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Biomedical subjects

C Bondy

Publications and source records attributed to C Bondy.

At least 37 records · Page 2Linked to original sources

Initial experience with a new algorithm for automatic mode switching from DDDR to DDIR mode.

UNLABELLED: Implantation of dual chamber devices in patients with paroxysmal atrial tachyarrhythmias who require permanent pacemakers may lead to significant complications due to an inappropriately triggered ventricular response. VVI/VVIR units cause loss of AV synchrony in the presence of sinus activity. A new DDDR device (THERA DR, model 7940), with an automatic mode switching (AMS) algorithm, was evaluated. When the mean atrial rate is > 182 beats/min, atrial tachyarrhythmia is detected, and AMS is activated. Twenty-three patients (12 males, mean age 71 +/- 7 years) underwent implantation of a THERA DDDR device with the AMS algorithm. Seventeen patients had AV block and/or sick sinus syndrome (SSS) and atrial arrhythmias, and 6 patients (2 with hypertrophic obstructive cardiomyopathy) had SSS and paroxysmal atrial fibrillation (PAF). The follow-up period was from 1-9 months. During follow-up, Holter monitoring and treadmill tests were performed. RESULTS: Eighty-seven episodes of AMS were recorded. Telemetered AMS recordings demonstrated episodes in which the DDDR mode switched to the DDIR mode in the presence of PAF, and reverted to DDDR when sinus rhythm returned. Paroxysmal supraventricular arrhythmias with a heart rate < 182 beats/min did not activate the mode switch. CONCLUSIONS: This early, short-term clinical experience with a DDDR device capable of AMS from DDDR to DDIR demonstrated appropriate clinical function and response to PAF. These preliminary results suggest that DDDR pacemakers with AMS to DDIR may significantly extend the current indications for dual chamber pacing.

Aged↗

Developmental gene expression and tissue distribution of the CHIP28 water-channel protein.

The CHIP28 water channel is a major component of red cell and renal tubule membranes; however, its ontogeny and tissue distribution remain undefined. Three patterns of expression were identified when CHIP28 mRNA was surveyed by in situ hybridization histochemistry in rats between embryonic day 14 and maturity. (i) CHIP28 mRNA and protein were very abundant in hematopoietic tissue and kidneys of mature rats, but strong expression did not occur until after birth, when it appeared in renal proximal tubules and descending thin limbs, red pulp of the spleen, and membranes of circulating red cells. (ii) CHIP28 mRNA was abundant in choroid plexus epithelium throughout fetal development and maturity. (iii) CHIP28 mRNA was transiently observed in periosteum, heart, vascular endothelium, and cornea during fetal development. The ontogeny of kidney and red cell CHIP28 expression coincides with the ability of kidneys to concentrate urine, suggesting that CHIP28 promotes water reabsorption in the proximal nephron and provides red cell osmoregulation needed for passage through the hypertonic medulla. Its presence in the choroid plexus suggests that CHIP28-mediated water transport contributes to secretion of cerebrospinal fluid. The functional role of CHIP28 in developing bone, heart, and eye is unclear. These findings further establish the general physiologic role of CHIP28 as a water channel involved in reabsorption, osmoregulation, and secretion. The studies also suggest other possible functions during fetal development and predict that complex mechanisms will be needed for regulation of CHIP28 gene expression in diverse tissues at distinct points in development.

Animals↗

Measurements of cardiac output by impedance cardiography in pacemaker patients at rest: effects of various atrioventricular delays.

