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Immunohistochemical detection of p53 and bcl-2 proteins in neoplastic and non-neoplastic endocervical glandular lesions.

The study examines p53 and bcl-2 protein expression in a variety of neoplastic and non-neoplastic endocervical glandular lesions. Immunohistochemical staining, using monoclonal antibodies against p53 (DO-7) and bcl-2, was performed on archival paraffin-embedded tissue following microwave antigen retrieval. With DO-7 there was positive nuclear staining in 23/33 cases of adenocarcinoma, 2/10 adenocarcinoma in situ, 2/10 tubo-endometrial metaplasia, 1/10 microglandular hyperplasia, and 1/17 normal endocervix. With adenocarcinoma in situ and non-neoplastic lesions, positive staining was confined to scattered cells. Nine of 23 positive cases of adenocarcinoma showed widespread staining. With anti-bcl-2 antibody, there was positive cytoplasmic staining in 9/33 cases of adenocarcinoma, 0/10 adenocarcinoma in situ, 7/10 tubo-endometrial metaplasia, 1/10 microglandular hyperplasia, and 0/17 normal endocervix. Five of nine positive adenocarcinomas showed widespread staining. There was widespread positive staining for bcl-2 in six of seven positive cases of tubo-endometrial metaplasia. The results indicate that p53 protein expression is frequent in endocervical adenocarcinoma and suggest that mutation of the p53 gene may be important in the evolution of some cases of endocervical adenocarcinoma. Scattered p53-positive cells may be seen in endocervical adenocarcinoma in situ and in non-neoplastic endocervical glandular lesions, the significance of which is uncertain. Bcl-2 protein expression is seen in a proportion of endocervical adenocarcinomas and may play a role in the evolution of these tumors through inhibition of apoptosis. Widespread positivity for bcl-2 protein is seen in most cases of tubo-endometrial metaplasia, suggesting that this type of metaplastic epithelium may represent an unusually stable population of cells.

Adenocarcinoma↗

Changing normal values for thyroid uptake of radioactive iodine.

The 24-hour radioactive iodine uptake remains a very useful clinical tool for evaluating the thyroid gland; however, the normal values have changed over the years. The traditional values of 15% to 45% are clearly not applicable today and the revised values of 9% to 32% are suspect in some areas where iodine content is rapidly changing in the general diet. The values in a relatively stable population in Ft. Smith, Arkansas, without significant access to a continuous-batch bread with a high iodine content do confirm the national trend of the early 1970's suggesting an overall normal range from 11% to 30%. Values in men were found to be lower with a range from 11% to 23%, whereas in women the values ranged from 13% to 32%. Each nuclear medicine department should be responsible for establishing its own normal range and reevaluating it on a fairly routine basis-certainly whenever known dietary iodine factors change.

Adolescent↗

HIV-1 risk and vaccine acceptability in the Ugandan military.

Between July and October 1993, 570 19- to 22-year-old volunteers were screened for HIV-1, with a resulting seroprevalence rate of 18.3% (95% CI: 14.0%, 22.6%). A cohort of 249 HIV-1-noninfected military recruits in the Ugandan Peoples' Defense Forces was followed prospectively for up to 18 months to document rates of HIV-1 seroprevalence, seroconversion, and knowledge and attitudes related to vaccine acceptability. The HIV-1 seroincidence rate was 3.56 per 100 person-years (95% CI: 1.49, 5.62) over 309 person-years of observation. At the 3- and 12-month visits, subjects were interviewed on issues of acceptance and knowledge about vaccines, including anti-HIV vaccines in particular. More than 90% believe that HIV vaccines will not cause HIV infection, and if offered, 88% report that they would take the vaccine if they were not already infected. Nonvaccine prevention methods were considered less reliable; monogamy and condom use were considered effective by only 33.5% and 69.3% of the cohort respectively. After completing the vaccine acceptability questionnaire at the 12-month visit, subjects were offered an approved polyvalent meningococcal vaccine as an indicator of general vaccine acceptance. All subjects reported receiving at least one previous vaccination, and 95% willingly accepted the meningococcal vaccination. The Ugandan military is a stable population at substantial risk for HIV-1 infection and may be a suitable population for vaccine efficacy trials.

