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Biomedical subjects

M Bean

Publications and source records attributed to M Bean.

At least 19 recordsLinked to original sources

Inhibition of collagen synthesis with prolyl 4-hydroxylase inhibitor improves left ventricular function and alters the pattern of left ventricular dilatation after myocardial infarction.

Background- Left ventricular (LV) remodeling after myocardial infarction (MI) is associated with fibrosis, dilatation, and dysfunction. We postulated that prevention of fibrosis after MI with a prolyl 4-hydroxylase inhibitor (P4HI) would preserve LV function and attenuate LV enlargement. Methods and Results- Adult female rats (200 to 250 g) had experimental MI and were then randomized to treatment with P4HI (MI-FG041, n=29) or vehicle (MI-control, n=29) 48 hours after MI for 4 weeks in 2 phases. Echocardiograms were performed weekly with a 15-MHz linear transducer, and at 4 weeks, collagen isoform determinations and in vivo hemodynamics were performed. At randomization, the infarct size and LV function and size were similar in MI-FG041 and MI-control but significantly different from shams (n=9). At week 4, the LV function in MI-FG041 was significantly better than in MI-controls (fractional shortening 21% versus 16%, P=0.01; fractional area change 30% versus 19%, P=0.002; ejection fraction 35% versus 23%, P=0.001). In the FG041 group, LV area in systole was less (P<0.05), the dP/dt(max) after isoproterenol was higher (P<0.05), and types I and III collagen in noninfarcted LV were less than in MI-control. The hydroxyproline/proline ratio was increased by 64% in MI-control and reduced to the sham value in MI-FG041 rats. In the scar tissue, it was reduced by 24% in MI-FG041. Conclusions- This study demonstrates that prevention of interstitial fibrosis with a P4H inhibitor alters the pattern of LV enlargement and produces partial recovery of LV function after MI.

Animals↗

Is the technically limited echocardiographic study an endangered species? endocardial border definition with native tissue harmonic imaging and Optison contrast: a review of 200 cases.

OBJECTIVE: Our goal was to determine whether contrast adds diagnostic value to both fundamental and native tissue harmonic imaging (NTHI) for endocardial border definition. METHODS: Two hundred consecutive patients who underwent stress echocardiography imaging were studied in either fundamental (n = 52) or NTHI mode (n = 148) with an Acuson Sequoia echocardiographic system. Contrast agent (Optison) was administered (0.5 to 1 mL) for enhancement of endocardial borders. Two- and 4-chamber views were analyzed before and after administration of contrast at peak stress for grading of 5 endocardial border segments. Scores from 0 to 5 were assigned to each study for all the images both before and after contrast (0 = 0 segments completely visualized; 5 = 5 segments completely visualized). RESULTS: The use of Optison contrast significantly enhanced border definition when imaging was performed in either fundamental or NTHI mode. Addition of contrast resulted in better endocardial border definition in fundamental mode (4.1 + or - 1.0 versus 2.3 + or - 1.3, P <.001). However, in NTHI mode, the presence of contrast resulted in enhanced definition of endocardial border compared with its absence (4.8 + or - 0.5 versus 3.3 + or - 1.1, P <.001). The combination of NTHI and contrast resulted in more visualization of endocardium when compared with the combination of fundamental imaging and contrast (4.8 + or - 0.5 versus 4.1 + or - 1.0, P <.001). In addition, interobserver agreement for border detection increased from 83% in fundamental mode without contrast to 95% with the use of NTHI with Optison (P <.001). CONCLUSION: As defined in 200 cases, the combination of NTHI with Optison contrast results in nearly complete and consistent endocardial border definition.

Albumins↗

Metabolism of carvedilol in dogs, rats, and mice.

The excretion and biotransformation of carvedilol [1-[carbazolyl-(4)-oxy]-3-[(2-methoxyphenoxyethyl)amino]-2-p ropanol], a new, multiple-action, neurohormonal antagonist that exhibits the combined pharmacological activities of beta-adrenoreceptor antagonism, vasodilation, and antioxidation, were investigated in dogs, rats, and mice. Carvedilol was absorbed well, and biliary secretion was predominant in each species. Carvedilol was metabolized extensively in each species, and elimination of unchanged compound was minor in bile duct-catheterized rats and dogs. In dogs, glucuronidation of the parent compound and hydroxylation of the carbazolyl ring, with subsequent glucuronidation, were the major metabolic pathways. Rats showed the simplest metabolite profile; the primary metabolites were formed by hydroxylation of the carbazolyl ring, with subsequent glucuronidation. Mice displayed the most complicated metabolite profile; glucuronidation of the parent compound and hydroxylation of either the carbazolyl or phenyl ring, with subsequent glucuronidation, were the major metabolic routes. O-Dealkylation was a minor pathway in all species examined.

