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[Separation and shunting of intramyocardial segments of the coronary arteries in their proximal affection by the arteriosclerotic process].

Operations for the formation of an aortocoronary shunt were performed on 395 patients in the period between October 1983 and January 1991. The anomalous position of one or more segments was found in 70 patients. The autologous vein was used as a graft in 65.7% of these patients and the internal thoracic artery in 34.3% of cases. The anterior interventricular branch (AIVB) was situated in the myocardium in 58.6% of cases and the circumflex branch (CB) in 31.4% of cases, in 8.6% of cases the segments of some arteries were situated anomalously. The AIVB was separated beginning from its segment distal in relation to its intramyocardial segment in the region of its subepicardial passage, after which an incision was made in the myocardium overlying the intramyocardial segment. The anomalously situated segments of the other coronary arteries were separated by the same techniques. In one case the AIVB was lying in the cavity, in another, it was stretched under the endocardium. After shunting these arteries were transposed to the surface of the left ventricle which allowed the ventriculotomy incision under them to be sutured. There were no complications linked with separation and shunting of intramyocardial segments of the coronary arteries. These segments of the coronary arteries have a larger lumen and are very rarely involved in an atherosclerotic process. Proceeding from the aforesaid, intramyocardial segments of coronary arteries whose proximal parts are affected by atherosclerosis must be separated and shunted.

Adult↗

[Nonischemic changes of the ST segment in dynamic electrocardiography].

Ambulatory ECG monitoring has become increasingly important in the diagnostic workup of patients investigated for chest pain and in the evaluation of patients with known ischemic heart disease. Following the demonstration of ischemic episodes not associated with anginal symptoms, the diagnosis of myocardial ischemia is based solely on the detection of ST segment shifts; however several conditions associated with non-ischemic ST segment changes during ambulatory ECG monitoring might potentially be misleading. These conditions include: 1) ST segment changes in the normal population: it is a rare finding in specifically designed studies that however are probably affected by a "pretest referral bias"; caution is therefore suggested in diagnosing ischemia when episodes of ST segment depression are mild (< 2 mm) and occur at high heart rates (> 120 beats/min); 2) postural changes, usually easily recognized by the typical "square" pattern of the ST segment trend; 3) ST segment changes related to respiratory manoeuvres, quite rare and usually mild; 4) ST segment changes due to drugs; 5) ST segment changes caused by rhythm and conduction disturbances. Lastly the significance of ST segment changes in patients with angina and normal coronary arteries is discussed, following recent observations of reduced coronary flow reserve and/or abnormal myocardial metabolism in a sizable proportion of these patients.

Arrhythmias, Cardiac↗

ST segment resolution predicts clinical outcome and response to dobutamine testing after primary percutaneous transluminal coronary angioplasty.

AIM: To assess clinical outcome and improvement in left ventricular (LV) contractility during a six-month follow-up after successful primary percutaneous transluminal coronary angioplasty (PTCA), according to rapid ST segment resolution. The usefulness of early dobutamine echocardiography (DE) in the prediction of LV functional recovery in patients treated with primary PTCA was tested. PATIENTS AND METHODS: One hundred ten consecutive patients with first acute myocardial infarction after successful primary PTCA (Thrombolysis in Myocardial Infarction (TIMI) 3 flow and stenosis of less than 30%) were divided into two groups according to whether ST segment resolution occurred 1 h after the procedure. The patients underwent clinical assessment and echocardiography (ejection fraction [EF] and wall motion index [WMI]) after primary PTCA, during DE on the fourth day of hospitalization, and again after three and six months. RESULTS: In patients with ST segment resolution (n=76 [69.1%]), LVEF increased significantly during the six-month follow-up (P=0.0001). Changes found in the group without ST segment resolution were insignificant (P=0.4). Early DE in patients with rapid ST segment resolution revealed significant improvements in LV contractility measured by EF and WMI. Patients without ST segment resolution had a higher incidence of death (three of 34 [8.8%] versus zero of 76 [0%], P=0.0086), reinfarction (five of 34 [14.7%] versus two of 76 [2.6%], P=0.28) and revascularization (four of 34 [11.8%] versus three of 76 [3.9%], P=0.12). The combined end point (death, reinfarction and revascularization) was significantly lower in patients with ST segment resolution (P=0.03). CONCLUSIONS: Rapid ST segment resolution is associated with LV contractility recovery, and a better clinical outcome and prognosis after successful primary PTCA. Early DE after primary PTCA predicts LV functional recovery. Patients with ST segment resolution are likely to respond to early dobutamine testing.

