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Biomedical subjects

C Wood

Publications and source records attributed to C Wood.

At least 145 records · Page 8Linked to original sources

Infection of primary human fetal astrocytes by human herpesvirus 6.

Human herpesvirus 6 (HHV-6) is a lymphotropic betaherpesvirus which productively infects human CD4+ T cells and monocytes. HHV-6 is the etiologic agent for exanthem subitum (roseola), and it is well-known that central nervous system complications occur frequently during the course of HHV-6-associated disease. In addition, HHV-6 has been associated with encephalitis or encephalopathy. However, very little is known about its tropism for neural cells. There are reports that HHV-6 may infect some glial cell lines, but whether it can infect any primary neural cells is not known. Our studies show that both HHV-6A (GS) and HHV-6B (Z-29) can infect highly purified primary fetal astrocytes in vitro. Infected cells showed cytopathic effects, forming giant syncytia. In dual immunofluorescence assays, the infected cells were detected by antibodies against the HHV-6 p41 nuclear antigen and glial fibrillary acidic protein, indicating that the infected cells are indeed astrocytes. PCR and Northern (RNA) blot analyses also confirmed that the astrocytes are infected by HHV-6. The progeny virus did not alter its host range and could reinfect T cells as well as primary astrocytes. These findings suggest that infection of primary human astrocytes may play a role in the neuropathogenesis of HHV-6.

Astrocytes↗

Longitudinal studies of viral sequence, viral phenotype, and immunologic parameters of human immunodeficiency virus type 1 infection in perinatally infected twins with discordant disease courses.

Perinatal human immunodeficiency virus type 1 (HIV-1) infections cause a broad spectrum of clinical disease and are variable in both the age of the patient at onset of serious disease and the progression of the clinical course. Heterozygotic perinatally infected twins with a marked difference in their clinical courses were monitored during the first 2 years of life. Twin B, the second-born twin, developed AIDS by 6 months of age and died at 22 months of age, while twin A remained minimally symptomatic through the first 2 years. Sequential blood specimens were obtained from the twins in order to characterize the immunologic properties of the children and the phenotypes and genotypes of the HIV-1 isolates at various times. Twin A developed neutralizing antibodies and a high-level antibody-mediated cellular cytotoxicity (ADCC) response, while twin B had no neutralizing antibody and a much lower ADCC response. The virus isolates obtained from the two children at various time points proliferated equally well in peripheral blood mononuclear cells, were nonsyncytium inducing, and could not infect established T-cell lines. They differed in their ability to infect primary macrophages. In parallel to the biological studies, the HIV-1 tat and part of the env gene sequences of the longitudinal isolates at four time points were determined. Sequences of virus from both twins at different time points were highly conserved; the viruses evolved at a similar rate until the last analyzed time point, at which there was a dramatic increase in sequence diversity for the sicker child, especially in the tat gene. Our results show that the viruses isolated at different times do not have significant changes in growth properties. The absence or low levels of neutralizing antibodies may correlate with disease progression in the twins.

Acquired Immunodeficiency Syndrome↗

Coordinate developmental control of the meiotic cell cycle and spermatid differentiation in Drosophila males.

Wild-type function of four Drosophila genes, spermatocyte arrest, cannonball, always early and meiosis I arrest, is required both for cell-cycle progression through the G2/M transition of meiosis I in males and for onset of spermatid differentiation. In males mutant for any one of these meiotic arrest genes, mature primary spermatocytes with partially condensed chromosomes accumulate and postmeiotic cells are lacking. The arrest in cell-cycle progression occurs prior to degradation of cyclin A protein. The block in spermatogenesis in these mutants is not simply a secondary consequence of meiotic cell-cycle arrest, as spermatid differentiation proceeds in males mutant for the cell cycle activating phosphatase twine. Instead, the arrest of both meiosis and spermiogenesis suggests a control point that may serve to coordinate the male meiotic cell cycle with the spermatid differentiation program. The phenotype of the Drosophila meiotic arrest mutants is strikingly similar to the histopathological features of meiosis I maturation arrest infertility in human males, suggesting that the control point may be conserved from flies to man.

Alleles↗

Intestinal base excretion in the seawater-adapted rainbow trout: a role in acid-base balance?