AIDS Vaccines↗

CD4+CD25+ T regulatory cells, immunotherapy of cancer, and interleukin-2.

CD4+CD25+ T regulatory (Treg) cells control immunologic tolerance to self-antigens and play a role in suppressing antitumor immune responses, but the mechanism of suppression in vivo remains uncertain. Recently, signaling through the high-affinity interleukin-2 (IL-2) receptor has been shown to be critical for Treg cell differentiation and survival in vivo. Mice deficient in IL-2 or its receptor (CD25 or CD122) or deficient in downstream signaling molecules, including JAK-3 and STAT-5, do not develop a stable population of Treg cells and subsequently acquire lymphoproliferative disease and autoimmunity. in vitro, IL-2 is required to expand Treg cells and to induce their suppressive characteristics. Conversely, IL-2-based regimens can activate cellular antitumor immunity and are the mainstay of immunotherapies directed against melanoma and kidney cancers. Given the seemingly disparate effects of IL-2, the authors discuss the possibility that IL-2 may not be the optimal T-cell growth factor in vivo, but rather an inducer of self-tolerance. The authors propose that other gamma c-signaling cytokines, including IL-15, may be alternative choices for the immunotherapy of cancer.

Adoptive Transfer↗

Long-term results of ossiculoplasty: reasons for surgical failure.

OBJECTIVES: To present the value of a dedicated ear audit clinic, the overall long-term results of ossiculoplasty, and the reasons for surgical failure. STUDY DESIGN: Retrospective analysis was performed on ossiculoplasty cases in a county hospital. The information was extracted from a computer database. Individual patient case records were reviewed in all cases of surgical failure. METHODS: All patients who had ossiculoplasty were routinely followed-up in a dedicated ear audit clinic on a yearly basis. Between 1988 and 1999, the author performed 242 ossiculoplasties and their outcomes were monitored in the ear audit clinic. The 5-year results are presented. RESULTS: Even with the benefit of a dedicated audit clinic and a stable population, only 74.4% of ears had a known outcome at 5 years after ossiculoplasty. In the present series, 61.1% of partial and 37.6% of total ossicular reconstructions have an air-bone gap of 20 dB or better at 5 years. Of 83 identifiable late failures, 47 were caused by persistent or recurrent abnormalities within the middle ear and only 36 were thought to be caused by prosthesis-related or surgeon-related problems. CONCLUSION: The overall long-term results of ossiculoplasty have not dramatically improved in recent years, in spite of all the great advances in biomedical technologies. Unless there is a breakthrough in the understanding and management of the underlying otitis media, the long-term outcome of ossiculoplasty is unlikely to improve dramatically.

Adolescent↗

Survival of a plasmid-bearing strain of Bacillus subtilis introduced into compost.

Survival of Bacillus subtilis strain 168 containing plasmid pAB224, which carries a gene for tetracycline resistance, was studied in mushroom compost under mesophilic and thermophilic conditions. Stable populations of B. subtilis were maintained as spores in both sterile and fresh mushroom compost incubated at 37 degrees C. At 65 degrees C, the introduced B. subtilis populations declined during incubation but spores were still detectable after 28 d. Survival at the higher temperature was greater in fresh than in sterile compost. There was no apparent loss of plasmid pAB224 or plasmid-determined phenotype from the introduced B. subtilis population at either incubation temperature. The frequency of tetracycline resistance in the indigenous Bacillus population was very low (10(-5), but some tetracycline-resistant isolates contained plasmid DNA. Four plasmid DNA profiles were found associated with five Bacillus phenotypes, and some evidence for homology with pAB224 was found. However, pAB224 was found to be a suitable marker for release studies because it was easily recovered, readily distinguished from indigenous plasmids on agarose gels, and was maintained in compost-grown B. subtilis 168 in the absence of any selective pressure.

