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Biomedical subjects

J D Jacobson

Publications and source records attributed to J D Jacobson.

48 records · Page 3Linked to original sources

Prevention of recurrent autoimmune diabetes in BB rats by anti-asialo-GM1 antibody.

BB rats exhibit a syndrome of spontaneous diabetes that has clinical and pathological characteristics analogous to those found in human insulin-dependent diabetes mellitus (IDDM). Islet tissue transplanted into spontaneously diabetic BB rats is uniformly destroyed by a recurrence of the autoimmune response that destroyed the diabetic subject's native islets. To examine recurrent autoimmune destruction of transplanted islets, it is necessary to exclude islet damage that might result from allograft rejection. We utilized neonatal tolerance induction to prevent rejection of Wistar-Furth (WF) (RT1u) islet allografts by spontaneously diabetic BB recipients. We determined that islet-recipient treatment with anti-asialo-GM1 (anti-AGM1) antibody prevents recurrent autoimmune diabetes that would otherwise destroy transplanted WF islet grafts. Anti-AGM1 therapy significantly decreased peripheral blood natural killer (NK) cell activity. These data suggest a role for NK cells in the pathogenesis of recurrent diabetes in neonatally tolerant BB rats.

Animals↗

Oxytocin augmentation of labor: a comparison of 15- and 30-minute dose increment intervals.

Two different regimens for oxytocin augmentation of labor were compared retrospectively in two institutions. In one regimen, the interval between dose increments was 15 minutes; in the other it was 30 minutes. All study patients were nulliparous and had uncomplicated pregnancies in spontaneous active labor; the 15-minute group consisted of 92 patients and the 30-minute group had 82 patients. No differences were demonstrated in age, dilation when oxytocin administration started, length of oxytocin administration, cesarean section rate, complications of delivery, birth weight, or Apgar scores. The maximal oxytocin dose in the 30-minute interval group was significantly lower. This group also had the oxytocin infusion stopped for evidence of uterine hyperstimulation and/or abnormal fetal heart rate tracing significantly less often (6.9% for the 30-minute interval versus 17.8% for the 15-minute interval; P = .0017). Overall, these results suggest that the longer interval does not increase the length of labor but decreases the incidence of uterine hyperstimulation.

Drug Administration Schedule↗

Sperm velocity in seminal plasma and the association with gender of offspring.

The gender of the offspring is determined by the fertilizing sperm. Previous gender studies were based on washed sperm, but not on sperm in seminal plasma. The objective was to correlate motility parameters assessed during semen analyses with the offspring gender. For comparison, fixed sperm head DNA quantitated by Hoechst 33342 fluorescence microscopy was also analyzed. Forty-six patients undergoing assisted reproduction procedures resulted in livebirth deliveries with either male or female-predominant offsprings. Sperm head fluorescence was weakly correlated to the gender in 61% of the cases. Sperm of patients with male offsprings had slower curvilinear (44.2 +/- 1.8 mean +/- SEM, versus, 49.9 +/- 2.7 micro /sec) and slower average path velocities (32.4 +/- 1.2 versus 36.3 +/- 1.7 micro /sec). Using cut-off values for the curvilinear (< 49 micro /sec) and average path (< 36 micro /sec) velocities of sperm swimming in seminal plasma, the two parameters predicted 75 and 68% of the male offspring births, respectively. The data suggest that sperm movement in seminal plasma is a marker for factors that skew the ratio of the X- to Y-sperm populations.

Benzimidazoles↗

Sperm apoptosis in nonpregnant luteal phase sera after in vitro fertilization as assessed by comparative genomic hybridization.

Toxicity in serum has been reported in cases of recurrent spontaneous abortions and endometriosis. The null hypothesis was that serum toxicity was not involved in failed pregnancies after in vitro fertilization procedures. The objective was to expose donor sperm to pregnant versus nonpregnant patient sera and analyze for sperm DNA damaging effects using a novel comparative genomic hybridization method. Luteal phase sera (N = 21 cases) were drawn one week after embryo transfer. Colloid-washed donor sperm were incubated (48 h, 37 degrees C, 5% CO2 in air) in 0% or 50% sera. Single-stranded DNA (ssDNA) of control sperm were stained in Hoechst 33342 and hybridized to Sybr Gold-stained ssDNA of sera-treated sperm. Image analyses were performed and fluorescent intensities analyzed. Nonpregnant patient sera (57% of cases) were associated with DNA fragmentation (64.4 +/- 8.8 pixels; mean +/- S.E.M.) when compared with pregnant patient sera (106.3 +/- 8.4 pixels). There were no differences in the sera of biochemical (108.2 +/- 15.3) versus clinical pregnancy cases (105.3 +/- 11.4). The results suggest that nonpregnant patient sera contained factor(s) that cause DNA fragmentation leading to pregnancy losses.

