Lack of efficacy of low-dose spironolactone as adjunct treatment to conventional congestive heart failure treatment in dogs.

Aldosterone plays an important role in the pathophysiology of heart failure. Aldosterone receptor blockade has been shown to reduce morbidity and mortality in human patients with advanced congestive left ventricular heart failure. This study was designed to assess the efficacy and tolerance of long-term low-dose spironolactone when added to conventional heart failure treatment in dogs with advanced heart failure. Eighteen client-owned dogs with advanced congestive heart failure due to either degenerative valve disease (n=11) or dilated cardiomyopathy (n=7) were included in this prospective, placebo-controlled, double-blinded, randomized clinical study. After initial stabilization including furosemide, angiotensin-converting enzyme inhibitors, pimobendan and digoxin, spironolactone at a median dose of 0.52 mg/kg (range 0.49-0.8 mg/kg) once daily (n=9) or placebo (n=9) was added to the treatment, and the dogs were reassessed 3 and 6 months later. Clinical scoring, echocardiography, electrocardiogram, systolic blood pressure measurement, thoracic radiography, sodium, potassium, urea, creatinine, alanine aminotransferase, aldosterone and aminoterminal atrial natriuretic propeptide were assessed at baseline, 3 and 6 months. Survival times were not significantly different between the two treatment groups. Spironolactone was well tolerated when combined with conventional heart failure treatment.

Specific transcripts are elevated in Saccharomyces cerevisiae in response to DNA damage.

Differential hybridization has been used to identify genes in Saccharomyces cerevisiae displaying increased transcript levels after treatment of cells with UV irradiation or with the mutagen/carcinogen 4-nitroquinoline-1-oxide (NQO). We describe the isolation and characterization of four DNA damage responsive genes obtained from screening ca. 9,000 yeast genomic clones. Two of these clones, lambda 78A and pBR178C, contain repetitive elements in the yeast genome as shown by Southern hybridization analysis. Although the genomic hybridization pattern is distinct for each of these two clones, both of these sequences hybridize to large polyadenylated transcripts ca. 5 kilobases in length. Two other DNA damage responsive sequences, pBRA2 and pBR3016B, are single-copy genes and hybridize to 0.5- and 3.2-kilobase transcripts, respectively. Kinetic analysis of the 0.5-kilobase transcript homologous to pBRA2 indicates that the level of this RNA increases more than 15-fold within 20 min after exposure to 4-nitroquinoline-1-oxide. Moreover, the level of this transcript is significantly elevated in cells containing the rad52-1 mutation which are deficient in DNA strand break repair and gene conversion. These results provide some of the first evidence that DNA damage stimulates transcription of specific genes in eucaryotic cells.

The DNA damage-inducible gene DIN1 of Saccharomyces cerevisiae encodes a regulatory subunit of ribonucleotide reductase and is identical to RNR3.

The sequence of the DIN1 gene of Saccharomyces cerevisiae is identical to RNR3, a gene encoding a DNA damage-inducible regulatory subunit of ribonucleotide reductase. Two sequence elements located upstream of DIN1 (RNR3) are homologous to putative DNA damage regulatory elements in the promoter of the reductase catalytic subunit gene, RNR2. The transcript start sites for DIN1(RNR3) have been localized, and induction by different agents has been compared with other DNA damage-regulated genes.

DNA damage and heat shock dually regulate genes in Saccharomyces cerevisiae.

Two Saccharomyces cerevisiae genes isolated in a differential hybridization screening for DNA damage regulation (DDR genes) were also transcriptionally regulated by heat shock treatment. A 0.45-kilobase transcript homologous to the DDRA2 gene and a 1.25-kilobase transcript homologous to the DDR48 gene accumulated after exposure of cells to 4-nitroquinoline-1-oxide (NQO; 1 to 1.5 microgram/ml) or brief heat shock (20 min at 37 degrees C). The DDRA2 transcript, which was undetectable in untreated cells, was induced to high levels by these treatments, and the DDR48 transcript increased more than 10-fold as demonstrated by Northern hybridization analysis. Two findings argue that dual regulation of stress-responsive genes is not common in S. cerevisiae. First, two members of the heat shock-inducible hsp70 family of S. cerevisiae, YG100 and YG102, were not induced by exposure to NQO. Second, at least one other DNA-damage-inducible gene, DIN1, was not regulated by heat shock treatment. We examined the structure of the induced RNA homologous to DDRA2 after heat shock and NQO treatments by S1 nuclease protection experiments. Our results demonstrated that the DDRA2 transcript initiates equally frequently at two sites separated by 5 base pairs. Both transcriptional start sites were utilized when cells were exposed to either NQO or heat shock treatment. These results indicate that DDRA2 and DDR48 are members of a unique dually regulated stress-responsive family of genes in S. cerevisiae.