Bacillus subtilis↗

High precision measurement of the superallowed 0+ --> 0+ beta decay of 22Mg.

The half-life, 3.8755(12) s, and superallowed branching ratio, 0.5315(12), for 22Mg beta decay have been measured with high precision. The latter depended on gamma-ray intensities being measured with an HPGe detector calibrated for relative efficiencies to an unprecedented 0.15%. Previous precise measurements of 0+ --> 0+ transitions have been restricted to the nine that populate stable daughter nuclei. No more such cases exist, and any improvement in a critical Cabibbo-Kobayashi-Maskawa unitarity test must depend on precise measurements of more exotic nuclei. With this branching-ratio measurement, we show those to be possible for T(z)=-1 parents. We obtain a corrected Ft value of 3071(9) s, in good agreement with expectations.

Journal Article↗

Note: inhibition of the growth of Yersinia enterocolitica O:3 by the microflora of porcine caecum and ileum in an in vitro model.

The growth of Yersinia enterocolitica O:3 was tested in an in vitro model of the porcine intestine at the physiological temperature of 39 degrees C of growing pigs. The model supported a stable population of Y. enterocolitica at a level 10(8)-10(9) cells ml-1. Plasmid profile analysis and the Ca(2+)-dependent proportion of the population suggested that the great majority of the Y. enterocolitica population retained the 70 kb virulence plasmid, pYV, throughout the experimental period of 5 d. The growth of Y. enterocolitica was substantially inhibited by the ileal and the caecal flora compared to the growth of the bacterium alone. Yersinia enterocolitica was not isolated after 3 d of cultivation.

Animals↗

Developmental expression of Go in neuronal cultures from rat mesencephalon and hypothalamus.

The developmental expression of the alpha-subunit of Go was examined in neuronal cultures derived from rat mesencephalon (MES) and hypothalamus (HYP). These cultures were essentially free of contaminating glia and were maintained as a stable population for periods up to 3 weeks. Immunoblotting utilizing specific antisera against Go indicated that in neurons from both brain regions, membrane concentrations of Go increased dramatically during the first 2 weeks in vitro. Thereafter, increases in the amount of Go per neuron kept pace with increasing process (axons and dendrites) formation. Multiple forms of immunoreactive Go were detected in MES and HYP neurons, and the proportions of these forms changed between 4 and 14 days in culture. Finally, increasing neuron density significantly increased membrane levels of Go in MES but not HYP cultures.

Animals↗

A review of ectopic pregnancies in Southern Tasmania.

Over the 10-year period 1968-1977, 131 patients with ectopic pregnancy were treated at the Royal Hobart Hospital. The clinical features of these patients are discussed. Using data on the number of ectopic pregnancies confirmed in Southern Tasmania in the period 1973-1977, it was shown that in terms of the ratio of ectopic pregnancies to total births, the incidence of ectopic gestation in the essentially stable population has risen from 1:130 to 1:72; possible reasons for this increase are discussed. The difficulty in diagnosis of the condition is emphasised.

Adult↗

Epidemiology of ulcerative colitis in Israel: a survey of Israeli kibbutz settlements.