Adrenergic beta-Antagonists↗

The use of methotrexate and arterial embolization to avoid surgery in a case of cervical pregnancy.

OBJECTIVE: To describe the management of a case of cervical ectopic pregnancy (EP) DESIGN: Case report. SETTING: University-affiliated teaching hospital. PATIENT(S): A 26-year-old woman, gravida 4, para 0-1-2-0 with the diagnosis of a cervical EP. INTERVENTION(S): Systemic methotrexate (MTX) and arterial embolization. RESULT(S): A cervical EP was diagnosed by ultrasonography. The patient was treated with systemic MTX. Vaginal bleeding began 4 days later and was treated with arterial embolization, thus eliminating the need for surgical intervention. The pregnancy resolved and the patient has resumed normal menstruation and again is attempting pregnancy. CONCLUSION(S): Arterial embolization can be used to avoid surgical intervention in cases of cervical EP in which hemorrhage occurs after treatment with chemotherapy.

Abortifacient Agents↗

Distant entry pneumothorax in a competitive fencer.

An elite level fencer sustained a penetrating wound to the upper arm after his opponent's blade broke. Standard care for a deep puncture wound was given but it was some time before the athlete presented symptoms of a pneumothorax, which was confirmed by radiograph. Although resolution of this case was unremarkable, the possibility of penetrating thoracic injury, even when the point of entry is well outside the thorax and the athlete is not immediately symptomatic, should be born in mind by medical personnel working with fencers.

Arm Injuries↗

Muscle function at the wrist following 9 d of immobilization and suspension.

The purpose of this study was to evaluate the effects of 9 d of immobilization and partial suspension on muscle function at the wrist. Twelve female subjects (19-27 yr) wore a cast suspended from the neck by a sling that immobilized muscles acting on the wrist. Atrophy, muscle damage indicators, isometric and isokinetic strength, reaction time, speed of movement, and fatigability were assessed. Forearm muscle cross-sectional area decreased by 4.1% following immobilization and suspension. There was no indication that significant muscle degeneration occurred during immobilization or when muscles resumed normal function. Isometric strength for flexion and extension decreased by 29.3 and 32.5%, respectively. Concentric strength decrements for flexion, extension, pronation, and supination ranged from 8.9-21.7% at 2.11 and 3.16 rad.s-1. Eccentric strength decrements at 2.11 rad.s-1 for the same movements ranged from 12.5-18.5%. Fatigability was unaffected. Greater relative strength losses compared to decreased muscle cross-sectional area may be the result of a decrease in contractile protein density or unidentified neural factors following immobilization and partial suspension. However, neuromuscular control of reaction time was not affected.

Adult↗

The relationship of early versus two-minute recovery echocardiographic values following maximal effort resistance exercise.

Two-dimensionally directed M-mode echocardiography was used to measure left ventricular systolic function following maximal dynamic resistance exercise (RE). Upright measurements were made from the long axis parasternal view at rest, 20 seconds post-exercise, and two minutes post-exercise. Thirty-two successful studies were recorded from a total of 37 trained and untrained male subjects who were heterogeneous as to mode and level of training. Resistance-trained men averaged 3.8 +/- 2.4 yrs of training for 9.7 +/- 3.0 hr/wk, and endurance-trained men averaged 6.4 +/- 3.9 yr of training at 202.5 +/- 112.6 km/wk of cycling, running, and swimming. The trained men competed at the state or regional level. The RE protocol (knee extensions) was performed as follows: Set 1 (10 s rest) Set 2 (10 s rest) Set 3 60% 1-RM@8 reps 60% 1-RM@8 reps 60% 1-RM to fatigue. The RE protocol produced significant post-exercise reductions in end-systolic diameter (p less than 0.0002) and significant post-exercise increases in fractional shortening (p less than 0.0001) and velocity of circumferential fiber shortening (p less than 0.0002). The inotropic variables were still significantly different at two minutes post-exercise compared to the 20 second measure, suggesting that early recovery is a better approximation of maximal values. Velocity of circumferential fiber shortening at 20 seconds and two minutes was significantly correlated (r = 0.39) and fractional shortening was not (r = 0.34) at these serial measurement times.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Induction of cylindrical confronting cisternae (AIDS inclusions) in Daudi lymphoblastoid cells by recombinant alpha-interferon.

