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Biomedical subjects

K Whittington

Publications and source records attributed to K Whittington.

At least 19 recordsLinked to original sources
PubMed2005

Prostasomes--their effects on human male reproduction and fertility.

The prostate is a glandular male accessory sex organ vital for normal fertility. It provides the prostatic component of seminal plasma which nourishes and protects sperm following ejaculation. Prostasomes are small (40-500 nm) membrane-bound vesicles produced by epithelial cells lining the prostate acini and are a component of prostatic secretions. Although the existence of these particles has been known for many years, their full function and relevance to reproductive health are largely unknown. Proteomic studies have shown a wide range of proteins (enzymes, structural proteins and novel, unannotated proteins) present in or on the surface of prostasomes providing them with a diverse nature. Interestingly prostasomes are able to fuse with sperm, this event and the associated transfer of proteins lies at the heart of many of their proposed functions. Sperm motility is increased by the presence of prostasomes and their fusion prevents premature acrosome reactions. Prostasomes have been shown to aid protection of sperm within the female reproductive tract because of immunosuppressive, antioxidant and antibacterial properties. Clinically these functions imply a role for prostasomes in male factor infertility. However, the very functions that promote fertility may have negative connotations in later life; recent work has suggested that prostasomes are involved in prostate cancer. Clearly more work is needed to clarify the role of these novel particles and their impact on men's health.

Cytoplasmic Vesicles↗
PubMed2001

Function and localization of oxytocin receptors in the reproductive tissue of rams.

Oxytocin is present in the male reproductive tract and has been shown to increase contractility in the epididymis and to modulate steroidogenesis. This study investigated the effects of oxytocin in the testis in vivo, and the presence and cellular localization of oxytocin receptors in the reproductive tract of rams. During the breeding season, mature rams underwent efferent duct ligation before injection of either oxytocin (20 microg) or oxytocin plus an oxytocin antagonist (20 microg) into the testicular artery; the contralateral testicular artery received saline. Injection of oxytocin caused a significant increase (P < 0.05) in the concentration of spermatozoa collected from the rete testis. This effect was not observed after treatment with the oxytocin antagonist plus oxytocin. Western blot analysis performed using a specific oxytocin receptor antibody (020) identified a single immunoreactive band of 66 kDa in testicular and epididymal tissue. This band was present in uterine tissue but not in liver or muscle. Immunocytochemistry identified oxytocin receptors on Leydig and Sertoli cells of the testis, on epithelial cells throughout the epididymis, on peritubular smooth muscle cells in the cauda epididymidis, and on the epithelial cells and circular smooth muscle layer of the ductus deferens. These findings indicate that oxytocin can modulate sperm transport in the ram testis. A role for oxytocin in promoting sperm transit is supported by the localization of oxytocin receptors in the cauda epididymis and ductus deferens, and the presence of receptors on Leydig, Sertoli and epididymal epithelial cells provides further evidence that oxytocin may be involved in the local regulation of steroidogenesis.

Animals↗
PubMed2000

A national study of pressure ulcer prevalence and incidence in acute care hospitals.

OBJECTIVE: This study sought to establish national benchmarks for pressure ulcer prevalence and incidence among acute care health organizations served by Novation LLC. SETTING AND SUBJECTS: One hundred sixteen acute care facilities from 34 states participated; the sample consisted of 17,560 patients in hospital-based medical-surgical or intensive care units. INSTRUMENTS: Standardized education kits were provided to each participating site. The kits included an educational video about pressure ulcer staging, a post-test and answer key, and assessment form for patient data collection. METHODS: Pressure ulcer prevalence was measured during a predetermined 24-hour period at each facility. Incidence was measured over the average length of stay determined for each participating facility. Subjects were assessed by teams consisting of a registered nurse and one other health care professional (e.g. licensed practical nurse, physical therapist). Demographic, wound, and other data were collected for these patients. Data collection forms were audited and submitted to a central site for database entry, analysis, and generation of reports. RESULTS: The average length of stay for the participating facilities was 5 days. Pressure ulcers developed in 7% of the subjects (n = 383); 90% were stage I or II pressure ulcers, and 73% occurred in patients older than 65 years. The most sites based on both prevalence and incidence measurements were the sacrum and coccyx at 26% and 31%, respectively. CONCLUSIONS: Prevalence and incidence studies must be routinely conducted to clearly identify the extent of the pressure ulcer problem to provide guidance for efficient and effective corrective action.