OBJECTIVE: The incidence of ulcerative colitis ranges from 3 to 15 cases per 100,000 persons per year with a prevalence of 50-80 cases per 100,000, and the disease is 3-5 times more common among Jews. In Israel, Ashkenazi Jews have a higher incidence than Sephardi Jews, but a lower incidence than Ashkenazi Jews in the United States or Northern Europe. The aim of this study was to examine the prevalence, mean annual incidence, and clinical patterns of ulcerative colitis in a stable population of communal settlements (kibbutz). METHODS: We repeated a community-based survey in 124,400 kibbutz residents, 10 yr after our first study. This population represents 2.5% of the Jewish population of Israel. All ulcerative colitis patients were located by contacting the kibbutz clinics of the 269 kibbutz settlements (100% compliance). Data were updated to December 31st, 1997, which was designated the point prevalence date, and included information on gender, age, origin, education, profession, extent of the inflammatory process, clinical spectrum of the disease, therapy, complications of the disease, and treatment. The mean annual incidence for the 10 yr was calculated from the prevalence data. Only cases with a definite diagnosis of ulcerative colitis made in a recognized gastroenterology unit were accepted into the study. RESULTS: There were 208 confirmed cases of ulcerative colitis disease, 113 women and 95 men (female:male ratio = 1.19). The prevalence rate rose from 121.0/100,000 in 1987 to 167.2/100,000 in 1997 (p < 0.001). The prevalence rates were higher in women than men. Prevalence was highest in Israeli-born members in 1987 but in European/American-born members in 1997. The average annual incidence rate for the 10-yr period was 5.04/100,000/yr. In 1987, 146 cases of ulcerative colitis were collected. During 10 yr of surveillance 17 patients left the kibbutz, 12 died, and 62 new cases were added. The mean age at presentation of the disease was lower in 1987 than in 1997, 46.14 +/- 11.10 and 51.43 +/- 16.67 yr, respectively. Prevalence was highest in men with >16 yr and in women with 9-10 yr of education, 259.3 and 242.9/100,000, respectively. CONCLUSIONS: The prevalence of ulcerative colitis in this Israeli population increased and has reached the upper range for European and American populations. The mean annual incidence rate of ulcerative colitis is in the lower range of that reported for the Western countries.

Adolescent↗

Neurological disorders in Nigerian Africans: a community-based study.

In a Nigerian town with a stable population of 20,000, a door-to-door survey was conducted, using a questionnaire involving a complete census and a simple neurological evaluation which had previously showed a 95% sensitivity and an 80% specificity for detecting neurological disease. Positive responders were evaluated and categorised, using agreed criteria for diagnoses. Nearly 100% cooperation was obtained. Life prevalence ratio for at least one episode of headache was 51/1000. Crude point prevalence ratio for migrainous headache was 5.3/100, and peak age-specific ratio was in the first decade. Prevalence ratio for epilepsy was 533/100,000 and peak age-specific prevalence ratio occurred in the 5-14 years age groups. The prevalence ratio for peripheral nerve disorders was 268/100,000, and age-specific prevalence ratio for tropical neuropathy increased with age. Prevalence ratio for stroke was rather low at 58/100,000, but was probably due to the people's attitude to the disabled elderly and high mortality of stroke which showed annual mortality rate of 70/100,000 which increased with age to 1519/100,000 per year in the eighth decade. Crude prevalence ratios (cases per 100,000) for others are 112 for neurological complications (including sciatica) of spondylosis, 15 each for poliomyelitis, motor neurone disease, development speech disorders, 10 each for syncope, hereditary neuropathies. Parkinson's disease, benign essential tremor, primary cerebellar degeneration, cerebral palsy, mental retardation, organic psychosis (probable intracranial tumor) and 5 each for muscular dystrophy, pyomyositis, spina bifida occulta, alcohol dependence and cerebral malaria. The implications of the findings are important for development of community neurological services in the developing countries.

Adolescent↗

Absence of HTLV-1 related sequences in MS from high prevalence areas in western Norway.

In Western Norway, long-term follow up epidemiological studies have revealed significant increases in the incidence and prevalence rates of multiple sclerosis (MS) in stable populations, indicating the impact of exogenous factors. In this study 183 MS patients and 102 controls from high prevalence areas in Western Norway were investigated for human T-lymphotropic virus type I (HTLV-1) related sequences by polymerase chain reaction. Using primers targeting the gag, pol and env genes in the HTLV-1 provirus genome, no amplification products were detected in the 183 MS patients or 102 controls. The results strongly suggest that neither HTLV-1 nor a closely related retrovirus participate in the aetiology of MS.

Adult↗

Reactions to Quaternium 15, Bronopol and Germall 115 in a standard series.

The incidence of positive patch test reactions to Quaternium 15 has increased by a factor of 3 within a relatively stable population over 2 years, while the incidence of reactions to Bronopol and Germall 115 has remained static. The problem of interpreting an apparent positive reaction to a formaldehyde-releasing preservative in a formaldehyde-sensitive patient is discussed.

