Pari Passu Research Articles

Comparative phenotypes in rhabdomyosarcomas and developing skeletal muscle

The morphological and immunohistochemical phenotypes of 51 rhabdomyosarcomas from young people have been described and contrasted with phenotypes in developing skeletal muscle from 20 fetuses and neonates. The tumours express markers in a cumulative and consistent sequence--vimentin, desmin, fast myosin, myoglobin--which evolves pari passu with morphological differentiation and follows the same pattern found in normal myogenesis. Changes in immunohistochemical phenotype are documented in residual and recurrent tumours excised after chemotherapy. The presumptive rhabdomyoblastic nature of some primitive tumours, marking with vimentin alone, is discussed.

Risk premia in forward exchange rates: systematic or unsystematic?

International traders frequently use forward exchange transactions to hedge their cash flows in foreign currencies. A key issue is whether the forward rates are efficiently priced. There is evidence of time-varying risk premia in forward exchange rates. Are these risk premia systematic or unsystematic? This article uses a market model to explain risk, implying that the risk premium in the forward rate varies pari passu with the beta of the return to speculative forward positions. Assuming the unobserved risk premium is proportional to the forward premium allows testing the predicted relations; the data reject the joint hypotheses of the model and systematic risk. In terms of a simple factor model explaining the covariation of the forward premium, the risk premium, and the expected percentage rate of change of the spot exchange rate, the assumption that the forward premium and the risk premium are proportional can be relaxed without changing the empirical results.

Accumulation of calcium in substantia nigra lesions induced by status epilepticus. A microprobe analysis

Status epilepticus of sufficient duration (>30min) causes a unique lesion of substantia nigra pars reticulata (SNPR), and of globus pallidus (GP). This lesion, which encompasses a pan-necrotic destruction of neurons and glial cells seems to develop during ongoing seizures. We decided to investigate if the lesion is accompanied by net calcium accumulation. Seizures of 20 and 60 min duration were induced by the administration of flurothyl, and the tissue was frozen in situ either at the end of the seizure periods, or after recovery periods of 15 or 120 min. The total calcium and potassium contents of caudoputamen, neocortex, GP and SNPR were measured using particle induced X-ray emission (PIXE) in the microprobe mode. Seizures of 20 min duration did not cause net accumulation of calcium. When the duration of seizures was extended to 60 min the results varied depending on the location. In caudoputamen, which does not incur neuronal damage, no calcium accumulation was observed. In GP and SNPR, such a rise was unequivocally demonstrated, with calcium content increasing to about 150% of controls. The increase in calcium correlated to a decrease in potassium content. It is concluded that epileptic cell death occurs pari passu with accumulation of calcium although it cannot be stated that this accumulation is the cause of the cell death. It is speculated that seizures increase the permeability of the blood-brain barrier to calcium, and that enhanced blood to tissue transfer increases the calcium load of metabolically strained cells.

The dependence of the time constant of left ventricular isovolumic relaxation (tau) on pericardial pressure.

The purpose of this study was to investigate the dependence of tau, the time constant of left ventricular (LV) isovolumic relaxation, on pericardial pressure and to compare values of tau as determined by the methods of previous investigators and by a standard exponential curve fit. All of the more recent methods involve an additional parameter--the pressure to which the exponential relaxation finally declines (PB, the pressure intercept in the method of Craig and Murgo and the asymptote in the exponential fits). An additional purpose of the study was to determine the relation of these parameters to pericardial pressure. In eight closed-chest anesthetized dogs, tau was calculated from intracavitary (Plv) and transmural LV pressure (Plv = Plv-Pper) by each method as pericardial (Pper) and LV end-diastolic pressure were changed by pericardial infusion and intravenous volume loading. The time constant determined by the method of Weiss et al was dependent on pericardial pressure; the time constants determined by the other methods were not. PB and the asymptotes were found to be similar and to increase almost equally with pericardial pressure. When pericardial pressure was zero, these values were approximately -20 mm Hg. Thus, both these parameters seem to indicate the same baseline pressure, a pressure that increases pari passu with pericardial pressure. Reported changes in the value of tau calculated from intracavitary LV pressure by the method of Weiss et al may reflect factors other than changes in LV diastolic function.

