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PubMed1991

Selective secretion of annexin 1, a protein without a signal sequence, by the human prostate gland.

Annexins are primarily intracellular proteins as would be predicted from their lack of hydrophobic signal sequences. However, we now report that the human prostate gland selectively secretes high concentrations of annexin 1 (also called lipocortin 1 and p35) and a proteolytic cleavage product, des1-29-annexin 1, into seminal plasma. Secreted annexin 1 had a blocked amino terminus and was structurally indistinguishable from intracellular annexin 1. Although annexin 1 and the structurally related protein, annexin 4, co-localized to many of the same cells of the ductal epithelium of the prostate, annexin 4 was not secreted. Thus, the secretion of annexin 1 appears to involve a highly selective mechanism that does not involve targeting to the endoplasmic reticulum by a hydrophobic signal sequence.

Amino Acid Sequence↗
PubMed1991

Detection of T-cell receptor gamma chain V gene rearrangements using the polymerase chain reaction: application to the study of clonal disease cells in acute lymphoblastic leukemia.

This report describes the development and characterization of a method for the amplification of rearranged V-J segments of the human T-cell receptor gamma chain (TCRG) locus using an adaptation of the polymerase chain reaction (PCR) technique. The technique uses a single pair of 'consensus' primers to amplify rearrangements involving the V gamma I subgroup genes, which are common in malignant cells from acute lymphoblastic leukemia (ALL) patients. Using this method we were able to detect rearrangements in the TCRG locus in disease cells from patients with T-cell ALL (12 of 12), common ALL (10 of 14), and Null cell ALL (2 of 2) at presentation. Monoallelic and biallelic rearrangements involving V gamma I subgroup genes were identified by restriction analysis of PCR products from DNA samples from a T-cell leukemic cell line, T-cell clones, and disease cells from patients with ALL of T-and B-cell lineage at presentation. These results confirmed the presence of cell clones within the presentation samples and, in one case, confirmed the persistence of the original malignant cell clone at relapse. This is a rapid and specific method for the detection and characterization of rearrangements of the TCRG locus without recourse to Southern blotting. Therefore, the PCR technique described herein can provide the basis for the study of clonal evolution and minimal residual disease on a high proportion of patients with ALL.

Alleles↗
PubMed1990

Production of interferon-gamma and tumour necrosis factor-alpha by human T-cell clones expressing different forms of the gamma delta receptor.

Panels of human T-cell clones bearing the gamma delta T-cell receptor (TcR) were obtained from peripheral blood and decidual tissue and maintained in the presence of interleukin-2 (IL-2). TcR V gamma and V delta gene expression was determined in 40 TcR delta 1+ clones using the gamma delta T-cell subset markers Ti gamma A and delta TCS1, in conjunction with Southern blot analysis using TcR J gamma and J delta probes. gamma delta T-cell clones, together with control alpha beta T-cell clones derived from the same lymphocyte populations, were stimulated with phytohaemagglutinin (PHA) and their ability to produce interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) tested using specific ELISA. Many clones representative of the major peripheral V gamma 9/V delta 2J1 subset produced high amounts of both cytokines and mean levels were not significantly different from those produced by alpha beta T-cell clones. Panels of clones expressing V gamma 9 and V delta 2J1 produced significantly higher levels of TNF-alpha than clones not expressing V delta 2J1 and those expressing V delta 1J1. There was no relationship between levels of IFN-gamma and TNF-alpha produced by individual gamma delta T-cell clones and also no relationship between their non-major histocompatibility complex (MHC)-restricted cytotoxic activity and levels of either cytokine. There was a significant tendency for gamma delta T-cell clones to produce more TNF-alpha than IFN-gamma in comparison to alpha beta T-cell clones. The significance of these findings is discussed in the light of the reported differences in distribution in vivo of V delta 1J1+ and V delta 2J1+ cells.

Blotting, Southern↗
PubMed1990

Phenotypic and functional analysis of human CD3- decidual leucocyte clones.

