the coding region and all of the exon-intron boundaries are conserved, as are the sizes of the introns. The corresponding mouse and human exons are similar, except for the length of the untranslated regions in exons 1a and 7 and two small insertion/deletion events in exons 1a and 4. The 5' flanking region of the mouse gene (-300 to -1) is GC rich and contains 16 CpG dinucleotides. A TATA box sequence and several transcription factor binding sequences are identified upstream of exon 1a. Comparison of the nucleotide sequences surrounding the TATA box (-300 to -1) between mouse and human CA IV genes revealed 70% identity, indicating that regulatory sequences are as highly conserved as coding sequences between mouse and human CA IV genes.

Animals↗
PubMed1981

Malignant retrorectal tumors: 28 years' experience at Memorial Sloan-Kettering Cancer Center.

From 1949 to 1977, 39 patients with localized malignant retrorectal tumors were treated at Memorial Sloan-Kettering Cancer Center. Chordomas were the most frequent histologic type (38 per cent of patients) followed by neurogenic tumors (15 per cent) chondrosarcomas, hemangiopericytomas, and embryonal adenocarcinomas (8 per cent each). Treatment consisted of surgical excision in 28 patients (18 of whom received adjuvant radiotherapy and/or chemotherapy). Ten patients were treated nonsurgically, receiving radiation and/or chemotherapy alone. Large tumors were most successfully managed by a combined surgical approach consisting of exploratory celiotomy, rectal mobilization, and bilateral hypogastric artery (with middle sacral artery and vein) ligation, followed by transsacral tumor excision with incontinuity sacrectomy. For all treated patients, survival at 5, 10, 15 and 20 years was 69 per cent, 50 per cent, 37 per cent and 20 per cent, respectively. Long-term disease-free survival (17 to 25 years post treatment) was noted in six patients. [Key words: Tumor(s), retrorectal, malignant; Tumor(s), treatment].

Adolescent↗
PubMed1988

Isolation, characterization, and long-term culture of fetal bovine tracheal epithelial cells.

Epithelial cells were isolated from fetal bovine trachea by exposing and stripping the mucosal epithelium from the adjacent connective tissue. The tissue was minced and enzymically dissociated in Ca-Mg-free medium containing dispase and dithiothreitol. The stripping procedure and selective trypsinization produced epithelial cell cultures free of fibroblasts. Seeded on plastic, the plating efficiency was 21.5% with a doubling time of 24 h. Dome formation, evidence of occluding junctions and active ion transport characteristic of epithelial cells, was common. Growth of the cells on glass, collagen, and Engelbreth-Holm-Swarm (EHS) substrate demonstrated a striking difference in morphology. Cells grown on EHS presented a more distinctly three-dimensional growth pattern and many more microvilli when compared to cells grown on glass or collagen. The cells retained their epithelioid characteristics through more than 30 passages as shown by the presence of distinct apical and basolateral membranes, tight junctions, and positive keratin staining.

Animals↗
PubMed1990

Microbiological cultivation of Mycoplasma hyorhinis from cell cultures.

The failure of many cell culture isolates of Mycoplasma hyorhinis to grow on microbiological media has stressed the need for alternate assays to detect these organisms. The use of freshly prepared yeast extract in mycoplasmal media together with incubation in 5% CO2/air successfully detected M. hyorhinis in 12 of 12 infected cultures. These were not detected by the use of conventional mycoplasmal media using aerobic or anaerobic incubation. This assay may also be helpful in detection of other mycoplasmal species commonly isolated from cell cultures.

Cells, Cultured↗
PubMedDate not supplied

Phenotypic differences between Syrian hamster embryo cells cultured at pH 6.7 or 7.3.

We have investigated the molecular phenotypic differences between Syrian hamster embryo (SHE) cells cultured at pH 6.7 or 7.3. Multiple pH-sensitive phenotypic differences were noted including changes in cellular morphology, a unique charge differential in a major cellular protein, nine uniquely expressed proteins, two unique phosphoserine/threonine phosphoproteins, one unique phosphotyrosine phosphoprotein, and the pH dependent mRNA level of a gap junctional gene (connexin 43). These differences, combined with previously described pH-specific differences (differential transformation rates and gap junctional communication), illustrate that culturing SHE cells in media that differ by 0.6 pH units (0.3 units on either side of pH 7.0) can have a profound influence on the cellular phenotype.