Renal Blood Flow and Glomerular Filtration Rate during the Heterologous Phase in Passive Heymann Nephritis in Rats

When passive Heymann nephritis (PHN) is induced by infusion of antibodies (anti-Fx1A), an acute fall in renal blood flow (RBF) and glomerular filtration rate (GFR) has been reported. Activation of the complement cascade by the local antigen-antibody reaction might be involved in this reaction. We therefore studied RBF and GFR during acute infusion of anti-Fx1A and after 3 days when heterologous antibodies are no longer present in the circulation. Two groups of rats were infused with 2 mg anti-Fx1A antibodies into the left renal artery; RBF was measured by the microsphere method and GFR by 125I-Na-iothalamate clearance. In the first group, the measurements were made 40 min after the infusion, and in the second group after 3 days. A third group was studied 3 days after infusion of 1 mg anti-Fx1A. Animals infused with normal IgG were used as controls. Forty minutes after infusion of 2 mg anti-Fx1A, GFR in the left kidney was reduced from 1.16 +/- 0.07 to 0.41 +/- 0.16 ml/min/g in the controls (p less than 0.05). Three days after the infusion, GFR was 1.04 +/- 0.07, not significantly different from control. RBF was reduced to 3.97 +/- 1.11 ml/min/g after 40 min, compared to 7.53 +/- 0.73 in controls (p less than 0.05), and was normalized after 3 days. The effect of 1 and 2 mg anti-Fx1A antibodies was not significantly different after 3 days. Anti-Fx1A antibodies were detected in serum in the acute stage, but not after 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Tubular basement membrane change occurs pari passu with the development of cyst formation

Our previous studies have shown that 2-amino-4,5-diphenyl thiazole hydrochloride (DPT) administered orally to rats induces a urine concentrating defect (within 1 to 2 days) and progressive, but reversible, cystic change of all collecting tubules (prominent between 4 and 8 weeks). Cystic change was characterized by tubular cell and basement membrane changes consisting of alterations in cellular biosynthetic/secretory organelles, followed by thickening of the basement membrane with marked reduction (approximately 50%) of the de novo synthesis of sulfated proteoglycans, suggesting that altered synthesis of tubular basement membrane plays a role in the development of cystic disease. In this study, following the administration of [14C]-DPT in vivo, a major urinary metabolite (greater than 70%) was isolated by HPLC and characterized by gas chromatographic-mass spectral and NMR analyses as 2-amino-4-hydroxyphenyl-5 phenyl thiazole, designated phenol II. Phenol II was synthesized and administered orally to rats for four days to compare its biological effects with DPT. Phenol II induced a significantly greater impairment of concentrating ability and tubular cystic transformation than DPT. At day 5, in phenol II treated animals, basement membranes lining cysts were thickened several-fold and exhibited extensive loss and disorder of ruthenium red binding sites, indicative of loss of sulfated proteoglycans (heparin sulfate proteoglycan). The basement membrane changes occurred in tandem with the development of cystic transformation and strongly suggests that the basement membrane has a key role in the pathogenesis of PKD. The findings support the hypothesis that PKD may be due to a defect in the synthesis/degradation of one or more basement membrane components (sulfated proteoglycans) resulting in faulty tubular morphogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Accumulation of calcium and loss of potassium in the hippocampus following transient cerebral ischemia: a proton microprobe study.

This study explored (a) whether postischemic accumulation of calcium in hippocampal neurons precedes or occurs pari passu with light microscopical signs of delayed neuronal necrosis, and (b) whether calcium initially accumulates in dendritic domains, presumed to have a high density of agonist-operated calcium channels. Transient ischemia of 10-min duration was induced in rats, and the animals were studied after 1, 2, 3, and 4 days of recovery. We measured total calcium and potassium contents in the stratum oriens, pyramidale, radiatum, and moleculare of the CA1 and CA3 sectors, using particle induced x-ray emission (PIXE) in the proton microprobe mode. The results showed significant accumulation of calcium and loss of potassium after 3 and 4 days of recovery in the CA1 sector, which developed neuronal necrosis, but not in the CA3 sector, which showed only occasional damage. In a few animals, calcium accumulation (and loss of potassium) was observed with no or only mild visible damage, but in the majority of animals the accumulation of calcium correlated to signs of neuronal necrosis. Since calcium accumulation was similar in all strata examined, the results failed to reveal preferential accumulation in dendritic or somal regions. Based on our results and those of Dux et al., we emphasize the possibility that delayed neuronal death is, at least in part, caused by increased calcium cycling of plasma membranes and gradual calcium overload of mitochondria.

Lumbar disc surgery and variations in C-reactive protein, erythrocyte sedimentation rate and the complement split product C 3 d.