Angioplasty, Balloon, Coronary↗

High risk of gallbladder carcinoma in elderly patients with segmental adenomyomatosis of the gallbladder.

The clinical significance of adenomyomatosis of the gallbladder remains unclear. This study aimed to clarify the relationship between segmental adenomyomatosis and gallbladder carcinoma, and to elucidate the histogenesis of gallbladder carcinoma associated with segmental adenomyomatosis. A total of 4,560 consecutive patients underwent cholecystectomy. The specimens were examined grossly and histologically. Adenomyomatosis of the gallbladder was divided into segmental, fundal, and diffuse types. Sixty noncancerous gallbladders with segmental adenomyomatosis were examined for epithelial metaplasia. The incidence of gallbladder carcinoma was higher in patients with segmental adenomyomatosis (22/334, 6.6%) than in those without (181/4226, 4.3%; P=0.049). This difference was more marked among patients equal to or older than 60 years of age (15/96,15.6% versus 147/2407, 6.1%, respectively; P<0.001). The other types of adenomyomatosis did not show any significant increases in the incidence of gallbladder carcinoma. In all 22 patients with both segmental adenomyomatosis and carcinoma, the tumors developed only in the fundal mucosa. Epithelial metaplasia was more marked in the fundal mucosa of segmental adenomyomatosis than in the neck mucosa (P=0.003). Segmental adenomyomatosis is a high-risk condition for gallbladder carcinoma, especially in elderly patients. Epithelial metaplasia appears to be related to increased carcinogenesis in the fundal mucosa of segmental adenomyomatosis.

Adenomyoma↗

[Segmental left ventricular function in patients with syndrome X].

Impulse tissue Doppler study of the left ventricle was carried out in 44 patients with cardiac syndrome X (age 47.15+/-6.27 years) and 46 healthy volunteers aged 35-55 years. Maximal peak velocities "s", "e", "a", "e/a" ratio and segmental isovolumic relaxation time "ivrt" were evaluated for each of 18 selected left ventricular segments. Criteria of disturbed segmental diastolic left ventricular function were e/a ratio <1.0 and ivrt >85 ms. Left ventricular filling was abnormal (E/A (min) <1.0) in 18 (40.9%) patients all of whom had segments with e/a <1.0. According to e/a values 18 of 26 patients (69,23%) with E/A (min) >1.0 had segmental dysfunction while 8 patients (30,77%) had intact segmental diastolic function. Patients with and without segmental diastolic dysfunction had different exercise tolerance, nocturnal blood pressure fall, blood levels of glucose and low density lipoprotein cholesterol. Patients with abnormal (IVRT >90 ms) and normal (IVRT 40-80 ms) left ventricular relaxation had similar numbers of dysfunctional segments. Patients with IVRT 80-40 ms and with (n=21) or without (n=4) disturbances of segmental relaxation had different age, left ventricular myocardial mass index and magnitude of myocardial hypoperfusion.

Adult↗

[ST-segment depressions correlate in patients with hypertensive heart disease with spontaneous changes in blood pressure].

