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PubMed2006

Control of compartment size by an EGF ligand from neighboring cells.

Insect bodies are subdivided into anterior (A) and posterior (P) compartments: cohesive fields of distinct cell lineage and cell affinity . Like organs in many animal species, compartments can develop to normal sizes despite considerable variation in cell division . This implies that overall compartment dimensions are subject to genetic control, but the mechanisms are unknown. Here, studying Drosophila's embryonic segments, I show that P compartment dimensions depend on epidermal growth factor receptor (EGFR) signaling. I suggest the primary activating ligand is Spitz, emanating from neighboring A compartment cells. Spi/EGFR activity stimulates P compartment cell enlargement and survival, but evidence is presented that Spitz is secreted in limited amounts, so that increasing the number of cells within the P compartment causes the per-cell Spitz level to drop. This leads to compensatory apoptosis and cell-size reductions that preserve compartment dimensions. Conversely, I propose that lowering P compartment cell numbers enhances per-cell Spitz availability; this increases cell survival and cell size, again safeguarding compartment size. The results argue that the gauging of P compartment size is due, at least in part, to cells surviving and growing according to Spi availability. These data offer mechanistic insight into how diffusible molecules control organ size.

Animals↗

PubMed1998

Myocardial effect compartment modeling of metoprolol and sotalol: importance of myocardial subsite drug concentration.

We have recently reported the time course of acute myocardial drug uptake and simultaneous pharmacodynamic effects for metoprolol (4 mg; n = 12) and sotalol (20 mg; n = 10) in patients with ischemic heart disease. The acute pharmacodynamic effects of the two drugs included reductions in both spontaneous heart rate and the contractile index peak positive rate of left ventricular pressure rise and prolongation of the electrocardiographic PR interval, all of which exhibited an equilibration delay compared with myocardial drug content. The objective of the current study was to analyze the relationship between myocardial drug content and effect for both metoprolol and sotalol using an effect compartment model, to examine the potential for the two drugs to share a common subsite of action in the myocardium. The time course of myocardial drug content was best described by a one-compartment model for metoprolol and a two-compartment model for sotalol. A linear pharmacodynamic model, relating the amount of drug at the effect-site (Ae) with each of the three effects, was used in the effect compartment modeling. The slope of each of these effects as a function of Ae was considerably flatter for sotalol than for metoprolol, reflecting the relative beta-adrenoceptor antagonistic potencies of the two drugs. The exit rate constant from the effect compartment (K(eo)) did not differ significantly from each other or from the exit rate constant from the "peripheral" compartment (K21) for sotalol. The results suggest that the effect compartment within the myocardium for both drugs may correspond to a "peripheral" compartment, even though a "peripheral" pharmacokinetic compartment for myocardial metoprolol content was not apparent. Thus, the effect compartment for many cardioactive drugs may correspond to a pharmacokinetically "peripheral" compartment, irrespective of localization of effect to a small (e.g. sinoatrial node) or large (e.g. ventricular myocardium) region of the heart.

Adrenergic beta-Antagonists↗

PubMed2006

Difference in organization of corticostriatal and thalamostriatal synapses between patch and matrix compartments of rat neostriatum.

The neostriatum, which possesses a mosaic organization consisting of patch and matrix compartments, receives glutamatergic excitatory afferents from the cerebral cortex and thalamus. Differences in the synaptic organization of these striatopetal afferents between the patch and matrix compartments were examined in the rat using confocal laser scanning and electron microscopes. Thalamostriatal terminals immunopositive for vesicular glutamate transporter (VGluT) 2 were less dense in the patch than in the matrix compartment, although the density of VGluT1-immunopositive corticostriatal terminals was almost evenly distributed in both the compartments. Quantitative analysis of ultrastructural images revealed that 84% of VGluT2-positive synapses in the patch compartment were formed with dendritic spines, whereas 70% in the matrix compartment were made with dendritic shafts. By contrast, VGluT1-positive terminals display a similar preference for specific synaptic targets in both compartments: about 80% made synapses with dendritic spines. In addition, VGluT2-positive axospinous synapses in the patch compartment were larger than the VGluT1-positive axospinous synapses in both compartments. As axospinous synapses are generally found in neuronal connections showing high synaptic plasticity, the present findings suggest that the thalamostriatal connection requires higher synaptic plasticity in the patch compartment than in the matrix compartment.

