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PubMed1997

Expression of Aleutian mink disease parvovirus capsid proteins in defined segments: localization of immunoreactive sites and neutralizing epitopes to specific regions.

The capsid proteins of the ADV-G isolate of Aleutian mink disease parvovirus (ADV) were expressed in 10 nonoverlapping segments as fusions with maltose-binding protein in pMAL-C2 (pVP1, pVP2a through pVP2i). The constructs were designed to capture the VP1 unique sequence and the portions analogous to the four variable surface loops of canine parvovirus (CPV) in individual fragments (pVP2b, pVP2d, pVP2e, and pVP2g, respectively). The panel of fusion proteins was immunoblotted with sera from mink infected with ADV. Seropositive mink infected with either ADV-TR, ADV-Utah, or ADV-Pullman reacted preferentially against certain segments, regardless of mink genotype or virus inoculum. The most consistently immunoreactive regions were pVP2g, pVP2e, and pVP2f, the segments that encompassed the analogs of CPV surface loops 3 and 4. The VP1 unique region was also consistently immunoreactive. These findings indicated that infected mink recognize linear epitopes that localized to certain regions of the capsid protein sequence. The segment containing the hypervariable region (pVP2d), corresponding to CPV loop 2, was also expressed from ADV-Utah. An anti-ADV-G monoclonal antibody and a rabbit anti-ADV-G capsid antibody reacted exclusively with the ADV-G pVP2d segment but not with the corresponding segment from ADV-Utah. Mink infected with ADV-TR or ADV-Utah also preferentially reacted with the pVP2d sequence characteristic of that virus. These results suggested that the loop 2 region may contain a type-specific linear epitope and that the epitope may also be specifically recognized by infected mink. Heterologous antisera were prepared against the VP1 unique region and the four segments capturing the variable surface loops of CPV. The antisera against the proteins containing loop 3 or loop 4, as well as the anticapsid antibody, neutralized ADV-G infectivity in vitro and bound to capsids in immune electron microscopy. These results suggested that regions of the ADV capsid proteins corresponding to surface loops 3 and 4 of CPV contain linear epitopes that are located on the external surface of the ADV capsid. Furthermore, these linear epitopes contain neutralizing determinants. Computer comparisons with the CPV crystal structure suggest that these sequences may be adjacent to the threefold axis of symmetry of the viral particle.

Aleutian Mink Disease Virus↗

PubMed1994

Reconstitution of transcriptional activation domains by reiteration of short peptide segments reveals the modular organization of a glutamine-rich activation domain.

The POU domain activator Oct-2 contains an N-terminal glutamine-rich transcriptional activation domain. An 18-amino-acid segment (Q18III) from this region reconstituted a fully functional activation domain when tandemly reiterated and fused to either the Oct-2 or GAL4 DNA-binding domain. A minimal transcriptional activation domain likely requires three tandem Q18III segments, because one or two tandem Q18III segments displayed little activity, whereas three to five tandem segments were active and displayed increasing activity with increasing copy number. As with natural Oct-2 activation domains, in our assay a reiterated activation domain required a second homologous or heterologous activation domain to stimulate transcription effectively when fused to the Oct-2 POU domain. These results suggest that there are different levels of synergy within and among activation domains. Analysis of reiterated activation domains containing mutated Q18III segments revealed that leucines and glutamines, but not serines or threonines, are critical for activity in vivo. Curiously, several reiterated activation domains that were inactive in vivo were active in vitro, suggesting that there are significant functional differences in our in vivo and in vitro assays. Reiteration of a second 18-amino-acid segment from the Oct-2 glutamine-rich activation domain (Q18II) was also active, but its activity was DNA-binding domain specific, because it was active when fused to the GAL4 than to the Oct-2 DNA-binding domain. The ability of separate short peptide segments derived from a single transcriptional activation domain to activate transcription after tandem reiteration emphasizes the flexible and modular nature of a transcriptional activation domain.

Amino Acid Sequence↗

PubMed1985

Reciprocal change in ST segment in acute myocardial infarction: correlation with findings on exercise electrocardiography and coronary angiography.