A potential role for the intestine of seawater-adapted teleosts in acid­base regulation was investigated following earlier reports of highly alkaline rectal fluids in the gulf toadfish Opsanus beta. Rectal samples taken from starved seawater-adapted rainbow trout had a high fluid pH (8.90±0.03; mean ± s.e.m., N=13) and base (HCO3-+2CO32-) content of 157±26 mequiv kg-1 (N=11). In trout fitted with rectal catheters, rectal fluid was voided at a rate of 0.47±0.11 ml kg-1 h-1 (N=8), giving a net base excretion rate of 114±15 µequiv kg-1 h-1 (N=7). Drinking rates averaged 3.12±0.48 ml kg-1 h-1 (N=8), and accounted for only 6 % of the base excreted via the intestine, indicating substantial net transport of endogenously derived base into the intestine. Rectally excreted base was approximately balanced by an equivalent efflux of net acid from non-rectal sources (possibly as NH4+ excretion via the gills). Samples taken from four sites along the intestine revealed that the most anterior region (the pyloric intestine) was responsible for the majority of HCO3-+2CO32- accumulation. The pyloric intestine was subsequently perfused in situ to investigate possible mechanisms of base secretion. Net base fluxes were found to be dependent on luminal Cl-, 76 % stimulated by amiloride, 20 % inhibited by 10(-4) mol l-1 acetazolamide, but unaffected by either 10(-4) mol l-1 SITS or 2x10(-5) mol l-1 DIDS. This suggests that the mechanism of base secretion within the pyloric intestine may involve a Cl-/HCO3--ATPase. It is speculated that intestinal base secretion may play a role in facilitating osmoregulation of seawater-adapted teleosts.

Journal Article↗

A portable system for measuring bone mineral density in the pre-term neonatal forearm.

Current systems used to measure bone mineral content (BMC) in the neonate have the major drawback that the child must be well enough to be moved to the scanner. Consequently, low birth weight pre-term neonates, a group at particular risk of mineral compromise, cannot be measured. This paper describes a portable neonatal bone mineral device capable of measuring bone mineral in the incubator. It uses a radiation sensitive, charge coupled device (CCD) to acquire a bone mineral image enabling bone mineral to be measured at various sites. It measures bone mineral density (BMD) with a precision of 5.5 mg cm-2 in vivo, reduced to 7.5 mg cm-2 when repositioning between scans is taken into account. The procedure takes under 5 min with an image acquisition time of 30 s and an absorbed radiation dose to skin of 6 microSv. Calibration has been undertaken with aluminium foils of differing thickness to confirm the linearity of the system throughout the intended measurement range. A regression line fitted to the data demonstrated linearity and correlation between BMD and aluminium thickness with r = 0.99 (p < 0.0001). Preliminary measurements on pre-term neonates show values of BMD ranging from 43 to 115 mg cm-2 in babies aged 23-41 weeks post-conception. These figures are within the linear range of the system.

Absorptiometry, Photon↗

The human immunodeficiency virus tat gene enhances replication of human herpesvirus-6.

Human herpesvirus-6 (HHV-6) can enhance the cytopathic effects of human immunodeficiency virus type 1 (HIV-1) in cells doubly infected by HIV-1 and HHV-6. HHV-6 enhances transcription of the HIV-1 long terminal repeat, and several HHV-6 trans-activator genes have been identified. Since HIV-1 and HHV-6 have similar cellular tropism, and since HIV-1 trans-activates other herpesviruses, a reciprocal interaction between the two viruses is possible. Interactions between HIV-1 and HHV-6 were analyzed in human umbilical cord blood (CB) lymphocytes and in a T-cell line by transfection and infection experiments. CB cells dually infected with HIV-1 and HHV-6 showed an increase in HHV-6 infectious titer, an increase in HHV-6-specific immediate early RNA, and an increase in HHV-6 protein synthesis. Similarly, T-lymphocyte cells transfected with the entire HIV-1 proviral genome displayed an increase in HHV-6. When T-cells were transfected with a plasmid containing the HIV-1 tat gene under control of the simian virus (SV40) promoter and infected with HHV-6, higher levels of HHV-6 proteins and infectious virus were detected. Therefore, the presence of HIV-1 gene products, such as tat, can lead to an activation of HHV-6 expression. Since HHV-6 is cytopathic, its activation by HIV-1 may accelerate the depletion of CD4+ T-cells in infected individuals.

Base Sequence↗

The analgesic effect of sucrose in full term infants: a randomised controlled trial.