In 15 patients with essential hypertension, anginal pain, and angiographically excluded coronary artery disease 24-h monitoring of the ST-segment and blood pressure was performed. 26 episodes with ST-segment depressions 0400.1 mV were recorded in 11/15 patients. In 10/26 episodes with ST-segment depressions blood pressure was elevated above 150/95 mm Hg or by more than 20% as compared to three successive measurements before the ST-segment depressions. Heart rate was increased by more than 20% in 20/26 ST-segment depressions. During 9 periods with ST-segment depressions angina pectoris was reported; in addition 27 anginal attacks without ST-segment depressions were observed. A significant, positive correlation between the diastolic (p less than 0.005) and systolic (p less than 0.02) blood pressure and the extent of the ST-segment depression was observed. These correlations imply a patho-physiological meaning of ST-segment depressions in hypertensive patients.

Angina Pectoris↗

In vitro motility of isolated adults and segments of Onchocerca volvulus, Brugia pahangi and Acanthocheilonema viteae.

Observations were made on the spontaneous motility in vitro of entire adult worms and segments of Onchocerca volvulus, Brugia pahangi and Acanthocheilonema viteae. Segment motility was recorded in a mechano-transducer apparatus and responses of worm tissues to anthelmintics and other pharmacological agents were compared. Entire adult female O. volvulus showed varied patterns of motor activity, ranging from continuous low level whole body motion to periodic spasmodic contractions interspersed between intervals of quiescence lasting from a few to 30 seconds. The same range characterized movements of 1.5-4 cm segments cut from worms liberated from collagenase digested nodules. However, fresh segments dissected directly from surgical specimens were completely inactive due to the paralyzing effect of xylocaine, used as local anesthetic. This effect wore off in 2-5 hours in vitro, and recovered segments behaved in the same way as those from enzymatically liberated worms. Segments of B. pahangi and A. viteae also showed motor activity patterns which reflected those of whole adults. Segments of O. volvulus behaved reproducibly, whether examined in the field in endemic areas, or after transport of nodules or freed worms to Michigan from Guatemala or Sudan. Segments of all worms were unresponsive to most anthelmintics, but O. volvulus was susceptible to paralysis by CGP 6140, levamisole, pyrantel and carbachol at concentrations of ten to a thousand times lower than those required to produce any influence on B. pahangi. Segments of A. viteae more closely resembled O. volvulus in their dose responses to these drugs, although CGP 6140 was without effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Greater activation of smooth muscle alpha-2 adrenoceptors by epinephrine in distal than in proximal segments of rat tail artery.

The effects of selective blockade of alpha-1 and alpha-2 adrenoceptors on the vasoconstrictor responses to epinephrine (EPI) and norepinephrine (NOR) were compared in perfused/superfused proximal and distal segments of rat tail artery. The influence of neuronal uptake and of activation of beta adrenoceptors was also investigated. EPI was more potent in distal than in proximal segments. The antagonistic effect of idazoxan (100 nM) against EPI was greater in distal than in proximal segments, whereas the opposite result was obtained with prazosin (0.1-10 nM). No such difference were observed when NOR was used as agonist. Reducing the calcium ion concentration had a greater inhibitory effect on EPI in distal than in proximal segments. Cocaine (4 microM) increased responses to EPI and NOR to a greater extent in proximal than in distal segments. In the presence of cocaine, in proximal segments, antagonism of EPI by prazosin was reduced, whereas in distal segments, antagonism by idazoxan and the inhibitory effect of a reduction in calcium ion concentration were reduced. Propranolol (1 microM) increased responses to EPI and NOR to a greater extent in proximal than in distal segments. In the presence of propranolol, antagonism of EPI by both prazosin and idazoxan was reduced in proximal segments, and the inhibitory effect of a reduction in calcium ion concentration was lost. Forskolin (1 microM) inhibited responses to EPI and prevented the antagonistic effect of idazoxan, but not that of prazosin. From the results obtained it is suggested that smooth muscle alpha-2 adrenoceptors are distributed differently in the proximal and distal ends of the rat tail artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The specification of metameric order in the insect Callosobruchus maculatus Fabr. (Coleoptera). I. Incomplete segment patterns can result from constriction-induced cytological damage to the egg.