Animals↗
PubMedDate not supplied

Establishment of immortalized alveolar type II epithelial cell lines from adult rats.

We developed methodology to isolate and culture rat alveolar Type II cells under conditions that preserved their proliferative capacity, and applied lipofection to introduce an immortalizing gene into the cells. Briefly, the alveolar Type II cells were isolated from male F344 rats using airway perfusion with a pronase solution followed by incubation for 30 min at 37 degrees C. Cells obtained by pronase digestion were predominantly epithelial in morphology and were positive for Papanicolaou and alkaline phosphatase staining. These cells could be maintained on an extracellular matrix of fibronectin and Type IV collagen in a low serum, insulin-supplemented Ham's F12 growth medium for four to five passages. Rat alveolar epithelial cells obtained by this method were transformed with the SV40-T antigen gene and two immortalized cell lines (RLE-6T and RLE-6TN) were obtained. The RLE-6T line exhibits positive nuclear immunostaining for the SV40-T antigen and the RLE-6TN line does not. PCR analysis of genomic DNA from the RLE-6T and RLE-6TN cells demonstrated the T-antigen gene was present only in the RLE-6T line indicating the RLE-6TN line is likely derived from a spontaneous transformant. After more than 50 population doublings, the RLE-6T cells stained positive for cytokeratin, possessed alkaline phosphatase activity, and contained lipid-containing inclusion bodies (phosphine 3R staining); all characteristics of alveolar Type II cells. The RLE-6TN cells exhibited similar characteristics except they did not express alkaline phosphatase activity. Early passage RLE-6T and 6TN cells showed a near diploid chromosome number.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Captopril pharmacokinetics and the acute hemodynamic and hormonal response in patients with severe chronic congestive heart failure.

Twelve patients with severe chronic congestive heart failure (CHF) underwent simultaneous evaluation of the pharmacokinetic, pharmacodynamic, and neurohumoral actions of a single 25 mg oral dose of the angiotensin-converting enzyme (ACE) inhibitor captopril (CPT). Following drug administration, which raised plasma renin activity (PRA) and thereby indicated significant ACE inhibition, both free (unchanged) and total CPT (including active metabolites) were detectable in the blood with 40 minutes and peak blood levels of the agent were recorded 1 hour after CPT. Total CPT concentration was higher and persisted longer than free CPT, which became virtually nondetectable 8 hours after ingestion. Concomitantly, left ventricular function was markedly augmented by the oral ACE inhibition in all patients, with the magnitude of this improvement being closely related to the baseline PRA. Thus, the overall hemodynamic response to CPT, which rapidly appears in the bloodstream following drug intake in patients with advanced CHF, is a function of the extent of baseline renin-angiotensin-aldosterone activity.

Adult↗
PubMed1982

Use of captopril to estimate renin-angiotensin-aldosterone activity in the pathophysiology of chronic heart failure.

Although the renin-angiotensin-aldosterone system has been implicated in the pathophysiology of chronic heart failure, the factors influencing the extent of renin activity have not been clarified. In the present study, we evaluated 34 patients with severe chronic congestive heart failure in terms of baseline plasma renin activity (PRA). No uniform relationships between PRA and urinary sodium excretion have been established. Although baseline PRA did not correlate with the baseline hemodynamic values, the extent of hemodynamic improvement following acute oral captopril (CPT) therapy (25 mg) was highly correlated with baseline PRA. The onset of action was rapid, so that the initial acute response could be readily assessed and at the same time could be used as a means to estimate baseline renin-angiotension-aldosterone activity. For long-term therapy, however, the response to CPT must be assessed in the context of several potentially simultaneous factors that might either enhance or compromise its effectiveness.