Blood Proteins↗

Correlation of sperm parameters with apoptosis assessed by dual fluorescence DNA integrity assay.

Failed fertilization after intracytoplasmic sperm injection or miscarriages occurs in cases involving apoptotic and necrotic sperm. Identifying normal sperm is important for successful assisted reproductive technologies (ART) procedures. The study was conducted to correlate sperm parameters with intact sperm with normal DNA assessed by the dual stain assay in 118 separate individuals. The results showed differences in percent DNA intact sperm in individuals with normal W.H.O. sperm features (62 +/- 1.1; mean +/- S.E.M.) compared with oligoasthenoteratozoospermia patients (38 +/- 5.3). Individuals whose sperm had fertilizing capacity had higher percentages of intact DNA (60 +/- 1.3 versus 47 +/- 2.4). The percentages of intact DNA sperm were significantly correlated to total motility in semen (R = 0.7), post-wash motility (R = 0.6), rapid progression (R = 0.6), intact acrosome (R = 0.5), and strict morphology (R = 0.5). There were no correlations with the remaining parameters. The dual stain assay identified sperm with normal physiology and fertilizing capacity. The dual stain assay measures DNA integrity and is a promising method to select normal sperm for ART.

DNA↗

A follow-up expanded study of the correlation of sperm velocity in seminal plasma and offspring gender.

A preliminary study reported finding higher sperm velocity in seminal plasma in males of partners that conceived female offsprings. The null hypothesis was that sperm velocity was not related to the offspring gender. The objectives were: (a) to expand the previous study, and (b) to correlate offspring gender results with motility parameters determined through the computer-aided sperm analyzer (CASA) system. In combined fresh and frozen cycles (N = 187), sperm from cases with all female offsprings displayed higher curvilinear (48 +/- 1.0 mu/sec versus male 46 +/- 1.0, P < 0.05) and average path velocities (36 +/- 0.7 mu/sec versus male 34 +/- 0.7, P < 0.01). A criteria of less than 30 mu/sec or over 41 mu/sec average path velocity predicted 73 or 72% of the male or female offspring cases, respectively. A curvilinear velocity of less than 49 mu/sec or over 55 mu/sec predicted 58 or 59 % of the male or female offspring cases, respectively. Semen viscosity reflected in sperm velocity was linked to predominantly male or female sperm populations. Paracrine signals from the gender-skewed sperm precursor populations controlling viscosity merit further exploration.

Female↗

Cardiovascular effects of topical ophthalmic 10% phenylephrine in dogs.

OBJECTIVE: To evaluate the effect of topical ophthalmic 10% phenylephrine on systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), pulse rate (PR) and electrocardiogram (ECG) in dogs. ANIMALS STUDIED: Nine clinically normal dogs. PROCEDURE: Arterial catheters were placed in the dorsal pedal artery of awake dogs and ECG leads were attached. After a 15-min acclimatization period, baseline PR, SAP, DAP and MAP were recorded every 5 min for 20 min. Two treatment groups (eight dogs each) were studied. Group I: one drop of phenylephrine was placed in each eye once. Group II: one drop of phenylephrine was placed in each eye three times at 5-min intervals. Following treatment, PR, SAP, DAP and MAP were recorded every 5 min for 90 min. The mixed procedure of the SAS system was used to perform a repeated measures analysis of variance to test for linear and quadratic trends across time. RESULTS: Group I: There was a significant quadratic decrease in PR across time (P = 0.0051). Systolic arterial pressure increased linearly with time (P = 0.0002), MAP increased linearly with time (P = 0.0131), and DAP increased linearly with time (P = 0.0001). Group II: There was a significant quadratic decrease in PR across time (P = 0.0023). There was a significant quadratic increase in SAP (P = 0.0324), MAP (P = 0.0103) and DAP (P = 0.0131) across time. CONCLUSIONS: Topical ophthalmic application of 10% phenylephrine in normal dogs results in elevation of arterial blood pressure and reflex bradycardia.