OBJECTIVE: To evaluate the effects of different sucrose concentrations on measures of neonatal pain. DESIGN: Randomised, double blind, placebo controlled trial of sterile water (control) or one of three solutions of sucrose--namely, 12.5%, 25%, and 50% wt/vol. SETTING: Postnatal ward. PATIENTS: 60 healthy infants of gestational age 37-42 weeks and postnatal age 1-6 days randomised to receive 2 ml of one of the four solutions on to the tongue two minutes before heel prick sampling for serum bilirubin concentrations. MAIN OUTCOME MEASURE: Duration of crying over the first three minutes after heel prick. RESULTS: There was a significant reduction in overall crying time and heart rate after three minutes in the babies given 50% sucrose as compared with controls. This was maximal one minute after heel prick in the 50% sucrose group and became statistically significant in the 25% sucrose group at two minutes. There was a significant trend for a reduction in crying time with increasing concentrations of sucrose over the first three minutes. CONCLUSION: Concentrated sucrose solution seems to reduce crying and the autonomic effects of a painful procedure in healthy normal babies. Sucrose may be a useful and safe analgesic for minor procedures in neonates.

Administration, Oral↗

Cytochrome c oxidase deficiency presenting as recurrent neonatal myoglobinuria.

Markedly reduced cytochrome c oxidase (COX) activity was found in cultured skin fibroblasts of an infant with recurrent episodes of acute myoglobinuria, hypertonia, muscle stiffness and elevated plasma levels of sarcoplasmic enzymes (creatine kinase 96950 U/l, normal below 150) since the age of 3 weeks (COX activity: 36 nmol/min/mg protein; normal 65-440; COX/succinate cytochrome c reductase ratio: 1.4, normal 3.0 +/- 0.4). The expression of the disease in cultured fibroblasts allowed us to carry out a prenatal diagnosis during the next pregnancy. Hitherto, mitochondrial respiratory chain deficiency has not been established as a cause of recurrent myoglobinuria in childhood. Since most cases of myoglobinurias remain poorly understood, we suggest giving consideration to respiratory chain deficiency in elucidating the origin of unexplained recurrent myoglobinuria in childhood, especially when seemingly unrelated symptoms are present.

Blotting, Southern↗

Alternative treatment.

Alternatives to endometrial ablation include re-education of the 20% or more women complaining of menorrhagia whose blood loss is normal, less than 35 ml, and the use of an increasing variety of drugs to find an effective regime with minimal side effects. Endometrial resection is an effective treatment, particularly in the short term. Laparoscopic and vaginal hysterectomy have advantages over endometrial resection in the long term, avoiding failure and retreatment for menorrhagia. Hysteroscopic, laparoscopic and open myomectomy are more suitable in treating fibroids of significant size, although these techniques may be used with endometrial resection to avoid hysterectomy. Myoma reduction may become a less morbid alternative to myomectomy.

Catheter Ablation↗

Excision of endometriosis in the pouch of Douglas by combined laparovaginal surgery using the Maher abdominal elevator.

Twenty-one patients with stage 3 or 4 endometriosis in the pouch of Douglas had combined laparovaginal surgery using the Maher abdominal wall elevator. Opening the pouch of Douglas at the beginning of the operation allowed the combined surgery. Instruments were introduced through both the vagina and accessory laparoscopic incision. And a finger was placed in the vagina to palpate and detect abnormal tissue and assist in blunt dissection. The extent of pathologic tissue in the pouch of Douglas was easily identified. This approach allowed flexibility in maximizing the optimum route, vaginal or laparoscopic, to remove the uterus, and facilitated rectal surgery. The alternatives of laparoscopic and laparotomy surgery have limitations compared with combined laparovaginal surgery, particularly deep in the pelvic cavity.

Abdomen↗

Loss of Gag-specific antibody reactivity in cattle experimentally infected with bovine immunodeficiency-like virus.

The development and persistence of virus-specific antibodies were investigated in eight cattle experimentally infected with the R29 isolate of bovine immunodeficiency-like virus (BIV). By 4 weeks postinoculation (p.i.), antibodies reactive to BIV gag- and env-encoded recombinant fusion proteins were detectable by immunoblotting in all animals. By 40 weeks p.i., seven of eight cattle had dramatically decreased Gag-specific antibodies, and anti-Gag reactivity remained very low or undetectable through 190 weeks p.i. Immunoprecipitation experiments revealed a similar loss of reactivity to nondenatured BIV Gag in these animals. In contrast, antibodies to a recombinant BIV Env protein were readily detectable throughout the study in all eight cattle. During the period of declining Gag antibody, infectious virus was recoverable from peripheral blood mononuclear cells of each animal. However, there was no evidence for sufficient amounts of BIV p26-containing immune complexes to explain the loss of anti-Gag reactivity. Interestingly, the single animal that maintained detectable anti-Gag reactivity throughout the study was repeatedly negative for virus recovery beyond 17 weeks p.i. All animals have remained clinically normal for over 4 years p.i., with no evidence of consistent changes in mononuclear cell subsets. These findings provide evidence that in BIV infection an early decline in Gag-specific antibody reactivity can occur without evidence of increasing viral replication or progression to overt clinical disease.