Adult↗
PubMed1999

Relative contribution of leukocytes and of spermatozoa to reactive oxygen species production in human sperm suspensions.

The contribution of leukocytes and of spermatozoa to reactive oxygen species (ROS) production in prepared sperm suspensions from donors and subfertility patients was compared. In both groups, more leukocytes/10(6) spermatozoa were counted in samples which produced detectable ROS than in those that did not: Donors-645 vs. 170 (medians, n = 7; p < 0.01, Kruskal-Wallis), Subfertile group-1785 (n = 18) vs. 11 (n = 8) (p < 0.005, Kruskal-Wallis), respectively. Leukocyte concentrations were correlated with basal (r = 0.826, p < 0.001) and with ROS production stimulated with 50 mumol N-formyl, met, leu, phe l-1 (N-FMLP) (r = 0.835, p < 0.001) and 100 nmol phorbol 12-myristate 13-acetate l-1 (PMA) (r = 0.835, p < 0.001) measured using a chemiluminescence assay. Leukocytes were removed from the sperm suspensions of 6 donors and from 96 ejaculates from 21 subfertility patients and ROS production was determined. Subsequently, in all 6 donors, N-FMLP did not stimulate ROS production indicating that leukocyte removal was complete, though in one case PMA stimulated low levels of ROS production. In 65 ejaculates from subfertile men the N-FMLP response was completely eliminated but in 7 of these samples PMA continued to stimulate ROS production. We conclude that infiltrating leukocytes are the predominant source of ROS production in unpurified sperm preparations. Some purified sperm suspensions could be stimulated to produce ROS by the addition of PMA indicating that spermatozoa themselves may produce ROS, albeit in much smaller amounts.

Humans↗
PubMed1999

Reactive oxygen species (ROS) production and the outcome of diagnostic tests of sperm function.

Washed sperm suspensions from 64 out of 89 (72%) randomly selected infertility patients produced detectable reactive oxygen species (ROS) compared to 17 out of 67 (25%) prospective semen donors (p < 0.01, Chi-square test). Among patients, the median sperm concentration in ejaculates which yielded sperm suspensions that generated detectable levels of ROS was lower than in those which did not: 36.2 (15.63-57.64) vs. 71.5 (22-108) x 10(6)/mL, respectively (median (interquartile range), p < 0.05, Kruskal-Wallis test). In samples that produced ROS, the basal rate of production and the rates after stimulation with 50 mumol N-formyl met leu phe (N-FMLP) l-1 or with 100 nmol phorbol 12-myristate 13-acetate (PMA) l-1 were significantly and inversely correlated with sperm concentration in the ejaculate (r = -0.43, -0.41 and -0.35, respectively, p < 0.01 Spearman's rank correlation). The rate of ROS production showed no relationship to the motility of spermatozoa in semen, whether evaluated visually or via computer assisted semen analysis. However, there was a significant negative correlation (r = -0.370) between the motile, normal sperm concentration (MNSC) and basal ROS production, and when stimulated with N-FMLP (r = -0.311) or with PMA (r = -0.249) (all p < 0.05). In patient samples that generated detectable ROS, the ability of the spermatozoa to retain motility for 24 h after preparation on a 40/80% Percoll gradient was negatively correlated with basal ROS production (r = -0.310, p < 0.05). ROS production was also related to the outcome of in vitro sperm mucus penetration tests. Unstimulated levels of ROS production showed a significant (p < 0.05), negative correlation with the number of progressively motile spermatozoa present in mucus after 15 (r = -0.379) and 60 (r = -0.362) min. These results suggest that sperm samples with increased ROS tend to have poor semen quality and reduced performance in a number of routine, diagnostic sperm function tests.