CD3- leucocyte clones were generated from human first-trimester decidualized uterine endometrium in a culture system containing interleukin-2 (IL-2) and phytohaemagglutinin (PHA). All CD3- clones tested by Southern blot analysis had T-cell receptor (TcR) gamma and delta genes in germ-line configuration. Thirty-six CD3- cell clones obtained from eight decidual samples were mostly CD2+CD56+ but, unlike fresh decidual leucocytes, many were also CD16+. Morphological differences were noted between CD16+CD56+ and CD16-CD56+ clones, with the latter cells possessing granules of more variable size. All CD16+ clones expressed strong cytotoxic activity against natural killer (NK) sensitive and NK-resistant cell targets, while CD16- clones had low or negligible activity. Some CD3- clones produced high levels of interferon-gamma, tumour necrosis factor-negligible activity. Some CD3- clones produced high levels of interferon-gamma, tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) upon stimulation, but there was no relationship between specific cytokine production and cell clone phenotype or cytotoxic function. Levels of TGF-beta were generally higher than those produced by decidual CD3+ T-cell clones. Since decidual CD3- CD16- leucocytes have a low proliferative capacity in response to IL-2, and as clones with this phenotype invariably possess low NK cell activity, it is suggested that the NK cell activity of fresh decidual leucocyte populations is mediated largely by the small numbers of CD3- CD16+ cells present.

Antigens, CD↗
PubMed1990

Nomograms for rapid estimation of intravascular intrauterine exchange transfusion.

Fetal exchange transfusion is complicated by the fact that vascular access must be maintained while the number of exchanges needed to achieve a desired post-transfusion hematocrit is calculated. A rapid method for estimating the number of exchange transfusions would greatly simplify fetal exchange transfusion for blood group isoimmunization. In this report, we present a graphic method for determining the number of exchange transfusions necessary to achieve a post-transfusion hematocrit of 45%, using a nomogram for 5- and 10-mL exchange transfusion volumes.

Blood Transfusion, Intrauterine↗
PubMed1990

The Auckland skin clinic tinea pedis and erythrasma study.

Three hundred consecutive patients attending the Auckland Hospital dermatology clinic were examined clinically and microbiologically for evidence of interdigital or plantar mycological or bacterial infection. One hundred and nine patients were shown by laboratory investigation to have an infection. Of these, only 89 displayed clinical signs of infection. Erythrasma, a desquamative condition caused by Corynebacterium minutissimum, was the commonest infection in this study. The commonest dermatophyte isolated was Trichophyton mentagrophytes var interdigitale. There was a significant rise in the incidence of both types of infection with age.

Adolescent↗
PubMed1987

Production of interferon and tumour necrosis factor by cloned human natural cytotoxic lymphocytes and T cells.

Cell lines and clones, derived from natural killer (NK) cell-enriched (B73.1+) peripheral blood lymphocytes (PBL) from several human donors, that expressed distinct surface phenotypes and were cytolytically active against K562 target cells were tested for their capacity to produce interferon (IFN) and tumour necrosis factor (TNF), IFN and TNF were measured firstly in biological assays and secondly in specific immunoassays for alpha-IFN, gamma-IFN and tumour necrosis factor (TNF alpha). It was found that the majority of NK-derived lines and clones were highly cytotoxic towards K562, but generally produced relatively low or undetectable levels of gamma-IFN and TNF alpha following stimulation with phytohaemagglutinin. No alpha-IFN was detected in supernatants from these cells. In comparison, cell lines and clones, derived from T lymphocyte (B73.1-) enriched PBL from the same donors were poorly cytotoxic towards K562, but generally produced higher levels of gamma-IFN and TNF than NK-derived cells. Thus, neither gamma-IFN nor TNF production were shown to correlate well with the capacity of NK-derived or T cell clones to effect cytotoxic action towards K562 in vitro. These results suggest that the co-production of gamma-IFN and TNF is not indicative of cytotoxic potential.

Antigens, Surface↗
PubMed1989

Concomitant infection with Neisseria gonorrhoeae and Chlamydia trachomatis in pregnancy.

Gonorrhea is an important marker for endocervical chlamydial infections in nonpregnant women. Concomitant infection rates as high as 50% have been reported. There are few data on concomitant infection rates in pregnant patients. The purpose of this study was to examine the prevalence of endocervical chlamydial infections in pregnant women with gonorrhea. Patients with cervical cultures positive for Neisseria gonorrhoeae at their initial prenatal visit had endocervical specimens for Chlamydia trachomatis culture obtained before anti-gonorrheal therapy. Control patients were selected at random from the same prenatal population. The prevalence of C trachomatis in patients with gonorrhea was significantly greater than that in the control population (46 versus 5%; P less than .001). Patients with gonorrhea were younger, less often married, and more often black than the control population, but these demographic differences did not account for the large difference in the chlamydial prevalence. Erythromycin 500 mg four times daily provided an excellent cure rate without intolerable side effects. Pregnant patients being evaluated or treated for gonorrhea should also be considered at high risk for concomitant cervical chlamydial infection.