Animals↗

PubMed1997

Assembly of complete, functionally active herpes simplex virus DNA replication compartments and recruitment of associated viral and cellular proteins in transient cotransfection assays.

Early during the herpes simplex virus (HSV) lytic cycle or in the presence of DNA synthesis inhibitors, core viral replication machinery proteins accumulate in intranuclear speckled punctate prereplicative foci, some of which colocalize with numerous sites of host cellular DNA synthesis initiation known as replisomes. At later times, in the absence of inhibitors, several globular or large irregularly shaped replication compartments are formed; these compartments also contain progeny viral DNA and incorporate the IE175(ICP4) transcription factor together with several cellular proteins involved in DNA replication and repair. In this study, we demonstrate that several forms of both prereplication foci and active viral replication compartments that display an appearance similar to that of the compartments in HSV-infected cells can be successfully assembled in transient assays in DNA-transfected cells receiving genes encoding all seven essential HSV replication fork proteins together with oriS target plasmid DNA. Furthermore, bromodeoxyuridine (BrdU)-pulse-labeled DNA synthesis initiation sites colocalized with the HSV single-stranded DNA-binding protein (SSB) in these replication compartments, implying that active viral DNA replication may be occurring. The assembly of complete HSV replication compartments and incorporation of BrdU were both abolished by treatment with phosphonoacetic acid (PAA) and by omission of any one of the seven viral replication proteins, UL5, UL8, UL9, UL42, UL52, SSB, and Pol, that are essential for viral DNA replication. Consistent with the fact that both HSV IE175 and IE63(ICP27) localize within replication compartments in HSV-infected cells, the assembled HSV replication compartments were also able to recruit both of these essential regulatory proteins. Blocking viral DNA synthesis with PAA, but not omission of oriS, prevented the association of IE175 with prereplication structures. The assembled HSV replication compartments also redistributed cotransfected cellular p53 into the viral replication compartments. However, the other two HSV immediate-early nuclear proteins IE110(ICP0) and IE68(ICP22) did not enter the replication compartments in either infected or transfected cells.

Animals↗

PubMed1986

Two-color flow-cytometric analysis of the growth cycle of Plasmodium falciparum in vitro: identification of cell cycle compartments.

A previous study (Hare JD, Bahler DW: J Histochem Cytochem 34:215, 1986) has shown that the flow cytometric analysis of acridine-orange-stained Plasmodium falciparum growing in vitro generates a complex two-color display, regions of which correlate with the major morphological stages. In this report, four cell cycle compartments (A-D) are defined by characteristic ratios of red and green fluorescence of cells distributed throughout the erythrocytic cycle as well as by the differential effects of several metabolic inhibitors. The primary characteristic of cells in compartment A is the significant increase in red fluorescence. Inhibition of DNA synthesis by either aphidicolin or hydroxyurea causes the accumulation of cells at the interface between compartments A and B, whereas n-butyrate prevents cells in compartment A from reaching the A-B interface. Cells in compartment A display a small increase in green fluorescence which is independent of DNA synthesis but is enhanced by n-butyrate treatment. Cells in compartment B display a continued increase in red fluorescence coupled with a significant increase in green fluorescence, reflecting the onset of DNA synthesis in compartment B. The transition to compartment C is more abrupt and is associated with a marked increase in green fluorescence and little increase in red fluorescence. Compartment D is characterized by an increase in red fluorescence and a continued rise in green fluorescence. It is postulated that these discontinuities in the two-color display reflect not only changes in the rates of RNA and DNA synthesis but also decondensation of parasite chromatin in compartment A as the organism prepares for DNA synthesis, and re-condensation in compartment D as the newly replicated chromatin prepares for segregation into merozoites. The method described promises to provide a sensitive and rapid technique to study the effects of various factors on the growth cycle of the parasite.

