Secretion of plasminogen activator activity from neonatal rat heart cells is regulated by hormones and growth factors.
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Animals↗
Biomedical subjects
R M Klein
Publications and source records attributed to R M Klein.
[Repeated ingestion with suicidal intent of potentially lethal amounts of thallium].
30 minutes after drinking half a cup of rat poison a 16-year-old girl was admitted to hospital. In addition to various enteric detoxification measures forced dialysis was instituted and, after the urinary thallium level had become known (9 mg/l), haemodialysis was begun and ferric ferrocyanide (Prussian blue) administered (0.5 mg daily for six days). She had no symptoms at any time. After 10 days she was discharged. Five days after discharge she was again admitted, with colic-like abdominal pain, vomiting, paraesthesias of the hands and feet, and in a state of agitation. She had once again ingested rat poison, about one cup. Physical examination revealed little of consequence, except diffuse alopecia. Urinary thallium concentration was 37 mg/l. In the electrocardiogram the P-R interval was shortened to 0.11 s and T waves inverted in leads III and V1. Electronmicroscopy of cardiac and skeletal biopsies revealed lipid droplets, increased sarcoplasm and widening of some of the tubules. Treatment consisted of haemodialysis, forced diuresis (1 l urine/h), administration of ferric ferrocyanide, orthograde intestinal infusions and potassium substitution (serum level: 5 mmol/l). After 28 days the patient was discharged into psychiatric care.
Adolescent↗
Against a role for attentional disengagement in the gap effect: a friendly amendment to Tam and Stelmach (1993).
Saccadic reaction time (RT) is reduced when the fixation point is removed shortly before target onset. Although Tam and Stelmach (1993) argued that this gap effect could not be explained solely by the idea that fixation offset disengaged visual attention and preferred an explanation based on disengagement of the oculomotor system, they felt that they could not rule out a hybrid model in which both oculomotor and attentional disengagement contribute to the gap effect. Our analysis of the dual response experiment (Experiment 4), upon which this hybrid model was based, shows that manual and saccadic responses were likely compromised by a grouping or delay strategy and that subjects may not have been attending as instructed. On these grounds, we argue that Tam and Stelmach (1993), like Kingstone and Klein (1990; 1993a) provide no evidence that attentional disengagement contributes to the gap effect. An alternative proposal (Klein & Kingstone, 1993), that motor preparation and oculomotor disengagement combine additively to produce the gap effect, is consistent with the data from Tam and Stelmach's Experiments 1-3, is similar to the explanation that they prefer, and has been strongly supported when directly tested (Kingstone, Klein, & Taylor, 1994).
Fixation, Ocular↗
[Arrhythmias in myocarditis. Diagnostic procedures and therapeutic principles].
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Anti-Arrhythmia Agents↗
[Diagnosis and therapy of myocarditis].
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Angina Pectoris↗
Diagnostic procedures for Paget's disease. Radiologic, pathologic, and laboratory testing.
Paget's disease is a relatively common skeletal disorder that affects older individuals. Although its causes are unknown, it is characterized by abnormal remodeling and a high rate of bone turnover that determines its pathologic, radiologic, and biochemical findings. The findings in the three phases of Paget's disease are described.
Humans↗
Atrial natriuretic peptide-like (ANP-LIR) and ANP prohormone immunoreactive astrocytes and neurons of human cerebral cortex.