Identification of cis and trans components of a novel heat shock stress regulatory pathway in Saccharomyces cerevisiae.

The stress-responsive DDR2 gene (previously called DDRA2) of Saccharomyces cerevisiae is transcribed at elevated levels following stress caused by heat shock or DNA damage. Previously, we identified a 51-bp promoter fragment, oligo31/32, which conferred heat shock inducibility on the heterologous CYC1-lacZ reporter gene in S. cerevisiae (N. Kobayashi and K. McEntee, Proc. Natl. Acad. Sci. USA 87:6550-6554, 1990). Using a series of synthetic oligonucleotides, we have identified a pentanucleotide, CCCCT (C4T), as an essential component of this stress response sequence. This element is not a binding site for the well-characterized heat shock transcription factor which recognizes a distinct cis-acting heat shock element in the promoters of many heat shock genes. Here we demonstrate the ability of oligonucleotides containing the C4T sequence to confer heat shock inducibility on the reporter gene and show that the presence of two such elements produces more than additive effects on induction. Gel retardation experiments have been used to demonstrate specific complex formation between C4T-containing fragments and one or more yeast proteins. Formation of these complexes was not competed by fragments containing mutations in the C4T sequence nor by heat shock element-containing competitor DNAs. Fragments containing the C4T element bound to a single 140-kDa polypeptide, distinct from heat shock transcription factors in yeast crude extracts. These experiments identify key cis- and trans-acting components of a novel heat shock stress response pathway in S. cerevisiae.

Structure of the DNA damage-inducible gene DDR48 and evidence for its role in mutagenesis in Saccharomyces cerevisiae.

The DDR48 gene of Saccharomyces cerevisiae is a member of a set of genes that displays increased transcription in response to treatments that produce DNA lesions or to heat-shock stress. Other members of this group include the DDRA2 and UBI4 genes. DNA sequence analysis of the DDR48 gene demonstrates the presence of two overlapping open reading frames, each of which has the capacity to encode a protein with a molecular mass of approximately 45 kilodaltons. Fusions of the DDR48 coding sequences to lacZ demonstrates that only one of these frames is expressed in yeast cells. The protein predicted from this sequence is extremely hydrophilic and contains multiple repeats of the peptide sequence Ser-Asn-Asn-X-Asp-Ser-Tyr-Gly where X is either Asn or Asp. Additionally, closely related sequences are found throughout the primary sequence. Primer extension data indicate that, after 4-nitroquinoline-1-oxide and heat-shock treatments, there are three major and two minor transcriptional start sites which are utilized. The function of the DDR48 gene was investigated by disrupting this gene in diploid cells. Viable haploid cells containing the DDR48 gene disruption were isolated after tetrad analysis. Although the ddr48 mutant showed a slightly altered sensitivity to killing by 4-nitroquinoline-1-oxide and to heat shock compared with the DDR48 haploid, the spontaneous mutation rate of reversion of a his4 mutation was reduced 6- to 14-fold in the ddr48 strain. These results implicate the DDR48 gene in the production or recovery of mutations in S. cerevisiae.

Expression of the yeast UB14 gene increases in response to DNA-damaging agents and in meiosis.

The polyubiquitin gene, UB14, of Saccharomyces cerevisiae is regulated by a variety of environmental stresses and physiological conditions. After exposure of rapidly growing yeast cells to DNA-damaging agents (4-nitroquinoline-1-oxide and N-methyl-N'-nitro-N-nitrosoguanidine), intracellular levels of UB14 transcript increased rapidly. Induction of UB14 transcripts occurred within 30 to 60 min of exposure to 4-nitroquinoline-1-oxide in RAD+, rad52, and rad6 repair-deficient yeast strains. In high-density RAD+ cultures, the effect of alkylating agents on UB14 transcript levels is attenuated, in part because of significant increases in the basal level of this message in untreated cells. We also observed that the levels of UB14 transcripts increased significantly when diploid cells were exposed to sporulation conditions. Maximal levels of UB14 transcripts were reached after 6 to 8 h in sporulation medium. Accumulation of UB14 transcripts occurred in a/alpha diploids that undergo meiosis but not in asporogenous alpha/alpha diploids exposed to the same nutritional conditions.