Animals↗

PubMed2002

Do cows prefer a barn compartment with a grooved or slotted floor?

Cow preferences for one of two compartments with different floors were tested in a barn with two symmetrical, connected compartments, each intended for 16 cows. Compartments were identical except for the floor. One floor was grooved longitudinally to the feeding barrier and the other was slotted perpendicular to that barrier. Sixteen pregnant, lactating Holstein-Friesian cows were used. After 14 d of habituation, cow behavior was videotaped for 10 full 24-h d, spread over 22 d. Their daily time budget spent on different activities performed in both compartments was analyzed, as was their relocation and use of the concentrate dispenser in each compartment. On average, cows spent 120 min longer per day in the slotted floor compartment than in the grooved floor compartment, and performed all activities in the daily time budget significantly longer in this compartment. However, testing the preference of individuals revealed that, although five cows significantly preferred the slotted floor compartment, two cows significantly preferred the other compartment, and nine cows had no preference. On the slotted floor, cows ate longer at the feeding barrier and more often drank front-on to the water trough; on the grooved floor they more often drank standing parallel to the water trough. Thus, they seemed to prefer to stand parallel to the slots. Relocation of cows, indicated by index of movement, was not significantly different between the floors. Relocation seemed to be stimulated more by the presence of concentrate dispensers in both compartments than by floor profile. Although one floor type was not clearly preferred over the other, the findings and methods of this study have implications for design and implementation of future preference tests for testing husbandry systems and their components.

Animal Husbandry↗

PubMed2000

Chromosome territories, interchromatin domain compartment, and nuclear matrix: an integrated view of the functional nuclear architecture.

Advances in the specific fluorescent labeling of chromatin in fixed and living human cells in combination with three-dimensional (3D) and 4D (space plus time) fluorescence microscopy and image analysis have opened the way for detailed studies of the dynamic, higher-order architecture of chromatin in the human cell nucleus and its potential role in gene regulation. Several features of this architecture are now well established: 1. Chromosomes occupy distinct territories in the cell nucleus with preferred nuclear locations, although there is no evidence of a rigid suprachromosomal order. 2. Chromosome territories (CTs) in turn contain distinct chromosome arm domains and smaller chromatin foci or domains with diameters of some 300 to 800 nm and a DNA content in the order of 1 Mbp. 3. Gene-dense, early-replicating and gene-poor, middle-to-late-replicating chromatin domains exhibit different higher-order nuclear patterns that persist through all stages of interphase. In mitotic chromosomes early replicating chromatin domains give rise to Giemsa light bands, whereas middle-to-late-replicating domains form Giemsa dark bands and C-bands. In an attempt to integrate these experimental data into a unified view of the functional nuclear architecture, we present a model of a modular and dynamic chromosome territory (CT) organization. We propose that basically three nuclear compartments exist, an "open" higher-order chromatin compartment with chromatin domains containing active genes, a "closed" chromatin compartment comprising inactive genes, and an interchromatin domain (ICD) compartment (Cremer et al., 1993; Zirbel et al., 1993) that contains macromolecular complexes for transcription, splicing, DNA replication, and repair. Genes in "open," but not in "closed" higher-order chromatin compartments have access to transcription and splicing complexes located in the ICD compartment. Chromatin domains that build the "open" chromatin compartment are organized in a way that allows the direct contact of genes and nascent RNA to transcription and splicing complexes, respectively, preformed in the ICD compartment. In contrast, chromatin domains that belong to the "closed" compartment are topologically arranged and compacted in a way that precludes the accessibility of genes to transcription complexes. We argue that the content of the ICD compartment is highly enriched in DNA depleted biochemical matrix preparations. The ICD compartment may be considered as the structural and functional equivalent of the in vivo nuclear matrix. A matrix in this functional sense is compatible with but does not necessitate the concept of a 3D nuclear skeleton existing of long, extensively arborized filaments. In the absence of unequivocal evidence for such a structural matrix in the nucleus of living cells we keep an agnostic attitude about its existence and possible properties in maintaining the higher-order nuclear architecture. Quantitative modeling of the 3D and 4D human genome architecture in situ shows that such an assumption is not necessary to explain presently known aspects of the higher-order nuclear architecture. We expect that the interplay of quantitative modeling and experimental tests will result in a better understanding of the compartmentalized nuclear architecture and its functional consequences.