Lumbar disc surgery was performed in fifty consecutive patients and variation in erythrocyte sedimentation rate (ESR), complement C 3 d, and C-reactive protein (CRP) levels before and after surgery were recorded. Preoperative values were within normal limits in all patients. Postoperatively, CRP increased immediately, with a maximum of 28.5 mg/l on the 2nd day and were normalized within 6 days. The maximum ESR elevation occurred after the 6th day and was followed by a slow decrease. After 12 weeks some patients still had an elevated ESR. Plasma C 3 varied pari passu with the ESR. Uncomplicated recovery after lumbar disc surgery seems to be indicated by a normalization of CRP, regardless of ESR values. Therefore, ESR may not be so useful as an indicator of disc space inflammation as previously accepted.

Squamous carcinoma arising in dermoid cysts and associated with hypercalcemia: A clinicopathologic study of six cases

Six cases of squamous carcinoma arising in dermoid cysts are reported. In four out of five cases in which serum calcium was measured hypercalcemia was present and increased pari passu with increases of tumor size. The presence of hypercalcemia in association with an ovarian tumor may therefore point to the possibility of this background. In all cases survival was short, ranging from 3 to 17 months. Five patients were treated with cisplatin, etoposide, and bleomycin but without great benefit. These cases, together with a review of the literature, suggest that a new treatment will be needed to improve survival in all but a few Stage I cases.

Commodity problem: What next?

Export commodity prices of developing countries are now at their lowest point since 1980–1981. International action to stem the decline in prices or provide sufficient compensatory finance has been limited, and no overall plan is under way to improve the situation. Under these circumstances the developing countries must fend for themselves, through expansion of their mutual trade with a minimum use of scarce convertible foreign exchange, and through improvement of their bargaining position in the world market, where feasible, through coordinated selling of their products. These actions call for: (1) an expansion of South-South compensable trade (“counter-trade”) and its better organization in order to reduce the excessive discounts and marketing margins which now prevail; (2) centralized selling in the world market at better prices of commodities for which the demand is price-inelastic (tropical beverages and to some degree metals); and (3) expansion of volume of sales at competitive prices of products which face substitution of synthetics or goods produced in developed countries, provided such expansion is profitable. This paper discusses these alternatives and the potential problems which may continue to interfere with progress. The author concludes that the need for international cooperative action will grow pari passu with the need to cooperate in money and finance, which are in as much trouble as commodities and international trade.

The impact of administrative stringency on applications for the old age assistance program in new jersey

The purpose of this paper is to examine the impact of stricter eligibility enforcement on the flow of applications of the Old Age Assistance (OAA) Program in New Jersey. Most of the previous research in the welfare area has focused entirely on explaining measures of the stock demand for public assistance. Higher claim denial rates may affect the stock demand by deterring those potential recipients with less legitimate claims. However, there is also a strictly mechanical relationship such that a claim period t or in state i reduces, pari passu, the stock demand in period t or in state i below the level that would have prevailed in the absence of the denial. Thus, if the objective is to isolate a deterence effect, it seems more appropriate to examine the impact of previous recent denial rates on the flow of new applications for public assistance. A time series of monthly applications for OAA in New Jersey are related to lagged values of the denial rate of such applications, cyclical activity, seasonal factors and trend. The results suggest that stricter enforcement of eligibility rules does deter future claims.

An immunohistochemical study of synaptogenesis in the electric organ of Torpedo marmorata by use of antisera to vesicular and presynaptic plasma membrane components

Synaptogenesis has been studied in the electric organ of embryonic Torpedo marmorata by use of two antisera directed against components of synaptic vesicles (anti-SV) and presynaptic plasma membranes (ap-anti-TSM), respectively. The anti-SV serum was previously shown to recognize a proteoglycan specific for synaptic vesicles. The ap-anti-TSM serum was raised to plasma membranes of synaptosomes derived from the electromotor nerve terminals and affinity-purified on electric-organ gangliosides. The vesicular antigen was first detectable at the 81-mm stage of development, which is 1-2 weeks earlier than the formation of morphologically mature presynaptic terminals, but is coincident with a rise in choline acetyltransferase levels and the ability of the electric organ to generate discharges. The gangliosidic antigen recognized by the ap-anti-TSM was first detectable on the ventral electrocyte surface at the 93-mm stage of development. This indicates that specific carbohydrate epitopes, not present on the growth cones, are expressed during maturation of the nerve terminal. The nerve terminal components recognized by these sera arose pari passu with neurite coverage of the ventral surface of the electrocyte, reaching a maximum in the adult. In contrast, postsynaptic aggregates of acetylcholine receptor, rendered visible with rhodamine-labeled alpha-bungarotoxin, arose previous to the presynaptic antigens, reaching a maximum surface density at 110 mm and then declining in the adult.