Crystallization of DNA polymerase II from Escherichia coli.

DNA polymerase II of Escherichia coli, an alpha-like or group B polymerase, has been crystallized. The crystals are orthorhombic, space group P2(1)2(1)2, with cell dimensions a = 94.4 A, b = 118.2 A, c = 84.2 A and diffract to at least 3.0 A resolution. This is the first example of a group B polymerase to be crystallized.

Measurement of right ventricular ejection fraction and volume by the thermodilution technique in the unsedated calf.

This study was designed to test the applicability and the reproducibility of the thermodilution method in the measurement of right ventricular ejection fraction (EF), end-diastolic volume (EDV) and end-systolic volume (ESV) in unsedated cattle. In the 16 healthy calves studied, it was possible, using a fast response thermodilution catheter, to obtain characteristic exponential steplike washout curves, allowing the calculation of right ventricular EF, EDV and ESV. Five to 10 successive thermodilution curves were recorded within a few minutes and two to five similar sets of measurements were performed throughout the same day to test the reproducibility of the technique. The same protocol was repeated the following day. Right ventricular EF, EDV and ESV were reproducible successively, throughout a given day and on following days. The mean intraset, intraday and interdays coefficients of variation ranged from a mean of 4.0 (SD 4.1) per cent to a mean of 18.2 (SD 7.9) per cent. Values of right ventricular volumes and EF agreed with those previously reported in various animal species. Thermodilution was, therefore, shown to be a useful method for measuring with a satisfactory reproducibility, right ventricular EF, EDV and ESV in the unsedated healthy calf.

Cardiac performance in conscious healthy dogs during dobutamine infusion.

The aim of this study was to determine the cardiac performance of conscious healthy dogs during stimulation with dobutamine. Eight healthy unsedated beagle dogs were used. Cardiac output was measured by the thermodilution technique and blood pressures by extravascular pressure transducers. Dobutamine challenge at a dosage ranging from 27.5 to 50 micrograms kg-1 min-1 induced a significant rise in cardiac power index (CPI), cardiac index (CI), stroke index (SI) and heart rate (HR) and a significant decrease in pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR). The highest CPI was 2.05 times greater than its basal resting value. The CI was primarily responsible for this increase in CPI. The SI and HR contributed approximately 55 per cent and 45 per cent respectively of the maximal increase in CI.

Effects of dobutamine on isovolumic and ejection phase indices of cardiac contractility in conscious healthy dogs.

The aim of this study was to determine cardiac contractility using indices derived from cardiac catheterisation in conscious healthy dogs during dobutamine infusion. Eight dogs were studied. An ECG was recorded together with left ventricular pressure and volume which were measured using a conductance catheter with an integrated microtip pressure sensor. Eight indices of left ventricular systolic performance were derived from these records. Measurements were realised under basal conditions and during an incremental dobutamine challenge. The maximal rate of rise in ventricular pressure (max dP/dt), max dP/dt divided by the developed pressure and the mean systolic ejection rate were the most sensitive indices to detect dobutamine induced changes in contractility with maximal percentage changes of 122+/-11 per cent, 130+/-7 per cent and 102+/-24 per cent respectively. Ejection fraction increased significantly during dobutamine infusion (maximal percentage change of 43+/-9 per cent) whereas the pre-ejection period (PEP) and the left ventricular ejection time (LVET) decreased significantly (maximal percentage change of -41+/-2 per cent and -28+/-3 per cent respectively). All these six indices were significantly correlated with each other. Conversely, the ratio PEP/LVET and the LVET corrected for heart rate dependency showed a maximal percentage change of only -10+/-1 per cent and -16+/-7 per cent, respectively, during the dobutamine infusion and were not significantly correlated with the other contractility indices. This study demonstrated the feasibility of the conductance method to determine cardiac contractility in conscious healthy dogs submitted to a pharmacological stress testing and provides control values for eight indices of left ventricular contractility during dobutamine infusion at increasing dosages.

Rhinitis/Bronchopneumonia syndrome in Irish Wolfhounds.