Animals↗

PubMed1997

Chronic exertional compartment syndrome in lower legs: localization and follow-up with thallium-201 SPECT imaging.

UNLABELLED: The purpose of this study was to ascertain whether 201Tl SPECT imaging of the leg is useful in precise localization of the ischemic compartment involved in chronic exertional compartment syndrome (CECS). METHODS: Imaging and quantitative analyses of postexercise 201Tl SPECT leg examinations were retrospectively performed in nine patients with clinically diagnosed CECS and eight control subjects. Imaging and quantitative criteria for the ischemic compartment were decreased 201Tl perfusion less than the lower limits of normal, which were defined as 2 s.d. below the mean percentage uptake of the control subjects. The SPECT imaging results were compared with those of quantitative analysis, postoperative SPECT images and clinical diagnoses. RESULTS: Postexercise normal legs had nonuniform 201Tl distribution in both legs and in the four compartments. Lower limits of normal mean percentage 201Tl uptake were about 60% for the anterior compartment and about 50% for the other three compartments. Redistribution was observed in 67% of normal compartments in the control subjects. The SPECT images demonstrated 16 ischemic compartments in eight of the nine patients. The SPECT results were consistent with those of quantitative analysis. There were discrepancies between the clinical and SPECT diagnoses in six legs (33% of the 18 legs) of five patients. Postoperative SPECT demonstrated 201Tl perfusion was improved in all involved compartments for that fasciotomy was performed. CONCLUSION: Thallium-201 SPECT imaging of the legs can easily provide precise localization of the ischemic compartment, which is demonstrated as decreased 201Tl distribution on the stress image. This technique is promising for the screening and follow-up of CECS.

Adult↗

PubMed2000

Intraoperative lower extremity compartment pressures in lithotomy-positioned patients.

PURPOSE: Measurement of anterior leg compartment pressures in eight patients (16 limbs) who were positioned in the lithotomy position for prolonged periods of time while undergoing colorectal intra-abdominal surgery. METHODS: Anterior leg compartment pressures were measured in eight patients (16 limbs) by using a slit catheter, whereas subjects were positioned in the lithotomy position for prolonged periods of time while undergoing colorectal intra-abdominal surgery. RESULTS: Compartment pressures had minor elevations after initial lithotomy positioning, and gradually increased over time. Levels elevated to 30 mmHg at an average of five (range, 3.5 to 6) hours. The maximum recorded leg compartment pressure was 70 mmHg. The addition of Trendelenburg positioning was noted to consistently increase compartment pressures. All pressures returned to less than 10 mmHg shortly after removing the limb from the stirrups and placing the limb supine. No patients developed clinical evidence of compartment syndrome. CONCLUSIONS: Leg anterior compartment pressures rise when limbs are placed in the lithotomy position for prolonged periods of time. The rise in pressure is increased with the addition of Trendelenburg positioning. Anterior compartment pressures reached a threshold of 30 mmHg at an average of five hours. The results of this study suggest that lithotomy positioning of the lower extremities has the potential to initiate leg compartment syndrome when the period of positioning approaches five hours. Removing the limbs from the stirrups and placing them in the supine position allows the pressure in the compartments to return to normal.

Aged↗

PubMed1996

Compartment syndrome of the buttock following a total hip arthroplasty.

An elevation of the interstitial pressure in a closed osseofascial compartment results in compartment syndrome. This may be caused by a decrease in compartment volume or an increase in compartment contents. The gluteal compartment syndrome is rare. Because the gluteal region has a large volume, this compartment requires a massive increase in content to cause a compartment syndrome. Also, this compartment blends anatomically with the muscles of the thigh, allowing extravasation of blood outside the compartmental envelope. This case report is of a patient whose medial circumflex femoral artery was severed during a total hip arthroplasty through a posterior approach leading to compartment syndrome of the buttock. Although this clinical presentation has not been described as compartment syndrome, one similar presentation was described in the literature.