Adult↗
PubMed1989

Patterns of T cell receptor gamma gene rearrangements in human CD3+ clones derived from WT31- or Leu7+ cells in relation to non-MHC-restricted cytotoxic activity.

Clones were obtained from human peripheral blood WT31-, WT31-CD4-8-, CD4-8- or Leu 7+ cells in the presence of interleukin 2 and phytohaemagglutinin. Almost all clones were CD3+, about 50% were CD4-8- and all clones tested derived from WT31- remained WT31-, indicating that they were expressing a gamma/delta heterodimer in association with CD3. Some clones derived from CD4-8- cells expressing CD3 were WT31- and some were WT31+. All CD3+ clones had T cell receptor (TCR) gamma gene rearrangements; most also had their TCR beta genes rearranged, including all clones derived from Leu 7+ cells. TCR gamma gene rearrangements were noted involving all five known J segments. There was a tendency for V gene segments from the VII and VIII subgroups to be rearranged to J gamma 2 less often than those from the more 5' VI subgroup. Two clones definitely had one rearrangement to C gamma 1 and one to C gamma 2. When clones derived from WT31- cells were considered, the only obvious relationship which emerged was that all clones with both chromosomes rearranged to C gamma 2 had low or negligible cytotoxic activity against natural killer (NK)-sensitive and NK-resistant targets. Several of these clones were expressing CD8 on about 30% of cells. Most clones with rearrangements involving only C gamma 1 had high non-MHC-restricted cytotoxicity while those with at least one C gamma 1 rearrangement had either high or low activity. The only exceptions noted were a clone with a single V9JP rearrangement and a clone with a V9JP and a VI/IIIJP1 rearrangement, which both had low activity. A similar pattern was also found with most clones derived from Leu 7+ cells. The data are consistent with the participation of most types of disulphide-linked (C gamma 1) gamma/delta heterodimers in non-MHC-restricted cytotoxic activity mediated by CD3+ gamma/delta + T cell clones.

Antigens, CD↗
PubMed1989

The effects of moclobemide on cognition.

The mental ability of the elderly is frequently compromised by age-associated cognitive declines, which may be result of cholinergic deterioration. Depression is accompanied by cognitive performance impairments, and recent work suggests these may be more severe in the elderly. Antidepressants with anticholinergic side-effects, such as the tricyclics, should thus be used with caution in the elderly. A potential advantage of new antidepressants which are relatively free of anticholinergic effects, may be in a reduced liability to impair cognition, whilst maintaining at least equal antidepressant potency. The effects of moclobemide, a novel reversible monoamine oxidase inhibitor, have been studied in both young and elderly volunteers using computerized assessment of a variety of aspects of cognition. In the young the drug was studied within a scopolamine model of the cognitive effects of aging and dementia, while, in the elderly, the cognitive effects of the drug were compared to those of trazodone. In the scopolamine model, moclobemide was significantly superior to placebo and other compounds in antagonizing the cognitive impairments resulting from cholinergic blockade. In the elderly, some improvements were found with moclobemide, particularly in memory, and while an impairment to vigilance was observed, this effect was considerably less marked than with trazodone. Moclobemide would thus appear to have an advantage over antidepressant compounds such as the tricyclics of having a lower liability to impair cognitive efficiency. However, to establish this in depressed patients it will be necessary to incorporate sensitive assessments of cognitive efficiency into trials of the drug in young and elderly populations.

Benzamides↗
PubMed1989

Examination of amniotic fluid in diagnosing congenital syphilis with fetal death.

The diagnosis of congenital syphilis is difficult, particularly in stillborn fetuses, who are often macerated and have undergone autolysis. These changes can obscure both syphilitic histologic findings and special stains for spirochetes in tissue specimens used to confirm the diagnosis of congenital syphilis. Five gravidas with untreated syphilis and fetal deaths underwent sonographic examination and amniocentesis. In all five cases, dark-field microscopic examination of the amniotic fluid showed spirochetes with morphology and motility characteristic of Treponema pallidum. Organisms were infrequent, but easily identified at 400x magnification and confirmed using an oil-immersion objective yielding a 900x magnification. After delivery, fetal-placental examination and autopsy showed clinical findings typical of congenital syphilis in all five cases. Histologic changes compatible with syphilis were found in all four autopsied fetuses. Silver impregnation stains were positive in two of five tissue specimens, and anti-treponemal monoclonal antibody immunofluorescence assays were positive in one of three amniotic fluid specimens examined retrospectively, further strengthening the specificity of the dark-field microscopic identification of spirochetes. This technique, which can make the diagnosis of congenital syphilis, is recommended for women with syphilis and a fetal death, especially if sonographic hydrops and/or edema is present or if an autopsy will not be performed.