Atrial natriuretic peptide (ANP) represents a family of related peptides originally isolated from cardiac atria that have potent natriuretic, diuretic, and vasorelaxant properties. ANP has previously been localized in neurons of the rat brain in regions subserving cardiovascular functions and fluid/electrolyte balance and has been localized in astroglia of the canine brain. To determine whether ANP is present in astrocytes of the human brain and to validate the canine model for future studies, human brain tissue was obtained from autopsy cases with no brain damage or neurological or vascular disease. Human brains were obtained less than 3 h postmortem, and anterior cingulate and striate cortices were dissected following perfusion or immersion fixation. Immunohistochemical processing utilized antibodies against the processed form of ANP (ANP IV, ANP104-128) and against rat proANP (amino terminus) and the avidin-biotin-peroxidase technique. Isolated, strongly ANP-immunoreactive protoplasmic astrocytes were observed in all layers of the cingulate and striate cortex gray matter. ANP-positive fibrous astrocytes were observed in the white matter. Additionally, distinctive immunopositive astrocytes were found both within and immediately subjacent to the glia limitans. Antibody against the prohormone stained only protoplasmic astrocytes and sublimitans astrocytes and processes. In addition to the astroglia, ANP was detected in scattered multipolar neurons in the cerebral gray matter. These results provide additional evidence for diversity of peptide localization in astrocytes and suggest roles for ANP in the local regulation of cerebral blood flow, blood-brain barrier permeability, or cerebrospinal fluid volume.
Adult↗
Developmental pattern of ventricular atrial natriuretic peptide (ANP) expression in chronically hypoxic rats as an indicator of the hypertrophic process.
Atrial natriuretic peptide (ANP) is a natriuretic, diuretic and vasodilatory peptide normally synthesized and secreted by the atria of the adult mammalian heart. Synthesis of ANP in the ventricle has also been demonstrated in the fetus and neonate. In the adult, ventricular ANP is expressed under pathological conditions such as hypertension and congestive heart failure. The purpose of the present study was to analyse the spatial and temporal development of ANP expression in the right ventricle of the rat heart during the onset, establishment, and recovery from hypoxia-induced pulmonary hypertension and right ventricular hypertrophy (RVH). Significant RVH and immunoreactive ANP (ir-ANP) were detected in the right ventricles of hypoxic rats after only 3 days of exposure and continued to increase with the duration of hypoxia through 21 days. The presence of ir-ANP became apparent in the left ventricle as well as the right after 14 days of hypoxic exposure. Twenty-one days of normoxia following 21 days of hypoxia reduced RVH and ir-ANP to the levels seen at 3 days. Light microscopic immunohistochemistry demonstrated initial focal concentrations of ir-ANP in cardiomyocytes near the junction of the right ventricular free wall and the septum, as well as surrounding isolated blood vessels in the right ventricular wall, after 3 days of exposure. With increasing duration of hypoxic exposure, these immunoreactive areas enlarged to encompass the entire right ventricular wall and right half of the septum by 14 days. While many right ventricular cardiomyocytes were intensely stained at the light level, electron microscopic immunocytochemistry revealed only a sparse number of ANP-positive secretory granules. In immunohistochemical studies with an anti-clathrin antibody, there was a homogeneous staining pattern for clathrin in cardiomyocytes from the hypertrophied right ventricles. This pattern was not typical of the staining observed in other secretory cells which typically exhibit a perinuclear localization of clathrin. The alterations in ultrastructural immunocytochemistry for ANP suggest that ventricular ANP synthesis differs from atrial synthesis of this peptide. The differences in clathrin staining indicate that its expression may also be related to the hypertrophic adaptation of ventricular cardiomyocytes. Our results suggest that ventricular ANP expression in the adult rat is a dynamic event which is regulated by stress in the ventricular wall. The initial sites of ventricular ANP expression may represent zones of maximum tension in the ventricular wall following increased workload. To our knowledge this is the first study to demonstrate topographical changes in ventricular ANP expression in response to the development and reversal of cardiac hypertrophy.(ABSTRACT TRUNCATED AT 400 WORDS)
Amino Acid Sequence↗
Optimized determination of angiotensin I-converting enzyme activity with hippuryl-L-histidyl-L-leucine as substrate.