Administration, Topical↗

Cardiorespiratory effects of four opioid-tranquilizer combinations in dogs.

The cardiorespiratory effects of four opioid-tranquilizer combinations were evaluated in six dogs. The four combinations were administered to each dog in a randomized order. Buprenorphine (BUP; 0.01 mg/kg IV) or oxymorphone (OXY; 0.1 mg/kg IV) was followed in 10.4 +/- 1.3 minutes by midazolam (MID; 0.3 mg/kg IV) or acepromazine (ACE; 0.05 mg/kg IV). Nalbuphine (0.16 mg/kg IV) was administered 94.1 +/- 2.3 minutes after the tranquilizer was given. Heart rate (HR) and mean arterial blood pressure (MAP) decreased significantly (P < .05) after each combination. MAP was significantly lower with combinations using ACE. Most dogs panted after opioid administration; this was associated with increased minute volume (VM) and decreased tidal volume (VT). After administration of the tranquilizer, mean breathing rate and VM index (VMI) were significantly lower with ACE combinations. There were no significant changes in pH and blood gas variables after BUP-ACE. The other three combinations were associated with significant (P < .05) decreases in pH and increases in PaCO2. Mean PaO2 decreased significantly (P < .05) with OXY combinations but not BUP combinations. Dysrhythmias (atrial or ventricular escape complexes) were seen with each combination. HR increased significantly (P < .05) after nalbuphine in dogs receiving OXY, but not BUP. Dogs receiving OXY became more alert after nalbuphine on six of 12 occasions, whereas dogs receiving BUP became less alert on six of 12 occasions. OXY-ACE provided the most chemical restraint/sedation and BUP-MID provided the least.

Acepromazine↗

Efficacy of an epidural combination of morphine and detomidine in alleviating experimentally induced hindlimb lameness in horses.

Amphotericin B-induced synovitis of the left tarsocrural joint was used to create a grade 3 of 4 lameness in 11 horses. Caudal epidural catheters were placed and advanced to the lumbosacral region. Baseline heart and respiratory rates were recorded and horses were videotaped at a walk and trot. Morphine sulphate (0.2 mg/kg) and detomidine hydrochloride (30 micrograms/kg) were administered to treated horses (n = 8) through the epidural catheter; an equivalent volume of physiologic saline solution was administered to control horses (n = 3) through the catheter. At hourly intervals after epidural injection for a total of 6 hours, heart and respiratory rates were recorded, and horses were videotaped walking and trotting. At the end of the observation period, video recordings were scrambled onto a master videotape. Lamenesses were scored by three investigators unaware of group assignment or treatment time. Lameness scores, heart rates, and respiratory rates were compared between groups using repeated measures analysis of variance. There was a significant decrease in lameness score after treatment with epidural morphine and detomidine (P = .0003); average lameness scores of treated horses were less than grade 1 at each hourly observation for 6 hours after drug administration. Early in the observation period, heart rates significantly increased in control horses and decreased in treated horses (P = .03). A similar trend occurred for respiratory rates (P = .07). Results of this study demonstrate that epidural administration of a combination of morphine and detomidine is capable of providing profound hindlimb analgesia in horses.

Adrenergic alpha-Agonists↗

Systemic and local effects associated with long-term epidural catheterization and morphine-detomidine administration in horses.