Aged↗

PubMed2005

Use of tissue ultrafiltration for treatment of compartment syndrome: a pilot study using porcine hindlimbs.

OBJECTIVES: To demonstrate the efficacy of compartment syndrome ultrafiltration for the treatment of acute compartment syndrome in an animal model. Our hypothesis is the removal of interstitial fluid will result in a reduction of intramuscular pressure compared with untreated controls in a model of bilateral induced compartment syndrome. DESIGN: Controlled experimental model. SETTING: Animal research facility. PATIENTS/PARTICIPANTS: Three pairs of porcine hindlimbs. INTERVENTION: Acute compartment syndrome was created in the pig hindlimb by infusion of saline to maintain the intramuscular pressure 30 mm Hg greater than the animal's mean arterial pressure for 8 hours. After a 2-hour reperfusion interval, ultrafiltration (removal of fluid through 1 mm diameter porous catheters, connected to -500 mm Hg suction) was commenced in 1 limb only and continued for 9.5 hours. MAIN OUTCOME MEASURES: Intramuscular pressure, ultrafiltrate volume, ultrafiltrate and serum levels of creatine kinase and lactate dehydrogenase, histologic measurement of extracellular and intracellular edema, as well as the degree of cellular necrosis. RESULTS: Intramuscular pressure tended to be lower on the treated side at the end of the treatment period [treated leg: 9.3 +/- 4.0 mm Hg (+/- SE), control leg: 19.3 +/- 1.4 mm Hg, P = 0.03]. Analysis of ultrafiltrate fluid showed that levels of creatine kinase and lactate dehydrogenase were elevated compared with serum levels. Creatine kinase levels in serum were measured at 4150 +/- 780 U/L, whereas ultrafiltrate levels of creatine kinase were 28,700 +/- 17,700 U/L (+/- SE) (P = 0.1). Lactate dehydrogenase was measured at 1950 +/- 180 U/L in serum, but markedly elevated in ultrafiltrate [160,000 +/- 88,900 U/L (+/- SE), P = 0.05]. Quantification of cellular and interstitial dimensions showed no difference in control and experimental limbs. Quantification of the degree of muscle necrosis revealed 6.1 +/- 2.7% necrosis in the treated limb compared to 11.3 +/- 1.6% necrosis in the control group (P = 0.02, df = 2, 1-tailed paired t test). CONCLUSION: This pilot study demonstrates the feasibility of tissue ultrafiltration for reduction of intramuscular pressure in this porcine model. Further studies are underway. Compartment syndrome ultrafiltration may be useful prophylactically in patients at risk for acute compartment syndrome. Sampling of interstitial fluid and frequent measurement of intramuscular pressure may allow earlier diagnosis and treatment of acute compartment syndrome, whereas the reduction of tissue pressure by compartment syndrome ultrafiltration may prevent acute compartment syndrome from occurring. Additionally, compartment syndrome ultrafiltration will not hinder the ability of clinicians to use the clinical examination and pressure monitoring as the gold standard.

Animals↗

PubMed2003

Review: acute compartment syndrome of the foot.

Foot compartment syndrome is a serious potential complication of foot crush injury, fractures, surgery, and vascular injury. The purpose of this article is to summarize and review the existing literature on this entity. Long-term sequelae of foot compartment syndrome (FCS) include contractures, deformity, weakness, paralysis, and sensory neuropathy. These complications are poorly tolerated, and often necessitate multiple procedures for rehabilitation. Therefore, the threshold for considering compartment syndrome and performing fasciotomy must be low to minimize such outcomes. The existence of nine foot compartments and frequent presence of complicating injuries necessitate multi-stick needle catheterization for direct measurement of compartment pressures. Fasciotomy is indicated when compartment pressure exceeds 30 mmHg, or if compartment pressure is greater than 10-30 mmHg below diastolic pressure. The approaches for compartment decompression generally include two dorsal incisions for access to forefoot compartments, and one medial incision for decompression of the calcaneal, medial, superficial, and lateral compartments.