OBJECTIVES: The purpose of this study was to evaluate the ability of impedance cardiography to determine the change in cardiac output caused by modifications in the atrioventricular (AV) delay in DDD (dual-chamber) pacing mode while pacing the atrium and ventricle at different programmed rates. BACKGROUND: Impedance cardiography permits continuous noninvasive monitoring of hemodynamic variables on a beat to beat basis. METHODS: Eleven patients with a DDD pacemaker were evaluated by impedance cardiography. Stroke volume, cardiac output and total peripheral resistance were assessed in the supine rest position during both DDD and ventricular (VVI) pacing. Hemodynamic variables were measured during DDD pacing at rates ranging from 60 to 110 beats/min in 10-beats/min increments with programmed AV delay varying from 50 to 250 ms in 50-ms increments. When the pacemaker was reprogrammed to the VVI pacing mode, these measurements were repeated at the same pacing rates. RESULTS: Cardiac output measurements during programmed conditions were found to be highly reproducible. The mean coefficient of variation was 3% during DDD pacing; it was 6% in the VVI pacing mode. A large decrease in cardiac output (approximately 30%) was found when a pacemaker was reprogrammed from the DDD to the VVI pacing mode. At DDD pacing rates between 70 to 110 beats/min, the highest cardiac output occurred at an average AV delay of < 120 ms from atrial stimulus to ventricular stimulus. At an average AV delay of > or = 200 ms, the cardiac output in the DDD and VVI pacing modes was similar. CONCLUSIONS: 1) Impedance cardiography allows highly reproducible noninvasive assessments of cardiac output in pacemaker patients; 2) inappropriate programming of the AV interval in patients with atrial and ventricular pacing can decrease cardiac output significantly, and the extent of the decrease is similar to or less than that observed in ventricular pacing; 3) hemodynamic measurements obtained with impedance cardiography can facilitate optimal programming of pacemaker variables.

Cardiac Output↗

Anatomy of the insulin-like growth factor system in the human testis.

OBJECTIVE: To study the cellular patterns of gene expression for insulin-like growth factors I and II (IGF-I and IGF-II), their receptors and specific high-affinity binding proteins (IGFBPs) in the human testis. DESIGN: In situ hybridization histochemistry was used to localize messenger ribonucleic acids (mRNAs) for IGF-I and IGF-II, the IGF-I and IGF-II receptors and IGFBP-1 to 6 in fresh-frozen testis sections from healthy young men who died of trauma. RESULTS: Insulin-like growth factor I mRNA was not detected. Insulin-like growth factors II mRNA was abundant in testicular blood vessels and peritubular connective tissue. Both IGF-I and IGF-II receptor mRNAs were most abundant in the germinal epithelium. Insulin-like growth factor binding protein 1 mRNA was not detected. Binding protein-2 mRNA was expressed in both Leydig and Sertoli cells. Binding protein-3 mRNA was detected only in the endothelium of testicular blood vessels. Binding protein-4 mRNA was also localized in endothelium but, in addition, was present in Leydig cells and interstitial connective tissue. Binding protein-5 mRNA was abundant in connective tissue and was detected at low levels in Leydig cells. Binding protein-6 mRNA was present in some of the peritubular cells and in some cells of the interstitial compartment. CONCLUSION: Our results suggest that IGFs may play significant roles in testicular function and germ cell development.

Adult↗

Anatomy of the human ovarian insulin-like growth factor system.

In situ hybridization was used to map insulin-like growth factor (IGF) system gene expression in ovaries from an anencephalic infant and several young women. Growing oocytes in infant and mature ovaries expressed transcripts for IGF-I and IGF-II, respectively, and all oocytes expressed abundant IGF-I receptor transcripts, raising the possibility of autocrine IGF function in oocyte maturation. IGF-I mRNA was not detected in the mature ovary, but IGF-II mRNA was localized in follicular blood vessels and in granulosa cells (GC) and was especially abundant in the GC of atretic as opposed to young follicles. IGF-I receptor mRNA was abundant in GC of antral and atretic follicles, and was expressed at low levels in the thecal and interstitial compartments. IGF-binding protein (IGFBP) 1 mRNA was not detected, but IGFBPs 2-5 mRNAs each demonstrated a unique ovarian distribution. IGFBP2 mRNA was abundant in GC and thecal cells at all stages of development. IGFBP3 mRNA was detected only in the endothelium of ovarian blood vessels. IGFBP4 mRNA was also localized in endothelium, but in addition was present in stromal connective tissue and in GC of the one Graafian follicle detected in this study, but not consistently in atretic follicles. IGFBP5 mRNA was expressed by luminal or cumulus GC in virtually all follicles and was highly abundant in stromal interstitial cells of the mature ovary.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Wilms' tumor (WT1) gene expression in rat decidual differentiation.