Amniotic Fluid↗
PubMed1978

A two year follow-up of a hypertension screening programme Napier 1973-1975.

Two years after a hypertension screening survey conducted at Napier in 1973 the blood pressure levels of 350 adults were re-examined. The sample comprised 152 persons previously referred for investigation because of high blood pressure detected during the 1973 survey, a matched control group of 146 normotensives and a small supplementary control group. Of the 152 persons in the referred group 31 (20.4%) were under medical supervision at the time of the 1973 survey, 89 (58.5%) attended a doctor within the next 12 months and 32 (21.1%) took no further action. Two years later the 31 cases previously under medical supervision had remained on therapy but only 43 of the 89 new cases were receiving treatment at the time of re-examination. More than 50% of the cases in the referred group showed a decrease in the mean systolic pressure of 10mmHg or greater over the two-year period compared with 20.5% of the normotensive control group. Only 32% of referred cases were regarded as effectively controlled at the time of re-examination ie had mean systolic pressures less than 160mmHg and mean diastolic pressures less than 95mmHg. The low level of effective control resulting from the earlier survey casts further doubt on the value of mass screening procedures for hypertension.

Adult↗
PubMed1988

T-cell receptor beta gene rearrangements in clones derived from human CD4-8- cells expressing natural killer cell activity.

Clones derived from highly purified human peripheral blood Leu 19+ cells in the presence of phytohaemagglutinin (PHA) and interleukin-2 (IL-2) expressed cytotoxic activity against natural killer (NK)-resistant as well as NK-sensitive targets. All 66 clones analysed had a germ line configuration of T-cell receptor (TCR) beta genes and 38/40 also had unrearranged TCR gamma genes. The two exceptions were both CD3+ clones, but these did not have a cytotoxic repertoire noticeably different from CD3- clones without TCR gamma gene rearrangements. Clones were also obtained from highly purified CD4-8- cells, most of which were also cytotoxic for NK-resistant and NK-sensitive targets. About 90% of these clones were CD3+ but only around 50% remained negative for CD4 and CD8 while a significant number (12.7%) were positive for both CD4 and CD8. All clones analysed had rearranged TCR gamma genes and most had also rearranged TCR beta genes, including 20/25 of the clones which were CD3+4-8-. Many of the clones showed two rearrangements of TCR beta genes, and 3/4 CD3- clones had rearranged TCR beta as well as TCR gamma genes. There was no correlation between cytotoxic activity and TCR gene status or phenotype of these CD4-8- derived clones, except that clones which were Leu 19+ tended to have higher cytotoxic activity against NK-sensitive and NK-resistant targets than Leu 19-clones. The results strongly indicate that TCR beta and gamma gene products are not involved in the cytotoxicity mediated by these clones. They also suggest that some CD4-8- cells may be capable of limited differentiation in vitro.

Cell Line↗
PubMed1977

Blood pressure levels of an urban adult New Zealand population: Napier 1973.

Ninety-seven percent of a randomly selected sample of 2600 adults (age range 21 to 92 years) from the Napier City electoral area were surveyed for age and sex distribution of blood pressure. The sample included those currently receiving drug treatment for elevated pressures. There were approximately 400 in each decade and the sex ratio slightly favoured females. Casual systolic pressures rose with age whereas the diastolic rose to approximately age 50 and thereafter remained steady or slightly declined. Before age 50 years males had higher systolic pressures than females and thereafter the mean levels for females exceeded those for the males. Mean systolic pressures for this New Zealand sample population were higher by 2-4mmHg for all ages than the levels reported for the United States National Health Survey 1960-62.

Adult↗
PubMed1988

Acute streptococcal necrotising fasciitis.

Two cases of acute streptococcal necrotising fasciitis are reported. Both patients were taking nonsteroidal antiinflammatory drugs when they developed this infection. Urgent surgical debridement was undertaken and resulted in a successful outcome in both patients. The clinical and histopathological features of this condition are reviewed.

Acute Disease↗