The clinical relevance of reciprocal changes in the ST segment occurring at the time of acute myocardial infarction was studied prospectively in 85 consecutive uncomplicated cases. Reciprocal depression of the ST segment was defined as depression of 1 mm or more in electrocardiogram leads other than those reflecting the infarct. All patients underwent maximal, symptom limited treadmill stress testing two weeks after the infarct and coronary angiography six weeks after infarction. Forty six patients had inferior, 34 anterior, and five true posterior infarction. Of the 51 patients with reciprocal changes, 45 (88%) developed exercise induced ST segment depression in areas remote from the infarction zone. At angiography all 45 patients were shown to have stenoses greater than 70% in at least two major vessels. Four patients had negative exercise electrocardiograms and were sequently shown to have single vessel disease subtending their infarct, and the remaining two patients had a false negative treadmill test result. Of the 27 patients without reciprocal changes, 21 (78%) had negative treadmill stress test results associated with single vessel coronary disease. Five had positive stress test results and multivessel coronary disease, and one had a false negative stress test result. The remaining seven patients had ST segment elevation without Q wave formation in the reciprocal areas and were assessed separately. Of these, six had positive stress test results and multivessel coronary disease and one had a negative stress test result and single vessel coronary disease to the infarct area. Twenty one patients with anterior infarcts (62%) and 27 with inferior infarcts (59%) had reciprocal changes. No differences emerged in the relation between infarct site, reciprocal change, and presence of additional coronary disease. At follow up of the 51 patients with reciprocal changes in the ST segment 36 had become symptomatic, of whom 29 had undergone coronary artery bypass surgery. By contrast, only four of the 27 patients without reciprocal changes in the ST segment had developed symptoms, and two of these had undergone coronary revascularisation. Reciprocal ST segment depression at the time of acute myocardial infarction may identify patients with severe coronary disease who are at risk of subsequent cardiac events and appears to be as reliable as results of early postinfarction treadmill stress testing in predicting the underlying coronary anatomy. When the electrocardiogram does not show reciprocal changes treadmill testing provides valuable additional information.

Adult↗

PubMed1992

Well shaped ST segment and risk of cardiovascular mortality.

OBJECTIVE: To investigate the prognostic value of frequently occurring slight variations in the ST segment for cardiovascular mortality in healthy subjects. DESIGN: Follow up study of mortality in relation to variations in ST segment level in a cohort over the 28 years from 1953 to 1981. A case-cohort sampling design was applied to limit the number of electrocardiograms that had to be coded by hand. SETTING: General health examination carried out in 1953 of civil servants in Amsterdam and assessment of subsequent mortality. SUBJECTS: Apparently healthy civil servants aged 40 to 65 years: 1583 men and 1508 women. MAIN OUTCOME MEASURES: Relative risk of variations in ST segment level for mortality from all causes, cardiovascular disease, and coronary heart disease. RESULTS: In men the multivariate relative risks of 15 year mortality from cardiovascular disease and coronary heart disease of slight ST elevation at 80 ms past the J point (compared with isoelectric ST segment) were 0.5 (95% confidence interval 0.3 to 0.9) and 0.4 (0.2 to 0.8), respectively. As expected, ST segment depression (greater than 0.25 mm) was associated with increased risk: 1.9 (1.1 to 3.0) and 2.2 (1.2 to 3.9), respectively. In women associations were weaker. The full 28 year period showed a similar pattern of somewhat weaker associations for men; among women, however, no predictive value was apparent. CONCLUSION: These results are empirical evidence for the intuitive opinion among doctors that a curved, upward sloping ST segment, resulting in slight ST elevation at 80 ms, indicates low risk compared with the isoelectric flat, stretched ST segment.

Adult↗

PubMed2004

Diagnostic and prognostic value of ST segment depression limited to the recovery phase of exercise stress test.

OBJECTIVES: To investigate the diagnostic and prognostic value of ST segment depression limited to the recovery phase of an exercise stress test, as compared with that of ST segment depression appearing during exercise. SETTING: Exercise stress test laboratory of a university hospital. PATIENTS AND DESIGN: Clinical and angiographic data were compared for 574 consecutive patients who developed ST segment depression during the active phase of an exercise test (group 1) and for 79 patients who developed ST segment depression only during the recovery phase of the exercise test (group 2). RESULTS: There were no differences between the two groups in major clinical features. Significant coronary artery stenoses were found in 488 group 1 patients (85%) and in 62 group 2 patients (78%, p = 0.14). Three vessel or left main disease was found in 166 (29%) group 1 and in 14 (18%) group 2 patients (p = 0.045). At a median follow up of 55.3 months of 321 group 1 and 54 group 2 patients, there were no significant differences in major cardiac events between the groups (univariate relative risk 0.81, 95% confidence interval 0.25 to 2.68, p = 0.72). CONCLUSION: The diagnostic and prognostic power of ST segment depression limited to the recovery phase of an exercise test is largely similar to that of ST segment depression induced during effort; thus, assessing ST segment depression during recovery can significantly improve the clinical information derived from exercise stress tests.