The determination of the angiotensin I-converting enzyme activity (ACE, kininase II, peptidyldipeptide hydrolase, EC 3.4.15.1) is necessary to control the course and the treatment of sarcoidosis, as well as to monitor the therapeutic use of enzyme inhibitors such as captopril in hypertension or congestive heart failure. Numerous synthetic substrates are known with which to measure the enzyme activity. A discontinuous method using hippuryl-L-histidyl-L-leucine was tested and improved. The cleavage product, hippurate, reacts with cyanuric chloride to give a yellow complex which can be measured at 405 nm using a spectral line photometer. Enzyme activity, kinetic constants and activation energy are dependent on the chloride ion concentration. Optimal test concentrations are 1.1 mol/l potassium chloride and 3.0 mmol/l hippuryl-L-histidyl-L-leucine at pH 8.3. Higher substrate concentrations effect an inhibition of the enzyme reaction. A Michaelis constant of 0.9 mmol/l was found with serum as enzyme source. An activation energy of 57 kJ/mol was obtained from the relation between the logarithm of velocity of enzyme reaction and reciprocal value of absolute temperature. Furthermore, a linear dependence on chloride ion concentration was observed. The histogram of the enzyme activities in sera from 146 healthy volunteers shows a non-gaussian distribution. The reference interval at 25 degrees C is characterized by a median of 24 units/l with the 2.5th and the 97.5th percentiles at 13 units/l and 42 units/l, respectively. The corresponding values at 37 degrees C are 27 units/l and 86 units/l with a median of 48 units/l. No significant sex and age dependence could be found. A potent ACE inhibitor such as captopril leads to a rapid decrease of the enzyme activity within 60 min after oral administration. In the following hours, the enzyme activity slowly increases.
Chromogenic Compounds↗
Perceptual-motor expectancies interact with covert visual orienting under conditions of endogenous but not exogenous control.
Central and peripheral cues were used to endogenously or exogenously direct the subject's attention to the location at which an increase or decrease in the size of a peripheral object was most likely to occur. For each subject, one size change was more likely to occur than the other, and the task was choice reaction time (expansion/contraction). Stimulus/response probability (particular size change) interacted with cue condition (valid, neutral and invalid) when the cues were central (endogenous), but the two variables were additive when the cues were peripheral (exogenous). These data, together with previous evidence, strongly suggest that qualitatively different attentional resources are recruited when visual orienting is endogenously and exogenously controlled.
Attention↗
A clathrin-coated vesicle-mediated pathway in atrial natriuretic peptide (ANP) secretion.
Atrial Natriuretic Peptide (ANP), produced by atrial cardiomyocytes, is an endogenous hypotensive agent that brings about vasodilation and diuresis. Similar to other polypeptide hormones, ANP is synthesized as a precursor, preproANP. The preprohormone is processed intracellularly and is stored in secretory granules as the prohormone. During the events of exocytosis, the prohormone is converted to its active form, ANP. In this study, a double-label immunocytochemistry experiment was performed using ANP and clathrin antibodies to determine if the transport of this hormone is mediated by clathrin-coated vesicles. Additionally, we have isolated clathrin-coated vesicles (CVs) from adult rat atria using immunoadsorption, and have characterized the fraction by using SDS PAGE, TEM, and Western blot analysis. The data demonstrate that: (1) ANP and clathrin co-localize in myocardial tissue, (2) clathrin-coated vesicles can be isolated from adult rat atria, and (3) clathrin-coated vesicles isolated from adult atrial myocardium contain predominantly proANP. The presence of proANP in clathrin-coated vesicles suggests that this polypeptide hormone is transported intracellularly via a clathrin-mediated pathway and during transit the prohormone is not significantly converted to its active form.