The Wilm's tumor suppressor gene (WT1) encodes a zinc-finger containing transcription factor that is selectively expressed in the developing urogenital tract, where it is thought to play a role in the differentiation of these tissues. We have used immunocytochemistry and in situ hybridization to study WT1 expression in the rat uterus during normal development and pregnancy from 0 to 20 days post coitum (p.c.). WT1 mRNA was abundant in uterine stroma from juvenile rats, but was much less abundant in uterine tissue from sexually mature rats; WT1 expression is not affected by ovariectomy or by treatment with estradiol or estradiol plus progesterone. WT1 gene was highly expressed, however, in the endometrial cells of early pregnancy. On day 6 p.c. WT1 mRNA was detected in anti-mesometrial decidual cells, and WT1 immunoreactivity was concentrated in the nuclei of these cells. All cells of fully-developed deciduoma at 7-8 days p.c. demonstrated WT1 expression. WT1 was not detected in trophoblast/placental tissues but remained abundant in the decidua basalis until parturition. The expression of WT1 was compared with insulin-like growth factor-II (IGF-II) and its receptor in the decidual since it has been shown that IGF-II gene transcription is repressed by WT1 in vitro. However, no spatiotemporal correlation in the expression of these three genes was found in differentiation of the rat decidua. In summary, these data suggest a role for WT1 in decidualization, since its expression is activated during the differentiation of uterine stromal cells into decidual cells.

Animals↗

Comparison between patients with and without reliable ventricular escape rhythm in the presence of long standing complete atrioventricular block.

The underlying heart rhythm was evaluated in 74 patients with complete atrioventricular block and had a permanent pacemaker implantation. The pacing was inhibited for 10 seconds or until the patient developed symptoms of presyncope or syncope. Fifty-six patients (74%) had a reliable escape with a mean cycle length of 2010 +/- 596 msec and a mean escape interval of 2335 +/- 971 msec. In 93% of these patients the escape interval was < 4 seconds. The patients without reliable escape (24%), developed symptoms only after a mean of 7153 +/- 1875 msec. The duration of the conduction disorder was longer in the patients without escape and the intraventricular conduction was slower. More patients without escape were treated and antiarrhythmic agents. Forty-eight patients were followed for 1 year and underwent at least two different studies and 13% had different results at different tests. In conclusion, patients without reliable escape have a longer history of conduction disorder, a slower intraventricular conduction, and are frequently treated with antiarrhythmic agents. Even patients with reliable escape occasionally may show a greater pacemaker dependence; therefore, they should also be considered as pacemaker dependent.

Aged↗

Anatomical and developmental patterns of facilitative glucose transporter gene expression in the rat kidney.

In situ hybridization was used to map cellular patterns of gene expression for facilitative glucose transporters (GTs) 1-5 in the developing and adult rat kidney. GT3 was not detected. GT1 mRNA was present in the proximal straight tubule (PST), distal nephron and collecting duct. GT2 mRNA was localized in both proximal convoluted and PST, while GT5 mRNA was detected only in the PST. GT4 mRNA and immunoreactivity were focally localized in the thick ascending limb of Henle's loop and were coexpressed with IGF-I. Thus, each of the four different isoforms demonstrated a distinct renal distribution, with GTs 1, 2, and 5 coexpressed in the PST. Renal GT1 and GT5 gene expression were unchanged throughout development, while GT2 was most abundant before weaning and GT4 was first detected after weaning. Only GT4 appeared to be hormonally regulated: It was decreased after hypophysectomy and increased after vasopressin treatment, but was not affected by 1 or 4 d of insulinopenic diabetes mellitus. The coexpression of GT4 and IGF-I in the thick ascending limb segment of the nephron suggests a novel autocrine/paracrine mechanism by which cells may control local fuel economy independently from that of the larger structure to which they belong and from the systemic hormonal milieu.

Animals↗

Correlation between insulin-like growth factor (IGF)-binding protein 5 and IGF-I gene expression during brain development.