Acute Disease↗

PubMed1990

Compartment syndromes of the foot: current concepts.

The foot has been mentioned as a site for the development of a compartment syndrome for approximately 9 years. Despite this, very little information exists in the literature containing specifics on the nature of the disorder. Very recent work has shown that crush injuries, forefoot and midfoot fractures and dislocations, and calcaneal fractures are prone to the development of foot compartment syndromes (FCS). The classical clinical signs of pain with passive stretch of the involved muscles, and dysfunction of the nerves that pass through the involved compartments are less helpful in the diagnosis of the syndrome in the foot than elsewhere. Tense swelling of the foot may be of some help in arousing suspicion that a FCS has developed, but the diagnosis is best made by invasive catheterization of the foot compartments. Since recent work has discovered that at least nine foot compartments exist, multi-stick catheterization is recommended. Fasciotomy should be performed when the pressures are significantly elevated, to prevent the development of late contractures. A communication exists between a newly-found compartment of the foot, the calcaneal compartment, and the deep posterior compartment of the leg. A combined pattern of FCS and deep posterior compartment syndromes of the leg exists, and should be remembered by the clinician treating injuries of the foot or leg. Also, a foot injury alone may cause a deep posterior compartment syndrome in the leg. Claw-toe deformity seems to be the primary late sequela of FCS. Local procedures may be of only temporary benefit.

Compartment Syndromes↗

PubMed2002

Intramuscular and blood pressures in legs positioned in the hemilithotomy position : clarification of risk factors for well-leg acute compartment syndrome.

BACKGROUND: Acute compartment syndrome has been widely reported in legs positioned in the lithotomy position for prolonged general surgical, urologic, and gynecologic procedures. The orthopaedic literature also contains reports of this complication in legs positioned on a fracture table in the hemilithotomy position. The purpose of this study was to identify the risk factors for development of acute compartment syndrome resulting from this type of leg positioning. METHODS: Eight healthy volunteers were positioned on a fracture table. Intramuscular pressures were continuously measured with a slit catheter in all four compartments of the left leg with the subject supine, in the hemilithotomy position with the calf supported, and in the hemilithotomy position with the heel supported but the calf free. Blood pressure was measured intermittently with use of automated pressure cuffs. RESULTS: Changing from the supine to the calf-supported position significantly increased the intramuscular pressure in the anterior compartment (from 11.6 to 19.4 mm Hg) and in the lateral compartment (from 13.0 to 25.8 mm Hg). Changing from the calf-supported to the heel-supported position significantly decreased intramuscular pressure in the anterior, lateral, and posterior compartments (to 2.8, 3.4, and 1.9 mm Hg, respectively). The mean diastolic blood pressure in the ankle averaged 63.9 mm Hg in the supine position, which significantly decreased to 34.6 mm Hg in the calf-supported position. Changing to the heel-supported position had no significant effect on the diastolic blood pressure in the ankle (mean, 32.8 mm Hg). The mean difference between intramuscular pressure and diastolic blood pressure in the supine position was approximately 50 mm Hg in each of the four compartments. This mean difference significantly decreased to <20 mm Hg in the calf-supported position and then, when the leg was moved into the heel-supported position, significantly increased to approximately 30 mm Hg in all compartments. CONCLUSIONS: The combination of increased intramuscular pressure due to external compression from the calf support and decreased perfusion pressure due to the elevated position causes a significant decrease in the difference between the diastolic blood pressure and the intramuscular pressure when the leg is placed in the hemilithotomy position in a well-leg holder on a fracture table. Combined with a prolonged surgical time, this position may cause an acute compartment syndrome of the well leg. Leaving the calf free, instead of using a standard well-leg holder, increases the difference between the diastolic blood pressure and the intramuscular pressure and may decrease the risk of acute compartment syndrome.

Adult↗

PubMed2007

Identification of aldolase C compartments in the mouse cerebellar cortex by olivocerebellar labeling.