Eggs of the pea-beetle Callosobruchus were divided into two at different stages of development. Both fragments were allowed to develop into partial larvae. The segment patterns of normal and partial larvae are described using cuticular markers of cell differentiation. To study the contribution of cytological damage to the segment gap phenomenon three different types of constriction were performed: complete and incomplete permanent constriction and complete temporary constriction. Changes in the structure of the egg can produce absence of segments resulting from two different effects. First, partial absence of segments results from a decreased egg circumference in the constriction region and involves the disturbance of a morphogenetic process (dorsal closure). Secondly, cytological damage can result in a gap between two arrays of segments. The loss of segments in the gap occurred in two different ways. In a spatial segment gap the two arrays of segments were physically discontinuous, whereas in a non-spatial gap the segments bordering the gap were juxtaposed in a physically continuous cuticle. The extent to which the gap phenomenon can be attributed to cytological damage is discussed. We also discuss, on the basis of certain dorsal defects, a possible stepwise specification of the dorsal transverse cuticular pattern.

Animals↗

[Electron microscopic and morphometric studies of the main kidney segment of male and female rats following castration and testosterone substitution].

The effect of testosterone on the 3 segments of the renal proximal tubule (S1, S2, S3) of male and female rats was studied by electronmicroscopic and morphometric methods. Only light, granulated and dark lysosomes as well as microbodies (peroxisomes) and dictyosomes (Golgi zones) were investigated. After castration the area density of light lysosomes in the S1 segment increases in males whereas it decreases in females; therefore the sex different pattern of light lysosomes, that is to be seen in normal animals, is reversed. The absolute size and number of light giant lysosomes is also elevated in castrated males in comparison to normal animals as well as to animals substituted by testosterone. - Dark lysosomes of the S1 segments are more numerous in castrated females and less numerous in castrated males than in normal animals. - The distinct sex difference in dark lysosomes of the S2 segment which is demonstrable in normal animals disappears after castration the area density of dark lysosomes increasing in castrated females and decreasing in castrated males. The three species of lysosomes in the S1 segments show no longer a sex difference after substitution with testosterone: substituted males develop the same pattern as normal animals and substituted females are almost comparable with normal males. However, the sex difference in dark lysosomes of the S2 segment is more pronounced after testosterone treatment. - The characteristic pattern of light lysosomes in the S1 and S2 segments as well as the change of the sex different lysosomal pattern after castration and substitution with testosterone, respectively - especially in S1 - seem to be caused by testosterone which results in an inhibition of resorption. Only after castration a sex difference appears in dark lysosomes of the S3 segment (males show more dark lysosomes than females). This sex difference is reversed by testosterone treatment. There are more numerous lysosomes with an non-homogeneous matrix in both sexes after castration which are seldom to be seen in normal and substituted animals. The area density of microbodies shows sex differences in all 3 segments of normal animals. While no significant changes in S1 and S2 are to be seen after castration and substitution, there is a pronounced decrease of the area density of microbodies in S3 of males after castration, so that no sex differences are then available.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Segmental distribution of the endocytosis receptor gp330 in renal proximal tubules.

The subcellular distribution and segmental variations in location of gp330, a scavenger receptor for filtered proteins in renal proximal tubules, was analyzed. Kidney tissue from rats (4 different strains), rabbits and humans were analyzed by light- and electron microscope immunocytochemistry, using cryosections or Lowicryl sections from cryosubstituted tissue. Gp330 was located mainly in apical coated pits, small and large endocytic vacuoles and in dense apical tubules in the proximal tubule cells. The labeling density was markedly higher in segments 1 and 2 as compared to segment 3 of the proximal tubule. In addition to the location in the early part of the endocytic pathway, gp330 was also present in lysosomes, especially in segments 1 and 2. The lysosomal labeling was not restricted to the membrane, but was also seen in the matrix. Localization of gp330 in lysosomes was confirmed on sections from purified lysosomal fractions from rat renal cortex. The brush border localization of gp330 in proximal tubules exhibited a characteristic segmental variation. In the initial part of segment 1, there was virtually no brush border labeling. In the remaining part of segment 1 and in segment 2, there was a distinct but sometimes patchy labeling of the brush border. In segment 3, groups of microvilli of approximately 10 as seen in sections were intensively labeled from bottom to tip and there were often more than one of these groups on a single cell, the remaining microvilli were unlabeled. No differences in the cellular and subcellular localization of gp330 were observed between species or rat strains. In conclusion, the present study demonstrates that in addition to its location in the early endocytic and recycling pathway, gp330 is also present in microvilli and the protein and degradation products thereof is present in lysosomes, consistent with its role as a protein scavenger receptor.