Adult↗
PubMed1999

Managing pressure ulcers: a multisite CQI challenge.

Think preventing and tracking pressure ulcers is expensive? Treatment may cost more. The Nurse Executive Council of VHA Alabama partnered with KCI USA, Inc., to implement a CQI project to manage pressure ulcer incidence.

Alabama↗
PubMed1998

The effect of incubation periods under 95% oxygen on the stimulated acrosome reaction and motility of human spermatozoa.

Human sperm samples were prepared on a 30% Percoll gradient and reactive oxygen species (ROS) production was measured. In samples that generated ROS incubation under 95%O2:5%CO2 for 30 min decreased the proportion of spermatozoa capable of the stimulated acrosome reaction by 40% in comparison to samples incubated under 95%N2:5%CO2 (P< 0.001, repeated measures analysis of variance), but the degree of inhibition did not increase after more prolonged incubation periods (up to 6 h). The addition of the antioxidants catalase and superoxide dismutase prevented the inhibitory effect of 95%O2:5%CO2. Leukocyte removal from samples prior to 95%O2:5%CO2 incubation preserved the ability of the spermatozoa to acrosome react. Sperm motility parameters were less affected by 95%O2:5%CO2 but track velocity was 64.1 microm/s+/-1.96 after 2 h incubation under 95%N2:5%CO2 compared with 54.7 microm/s+/-1.41 after 2 h incubation under 95%O2:5%CO2 (P < 0.05, repeated measures analysis of variance). Sperm samples that did not generate detectable ROS were not affected by 95%O2:5%CO2. The toxic effects of incubation under 95%O2:5%CO2 on human spermatozoa result from increased endogenous ROS production, mostly from leukocytes. High ROS levels inhibit sperm function, with the stimulated acrosome reaction being more susceptible than motility parameters.

Acrosome Reaction↗
PubMed1997

Reactive oxygen species in human sperm suspensions: production by leukocytes and the generation of NADPH to protect sperm against their effects.

In men from couples consulting for infertility, 72% of washed sperm preparations produced detectable amounts of reactive oxygen species (ROS) compared to only 25% of preparations from a population of fertile donors. High ROS production was associated with oligozoospermia and poor sperm function. The rate of ROS production was closely correlated with the concentration of leukocytes (r = 0.826) and the degrees of stimulation by N-formyl-methionyl-leucyl-phenyl alanine (NFMLP) and by phorbol 12-myristate 13 acetate (PMA) were similar (r = 0.923). The removal of leukocytes with 'Dynabeads' either abolished or substantially decreased ROS production but in a few cases ROS production that could be stimulated by PMA but not NFMLP was observed in leukocyte-free preparations. When sperm preparations which produced ROS were incubated under 95% O2 there was a rapid 40% decrease in the number of sperm that could be stimulated to acrosome react although the acrosome reaction was unaffected by incubation under 95% N2 for up to 6 h. The harmful effect of oxygen was not seen in preparations that produced no ROS and could be prevented by removing leukocytes from the suspension or by adding superoxide dismutase and catalase. We conclude that leukocytes are the predominant source of ROS in human sperm preparations and that the ROS they produce are harmful to sperm. On the other hand these data confirm that highly purified sperm can produce ROS albeit in smaller amounts. We have demonstrated that flux through the pentose phosphate pathway (PPP) in purified sperm preparations increases in response to oxidative stress. This is required to make reduced glutathione available for glutathione peroxidase and we suggest that measurement of PPP flux provides an index of the capacity of glutathione peroxidase to protect sperm against oxidation.