Cylindrical confronting cisternae (CCC), also known as test-tube and ring-shaped forms, are frequently present in the cytoplasm of lymphocytes and occasionally in other cells from patients with acquired immunodeficiency syndrome (AIDS). Recent data indicate that the presence of these cisternae and tubuloreticular structures (TRS) in lymphocytes from patients at risk for AIDS is predictive of the development of this syndrome. CCC are formed by an alteration of the membranes of the rough endoplasmic reticulum, but the mechanism by which they are formed or demonstration of their induction by specific agents has not been previously reported. We cultured Daudi lymphoblastoid cells in medium containing recombinant alpha-interferon and induced the formation of both TRS and CCC. The number of CCC formed in Daudi cells was directly proportional to the concentration of interferon used and the length of culture. CCC were in direct continuity with TRS, which were induced in cells by interferon at an earlier time. The percentage of cell sections containing TRS stayed the same or decreased somewhat after 72 hours of culture, whereas the number of CCC increased. Our results indicate that CCC could be present in various cells from patients with AIDS and other diseases as a result of elevated interferon levels in these conditions.

Acquired Immunodeficiency Syndrome↗

Non-specific peptide size effects in the recognition by site-specific T-cell clones. Demonstration with a T site of myoglobin.

Six regions (T sites) of myoglobin (Mb) were found by a comprehensive synthetic strategy to stimulate Mb-primed lymph-node cells. To define precisely the N-terminal boundary of the immunodominant T site (residues 107-120) with site-specific T-cell clones and to determine the effects of peptide size on their stimulation, two sets of peptides were employed. In one set, the peptides were elongated to the left from His-113 by one-residue increments of the Mb sequence. The other set represented an identical stepwise elongation by one-residue increments of the Mb sequence, but which were extended by additional unrelated ('nonsense') residues to a uniform size of 14 residues. Examination of the proliferative responses of eight T-cell clones, derived from Mb-primed DBA/2 (H-2d) or SJL (H-2s) mice, revealed a dramatic non-specific size requirement. In every clone, the longer nonsense-extended peptides achieved maximum stimulating activity at a lower optimum peptide dose than its natural-sequence, but shorter, analogue. In addition, slight (one-residue) differences in the N-terminal boundaries among the clones was observed. Thus, the fine specificity of each clone was mapped to the region from residue 111 or 112 to about residue 120 of Mb, which coincides with the site of B-cell recognition and resides in a small discrete surface region of the protein chain.

Animals↗

Site recognition by protein-primed T cells shows a non-specific peptide size requirement beyond the essential residues of the site. Demonstration by defining an immunodominant T site in myoglobin.

In previous studies, six T sites within myoglobin (Mb) were localized. To define precisely the boundaries of the T sites, a new approach is introduced and applied here to the T site residing within residues 107-120 of Mb. Two sets of peptides were synthesized. One set represents a stepwise elongation by one-residue increments of the Mb sequence. The other set represents an identical stepwise addition of one-residue increments of the Mb sequence, but which were extended by additional unrelated (nonsense) residues to a uniform size of 14 residues. The longer peptides (nonsense-extended) usually gave higher proliferative responses than did their shorter counterparts having the same Mb region. Thus a minimum peptide size is required for optimal T-cell stimulation. The T site subtends, in three high-responder mouse strains, residues 109-119 or 110-120, depending on strain, and, in three low-responder strains, maps to residues 108-120. Thus, in this case, the T site coincides with the site of B-cell recognition and resides in a small discrete surface region of the protein chain.

Amino Acids↗

Argininosuccinic aciduria: prenatal studies in a family at risk.

We have monitored two successive pregnancies in a family which we found to be at risk for argininosuccinic aciduria. We measured argininosuccinic acid (ASA) concentrations in amniotic fluid and utilized an indirect assay of ASA lyase activity in cultured amniotic fluid cells. The assay procedure is based on the uptake of 14C from [14C]citrulline and of [3H]leucine into protein. ASA was easily measured in amniotic fluid from the first fetus at risk, whereas none was detectable in control fluids. Amniotic fluid cells cultured from this fetus had only 5.5% of control ASA lyase activity. The pregnancy was terminated, and hepatic ASA lyase activity in the fetus was shown to be about 1.3% of control values. In addition, eight fetal tissues were analyzed for ASA, and all had significant accumulation. ASA was not detected in amniotic fluid from the second fetus at risk, and ASA lyase activity in cultured cells was 80% of control activity. Enzymatic analysis of erythrocyte lysate confirmed the diagnosis of an unaffected child (ASA lyase = 46% of control) and indicated heterozygosity. Thus, we provide further evidence that argininosuccinic aciduria can be diagnosed successfully in utero by indirect assay of ASA lyase activity in cultured amniotic fluid cells. In addition, high amniotic fluid ASA concentrations provide strong adjunctive evidence for such a prenatal determination, and may prove to be sufficient for diagnosis.

Adult↗