In-vitro fertilization: the ethics.

This paper is addressed to practitioners. It seeks to acquaint them with 'ethical' arguments against their work which, because they are simple and plausible, persuade many people. These arguments are briefly rehearsed and as briefly examined. A more positive ethics of in-vitro fertilization is presented which seeks to respect (a) what is known in the relevant science and done in developing practice; (b) the inseparability of research from clinical application; (c) a moral tradition of long-standing which relates the protection of fetal life pari passu with its own morphological growth towards maturity; (d) the moral sense of properly informed persons whose judgements we trust in other areas of life. Practitioners themselves are to be defended as the proper moral agents (that is, to be entrusted with decisions) provided that they are careful (a) to keep public confidence by means of a corporate self-discipline; (b) to keep faith with patients and research subjects; (c) to maintain mutual trust between research scientists and clinical practitioners; (d) to safeguard the liberty of disciplined enquiry, of purposeful curiosity, as being inherent in the notion of a science, necessary to therapeutic advance, and proper to the nature of man. The author writes from within the theological tradition of the Church of England.

The etiology of the Klippel-Trenaunay syndrome.

The etiology of the Klippel-Trenaunay syndrome (KTS) remains obscure. Although venous hypertension secondary to deep venous obstruction has been suggested as a cause, recent studies have demonstrated that most patients have unimpeded venous drainage. Calf blood flows have been measured in 33 patients with KTS using venous occlusion plethysmography. Although all flow rates were within normal limits, flow in affected limbs was invariably greater than in normal limbs (p less than 0.001), and this is related to the presence of the nevus. Biopsies of subcutaneous veins demonstrate the histological features of a response to chronically raised flow. The authors suggest that KTS is caused by mesodermal abnormality during fetal development, leading to the maintenance of microscopic arteriovenous communications in the limb bud, as a result of which the triad of nevus, hypertrophy, and superficial varices is produced. Deep venous abnormalities occur pari passu with the triad and are not responsible for its development.

Aspects of ingestive behavior in cattle.

Ingestive behavior in cattle differs from other species because of physiological mechanisms developed pari passu with fermentative digestion. The secondary refection of rumination allows remastication and reinsalivation of the large bulk of vegetable food ingested. The need to buffer acid products of cellulose digestion demands continuous high secretion of alkaline saliva. Nervous and hormonal stimuli emanating from the gastrointestinal tract evoke centrally controlled behavior of hunger and satiety. The four primary taste receptors occur in cattle but thresholds are low. Because of the low Na level in plants, cattle have developed the behavior of seeking salt by taste and smell. During Na deficiency it can be shown that cattle readily learn and develop memory, providing a powerful behavioral dimension in the search for food.

Endorphins and exercise.

It is generally accepted that serious exercise training leads to marked menstrual irregularity and frequently complete amenorrhea in females, due to a decrease in the release of hypothalamic gonadotrophin releasing hormone (GmRH). The recent demonstration of a rise in plasma met-enkephalin during this process suggests an etiological role for endogenous opiates, but further studies in the presence of naloxone or other opiate antagonists are necessary to define the situation further. It may be relevant that naloxone does not overcome the inhibition of GnRH release seen in anorexia nervosa (Grossman et al., 1982b). In male subjects, severe exercise leads to an opiate inhibition of ventilation and catecholamine release, pari passu with a decrease in effort perception. It is probable that these are central effects of opiates, and possible that the decrement in effort perception is causally related to the partial inhibition in catecholamine response. This suggests that the capacity to undergo severe stress is modulated by endogenous peptides - an alteration in the sympathetic and adrenomedullary response to stress may also have long-term sequelae in terms of hypertension and cardiovascular damage (Brown, 1981). We have some data that demonstrate a correlation between the level of opiate inhibition (measured by naloxone-induced changes in hormone levels) and personality variables, and it is possible that interindividual variation in stress responsiveness is opiate-mediated. Of course, opiates are only a small family in a network of neuropeptides that may control cardiac and sympathetic function, including the recently isolated 'neuropeptide tyrosine'. Nevertheless, it seems increasingly likely that endogenous opiates will be seen to be important modulators of the neuroendocrine responses to stress.

Ca2+ regulation of tight-junction permeability and structure in Necturus gallbladder.