Aldolase C (zebrin II) is expressed in Purkinje cells aligned in complicated longitudinal stripe-shaped compartments. The tight link between these aldolase C compartments and the topographic olivocerebellar projection to them has made it possible to identify each compartment as a target of a specific subarea of the inferior olive and thus as a functionally distinct entity in the rat. However, it is unknown whether the overall organization of aldolase C compartments is preserved in other mammals. In this study, we tried to clarify this organization in the mouse, which is more useful in genetic studies than the rat, by identifying each aldolase C compartment in terms of the olivocerebellar projection pattern. First, aldolase C compartments were reconstructed from serial sections throughout the cerebellar cortex. Aldolase C and olivocerebellar climbing fibers were then doubly labeled by small injections of biotinylated dextran amine into various areas of the inferior olive. Climbing fibers were topographically distributed on a specific linked pair of aldolase C compartments in the rostral and caudal cerebellum. The overall relationship between aldolase C compartments and the topographic olivocerebellar projection to them in the mouse was similar to that in the rat, except for some minor differences, suggesting that the aldolase C compartments and olivocerebellar projection are organized according to a common fundamental organization in the mouse and rat. This allowed the unequivocal identification of all aldolase C compartments in the mouse by referring to the definition and nomenclature in the rat.

Animals↗

PubMed1994

Sulfated glycoprotein-2 synthesized by nonciliated cells of the efferent ducts is targeted to the lysosomal compartment.

The epithelial nonciliated cells of the efferent ducts are specialized in internalizing many luminal substances. The nonciliated cells actively endocytose sulfated glycoprotein-2 (SGP-2), a major secretory protein of Sertoli cells and a homologue of human apolipoprotein J. This study was undertaken to investigate the internalization of Sertoli-derived SGP-2 and synthesis of an endogenous efferent duct form of SGP-2 by nonciliated cells targeted to their secondary lysosomes on animals whose efferent ducts were ligated and/or received injections of tunicamycin. The regulation of synthesis of the endogenous form of SGP-2 within nonciliated cells by hormones in general and testosterone in particular was also examined using hypophysectomized and castrated animals with or without subsequent testosterone replacement. Quantitative electron microscope immunocytochemistry was performed on groups of animals fixed with 4% paraformaldehyde and 0.5% glutaraldehyde in phosphate buffer for each experimental condition and their controls. In each case, the labeling density (number of gold particles/micron 2) within the endosomal (endosomes) and lysosomal (dense multivesicular bodies and secondary lysosomes) compartments was calculated. The results revealed that ligation of the efferent ducts resulted in a significant decrease in the labeling density of the endosomal and lysosomal compartments. However, a baseline of about 18% of controls was still observed in the lysosomal compartment 24 h after ligation. In this compartment similar values were noted 24 h after tunicamycin treatment in conjunction with or without ligation. These results suggest that an endogenous form of SGP-2 is synthesized by nonciliated cells and presumably targeted via small vesicles from the Golgi apparatus to the lysosomal compartment, but that the major portion of SGP-2 within this compartment is derived via endocytosis of testicular SGP-2. Hypophysectomy and castration also showed significant decreases in the labeling densities of these two compartments, but again a baseline level of labeling was noted in the lysosomal compartment. Subsequent testosterone administration to 7-day hypophysectomized or castrated animals had no effect on the labeling density of the lysosomal compartment, as values comparable to the effect of hypophysectomy or castration alone were noted. Taken together these results suggest that the nonciliated cells of the efferent ducts synthesize an endogenous form of SGP-2 that is targeted to the lysosomal compartment and which is not regulated by pituitary factors or testosterone.

Animals↗

PubMed1996

New aspects of pulmonary mechanics: "slowly" distensible compartments of the respiratory system, identified by a PEEP step maneuver.