Blood Pressure↗

PubMed1976

Failure of ST segment elevation to predict severity of acute myocardial infarction.

Praecordial ST segment elevation was measured at 35 electrode positions in each of 40 patients admitted to a coronary care unit after acute transmural anterior myocardial infarction. Serial praecordial electrocardiographic maps were recorded to determine (a) the time course as well as reproducibility of measurements of ST segment alterations, and (b) the degree of correlation between the magnitude of ST segment elevation and the severity of infarction, as assessed clinically or by sequential estimations of serum creatine kinase activity. Large variations in ST segment elevation were found in different patients with a comparable degree of myocardial damage, and at intervals of as little as four hours in the same patient. These variations were greater than could be explained by technical factors, and were not related to apparent changes in the patients' clinical status. The patterns of release of myocardial creatine kinase showed that the time course of ST segment elevation was longer than the period of myocardial necrosis. No correlation was found between the myocardial infarct size as determined by enzyme release and the highest levels of ST segment elevation recorded. The findings suggest that ST segment elevation as measured by praecordial electrocardiographic mapping does not constitute a reliable index of the size or severity of myocardial infarcts in man.

Adult↗

PubMed1998

Relation of biophysical response of coarcted aortic segment to balloon dilatation with development of recoarctation following balloon angioplasty of native coarctation.

OBJECTIVE: To evaluate the role of biophysical response of the coarcted segment to balloon dilatation in the causation of aortic recoarctation. SETTING: Tertiary care centre/university hospital. DESIGN: Retrospective case series. METHODS: Records of 67 consecutive infants and children undergoing balloon angioplasty of native aortic coarctations were examined for an 8.7 year period ending September 1993. At 12 months (median) follow up catheterisation, 15 (25%) of 59 children developed recoarctation, defined as a gradient > 20 mm Hg. Stretch (balloon circumference--preballoon coarcted segment circumference/preballoon coarcted segment circumference), gain (postballoon coarcted segment circumference--preballoon coarcted segment circumference), and recoil (balloon circumference--postballoon coarcted segment circumference) were calculated from measurements obtained from cineangiograms performed before and immediately after balloon dilatation. RESULTS: The stretch in 44 children without recoarctation (2.18 (1.23)) was similar (p > 0.1) to that in 15 children with recoarctation (1.90 (0.65)), implying that similar balloon dilating stretch was applied in both groups. Greater gain (p < 0.05) was observed in the group without recoarctation (8.8 (8.0) mm) than in the recoarctation group (5.7 (2.7) mm) but this was not substantiated in the infant population. However, the recoil was greater (p < 0.001) in the group without recoarctation (5.1 (4.3) mm) than in the recoarctation group (2.1 (1.1) mm); this was also true in the infant group. CONCLUSIONS: Greater recoil in the patients without recoarctation implies preservation of intact elastic tissue in the coarcted segment. In the recoarctation group, with less recoil, the elastic properties may not have been preserved, thereby causing recoarctation. There might be a more severe degree of cystic medial necrosis in the recoarctation group than in the no recoarctation group. This needs confirmation in future studies.

Adolescent↗

PubMed2003

Radiation dose is reduced with a single-pass whole-body multi-detector row CT trauma protocol compared with a conventional segmented method: initial experience.

Radiation dose data were collected from a calibrated multi-detector row computed tomographic (CT) scanner during trauma CT. One protocol (used with 10 case subjects) involved a single-pass continuous whole-body acquisition from cranial vertex to symphysis pubis, while the other, conventional protocol (used with 10 control subjects) involved scouting and scanning body segments (head, cervical spine, chest, abdomen, and pelvis) individually. Technical factors were kept constant within each body segment for the single-pass and the segmented protocols. Statistics included univariate analysis, two-tailed t testing to evaluate statistical significance of the summary statistic, and power and subject population contingency tables. The mean dose length product (DLP) with the single-pass protocol was 17% lower than the sum of the DLPs of each of the individual body segment scans (P <.001). Analysis of power and subject population by using a difference in mean of 500 mGy. cm and an alpha of.05 revealed a (1-beta) of higher than 0.90 for a sample of 10 patients. Thus, a whole-body single-pass trauma protocol, compared with a typical segmented acquisition protocol matched for imaging technique, resulted in reduced total radiation dose. The reduction in radiation dose is thought to represent a reduction in redundant imaging at overlap zones between body segments scanned in the segmental protocol but not in the continuous acquisition.