Animals↗
Hemodynamic findings in patients with left bundle branch block after myectomy in hypertrophic obstructive cardiomyopathy (HOCM)
To determine the hemodynamic effects of postoperative left bundle branch block (LBBB) in patients with hypertrophic obstructive cardiomyopathy (HOCM), we investigated 28 patients using Swan-Ganz pulmonary artery catheterization at rest and on exercise. Fourteen patients had postoperative LBBB (group A) and 14 had undisturbed intraventricular conduction (group B). All patients were examined by clinical investigation, electrocardiogram and bicycle ergometer exercise preoperatively and postoperatively (mean 6 months). Pulmonary artery pressure and pulmonary capillary wedge pressure were continuously measured, stroke volume index and cardiac index were obtained by the thermodilution method. All patients showed an improvement of their clinical symptoms (NYHA class: 2.8 +/- 0.45 before and 1.7 +/- 0.22 after operation) (P < 0.05). The postoperative exercise capacity (Watt) increased significantly (P < 0.05) in group A by 38% and in group B by 30%. The maximum mean pulmonary artery pressure on physical exercise decreased in group A from 40.7 +/- 9.1 to 32.5 +/- 8.7 mmHg and in group B from 42.8 +/- 12.4 to 32.4 +/- 9.2 mmHg (P < 0.05). The maximal stroke volume index and cardiac index improved significantly in 9 of 14 patients in each group. Thus, patients with HOCM and LBBB after myectomy have a marked improvement in postoperative hemodynamics, the results equaling those of patients with undisturbed intraventricular conduction.
Adolescent↗
Visual offsets facilitate saccadic latency: does predisengagement of visuospatial attention mediate this gap effect?
Saccadic reaction time (RT) is reduced when a fixation stimulus is extinguished 200 ms before a target appears. An attentional predisengagement theory (APT) may explain this gap effect: When covert attention is engaged (e.g., on fixation), the saccadic system is inhibited and RT is delayed; when the attended stimulus is extinguished, attention is disengaged, the inhibition is removed, and RT is facilitated. In 3 experiments covert attention was endogenously or exogenously cued to an object on the vertical meridian. Onset of a saccadic target on the horizontal meridian could be preceded by the offset of an attended or unattended object. Contrary to APT, RTs were identical after attended and unattended offsets. Results suggest that the gap effect has 2 components, and covert visual attention plays no role. One component is motor system preparation; the other is a fixation offset effect specific to the oculomotor system.
Attention↗
Developmental regulation of cytokine expression in the mouse brain.
Expression of four cytokine genes, transforming growth factor (TGF) beta 2, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and macrophage colony-stimulating factor (CSF-1 also known as M-CSF) was examined to determine whether these genes are developmentally regulated in the brain. Northern blots were performed on RNA isolated from the mouse brain from embryonic day 15 (E15) through postnatal day 9. TGF beta 2 gene expression was relatively high in the earliest embryos studied and decreased after E16-E17, and the three transcripts were developmentally regulated. TNF-alpha and IL-6 were detected in total RNA on all days studied. CSF-1 was detected only in polyadenylated RNA. The data suggest that expression of these cytokines is related to specific developmental events that share cellular functions with regenerative or inflammatory processes.
Animals↗
What are human express saccades?
When a fixation point is removed 200 msec prior to target onset (the gap condition), human subjects are said to produce eye movements that have a short latency (80-120 msec), that form the early peak of a bimodal latency distribution, and that have been labeled "human express saccades" (see, e.g., Fischer, 1987; Fischer & Breitmeyer, 1987; Fischer & Ramsperger, 1984, 1986). In three experiments, we sought to obtain this express saccade diagnostic pattern in the gap condition. We orthogonally combined target location predictability with the presence versus absence of catch trials (Experiment 1). When target location was fixed and catch trials were not used, we found mostly anticipations. In the remaining conditions, where responses were under stimulus control, bimodality was not frequently observed, and, whether it was or not, latencies were not in the express saccade range. Using random target locations, we then varied stimulus luminance and the mode of stimulus presentation (LEDs vs. oscilloscope) in the gap and overlap (fixation is not removed) conditions (Experiment 2). Bimodality was rarely observed, the gap effect (overlap minus gap reaction time) was additive with luminance, and only the brightest targets elicited saccades in the express range. When fixed locations and no catch trials were combined with latency feedback (Experiment 3), we observed many responses in the express saccade range and some evidence for bimodality, but the sudden introduction of catch trials revealed that many early responses were not under stimulus control. Humans can make stimulus-controlled saccades that are initiated very rapidly (80-120 msec), but unless catch trials or choice reaction time is used, it is not possible to distinguish such saccades from anticipatory responses that are prepared in advance and timed to occur shortly after target onset. Because the express saccade diagnostic pattern is not a characteristic feature of human saccadic performance, we urge investigators to focus their attention on the robust gap effect.