This study describes the clinical, immunologic, genetic, and pathologic features of Irish Wolfhounds with rhinitis/bronchopneumonia syndrome. The dogs examined were from Belgium, The Netherlands, UK, Canada, Germany, and Switzerland. Signs included transient to persistent mucoid or mucopurulent rhinorrhea, cough, and respiratory dyspnea. Radiographic, rhinoscopic, and bronchoscopic findings were variable. Analysis of ciliary ultrastructure was performed in 5 affected dogs, but no characteristic primary ciliary defects (primary ciliary dyskinesia) were detected. Serum and bronchoalveolar lavage fluid (BALF) concentrations of IgA, IgG, and IgM were determined in some affected dogs and clinically normal Irish Wolfhounds. Serum IgA concentration was below the reference range in 5 of 8 affected dogs tested, whereas BALF IgA concentration was above the normal range in 2 affected adult dogs. The CD4 to CD8 lymphocyte subset ratio (CD4:CD8) in peripheral blood was tested in 3 affected dogs and was within the normal range. BALF CD4:CD8 was tested in 1 affected dog and was higher than the normal range. Decreased neutrophil phagocytosis was observed in 1 of the 4 dogs tested. Analysis of pedigrees of the Belgian, Canadian, German, and Swiss dogs revealed common ancestry, suggesting a heritable syndrome.

Eosinophilic bronchopneumopathy in dogs.

Eosinophilic bronchopneumopathy was diagnosed in 23 young dogs. Clinical signs included cough, gagging, and retching in all dogs, dyspnea in 21 dogs (91%), and nasal discharge in 12 dogs (52%). The most common radiographic findings were a moderate to severe bronchointerstitial pattern (68%, 13 of 19 dogs). Bronchoscopic findings included the presence of abundant yellow-green mucus or mucopurulent material (70%, 16 of 23 dogs) and severe mucosal thickening with an irregular or polypoid appearance (52%, 12 of 23 dogs), with partial airway closure during expiration in 3 dogs (13%). Peripheral blood eosinophilia was noted in 14 of 23 dogs (61%). Inflammatory cells in brush or bronchoalveolar lavage fluid cytologic preparations comprised more than 50% eosinophils in 14 of 23 dogs (61%), and 20-50% eosinophils in 6 dogs (26%). Eosinophilic infiltration of the bronchial mucosa was observed in biopsies from 19 dogs and was graded as mild (37%, 7 dogs), moderate (32%, 6 dogs), or severe (32%, 6 dogs). The mean serum immunoglobulin A concentration was almost double that of a population of 20 healthy dogs of various breeds. Oral glucocorticoids were administered on alternate days with progressive tapering of the dose; the dosage at maintenance varied between 0.1 and 1.0 mg/kg every other day. No relationship was found between the duration of clinical signs and the maintenance dosage or the cytologic and histopathologic grades.

Comparative assessment of right ventricular performance from the pressure-volume relationship in double-muscled and conventional calves.

Forty-one and 55 records of right-sided and systemic arterial pressures, cardiac output, and end-diastolic and end-systolic right ventricular volumes were collected from a group of 6 conventional and 6 double-muscled calves, respectively. In each group, the mean right ventricular pressure-volume loop was constructed. Global cardiac performance was significantly lower in the double-muscled than in the conventional calves. The right ventricular end-diastolic and end-systolic volumes, as well as the diastolic portion of the mean pressure-volume loop, were similar in the 2 groups. Those results suggest that the reduced cardiac performance of double-muscled calves is not due to a lowered ventricular preload and that diastolic properties of their myocardium are similar to those of conventional calves. When expressed on a body weight basis, however, the right ventricular end-diastolic and end-systolic volumes were lower in the double-muscled than in conventional calves. When expressed as a function of probable metabolic demand, therefore, the volumetric capacity of the cardiac pump appears to be reduced in double-muscled calves. The significantly lower right ventricular ejection fraction, maximal rate of ventricular pressure rise and right ventricular peak-systolic pressure to end-systolic volume ratio measured in double-muscled as compared with conventional calves suggest that reduced myocardial contractility may also be partly responsible for the significantly lower stroke index of the former calves. The cardiac pump of double-muscled cattle thus seems to be less effective than that of conventional cattle because of reduced volumetric capacity and lowered strength of contraction.

Ductuli efferentes in the epididymis of boar, goat, ram, bull, and stallion.