OBJECTIVE: The purpose of this study was to determine the systemic and local effects associated with long-term epidural catheterization and epidural morphine-detomidine administration in horses. STUDY DESIGN: Development of systemic or local effects was assessed by placing caudal epidural catheters in study horses and administering injections through the catheters every 12 hours for 14 days. ANIMALS: Ten horses with epidural catheters that received daily injections; six uncatheterized horses presented for euthanasia. METHODS: Horses received either 0.2 mg/kg morphine sulfate and 30 micrograms/kg detomidine hydrochloride or an equivalent volume of physiologic saline solution through epidural catheters. Systemic effects were compared between control and treatment horses by measuring physical parameters and hay and water consumption, as well as by evaluating major organs after euthanasia. Local effects were studied by examining cerebrospinal fluid and by grading representative samples of the spinal cord and surrounding tissues histologically for inflammation and fibrosis. Local effects were compared between control and treatment horses, as well as between catheterized (control plus treatment) horses and uncatheterized horses. RESULTS: No significant difference was identified in daily variables or hay and water consumption between control and treatment horses. No growth was obtained from cerebrospinal fluid cultures. No significant difference in cerebrospinal fluid values or spinal tissue inflammation or fibrosis grades was shown between control and treatment horses. However, when compared with uncatheterized horses, cerebrospinal fluid red blood cell values were marginally higher and protein concentrations were significantly higher in the catheterized group. Lumbosacral and sacral spinal tissue segment inflammation grades, and sacral segment fibrosis grades were significantly higher in catheterized horses. CONCLUSIONS: Long-term epidural administration of a morphine-detomidine combination is not associated with apparent adverse systemic effects in horses. Localized inflammation and fibrosis seem to be catheter-related. CLINICAL RELEVANCE: Potential systemic and local effects are important considerations with long-term administration of a morphine-detomidine combination through indwelling epidural catheters for alleviation of chronic musculoskeletal pain in horses.

Analgesics↗

Correlation between intact sperm acrosome assessed using the Spermac stain and sperm fertilizing capacity.

Accurate determination of sperm acrosomal status is important in fertility studies. The objective was to correlate the percentage of intact acrosome assessed using the new Spermac stain with the capacity of sperm to fertilize oocytes. Sperm specimens were processed either by centrifuge wash, 48:95 Percoll gradient or test yolk buffer (TYB) wash, and tested using the zona-free hamster oocyte assay. The results indicated a correlation between the percentage of sperm with intact acrosome reaction and the percentage of sperm penetrating the oocytes in the TYB-washed group. The data suggest the usefulness of the Spermac stain for assessing the acrosomal status and in predicting the fertilizing capacity of the sperm.

Acrosome↗

Sperm kinetics and morphology before and after fractionation on discontinuous Percoll gradient for sex preselection: computerized analyses.

The multiple-layer discontinuous Percoll density gradient centrifugation procedure is being used for gender selection and several reports suggested separation efficiencies of over 77%. The mechanism involved in the separation of X- and Y-bearing sperm using this method seems to be the difference in sperm head dimensions or motility but supporting data are inconsistent. The specific aims of the study were to evaluate the head dimensions of sperm at the upper and lower fractions after the 8-layer Percoll gradient procedure for sex preselection and to ascertain the kinematic parameters and tail lengths of sperm derived from the 2 separate Percoll fractions. Sperm cells were obtained from thawed donor specimens (N = 20) and were layered on top of the 8-layer discontinuous Percoll gradient, which ranged from 34 to 85% in increments of 7%. After centrifugation, the resuspended sperm cells derived from the upper and lower fractions of the Percoll gradient were analyzed on the Hamilton Thorn HTM-C analyzer for differences in sperm motility patterns and sperm head dimensions. Aliquots of sperm from the 2 fractions were fixed and stained using the Spermac stain, and the lengths of each sperm tail (N = 600) were measured on the HTM-C analyzer. Sperm derived from the bottom Percoll (X) fraction had a threefold higher (p < .05) percent motility when compared with sperm from the top (Y) fraction. Sperm derived from the bottom (X) fraction maintained the higher percentage motility after 24 h of incubation. The percent total progression, rapid progression, and hyperactivation were also significantly higher (p < .05) in sperm from the bottom (X) fraction. Similarly, the curvilinear (Vcl), average path (Vap) and straight line (Vsl) velocities were significantly faster in sperm (p < .05) from the bottom (X) fraction. In contrast, the percent linearity and straightness were significantly (p < .05) higher for the top (Y) fraction. Sperm from the bottom (X) fraction have shorter (p < .07) tail length (1.6% difference) when compared with sperm from the top (Y) fraction. Although the dimensions of the sperm head from the bottom (X) fraction were numerically greater than top fraction sperm, they were not significant (p > .05). The results suggest that bottom (X) fraction sperm derived from the 8-layer discontinuous Percoll gradient for sex preselection have higher motility, progression, and hyperactivation when compared with top (Y) fraction sperm. The bottom (X) fraction sperm have greater longevity in motility and have shorter tails, supporting earlier hypotheses of sex differences in sperm parameters. However, the present data do not support observations of differences in sperm head dimensions in sperm processed for sex preselection, and an inference of a larger sperm due to more chromosome material originating from the X chromosome cannot be made.

Cell Separation↗