Animals↗

Segmental flow-resistance relationship in pulmonary lobar transplantation: possibility for donor lobe evaluation in pediatric lung transplantation.

Pulmonary lobar transplantation is an option for pediatric lung transplantation, and it has the potential of extended applications. We compared the relationship between segmental blood flow and segmental vascular resistance of the pulmonary lobe with that of the transplanted single lung. Eight of 14 puppies received a left upper pulmonary lobe from double-weighed adult dogs, and the other six puppies received a left lung from puppies. All recipient dogs were treated with oral cyclosporine (15 mg/kg/day) and intramuscular prednisolone (1.0 mg/kg/day), after the operation. Pulmonary arterial and left atrial pressures and segmental flow of the lungs were measured at rest and while the inferior vena cava or right pulmonary artery was clamped, before and 1 hour and 2 weeks after lung transplantation. Vascular resistance of the lung segment was calculated at each hemodynamic state. Segmental resistance of the lung at rest significantly increased from pretransplantation to 1 hour after transplantation (pulmonary lobe group, 2211 +/- 42 to 2555 +/- 61 dyne.sec.cm-5; single lung group, 2126 +/- 56 to 2557 +/- 72 dyne.sec.cm-5) and recovered 2 weeks after transplantation in both groups. However, by means of partial clamp of the right pulmonary artery, segmental resistances of 1 hour after transplantation pulmonary lobe (2248 +/- 37 dyne.sec.cm-5), and single lung (2206 +/- 34 dyne.sec.cm-5) at the same segmental flow of the pretransplantation state (310 to 320 ml/min) were equivalent to those of the pretransplantation lungs. There was no significant difference in the segmental resistance at any segmental flow between the pulmonary lobe and single lung before and after lung transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[The projections of the ventral field of the tegmentum mesencephali, substantia nigra and amygdaloid nuclei to different segments of the putamen in the dog].

Organization of protections of the complex "substantia nigraventral tegmental field" (SN-VTA) to dorsal and ventral segments of rostral and caudal regions of putamen was studied in dog by method based on retrograde axonic transport of horseradish peroxidase. A difference is found in organization of projections of subcortical formations studied both in rostro-caudal and dorso-ventral directions. Only compact SN part projects to putamen rostral region dorsal segment and both compact and dorsal SN parts--to this region ventral segment. Apart from these two parts of lateral SN area also project to putamen caudal regions dorsal and ventral segments. Limbic system structures projections to putamen dorsal and ventral segments make a significant difference as well. VTA and amygdala were found to project only to putamen anterior and posterior regions ventral segments and not to dorsal. Putamen rostral region ventral segment receive projection from all fibres from neurons of macro- and mediocellular parts of amygdala basal nucleus to the same extent and same segment located more caudally--mostly from its macrocellular part. In putamen ventral segments SN projection fibres end too and thus on this area overlapping of functionally different subcortical formations projections occurs.

Amygdala↗

[Does left ventricular wall motion of akinetic segment improve after reperfusion therapy in patients with acute myocardial infarction?: assessment by myocardial contrast echocardiography].