Humans↗
PubMed1991

Specific amino acid residues in the second hypervariable region of HLA-DQA1 and DQB1 chain genes promote the Ro (SS-A)/La (SS-B) autoantibody responses.

In order to define the HLA-DR and DQ alleles, as well as the specific DQA1 and DQB1 chain genes involved in the anti-Ro/La autoantibody responses, RFLP analysis and sequence-specific oligonucleotide typing was carried out on 58 Caucasians and 48 American blacks with SLE or Sjögren's syndrome and anti-Ro antibodies. Among both Caucasian and black patients, the highest relative risk for the anti-Ro response (both with and without accompanying anti-La) was conferred by heterozygosity for the DQw2.1 (in linkage disequilibrium with HLA-DR3) and DQw6 (a subtype of DQw1) alleles compared with either 269 normal race-matched controls or 80 anti-Ro negative SLE/Sjögren's syndrome patients. Analysis of individual DQA1 and DQB1 chain alleles revealed that DQA1*0501 and DQB1*0201 were most frequent, followed by DQA1 and DQB1 alleles comprising DQw6. In patients not possessing DQw2.1 and/or DQw6 alleles, HLA-DQB1*0302 and HLA-DQA1*0401 (especially in blacks) were significantly increased. Nucleotide sequence analysis of these associated alleles showed that 100% of patients with anti-Ro had a glutamine residue at position 34 of the outermost domain of the DQA1 chain and/or a leucine at position 26 of the outermost domain of the DQB1 chain. Patients with anti-Ro plus La were more likely to have all four of their DQA1/DQB1 chains containing these amino acid residues than either anti-Ro-negative SLE patients or controls. These data implicate specific amino acid residues on both DQA1 and DQB1 chains located in the floor of the Ag binding cleft of the HLA-DQA1:B1 heterodimer and further suggest a role for "gene dosage" in the anti-Ro (+/- La) autoantibody response.

Alleles↗
PubMed1990

Successful islet/abdominal testis transplantation does not require Leydig cells.

Pancreatic islet allo- and xenografts are not rejected and exhibit long-term beta-cell function if transplanted into the abdominal testis of the diabetic host. Successful transplantation appears dependent on local factors unique to the abdominal testis. Because Leydig cells remain viable in abdominal testes, which also retain high levels of testosterone, the following question was addressed: do Leydig cells and/or their secretory products influence islet transplantability in the successful islet/abdominal testis transplantation model? Streptozotocin-induced diabetic rats (Sprague-Dawley) were injected with 75 mg/kg ethane dimethanesulfonate (EDS) to selectively eliminate Leydig cells prior to or following transplantation with islets isolated from the BBWORdr rat. Subcutaneous silastic tubes packed with estradiol prevented Leydig cell repopulation in the EDS-treated recipient. Grafted diabetic animals, including the EDS-treated rats with serum testosterone at castration levels, became nornoglycemic following islet transplantation and remained so far for up to ten months. Leydig cells were not observed in testes of the EDS- or EDS/estradiol-treated rats, whereas the transplanted islets within these testes appeared structurally normal and highly vascularized. Islets resided within the testicular interstitial compartment and contained alpha-, beta and delta-cells, as identified by electron microscopy. Beta cells were most prominent, contained secretory granules and exhibited a close structural and functional relationship with adjacent intraislet capillaries. We conclude that Leydig cells and Leydig cell secretory products, including testosterone, are not necessary for protecting islets against rejection and they do not play an obligatory role in the success of the islet/abdominal testis transplantation protocol. Leydig cells and Leydig cell secretory products do not promote long-term beta-cell function and are not required for the return to and maintenance of normoglycemia in the grafted diabetic rat.

Animals↗
PubMed1988

Effects of islet grafts of MHC-compatible donors on glucose metabolism in the spontaneously diabetic BB/Wor rat.