Insulin-like growth factor (IGF)-binding proteins (IGFBPs) potently modulate the interactions of IGF-I and -II with the IGF-I receptor. Previous studies have shown that IGFBP2 gene expression is localized in astroglia, where it is anatomically and temporally coordinated with neuronal IGF-I expression during postnatal brain development. The present study shows that IGFBP5 gene expression is also highly abundant during brain development and also demonstrates significant spatiotemporal correlation with IGF-I, but exhibits a neuroanatomical distribution that is entirely distinct from IGFBP2. IGFBP5 and IGF-I mRNAs are synchronously coexpressed in principal neurons of sensory relay systems, including the olfactory bulb, medial and dorsal lateral geniculate bodies, and ventral tier, cochlear, lemniscal, and vestibular nuclei. They are also transiently coexpressed in principal neurons of the anterodorsal nucleus, but IGF-I mRNA disappears from this structure shortly after birth, while IGFBP5 mRNA remains highly abundant here in the adult. IGFBP5 and IGF-I gene expression demonstrate a temporally coordinated laminar association in the developing cerebellar cortex and hippocampal formation. IGF-I mRNA is concentrated in Purkinje cells, while IGFBP5 mRNA is localized in the external germinal zone in the developing cerebellar cortex. IGFBP5 mRNA is transiently expressed in the retrosplenial and cingulate cortex, subiculum, Ammon's horn, and amygdala, while IGF-I mRNA is contemporaneously localized in large interneurons distributed throughout the hippocampal formation. IGFBP5 mRNA is localized in the lateral ventricular germinal zone at birth and remains in the subventricular zone into maturity. It is also detected in forebrain white matter tracts and olfactory nerve from the second week after birth into maturity. Thus IGFBP5, in addition to IGFBP2, may be a significant determinant of IGF action in the brain. Colocalization in some sites and paralocalization with IGF-I in other sites suggests the potential for autocrine and paracrine interaction between the binding protein and IGF-I in different settings. Arguments are advanced suggesting a role for IGFBPs in the targeting of IGF action to specific cell addresses during brain development.

Animals↗

Cellular pattern of type-I insulin-like growth factor receptor gene expression during maturation of the rat brain: comparison with insulin-like growth factors I and II.

Insulin-like growth factors have a number of potent trophic effects on cultured neural tissue and most if not all of these effects appear to be mediated by the type-I insulin-like growth factor receptor. In order to establish the identity of cell types expressing this receptor in the rat central nervous system during development and maturity, we have used in situ hybridization to map sites of type-I insulin-like growth factor receptor mRNA synthesis in the developing and adult rat brain. In order to identify possible local sources of peptide ligands for this receptor, we have also mapped the sites of insulin-like growth factors I and II mRNA synthesis in parallel brain sections. From early development onward, there is a uniform and stable pattern of type-I insulin-like growth factor receptor gene expression in all neuroepithelial cell lineages, in which regional variations reflect primarily differences in cell density. In addition to this generalized pattern, during late postnatal development, high levels of type-I insulin-like growth factor receptor gene expression are found in specific sets of sensory and cerebellar projection neurons in conjunction with abundant insulin-like growth factor-I gene expression in these same neurons. While insulin-like growth factor-I expression is confined to the principal neurons in each system, receptor mRNA is also found in local interneurons. In the cerebral cortex and hippocampal formation, type-I insulin-like growth factor receptor mRNA and insulin-like growth factor-I are concentrated in different cell populations: receptor mRNA is abundant in pyramidal cells in Ammon's horn, in granule cells in the dentate gyrus, and in pyramidal cells in lamina VI of the cerebral cortex. Insulin-like growth factor-I mRNA is found in isolated medium- to large-sized cells which are rather irregularly distributed throughout the hippocampus and isocortex. In the hypothalamus, receptor mRNA is concentrated in the suprachiasmatic nucleus but is in low abundance elsewhere, including the median eminence, while insulin-like growth factor-I mRNA is not detected in this region at all. Type-I insulin-like growth factor receptor and insulin-like growth factor-II mRNAs are both abundant in choroid plexus, meninges and vascular sheaths from early development to maturity, but insulin-like growth factor-II mRNA is not detected in cells of neuroepithelial origin at any stage of development. This study provides evidence for two fundamentally different patterns of gene expression for the brain type-I insulin-like growth factor receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

First derivative of right ventricular pressure, dP/dt, as a sensor for a rate adaptive VVI pacemaker: initial experience.