The relationship between myocardial perfusion and left ventricular wall motion was studied by myocardial contrast echocardiography in 22 patients with acute myocardial infarction treated by successful direct percutaneous transluminal coronary angioplasty (PTCA). Myocardial contrast echocardiography was performed 4 times to assess the serial changes of wall motion score and opacification score, before and immediately after PTCA, and 2 weeks and 3 months after the onset of infarction, by injecting 2 ml Albunex into the infarct-related artery. Two-dimensional echocardiography was visualized at the level of the papillary muscle on the short-axis view or apical long-axis view. Wall motion score was graded visually as grade 0: dyskinesis/akinesis, to 3: normokinesis/hyperkinesis and opacification score was graded as grade 0: no opacification, to 2: homogeneous opacification using the 6-segment model of the short-axis view or 5-segment model of the apical long-axis view. Immediately after PTCA, we observed 30 segments with the dyskinesis/akinesis, which were divided into 3 groups (no opacification group, partial opacification group and homogeneous opacification group) by opacification score immediately after PTCA. The recovery of left ventricular wall motion in the partial opacification group (10 segments) and homogeneous opacification group (7 segments) were significantly better than the no opacification group (13 segments). Six (46%) of 13 segments in the no opacification group had improved contrast enhancement 3 months later, and 4 of these 6 segments showed improved left ventricular wall motion. The area opacified immediately after PTCA showed recovery of left ventricular wall motion in the chronic stage. However, some segments of the no-opacified area immediately after PTCA also showed improved myocardial opacification as well as improved left ventricular wall motion in the chronic stage. The results suggest that myocardial contrast echocardiography is an important method to predict myocardial viability, but it is difficult to assess the viability by contrast enhancement performed only in the acute stage of acute myocardial infarction.

Adult↗

Freeze-fracture study of filipin binding in photoreceptor outer segments and pigment epithelium of dystrophic and normal retinas.

We have studied sterol distribution in the retinal pigment epithelial (RPE) microvillous and outer segment disc membranes of rats with inherited retinal degeneration (RCS; RCS-p/+) and of normal genetic controls (RCS-rdy+, RCS-rdy+-p/+) by using the polyene antibiotic filipin, which binds specifically to 3-B-hydroxy-sterols, and freeze-fracture techniques. Retinas were perfusion-fixed, incubated with filipin in the same fixative, and prepared routinely for freeze-fracture electron microscopy. In the normal retina, the distribution of filipin binding sites on both RPE microvillous and outer segment disc membranes changes during development. Prior to outer segment elongation and the onset of phagocytosis (10 days postnatal), filipin sterol complexes are homogeneously distributed in both microvillous and outer segment membranes. With the onset of phagocytosis (2 weeks postnatal and later) filipin binding in both tissues forms a proximal-to-distal gradient, and binding sites decrease as distance from the cell body increases. In the normal RPE microvillous membranes, binding sites are numerous proximally and sparse on the distal tips. In the normal outer segment disc membranes, binding sites are often present on the basal discs, but are sparse on the intact apical discs prior to shedding. As the discs are cast off and engulfed by the RPE, however, filipin binding increases on both disc and phagosome membranes. In the dystrophic retina, the distribution of filipin binding sites differs from the normal. First, in the microvillous membranes, the proximal-to-distal gradient in filipin binding is rarely present at 2 weeks postnatal and becomes prominent only after the buildup of membranous debris has begun (3-5 weeks postnatal). Second, as the photoreceptors degenerate and the membrane debris disappears (4 months postnatal), filipin binding on the microvillous membranes becomes relatively sparse and homogeneous. Third, filipin binding on the intact disc membranes does not change with outer segment elongation, and numerous filipin binding sites are present on both apical and basal outer segment disc membranes. Fourth, large aggregates of filipin binding sites occupy the vast expanses of particle-free areas of debris membranes which accumulate between the photoreceptors and the RPE. These changes in the amount and distribution of filipin binding sites in the dystrophic retina add to the evidence that the disease process involves outer segment as well as RPE membranes and suggest that alterations in cholesterol distribution could contribute to the phagocytic defect.