Attention↗
Diagnostic and therapeutic considerations in acute, severe mitral regurgitation: experience in 42 consecutive patients entering the intensive care unit with pulmonary edema.
Forty-two consecutive patients received emergency treatment for acute mitral insufficiency causing pulmonary edema between 1984 and 1992. The underlying diagnoses were acute myocardial infarction (n = 21), acute bacterial endocarditis on the native mitral valve (n = 9), prosthetic endocarditis in the mitral position (n = 4), acute failure of a replacement valve (n = 5), blunt chest trauma (n = 1) and chordal rupture in Marfan's syndrome (n = 2). Dysfunction of the subvalvular apparatus was present in 24 patients, verified by transthoracic echocardiography in 18 (75%) and by transoesophageal echocardiography in all patients in whom this technique was used. There were four cases of outflow strut fracture of a Björk-Shiley mitral prosthesis; a reliable diagnosis was made by fluoroscopy in all patients. Bedside hemodynamic monitoring was found to be unreliable both for differential diagnosis and for the quantitative assessment of the degree of mitral insufficiency. The right ventricular filling pressure was normal in 32/39 patients (82%), and the pulmonary artery and pulmonary capillary pressures elevated in 37/39 (95%). Diagnostically important, high pulmonary capillary v-waves were documented in 13 patients (33%). The left ventricular impedance could be influenced with sodium nitroprussid combined in some cases with dobutamin, and the resultant decrease of the peripheral vascular resistance from 1480 +/- 222 to 702 +/- 86 dyn x sec x cm-5 was followed by a proportionate reduction in the transmitral regurgitant fraction. Three patients died prior to the intended emergency surgical intervention. Emergency surgery was completed in 21 patients with an early mortality of 23.8% (n = 5). Ten patients underwent elective surgery within, and another three later than one year from the onset of the acute symptoms with an early mortality of 7.7% (n = 1). Four patients are alive and clinically well with medical treatment alone.
Adult↗
[The local lysis therapy of spontaneous renal artery dissection with arterial thrombosis].
A 33-year-old previously completely healthy man developed severe, at first colicky then persisting, pain in the left flank. The blood pressure was 190/110 mm Hg and he had pain over the left kidney on percussion. There was a mild leucocytosis (10,300/microliters), serum creatinine of 1.5 mg/dl and a rise in lactate dehydrogenase level to 395 U/l, while the urine was unremarkable. The pyelogram demonstrated on the left the upper calyceal system only and this very weakly. Colour Doppler ultrasound showed a massively reduced blood flow in the left renal vein while the artery was not visible. Digital subtraction angiography demonstrated eccentric narrowing of the left renal artery by an intravascular thrombus, providing the diagnosis of spontaneous renal artery dissection with thrombosis. Complete recanalization occurred after local thrombolysis with 500,000 IU urokinase over 7 hours, and subsequent administration of four times 40 mg tissue plasminogen activator over 4 hours. But the scintigram still demonstrated impaired renal function with decrease in clearance to 10% of total. The patient was still symptom-free on re-examination 16 months later, serum creatinine concentration was stable at 1.3 mg/dl and the blood pressure was normal.
Adult↗
Effects of green light on biological systems.
Green light (510-565 nm) constitutes a significant portion of the visible spectrum impinging on biological systems. It plays many different roles in the biochemistry, physiology and structure of plants and animals. In only a relatively small number of responses to green light is the photoreceptor known with certainty or even provisionally and in even fewer systems has the chain of events leading from perception to response been examined experimentally. This review provides a detailed view of those biological systems shown to respond to green light, an evaluation of possible photoreceptors and a review of the known and postulated mechanisms leading to the responses.
Animal Population Groups↗