Complete recovery of the diabetic process occurred in spontaneously diabetic BB/Wor rats after the transplantation of islets of MHC-compatible donor rats. Islets were isolated from diabetes-resistant BB/Wor rats and were cultured for 4 days at 37 degrees C. The islets were then hand-picked and each BB/Wor rat with spontaneous diabetes received a total of 10 islets per g of body weight injected either into the immunologically privileged abdominal testis or into the non-immunologically favored renal subcapsular space. No immunosuppression was given to the recipients. After a period of at least 80 days of normoglycemia, the effects of an intravenous glucose injection on serum glucose and insulin levels were assessed. The grafts and the pancreases were then surgically removed and the insulin content of each organ site determined. The results showed that normoglycemia and a rapid weight gain were induced whether the rats were given an intratesticular or a renal, subcapsular islet graft. The amounts of extracted insulin recovered from the grafts after 83-259 days of normoglycemia were not significantly different from the pancreatic insulin content of age-matched control rats. But, despite the survival of a large mass of insulin-producing cells, glucose tolerance was impaired with a blunted insulin response and a delayed return of serum glucose to basal levels. Histologic examination of the islet grafts between 214 and 269 days after transplantation showed remarkable preservation of the islets with no evidence of an inflammatory reaction. Successful transplantation did not, however, lead to a recovery of the native pancreas of the BB/Wor recipient.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Extended survival of MHC-compatible islet grafts from diabetes-resistant donors in spontaneously diabetic BB/W rat.

Transplantation of a large inoculum of incubated islets of MHC-compatible donors led to an extended survival of the grafts to an average of greater than 86 days in 71% of male diabetic BB/W recipients. Identical results were obtained whether the immunologically privileged abdominal testis or the nonimmunologically favored renal subcapsular space was used as the organ site for the injection of the islets. Survival of the islet grafts was also independent of the duration of diabetes in the BB/W rats at the time of transplantation. These results showed that under our experimental conditions the grafted islets were able to become established and survive for extended periods in nonimmunosuppressed spontaneously diabetic BB/W hosts.

Animals↗
PubMed1985

Intratesticular islet allografts in the spontaneously diabetic BB/W rat.

UNLABELLED: Thirty-three male BB/W rats with diabetes of 11-145 days duration were divided into 3 groups: six received abdominal, intratesticular islet allografts and no immunosuppression posttransplantation; 15 were similarly grafted and in addition were given four injections of ALS regularly at 10-day intervals for 30 days after transplantation; and 12 rats received scrotal, intratesticular islet allografts and four injections of ALS. THE RESULTS: in the absence of immunosuppression all six of the rats with abdominal, intratesticular islet allografts became normoglycemic within 2 days after transplantation but in none did graft survival exceed 17 days; a marked prolongation of graft survival of greater than 65-441 days occurred in 13 of the 15 animals with identical intratesticular allografts; sustained immunosuppression was not needed for prolonged islet allograft survival in rats with cryptorchid islet allografts; and (4) only one of the 12 rats with scrotal, intratesticular allografts became normoglycemic whereas 11 remained severely glycosuric. However, on surgical translocation of the grafted testes from the scrotum into the abdominal cavity, the rats promptly became normoglycemic in the absence of any additional therapy.

Animals↗
PubMed1984

Extended allograft survival of islets grafted into intra-abdominally placed testis.

Isolated islets of ACI donor rats were cultured for 4 days at 37 degrees C and then grafted into male diabetic Wistar-Lewis rats into three different organ sites without adjuvant immunosuppression. None of 6 recipients of the intraportal injection of 10 islets per gram of body weight became normoglycemic. Similarly, six rats that received islets injected under the renal capsule remained diabetic. None of six rats that received an intratesticular islet allograft became normoglycemic while these organs remained within the scrotum. By contrast, six rats that were transplanted with an identical number of islets into the testis, which were then surgically placed into the abdominal cavity, promptly became aglycosuric and have remained so for more than 50 days.

Animals↗