Animals↗

Segmental sclerosing glomerular lesions.

Segmental sclerosing glomerular lesions are usually all grouped together and called focal segmental glomerulosclerosis. This has meant that the term that was originally used for a defined clinical entity is now applied to a variety of conditions in man and experimental animals, with the assumption that the morphological changes are the same in all conditions. Studies of the position of segmental lesions within glomeruli, the size of glomeruli and the proportion of glomeruli affected have shown that this assumption is wrong. Such studies have identified a disease that corresponds to the original clinical concept of focal segmental glomerulosclerosis. This begins with the nephrotic syndrome in patients whose renal biopsies show large glomeruli with mesangial hypercellularity and segmental lesions at every tubular origin. Later the biopsies have segmental lesions throughout the glomerular tuft. This disease differs clinically and pathologically from other conditions that have segmental sclerosing lesions, such as in patients with reduced renal mass or patients with hypertension and proteinuria. The term focal segmental glomerulosclerosis is now too ambiguous and unsatisfactory to be used without qualification.

Adult↗

Tunicamycin does not inhibit transport of phosphatidylinositol to Xenopus rod outer segments.

Tunicamycin inhibits the dolichol pathway for N-linked glycosylation of proteins, including photoreceptor opsin, and causes a buildup of tubulo-vesicular profiles in the intersegmental space between photoreceptor rod inner and outer segments associated with disruption of new disc assembly. We tested the hypothesis that a tunicamycin lesion in photoreceptors would block lipid transport into the outer segment. Adult Xenopus retinas were preincubated in dim red light with 20 micrograms ml-1 of tunicamycin for one hour followed by incubation in the light for 2-6 h with tunicamycin plus either [3H]mannose, [3H]leucine, [2-(3)H]glycerol or [3H]myo-inositol. Tunicamycin caused accumulation of tubulo-vesicular membranes in the intersegmental space and significantly reduced both [3H]leucine and [3H]mannose incorporation into the basal region of rod outer segments. However, tunicamycin had no effect on [3H]glycerol incorporation into the rod outer segment phospholipids. After 5 h incubation with [3H]glycerol, radiolabel in outer segment fractions was associated primarily with phosphatidylinositol in both control and tunicamycin treated retinas. Quantitative light microscope autoradiography of both [3H]glycerol and [3H]inositol labelled retinas showed diffuse labelling over the entire rod outer segment in both control and tunicamycin treated retinas with no accumulation of radioactivity in the basal discs of control retinas or in the tubulo-vesicular structures in the intersegmental space of tunicamycin treated retinas. Our results indicate that despite the morphological disruption and inhibition of glycoprotein transport to outer segments after tunicamycin treatment, transport of labelled phosphatidylinositol occurs normally. These data add to a growing body of evidence separating the lipid and protein transport pathways to the outer segment.

Animals↗

Proteolytic shedding of the extracellular domain of photoreceptor cadherin. Implications for outer segment assembly.

Photoreceptor cadherin (prCAD) is a distinctive cadherin family member that is concentrated at the base of rod and cone outer segments and is required for their structural integrity. During retinal development, prCAD localizes to the site of the future outer segment before rhodopsin or other phototransduction proteins. In vivo, prCAD undergoes a single proteolytic cleavage that releases the ectodomain as a soluble fragment. The C-terminal fragment containing the transmembrane and cytosolic domains remains associated with the outer segment. In rds(-/-) retinas, in which outer segment assembly is severely disrupted because of the absence of retinal degeneration slow (RDS)/peripherin, an essential outer segment structural protein, the level of prCAD is increased, whereas the levels of other outer segment proteins are decreased relative to wild type retinas. Additionally, the ratio of intact:cleaved prCAD polypeptides is increased in rds(-/-) retinas. These data imply that prCAD ectodomain cleavage is an integral part of the outer segment assembly process, and they further suggest that outer segment assembly might be driven, at least in part, by the near irreversibility of proteolysis.

Amino Acid Sequence↗