Adult↗
PubMed1982

The effect of captopril on postural hemodynamics and autonomic responses in chronic heart failure.

Both postural abnormalities and autonomic dysfunction have been identified in patients with chronic congestive heart failure (CHF). However, the effect of long-term vasodilator therapy on these phenomena has not been assessed. In this study the hemodynamic and plasma norepinephrine (PNE) responses to upright posture, as well as the cold pressor test and Valsalva's maneuver in 12 patients with severe chronic CHF during both acute and long-term captopril (CPT) therapy, were evaluated. This revealed an absence of the normal hemodynamic adjustments to upright posture and a blunted response of PNE. The heart rate and blood pressure responses to the cold pressor test and Valsalva's maneuver were similarly blunted. The reflex adjustments of systemic resistance during tilt improved with CPT therapy, but the absence of reflex tachycardia in the upright posture persisted. Additionally, there was improvement of the PNE response, and the responses of heart rate and blood pressure to the cold pressor test were virtually normalized during long-term CPT therapy. The abnormal response to the Valsalva maneuver persisted. In conclusion, hemodynamic and reflex-mediated responses to upright posture and the standard assessment of autonomic control mechanisms revealed abnormal patterns in heart failure. While the hemodynamic adjustment to postural changes and sympathetic responsiveness were improved with CPT, complete correction of these abnormalities did not occur. Whether the improvement was a nonspecific vasodilator effect or the result of specific CPT therapy remains to be determined.

Adult↗
PubMed1982

Postural hypotension during tilt with chronic captopril and diuretic therapy of severe congestive heart failure.

The hemodynamic mechanism by which patients with chronic congestive heart failure (CHF) maintain their blood pressure (BP) in the upright posture is distinct from that of normal and hypertensive individuals. There are little data regarding the effects of chronic vasodilator therapy on the mechanisms controlling this response, especially in the presence of diuretic therapy. Therefore, 10 consecutive patients with severe chronic CHF underwent hemodynamic tilt study following acute and chronic captopril therapy. One patient developed orthostatic hypotension following first-dose captopril, but 6 of 10 had a mean BP decrease of 70 +/- 6 to 56 +/- 3 mm Hg on tilt following chronic captopril. This associated with significant reduction of plasma aldosterone, and was abolished on re-tilt following acute saline infusion. Therefore, during chronic captopril therapy of CHF, a reduction of diuretic dosage may be necessary to prevent orthostatic hypotension.

Adult↗
PubMed1983

Combined vasodilator therapy for chronic congestive heart failure.

There are few data to support the potential efficacy of combined vasodilator therapy for severe congestive heart failure. For documentation of the feasibility of such an approach, a short-term hemodynamic study utilizing captopril, an oral converting enzyme inhibitor, followed by the addition of nitroprusside infusion, was made of 11 patients with severe chronic congestive heart failure. Captopril alone resulted in reduction of mean arterial pressure (84 +/- 7 to 70 +/- 3 mm Hg), associated with increase of cardiac index and stroke index. There was also a significant reduction of systemic resistance and pulmonary wedge pressure. The initial hemodynamic response to captopril was correlated with initial plasma renin activity (all values at least p less than 0.05). The addition of nitroprusside to captopril resulted in further hemodynamic improvement. Reduction of mean arterial pressure, systemic vascular resistance, and pulmonary wedge pressure were all significant, as were increases of cardiac index and stroke index. The degree of hemodynamic improvement with this sequence of vasodilator therapy was linearly related to the reduction of mean arterial pressure. Therefore vasodilators with dissimilar mechanisms of action may have an additive effect. These data support the potential feasibility of combined, long-term oral vasodilator therapy in selected subgroups of patients with congestive heart failure.

Adult↗
PubMed1984

Estimation of angiotensin II receptor activity in chronic congestive heart failure.