To explore the role of Ca2+ in tight-junction permeability, the Necturus gallbladder was exposed to varying Ca2+ concentrations and to the Ca2+ ionophore A23187 added to the mucosal side (1.9 X 10(-6) to 6.8 X 10(-5) M). Electrophysiological parameters measured in an Ussing-type chamber were correlated with tight-junction morphology revealed by freeze-fracture electron microscopy. In Ca2+-free bathing media, transepithelial resistance decreases and tight-junctional ultrastructure is fragmented. In 1.8 mM Ca2+ media, A23187 induces an initial drop in transepithelial resistance, followed by an increase in transepithelial resistance to a value 20% above base line. At peak response to A23187, NaCl diffusion potentials decrease. Freeze-fracture replicas reveal that the number of junctional strands increase pari passu with junctional depth. Both physiological and morphological changes were partially reversible. The initial decrease in transepithelial resistance coincided with a persistent hyperpolarization of the mucosal cell membrane potential difference and a decrease in the mucosal-to-serosal cell membrane resistance ratio. Thus A23187 alters both the transcellular and paracellular pathway, resulting in opposing effects on transepithelial resistance.

Cardiac versus coronary vasodilator actions of KB-944, a new calcium antagonist, assessed in isolated, blood-perfused heart preparations of dogs.

We compared the cardiac and coronary vasodilator actions of a new calcium-antagonistic vasodilator, KB-944, in isolated, blood-perfused heart preparations of dogs. In all preparations KB-944 injected intra-arterially produced an increase in blood flow. In sinoatrial (SA) node preparations KB-944 decreased sinus rate and in large doses produced atrial standstill. In atrioventricular (AV) node preparations KB-944 increased AV conduction time and in large doses produced second- or third-degree AV block only when injected into the artery supplying the AV node. In the same preparations KB-944 had virtually no effect on AV conduction when injected into the artery supplying the His-Purkinje-ventricular system. In papillary muscle preparations KB-944 in medium and large doses depressed force of contraction, the depressant action being greater at high rates of contraction. In the same kind of preparations KB-944 affected automaticity slightly and inconsistently. Depression by KB-944 of SA nodal automaticity and AV nodal conduction occurred pari passu with coronary vasodilation, whereas force of contraction was depressed to a lesser extent in coronary vasodilator doses. In these respects, KB-944 resembles verapamil and diltiazem rather than nifedipine and nicardipine.

Coronary physiology.

The major areas of normal coronary physiological research since Berne's 1964 review have been the measurement of ventricular transmural blood flow distribution with microspheres, the adenosine hypothesis of local metabolic control of coronary blood flow, and the autonomic control of coronary blood flow. There is an improved understanding of intramyocardial tissue pressure and extravascular compressive forces on coronary vessels. However, the unexpected finding of zero flow during a prolonged diastole with a coronary artery pressure of 40 mmHg (PZF) is a reminder that the physical forces, including vascular smooth muscle contraction, that determine coronary vascular resistance are incompletely understood. During normal circumstances, the left ventricular subendocardium probably receives more blood flow than the subepicardium does, but the difference is small. When the coronary circulation is compromised by stenosis or aortic valve lesions, the subendocardium is much more vulnerable to underperfusion than is the subepicardium. The coronary vasodilating effect of arterial hypoxia has been confirmed in many studies, but the role of tissue oxygen tension in local metabolic control of coronary blood flow during normoxia is unknown. The coronary vasodilating action of carbon dioxide has received renewed attention, but its role in local control is also unknown. The adenosine hypothesis has passed several critical tests, but despite much research the importance of adenosine in normal coronary regulation is not established. Local metabolic control of coronary blood flow probably involves more than just one factor, but a unified hypothesis has not been put forward. Sympathetic alpha-receptor-mediated coronary vasoconstriction has been demonstrated by nerve stimulation and during a carotid sinus baroreceptor reflex. Sympathetic coronary vasoconstriction is capable of competing with local metabolic control to lower coronary venous oxygen tension under experimental circumstances, but its importance during normal resting conditions is not established. Parasympathetic muscarinic coronary vasodilation has been shown by vagal nerve stimulation, but a role for it during normal blood flow regulation has yet to be demonstrated. There have been elegant descriptive studies of the coronary blood flow response during excitement and exercise, where coronary blood flow increases pari passu with myocardial metabolism; however, there are also data that indicate a concomitant sympathetic vasoconstrictor effect during strenuous exercise. Overall there has been encouraging progress in coronary physiology. Inevitably new knowledge has focused old questions and presented new ones.

Foreign Currency Claims: Pari Passu May Not Mean Equal

Foreign Currency Claims: Pari Passu May Not Mean Equal