Animals↗

Blastocyst development and birth after in-vitro maturation of human primary oocytes, intracytoplasmic sperm injection and assisted hatching.

Immature oocyte recovery followed by in-vitro oocyte maturation and in-vitro fertilization is a promising new technology for the treatment of human infertility. The technology is attractive to potential oocyte donors and infertile couples because of its reduced treatment intervention. Immature oocytes were recovered by ultrasound-guided transvaginal follicular aspiration. Oocytes were matured in vitro for 36-48 h followed by intracytoplasmic sperm injection (ICSI). Embryos were cultured in vitro for 3 or 5 days before replacement. Assisted hatching was performed on a day 5 blastocyst stage embryo. Embryo and uterine synchrony were potentially enhanced by luteinization of the dominant follicle at the time of immature oocyte recovery. Mature oocyte and embryo production from immature oocyte recovery were similar to the previous IVF results of the patients. A blastocyst stage embryo, produced as a result of in-vitro maturation, ICSI, in-vitro culture and assisted hatching, resulted in the birth of a healthy baby girl at 39 weeks of gestation.

Blastocyst↗

Initial experience with a new microlaparoscope 2 mm in external diameter.

The microlaparoscope was used for diagnostic and operative purpose in 20 patients, including 6 GIFT and 2 microoperative procedures. No complications occurred and there was only 1 failure of the technique. Microlaparoscopy was performed successfully under local analgesia in 2 patients. The microlaparoscope may be safer and less traumatic than traditional laparoscopy. The technique is simple, effective and easy to learn. Its current place is mainly in diagnosis but with planned future improvement in instrumentation it will have a place in operative laparoscopy.

Female↗

Laparoscopic minilaparotomy hysterectomy.

A laparoscopic minilaparotomy hysterectomy technique is described. An abdominal elevator allowed the use of an open 2 cm port in the lower abdomen to introduce the finger and instruments used for laparotomy. The technique was developed in 3 patients with moderate to severe endometriosis. The second and third operations were quicker than could be expected by laparovaginal surgery. The use of laparotomy instruments and techniques make the technique easier to learn, cheaper than techniques using disposable products and has the potential to be faster and possibly safer than current techniques. It retains the advantage of laparoscopy surgery, reduced postoperative pain, small incisions and early discharge from hospital.

Female↗

Comparison of patients' needs for information on prostate surgery with printed materials provided by surgeons.

OBJECTIVES: To identify strengths, weaknesses, and omissions in existing leaflets and factsheets on prostatectomy given by surgeons to patients. DESIGN: Comparison of content of leaflets and factsheets with patients' needs and discontents in a questionnaire survey as part of the national prostatectomy audit. SETTING: All NHS and independent hospitals performing prostatectomy in four health regions. SUBJECTS: 87 surgeons, 53 of whom used printed material to inform patients about their operations; a total of 25 different factsheets being used. 5361 men undergoing prostatectomy were sent a closed response questionnaire about their treatment; 4226 men returned it completed. A random sample of 2000 patients was asked for further comments, of whom 807 supplied pertinent comments. MAIN MEASURES: Content of the 25 factsheets compared with patients' needs identified in the questionnaires. RESULTS: Much of the information distributed had considerable shortcomings: it lacked uniformity in form and content, topics of relevance to patients were omitted, terminology was often poor, and patients' experience was at variance with what their surgeons said. For example, only one factsheet discussed the potential consequences of malignancy. Patients wanted more information on prostate cancer (1250(29%)) and some thought that the explanation of biopsy results was inadequate (29(4%)). Only six factsheets discussed the possible changes in sexual sensation after transurethral resection of the prostate, stating that patients would feel no change. However, 1490(35%) patients reported a change and 500(12%) were worried about it. CONCLUSION: Current standards of printed information do not meet the needs and requirements of patients undergoing prostatectomy.

General Surgery↗