Humans↗

PubMed2003

Left ventricular mass: manual and automatic segmentation of true FISP and FLASH cine MR images in dogs and pigs.

PURPOSE: To evaluate the accuracy of manually and automatically segmented true fast imaging with steady-state precession (FISP) and fast low-angle shot (FLASH) cine magnetic resonance (MR) imaging in the determination of left ventricular (LV) mass. MATERIALS AND METHODS: Nine dogs and five pigs underwent cine MR imaging of the entire LV from base to apex. Manual and automatic segmentation times were recorded, and LV masses determined with each were compared with each other and with the true LV mass at autopsy. Estimated mass and true mass at autopsy were compared by calculating the correlation coefficient and the mean difference between the two for each MR sequence and segmentation method. RESULTS: True LV mass at autopsy correlated well with masses determined with manual and automatic contours on true FISP MR images. Mean differences between true LV mass and masses determined from manual contours on true FISP and FLASH images were -0.8 g +/- 2.6 and 3.7 g +/- 6.8, respectively. When manually drawn end-diastolic contours were automatically propagated to end systole, mean differences were 2.0 g +/- 3.6 (P =.05) and 9.1 g +/- 6.5 (P <.05) for true FISP and FLASH images, respectively. For automatic contours, mean differences were 10.6 g +/- 8.5 (P <.05) and 27.7 g +/- 13.4 (P <.05) for true FISP and FLASH images, respectively. Mean automatic segmentation time was six times less than mean manual segmentation time. CONCLUSION: LV mass was determined most accurately by using manual contours on true FISP images. In these animal models, fully automatic segmentation of true FISP images was performed in one-sixth of the time of manual segmentation and yielded LV masses with a mean error of approximately 5% of true LV mass.

Animals↗

PubMed1983

Measurement of renin in segmental renal veins of hypertensives.

In 27 of 270 patients studies for possible renovascular hypertension, a lesion affecting a segmental renal artery was seen on angiography. In 22 patients who had sufficient data, the significance of measuring segmental-renal-vein renin in the diagnosis and treatment of segmental disease was evaluated. In 11 (50%), the renin values of segmental vessels supported the clinical diagnosis. In four (36%) of these 11, a high-renin-release area would not have been identified without the stress of upright posture. Successful treatment of hypertension was achieved in six of nine patients who had a revascularization procedure or resection of the segmental vessels. Samples from involved and uninvolved segments of the kidney as well as from the contralateral renal vein and inferior vena cava, together with the stimuli of sodium and volume depletion augmented by upright posture, enabled confirmation of the angiographic diagnosis of segmental-renovascular hypertension.

Adult↗

PubMed1988

Basilar segmental bronchi: thin-section CT evaluation.

Thin (1.5- and 5.0-mm) section contiguous computed tomographic (CT) scans obtained through the basilar segmental bronchi in 31 patients were reviewed in order to delineate normal anatomy and common variations of lower lobe airways. In each case, the frequency with which individual segmental and subsegmental bronchi were seen was established, as were variations in branching patterns. All basilar segmental bronchi were identified except in one case in which images of the left lung were obscured due to respiratory and cardiac motion. In the right lung, a division into subsegmental bronchi was identified in 84 of 150 (56%) visualized segmental bronchi. Six separate patterns of basilar segmental subdivision were found. In the left lung, subsegmental bronchi were identified arising from 51 of 145 (35%) visualized segmental bronchi. Five separate patterns of bronchial subdivision were found in the left lung. It is concluded that thin-section CT allows precise identification of all basilar segmental bronchi and, consequently, can play a significant role in the cross-sectional evaluation of lower lobe bronchial and parenchymal abnormalities.

Bronchi↗

PubMed1982

Contractile properties of bundles of fiber segments from skeletal muscles.