The renin-angiotensin system has been shown to participate in the pathophysiology of chronic heart failure in many patients. However, the immediate assessment of this contribution in individual patients may sometimes be difficult. As a pharmacologic estimate of angiotensin II receptor activity, we infused the angiotensin II analogue, saralasin, in 20 patients with severe chronic congestive heart failure (CHF). The infusion resulted in blood pressure responses ranging from an agonist pressor response (increased systemic resistance) in patients with low intrinsic renin-angiotensin system activity, to an antagonist depressor response (decreased systemic resistance) in patients with marked activation of the renin-angiotensin system. The ability of the saralasin response to pharmacologically estimate angiotensin II receptor activity in CHF was further revealed by two physiologic maneuvers that decrease endogenous circulating angiotensin II and angiotensin II receptor occupancy. Both converting enzyme inhibition with captopril and sodium repletion, factors known to decrease endogenous angiotensin II activity, provoked agonist responses to saralasin infusion. Furthermore, saralasin was able to reverse the orthostatic hypotension precipitated by converting enzyme inhibition of angiotensin-dependent vascular tone. In summary, saralasin provided a means to estimate angiotensin receptor activity and may therefore serve as a probe of angiotensin-mediated vasoconstriction in the pathophysiology of chronic CHF.

Adult↗
PubMed1985

Combined hemodynamic effects of nifedipine and nitroglycerin in congestive heart failure.

To determine if the addition of preload reduction with nitrates would potentiate the acute vasodilator actions of nifedipine, we titered intravenous nitroglycerin in seven patients with severe congestive heart failure after they received a single oral dose of nifedipine. The peak hemodynamic effect of nifedipine occurred at 30 minutes, with large reductions of systemic vascular resistance (1831 +/- 128 to 1132 +/- 154 dynes X sec X cm-5; p less than 0.001) and mean arterial pressure (87 +/- 7 to 71 +/- 7 mm Hg; p less than 0.01). This was associated with an increase of stroke volume index from 22 +/- 3 to 27 +/- 3 ml/m2 (p less than 0.01) but no significant changes in heart rate, right atrial pressure, or pulmonary wedge pressure. These hemodynamic changes were attenuated over a 2-hour observation period. At 2 hours, the addition of intravenous nitroglycerin resulted in large reductions in right atrial pressure (9 +/- 2 to 6 +/- 1; p less than 0.01) and pulmonary wedge pressure (23 +/- 2 to 17 +/- 2; p less than 0.001). This was associated with further increases in cardiac index (from 1.99 +/- .15 to 2.25 +/- .14 L/min/m2; p less than 0.001) and stroke volume index (26 +/- 3 to 29 +/- 3 ml/m2; p less than 0.01). Thus, the addition of nitroglycerin to nifedipine will optimize preload reduction and enhance the vasodilator action of nifedipine. Further controlled studies are necessary to determine the long-term hemodynamic effects and the clinical role of nifedipine and its combination with nitrates in patients with severe congestive heart failure.

Adult↗
PubMed1985

Milrinone in congestive heart failure: observations on ambulatory ventricular arrhythmias.

Milrinone is a potent non-catecholamine, non-glycoside inotropic agent that can improve hemodynamic performance and functional capacity in patients with severe congestive heart failure. However, the potential effect of chronic inotropic stimulation on ventricular arrhythmias in patients with heart failure requires evaluation. We compared 24-hour ambulatory ECGs before and 2 to 4 weeks after initiation of chronic milrinone therapy in 20 patients with severe congestive heart failure (mean cardiac index 1.79 +/- 0.43 L/min/m2). A greater than tenfold increase in simple ventricular premature complex (VPC) density, a greater than tenfold increase in complex VPC form density, or an increase from 0 to greater than 5 episodes per 24 hours of any complex VPC form occurred in 35% (7 of 20) of patients. A greater than tenfold reduction in simple VPC density was noted in 5% (1 of 20), while 60% (12 of 20) of the study group had no significant change in ventricular arrhythmia profile on milrinone. The hemodynamic and functional response to milrinone, as well as entry hemodynamic profiles, were unrelated to the change in frequency or complexity of ventricular arrhythmias during therapy. Thus, milrinone therapy in congestive heart failure may be associated with the development of VPC complexity and with a significantly increased density of complex VPC forms.

Administration, Oral↗