Cosmetics↗

Langerhans cell density in normal human oral mucosa and skin: relationship to age, smoking and alcohol consumption.

The immune function of skin has been studied extensively and it has been suggested that epidermal Langerhans cell (LC) density and function decreases with increasing age. Little is known, however, about the effect of age on oral mucosal LC. Cryostat sections from biopsies of buccal mucosa, lip, hard palate, lateral border of tongue, floor of mouth and abdominal skin, obtained from 91 subjects (aged 16-96 yr), were reacted immunocytochemically with a monoclonal antibody against CD1a and then LC density was expressed as LC/mm epithelial surface length. No significant effect of age on mucosal or skin LC density was found, whilst a history of smoking was associated with an increase in LC density in lateral border of tongue and in biopsies of labial mucosa taken from men (P < 0.05). There was no significant difference between LC density in men and women in oral mucosa. Oral mucosal LC may therefore form a relatively stable population in the adult and thus the increased incidence of mucosal disease in the elderly may be the result of subtle changes in cell mediated immune function rather than changes in LC density.

Adolescent↗

A standardized test for the identification and characterization of melanins using electron paramagnetic resonance (EPR) spectroscopy.

Melanins are complex, incompletely understood polymeric pigments that historically have been difficult to investigate with common chemical, histochemical, and physicochemical techniques. Because these pigments uniquely contain a stable population of organic free radicals, electron paramagnetic resonance (EPR) spectroscopy is a particularly effective method for studying them, and a set of qualitative EPR criteria has been established for their identification. However, a number of practical problems have arisen in applying these criteria to identify and characterize unknown pigments in relatively scarce pathological specimens, indicating that a standardized approach is needed. As reported here, a standardized EPR test for melanin based on the EPR criteria has been developed, guided by the requirements that it be sensitive, accurate, simple, and easy to interpret. It has been evaluated using the well-characterized synthetic melanin prepared by alkaline autooxidation of 5,6-dihydroxyphenylalanine (Dopa) and initially applied to the identification and characterization of an unknown pigment purified from an unusual malignant lung tumor.

Chemistry Techniques, Analytical↗

DNA synthesis and cell division in the adult primate brain.

Autoradiographic analysis of juvenile and adult monkeys that received single or multiple injection of the specific DNA precursor, [3H]thymidine, demonstrates slight turnover of glial cells, but failed to provide any evidence of either neuronal addition or replacement. Therefore, while the brains of nonmammalian vertebrates and possibly some nonprimate mammals may display variable degrees of postembryonic neurogenesis, all neurons of the primate central nervous system are generated during restricted developmental periods, mostly before birth and not after infancy. It is not surprising that a stable population of neurons in mature primates, including man, may be essential for the retention of memory and learned behavior.

Aging↗

Viral-specific immunization in AIDS-related complex by photopheresis.

The potential for therapeutic intervention in 7 patients with AIDS-related complex (ARC) was evaluated through the use of photopheresis. The rationale for the study was based on: 1. the demonstration that psoralen and UVA could inactivate HIV/virus in vitro; 2. CD4 cells are the primary target population effected by HIV and photopheresis; and 3. reinfusion of inactivated virus and cell-associated virus might serve to engender an immune response. Preliminary results in 7 patients with ARC over 6 to 18 months revealed a virus-specific response with an elevation of HIV antibodies, while EBV and CMV titers remained unchanged. The immunologic results revealed an increase in the CD8 lymphocyte population, stable activation markers (B2 microglobulin neopterin), a decrease in p24 antigen titers and inability to culture HIV virus in 3 patients. All of these results were in the context of a stable or increasing CD4+ percent. Six patients did not reveal a generalized inhibition of other immune responses as demonstrated by recovery of DTH. In addition, the resolution of lymphadenopathy, night sweats, fever and weight loss, paralleled the immunologic response.

AIDS-Related Complex↗