Dutculi efferentes were studied by microdissection and histologic methods in 2 boar, 6 goat, 5 ram, 25 bull, and 19 stallion epididymides. On the basis of the present findings and the data of others and relating them to the total number of specimens examined in each species, an estimate (narrow range) was made of the minimal-maximal numbers of efferent ductules as follows: dog 13 to 15; cat 14 to 17; boar 14 to 16; goat 18 to 19; ram 17 to 20; bull 13 to 16; and stallion 14 to 17. The histologic appearance of the efferent ductules of the bull, including measurements of their diameter, lumen, and epithelium, was briefly described. Attention was focused on the presence of blind-ending ductules, because it was thought that they might be a factor in the cause of spermiostasis. Blind-ending ductules were found in 1 of 2 porcine, 1 of 6 caprine, 2 of 5 ovine, 8 of 25 bovine, and 13 of 19 equine ductules per affected male were 4 in the boar, 1 in the goat, 2 to 3 in the ram, 1 to 5 in the bull, and 1 to 14 in the stallion. From our work, it appears that in the bull and stallion at least, blind-ending ductules were present in sufficient numbers to be considered a factor in spermiostasis and the infertility resulting from it.

Changes in basal lamina of seminiferous tubules associated with deranged spermatogenesis in the bull.

The basal lamina of seminiferous tubules of 16 beef bulls, with scrotal circumferences (SC) from 40.5 to 28 cm, was characterized. The mean thickness of basal laminae was from 0.55 to 0.94 micron in normospermic bulls with SC greater than 30 cm. Of 3 bulls that had a SC less than 30 cm, 1 had hypoplastic testes and was azoospermic, whereas 2 bulls had atrophic changes in their testes and were oligospermic. The latter 2 bulls had thick basal laminae, with a mean of 1.35 micron and 1.68 micron, respectively, whereas basal laminae of the bull with hypoplastic testes had a mean thickness of 0.96 micron, comparable with that of bulls with normal testes (SC, greater than 30 cm). Thickness of the basal lamina of seminiferous tubules might be a useful criterion in differentiating atrophy from hypoplasia.

Doppler echocardiographic study of left and right ventricular function during dobutamine stress testing in conscious healthy dogs.

OBJECTIVE: To evaluate left and right ventricular filling and ejection performances by use of Doppler echocardiography in healthy, conscious dogs submitted to dobutamine stress testing. ANIMALS: 10 unsedated, healthy adult Beagles. PROCEDURE: Doppler echocardiography was performed during cardiac stress testing on each dog twice at 24-hour intervals. Dobutamine was infused in 10 micrograms/kg of body weight/min incremental dosages, from 12.5 to 42.5 micrograms/kg/min. Duration of each step was 15 minutes. Doppler measurements were recorded at baseline and at each stage of dobutamine infusion, whereas aortic diameter was measured at baseline and at peak dosage by use of two-dimensional echocardiography. RESULTS: Dobutamine infusion induced a significant increase in velocity time integrals and in peak flow velocities at the aortic, pulmonic, mitral, and tricuspid valves. Acceleration time-to-deceleration time ratio at the aortic wave also was increased significantly. On the other hand, ejection time, acceleration time, and deceleration time at the aortic and pulmonic valves and peak flow velocity of the E wave-to-peak flow velocity of the A wave ratio at the mitral and tricuspid valves decreased significantly during the test. The acceleration time-to-deceleration time ratio at the pulmonic wave was unchanged. A significant, progressive increase in cardiac index also was observed during dobutamine infusion, with a maximal increase of 104% from baseline. This was mediated initially by an increase in stroke index and, at higher dosages, by an increase in heart rate. CONCLUSIONS AND CLINICAL RELEVANCE: Doppler echocardiography performed during dobutamine stress testing may be a reliable method of assessing myocardial function in dogs with cardiovascular disease.

Physiologic response to dobutamine infusion during cardiac stress testing of dogs.

OBJECTIVE: To evaluate response of various cardiovascular variables after administration of incremental doses of dobutamine in healthy conscious dogs, using standardized dobutamine stress echocardiography (DSE). ANIMALS: 8 healthy dogs. PROCEDURE: A DSE was performed twice on each dog within 24 hours. Dobutamine was infused at a rate of 12.5 to 42.5 microg/kg/min, using incremental increases of 10 microg/kg/min. Doppler sphygmomanometry, electrocardiography, and echocardiography were performed. Left ventricular size, global ventricular performance, and left ventricular systolic myocardial function were measured by means of echocardiography. RESULTS: At the highest dosage, dobutamine induced an increase of 20+/-3% and 109+/-12% in systolic blood pressure and cardiac index, respectively. The latter was associated with a significant increase in heart rate and stroke index. Fractional shortening of the left ventricle, fractional thickening of the left ventricular free wall and interventricular septum, ejection fraction, and mean velocity of fiber shortening had a progressive and significant increase during dobutamine infusion. Preejection period and left ventricular ejection time had a progressive and significative decrease during the stress test. CONCLUSIONS: The technique used was feasable, safe, and repeatable in healthy conscious dogs. Control values were determined. CLINICAL RELEVANCE: Data for these healthy dogs might be useful for comparison with results obtained from dogs with known or suspected cardiovascular disease.