OBJECTIVE: The aims of the present study were 1) to evaluate a method for identification of "slowly" distensible compartments of the respiratory system (rs), which are characterized by long mechanical time constants (RC) and 2) to identify "slowly" distensible rs-compartments in mechanically ventilated patients. DESIGN: Prospective study on a physical lung model. SETTING: Intensive Care Unit, University Hospital, Tübingen. PATIENTS AND PARTICIPANTS: 19 patients with severe lung injury (acute respiratory distress syndrome, ARDS) and on 10 patients with mild lung injury. MEASUREMENTS AND RESULTS: Positive end-expiratory pressure (PEEP)-increasing and -decreasing steps of about 5 cmH2O were applied and the breath-by-breath differences of inspiratory and expiratory volumes (delta V) were measured. The sequence of delta Vs were analyzed in terms of volume change in the "fast" compartment (Vfast), the "slow" compartment (Vslow), total change in lung volume (delta VL) and mechanical time constant of the slow compartment (RCslow). Thirty-eight measurements in a lung model revealed a good correlation between the preset Vslow/delta VL and Vslow/delta VL measured: r2 = 0.91. The Vslow/delta VL measured amounted to 0.94 +/- 0.15 of Vslow/delta VL in the lung model. RCslow measured was 0.92 +/- 0.43 of the RCslow reference. Starting from a PEEP level of 11 cmH2O PEEP-increasing and PEEP-decreasing steps were applied to the mechanically ventilated patients. Three out of ten patients with mild lung injury (30%) and 7/19 patients with ARDS (36.8%) revealed "slowly" distensible rs-compartments in a PEEP-increasing step, whereas 15/19 ARDS patients and 1/10 patients with mild lung injury showed "slowly" distensible rs-compartments in a PEEP-decreasing step (78.9% vs 10%, P < 0.002, chi-square test). CONCLUSIONS: The gas distribution properties of the respiratory system can be easily studied by a PEEP-step maneuver. The relative contribution of the "slow" units to the total increase of lung volume following a PEEP step could be adequately assessed. "Slowly" distensible rs-compartments could be detected in patients with severe and mild lung injury, however significantly more ARDS patients revealed "slow" rs-compartments in PEEP-decreasing steps. The influence of "slowly" distensible rs-compartments on pulmonary gas exchange is unknown and has yet to be studied.

Adult↗

PubMed1982

Microelectrode studies of the tegument and sub-tegumental compartments of male Schistosoma mansoni: an analysis of electrophysiological properties.

Standard intracellular microelectrode techniques were used to determine the electrical properties of the tegument and sub-tegumental regions in male Schistosoma mansoni. Three distinct compartments of electrical potential were observed. The resting potentials recovered in these compartments of -45.9 +/- 2.5 mV (Eteg), -22.0 +/- 1.1 mV (E2) and -4.7 +/- 03 mV (E3) corroborate those previously reported by Fetterer, Pax & Bennett (1980) and Bricker, Pax & Bennett (1981). Input resistance was measured in each compartment and was found to be 4. 5 M omega (tegument), 9.2 M omega (E2) and 3.5 M omega (E3). Time-constants for the tegument, E2 and E3 were 0.24 +/- 0.01 msec, 0.25 +/- 0.01 msec and 0.13 +/- 0.01 msec, respectively. Multiple electrode experiments revealed that the tegument and E2 compartment are electrical syncytia with similar current-spreading capabilities. Low resistance pathways also appear to connect the tegument and E2 region, since electrotonic signals initiated in either of those compartments experience only a 15-25% reduction upon passing into the other. Injecting large (greater than 200 nA) depolarizing current pulses into the tegument or E2 compartment often resulted in the initiation of active membrane responses. These spikes were highly variable, ranging from 4 to 75 mV in magnitude (occasionally overshooting zero potential by as much as 25 mV) and from 10-40 msec in duration. The responses were not actively propagated along the parasite, and their decay over distance was approximately equal to that predicted on the basis of length constant values obtained from electronic signals. The addition of a non-diffusible solute to the recording medium resulted in a significant reduction in the current-spreading capacity of both the tegument and E2 compartment. Coupling ratios between the tegument and E2 compartment. Coupling ratios between the tegument and E2 compartment were decreased, and the input resistance for both compartments increased, while resting potentials remained constant. Active responses could not be evoked in schistosomes exposed to the hyperosmotic medium.

Animals↗