Our purpose was to determine whether contractile properties of bundles of skeletal muscle fiber segments were significantly different from those of bundles of intact fibers. In frog muscles, the only difference between the contractile properties of fiber segments and intact fibers was a lower maximum velocity of shortening (Vo) for the fiber segments. In mammalian muscles, the contraction time (TPT), relaxation time (RT1/2), and maximum tetanus tension (Po) of bundles of fiber segments were not different from those of intact fibers, but the rate of tension development (dP/dt), twitch-to-tetanus ratio (Pt/Po) and Vo were lower. The lower dP/dt and Pt/Po resulted from increased compliance due to damaged sarcomeres near cut ends. Within 4-9 mm of a cut end, membrane potentials were less than control values, and sarcomeres lengthened during a fixed-end contraction. after the length of fiber segments was corrected for the exact portion that was not shortening, the Vo of fiber segments was not different from that of intact fibers. We conclude that valid estimates of contractile properties can be obtained from bundles of skeletal muscle fiber segments.

Action Potentials↗

PubMed1981

Fluid propulsion by cat intestinal segments under conditions requiring hydrostatic work.

The intrinsic ability of duodenal, jejunal, and ileal segments of cats to propel fluid by doing hydrostatic work was investigated in vitro. Segments of terminal ileum demonstrated two functional states. In the net propulsive state, propulsive complexes occurred at an average interval of 7.9 min. These complexes consisted of an initial phase characterized by the simultaneous ejection of equal fluid volumes from both ends of a segment at a frequency of 8/min and a second phase that ejected a net volume of fluid from the aboral end. Ileal segments not in the net propulsive state demonstrated complexes consisting only of the 8/min ejections. Segments of proximal duodenum and midjejunum failed to produce net propulsion when evaluated under similar conditions. These results indicate that 1) ileal segments can intrinsically produce net fluid transport in the aboral direction when hydrostatic work is required for propulsion, 2) propulsive activity intrinsic to ileal segments is regulated by intrinsic control mechanisms having an effective oscillatory period of 8 min, and 3) basic differences exist in the intrinsic control structures between ileal and other intestinal regions.

Animals↗

PubMed1983

Myocardial segment velocity at a low load: time, length, and calcium dependence.

The length and time dependence of shortening velocity (VL) at a very light load (1 mN) was determined for central segments of ferret papillary muscle at 27 degrees C. A recently developed technique that measures the cross-sectional area of the chosen segment was used to assess segment length. Segment length (SL) or force could be used as a feedback control signal. VL was determined by releasing the muscle to a 1-mN load (less than or equal to 3% maximum force) at various times during a segment isometric twitch. Segment isometric twitches were typically performed at 95-98% SLmax, SLmax being the longest segment length attainable in the preparation. VL, as a function of time and SL, was determined from SL shortening during the load clamp. Muscle responses were sampled, stored, and analyzed with an on-line digital computer. The data indicate that 1) at a given SL, VL declines from 20 to 50% of its peak value by the time of peak force production, 2) VL declines linearly with SL below 90% SLmax in 1.125, 2.25, and 4.5 mM extracellular Ca2+, 3) VL exhibits a dependence on extracellular Ca2+, having peak values at 90% SLmax of 3.32 +/- 0.33, 2.66 +/- 0.17, and 1.89 +/- 0.17 SL/s in 4.5, 2.25, and 1.125 mM extracellular Ca2+, respectively.

Animals↗

PubMed1976

Response to parathyroid hormone in defined segments of proximal tubule.

Previous investigations have suggested that there is a functional heterogeneity along the length of the proximal convoluted tubule. This study was designed to confirm and extend these suggestions by examining the intrinsic absorption of fluid and the effect of parathyroid hormone (PTH) on net fluid absorption in isolated, anatomically defined segments of rabbit superficial proximal tubules. The EPCT (early proximal convoluted tubule), LPCT (late proximal convoluted tubule), and PR (pars recta) segments were studied under controlled conditions by the isolated perfused tubule technique. In 23 EPCT, base-line fluid absorption was 1.38 +/- 0.04 (SE), a rate significantly higher than those of 11 LPCT (0.62 +/- 0.02; P less than 0.001) and 12 PR (0.52 +/- 0.03 nl mm-1 min-1, P less than 0.001) segments. In 10 EPCT, mean control fluid absorption was 1.31 +/- 0.04 nl mm-1 min-1; addition of PTH resulted in a decrease to 0.95 +/- 0.05 nl mm-1 min-1 (P less than 0.001); and, after removal of PTH, fluid absorption increased (P less than 0.001). Parathyroid hormone had no effect on either seven LPCT segments or six PR segments. These results demonstrate differences in intrinsic capacity to absorb fluid by anatomically defined segments of the rabbit proximal tubule. This functional heterogeneity is further supported by the observed differential response to PTH by the various anatomic segments of the proximal tubule.