Effects of zeranol on reproduction in beef bulls: scrotal circumference, serving ability, semen characteristics, and pathologic changes of the reproductive organs.

Effects of zeranol on scrotal circumference, serving ability, semen characteristics, and postmortem measurements of the genital organs were determined in beef bulls from 9 to 20 months of age. Group 1 (n = 5) served as a nonimplanted control group. Group 2A (n = 5) was implanted with 36 mg of zeranol at birth and at 3 and 6 months of age. Group 2B (n = 5) was implanted with 36 mg of zeranol every 3 months from birth through 18 months of age. Scrotal circumference was adversely affected by zeranol in groups 2A and 2B, but values approached those of group 1 with increasing age. Serving ability was also affected adversely but tended to recover with increasing age. Semen quality was low in groups 2A and 2B and did not improve with increasing age. There was no difference in testicular weight, vesicular gland weight, and penis length among groups when bulls were slaughtered at 20 months of age. Epididymal weight was greater in group-2B bulls and was most likely a consequence of epididymal lesions. Histologic examination of the genital organs revealed that zeranol induced adenomyosis and sperm granulomas in the caudae epididymidis and markedly altered the structure of the sexual accessory glands of bulls in groups 2A and 2B. Alterations in the vesicular glands were characterized by reduced alveolar development and an increase in connective tissue. Low epithelium associated with focal areas of squamous metaplasia were common in the prostate of groups 2A and 2B bulls. Lesions in the bulbourethral glands were characterized by low glandular epithelium, focal areas of squamous metaplasia, cystic collecting ducts, and an increase in connective tissue. Groups 2A and 2B had more abnormal seminiferous tubules than did group 1. Lesions in groups 2A and 2B may have been direct effects of zeranol or may have resulted from reduced testosterone secretion.

Pathophysiology of small testes in beef bulls: relationship between scrotal circumference, histopathologic features of testes and epididymides, seminal characteristics, and endocrine profiles.

Tissue sections from testes and epididymides obtained from 17 young beef bulls with scrotal circumference (SC) between 27 and 40.5 cm were studied to determine whether small testes were a manifestation of lesions or a result of less, but otherwise normal, seminiferous epithelium. The SC correlated negatively with the estimates of germinal epithelial loss and positively with seminiferous epithelial area. Four bulls with SC less than 30 cm had severe lesions in their testes. Hypoplastic tubules were characterized by Sertoli's cells only with no evidence of germinal cells. Loss of germinal cells, leaving vacuolated epithelium and atrophy, were observed in degenerated tubules. Hyperplasia of Leydig's cells was observed in the vicinity of Sertoli's cell-only tubules, resulting either from degeneration or hypoplasia, and atrophy of Leydig's cells was associated with tubules devoid of Sertoli's cells. These findings indicated that Sertoli's cells may produce a factor(s) required for maintenance and regulation of Leydig's cell function. Epididymal epithelium, especially in the head, had regressed in bulls with hypoplastic and degenerative changes in their testes. Decreased sperm concentration and motility and an increased frequency of morphologic defects were observed in the 4 bulls with testicular lesions and regressed epididymal epithelium. Blood plasma profiles of cortisol, follicle-stimulating hormone, luteinizing hormone, and testosterone were determined in the 4 bulls with SC less than 30 cm and 10 of the 13 bulls with SC greater than 30 cm. There were no statistically significant (P greater than 0.1) differences in the responses to exogenous gonadotropin-releasing hormone or base-line patterns of blood plasma follicle-stimulating hormone and luteinizing hormone between the 2 groups. However, in the bulls with SC less than 30 cm, the mean concentration of testosterone was lower, whether spontaneous (P less than 0.05) or exogenous gonadotropin-releasing hormone induced (P less than 0.1). The fact that these bulls were not deficient in gonadotropins indicated that Leydig's cell function was impaired by local factors, either the factors that caused the tubular damage or those consequent to the tubular damage.