Ten patients underwent implantation of a rate adaptive ventricular pacing system with a new pulse generator and lead. The unipolar lead has a steroid eluting tip and a pressure sensor. The first derivative of the signal from this sensor, dP/dt, is determined and the pacemaker rate is varied in response to changes in the right ventricular dP/dtMAX. During implantation, dP/dt values were in the range of 180-720 mm Hg/sec. The autothreshold for pacing at 2.5 V remained unchanged 1 month after implantation (0.065 +/- 0.045 msec, range 0.05-2.00 msec) and only slightly increased after 3 months (0.075 +/- 0.045 msec, range 0.05-2.00 msec). A significant correlation existed between the dP/dt measured during implantation and the right ventricular pressure measured by telemetry at follow-up visits (r = 0.93, P = 0.0001). Initial pacemaker programming was performed on the second day after implantation following a short walk and was adjusted subsequent to follow-up visits according to the patient's subjective assessment and in accordance with the results of exercise tests and Holter monitoring. Exercise and Holter tests did not significantly change initial programming. There was a significant correlation between right ventricular systolic pressure and the rate response setting (r = -0.66, P less than 0.05). During dP/dt pacing, all patients felt well, and eight of these reported an improvement compared to nonrate adaptive pacing. The heart rate response to effort and recovery was appropriate. It was concluded that: (1) right ventricular dP/dt is a suitable parameter for controlling the pacing rate; (2) appropriate programming of the dP/dt pacemaker results in a suitable heart rate response to exercise and recovery.

Aged↗

Altered expression of insulin-like growth factor-I (IGF-I) and IGF receptor genes after unilateral nephrectomy in immature rats.

There is a developmental difference in the initial phase of compensatory renal growth (CRG) following unilateral nephrectomy (UNX), in that CRG is GH-dependent in adult rats and GH-independent in immature rats. Furthermore, CRG in immature rats is associated with an increase in renal IGF-I mRNA, an effect not seen in adult rats. In this study we have examined the age-related differences in expression of the insulin-like growth factor-I (IGF-I) and IGF-II genes as well as in IGF-I and IGF-II receptors and membrane binding after UNX. Immature (22-24 days of age) and adult (4 months of age) male Wistar rats underwent a sham operation or left UNX and were killed 24 or 48 h later. Levels of mRNA for IGF-I and IGF-II and their receptors were determined in the left (control) and right (compensated) remnant kidneys using solution hybridization/RNase protection assays. Steady state levels of IGF-I mRNA as well as IGF-I receptor and IGF-II/mannose-6-phosphate receptor mRNAs were increased 3- to 4-fold in immature remnant kidneys, but not in adult kidneys. The findings related to IGF-I gene expression were confirmed by in situ hybridization to immature and adult kidney slices. The increase in IGF-I gene expression in the immature remnant kidneys was localized to the thick ascending limbs of the loops of Henle. Furthermore, in concert with the changes in mRNA levels, membrane binding studies showed significant increases in specific binding to IGF-I in cortical membranes and increases in specific binding to IGF-II in whole kidney membranes from immature, but not adult, rats. Thus, these findings demonstrate that the initial phase of CRG in the immature rat is associated with increased renal IGF-I gene expression as well as enhanced specific renal binding of IGF-I and IGF-II to plasma membranes and support the notion that this period of rapid renal growth in the immature UNX rat may involve the paracrine influence of the IGFs.

Animals↗

Anatomical relationships in the patterns of insulin-like growth factor (IGF)-I, IGF binding protein-1, and IGF-I receptor gene expression in the rat kidney.