Animals↗

PubMed1985

Lactate production in isolated segments of the rat nephron.

Lactate production was measured directly in individual segments of the rat nephron. Tubules were dissected and then incubated in vitro with glucose as the only metabolic substrate. Each segment was incubated with and without antimycin A, an inhibitor of oxidative metabolism. Proximal tubules produced no lactate with or without antimycin A. The distal segments all produced lactate. The rate of lactate production without antimycin A ranged from 0.4 to 0.9 pmol X min-1 X mm-1 in all distal segments except one, the inner medullary collecting duct, which produced lactate at the significantly higher rate of 2.8 pmol X min-1 X mm-1. Antimycin A increased lactate production significantly in all of the distal segments. The increase was largest in medullary thick ascending limbs (1,400%) and cortical (798%) and outer medullary collecting ducts (357%). Increments were smaller in cortical thick ascending limbs (98%) and distal convoluted tubules (98%) and least in the inner medullary collecting ducts (28%). We conclude that lactate production occurs only in distal segments of the nephron and that under anoxic conditions significant amounts of ATP are produced by anaerobic glycolysis in these segments.

Animals↗

PubMed1989

Aldose reductase activities in microdissected rat renal tubule segments.

Osmoregulation in inner medullary cells depends in part on cellular accumulation of sorbitol, the production of which from glucose is catalyzed by aldose reductase. To identify nephron segments that contain aldose reductase, we developed a fluorometric ultramicroassay to measure aldose reductase activity in microdissected nephron segments from collagenase-treated kidneys of Sprague-Dawley rats. DL-Glyceraldehyde (10 mM) was used as a substrate. Substantial aldose reductase activities were found in all three inner medullary renal tubule segments: thin descending limbs, thin ascending limbs, and inner medullary collecting ducts. Activity increased with depth into the inner medulla in all three segments. When aldose reductase activities were normalized by cell volume the activities in the three inner medullary segments were similar. Little or no aldose reductase activity was measured in glomeruli or any cortical or outer medullary nephron segment. Both proximal convoluted and proximal straight tubules were found to have a substantial capacity to reduce DL-glyceraldehyde, but the finding of greater reductase activity with D-glucuronate (10 mM) than with D-xylose (10 mM) indicated that the activity was due to aldehyde reductase. Sorbitol dehydrogenase (measured by a similar ultramicroassay method) was present in substantial amounts in proximal tubules, but not in inner medullary collecting ducts. The overall pattern of enzyme activities is consistent with the proposed osmoregulatory role for sorbitol in all three inner medullary renal tubule segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗

PubMed1992

Age-associated changes in ammoniagenesis in isolated rat renal tubule segments.

We investigated renal ammoniagenesis in isolated nephron segments from control and acidotic senescent and young adult rats. When young (6 mo) and senescent (24 mo) control groups were compared, there was no significant difference in glutamine-dependent ammonia production in any nephron tubule segments. However, ammonia production rates in glomeruli from old rats were significantly greater than the rate from young rats and were correlated with the serum creatinine and blood urea nitrogen (BUN) levels. After giving young and old rats an equivalent acid load (by gavage) of ammonia chloride solutions (6 mo, blood pH 7.34; 24 mo, blood pH 7.07), we measured a significant increase in ammoniagenesis on the S1 and S2 segments of proximal tubules and the distal convoluted tubules from old rats, and no increase in any segment from young rats. When we increased the acid load in young rats to an equivalent severity of acidosis (blood pH 7.07), we found significant increases in ammonia production in the S1, S2, S3, and distal convoluted tubule. With comparable blood pH values, ammoniagenesis in S1, S2, and S3 segments from young rats was about double the values measured in segments from senescent rats. The severity of the acidosis in the 24-mo-old rats was related to serum creatinine and BUN. Our findings show that ammoniagenesis in isolated segments from senescent rats is qualitatively similar to their younger counterparts but that this maximum capacity to generate ammonia is reduced. The change in nephron capacity to synthesize ammonia may be the result of age-associated physiological changes and/or the chronic renal failure exhibited in old rats.

Acidosis↗