The rat kidney is both a target of circulating insulin-like growth factor-I (IGF-I) and a site of local IGF-I production. In order to identify which renal structures produce IGF-I and the functionally related IGF binding protein 1 (IGFBP-1), and which structures are potential sites of circulating or endogenous renal IGF action, we have employed in situ hybridization to localize IGF-I, IGFBP-1, and IGF-I receptor messenger RNAs (mRNAs) in the rat kidney. The effects of hypophysectomy (Hx) and GH replacement on renal IGF-I, IGFBP-1, and IGF-I receptor gene expression have also been evaluated. IGF-I and IGFBP-1 mRNAs are both localized in the epithelial cells of medullary thick ascending limbs (TALs) of Henle's loops in the normal rat kidney. IGF-I receptor mRNA is also abundant in TALs, but, in addition, is distributed throughout the distal nephron and collecting duct, and in the glomerulus, with lowest levels found in proximal tubules. Hx and GH treatment had complex effects on patterns of renal IGF-I and IGFBP-1 gene expression. In general, Hx resulted in decreased IGF-I and increased IGFBP-1 mRNA levels, and GH treatment produced the opposite effects, while IGF-I receptor mRNA levels were not significantly effected by either treatment. However, the most dramatic effect produced by the interruption of the pituitary-renal axis was the demonstration of reciprocal changes in IGF-I vs. IGFBP-1 gene expression in individual kidneys and even in individual nephrons, suggesting a local interaction between IGF-I and IGFBP-1 in the regulation of their respective mRNA levels. Functional implications issuing from these anatomical relationships in renal patterns of IGF-I, IGFBP-1, and IGF-I receptor gene expression are that IGF-I, if secreted into the tubular lumen, possibly carried or modulated by IGFBP-1, may act on luminal TAL and downstream receptor sites. The specific physiological role of IGF-I produced in TALs is open to speculation. Glomerular IGF-I receptor sites, based on their localization upstream and distant from local sources of IGF-I production, are predicted to be targets for circulating IGFs.

Aging↗

Insulin-like growth factor-II and its binding proteins in placental development.

To identify potential mediators or modulators of insulin-like growth factor-II (IGF-II) action in the placenta, we used in situ hybridization to map patterns of gene expression for IGF-II, the functionally related IGF-binding proteins (IGFBPs) 1-4, and the type 1 and 2 IGF receptors in developing rat and term human placentas. IGF-II mRNA was highly abundant in trophoblast-derived elements of the rat placenta from implantation to maturity, except for a significant local reduction in IGF-II gene expression in the junctional zone just before term. IGFBP2 mRNA was barely detected during early placental development, but increased significantly toward term and was most abundant in the junctional zone. The basal plate of the term human placenta showed a similar pattern, with a superficial layer of cytotrophoblasts containing IGF-II mRNA anatomically apposed to a deeper layer of cells expressing IGFBP2 mRNA. Placental IGFBP1, -3, and -4 mRNAs were much less abundant than IGFBP2 and were restricted to the yolk sac and vasculature. Type 1 and 2 IGF receptor mRNAs were abundant and shared the same distribution, together with IGF-II, in the labyrinthine zone. These findings suggest that IGFBP2 may be an important modulator of IGF-II action in placental development. Furthermore, the colocalization of both types of IGF receptor mRNA supports the view that these receptors may compete for IGF-II binding in the placenta.

Animals↗

Insulin-like growth factor system gene expression in the human kidney.

Insulin-like growth factors (IGFs) have significant effects on renal function and have been implicated in renal development and hypertrophy. In order to investigate the renal IGF system in the human, we have used in situ hybridization to map the patterns of gene expression for IGF-I, IGF-II, IGF binding proteins-1 and -2 and both the type-I and type-II IGF receptors in the adult kidney. Since the rat is a model for the study of IGFs in renal physiology and pathophysiology, we compared patterns of IGF gene expression in the rat and human kidney. IGF-I messenger RNA (mRNA) is not detected in the human but is abundant in the rat kidney, while IGF-II is abundant in the human but not detected in the adult rat kidney. IGF-II mRNA is concentrated in renal vascular system, including afferent arterioles and the medullary interstitium. IGF-I and IGF binding protein-1 mRNAs are colocalized in the rat medullary thick ascending limbs of Henle's loops, but neither is detected in the human kidney. IGF binding protein-2 mRNA is concentrated in glomeruli in both species, but, whereas in the human it is expressed in the epithelium of the distal nephron and collecting ducts, in the rat it is localized in the medullary interstitium. The patterns for both type-I and type-II IGF receptor gene expression are identical in both species; however, type-I receptor, mRNA is distinctly more abundant than type-II. Both IGF receptor mRNAs are abundant in the renal tubular epithelium of the medulla and both are barely detectable in proximal tubules. Type I receptor mRNA alone is abundant in glomerular structures. These observations suggest that the autocrine/paracrine roles of IGFs are quite different in rat and human kidney. The conserved patterns of IGF receptor expression, however, suggests that the role of circulating IGFs in regulating renal function may be similar across the species.

Adult↗