The Church Partnership Program.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
C Chapman
Publications and source records attributed to C Chapman.
Gentamicin concentration and toxicity.
Explore the source record for details and available documents.
Gentamicins↗
The HPV-activating cellular transcription factor Brn-3a is overexpressed in CIN3 cervical lesions.
The cervical cellular transcription factors Brn-3a and Brn-3b have antagonistic effects on transcription of the human papilloma virus types 16 and 18 E6 and E7 oncogenes, with Brn-3a activating expression and Brn-3b repressing it. We therefore measured expression of Brn-3a and Brn-3b mRNAs in biopsies from 16 women with no detectable cervical abnormality, and in 14 women with cervical intraepithelial neoplasia grade 3 (CIN3) lesions. Although the mean level of Brn-3b expression was similar in both groups, the mean level of Brn-3a expression was over 300-fold higher in the CIN3 samples when compared with normals. Elevated expression of Brn-3a was also detected in 16 histologically normal regions of the cervix adjacent to the CIN3 lesions, indicating that elevation of Brn-3a levels is not confined to the lesion in women with CIN3, and is thus not a consequence of the oncogenic process. The elevated levels of Brn-3a in the CIN3 patient samples, together with the activating effect of Brn-3a on HPV-16 and -18 oncogene expression, suggest that induction of this factor is involved in activating HPV-16 and -18 oncogene expression in the cervix, and hence in the production of cervical cancers induced by HPV.
Base Sequence↗
Anti-hepatocyte growth factor antibody inhibits hepatocyte proliferation during liver regeneration.
In vitro studies have shown hepatocyte growth factor (HGF) to be a potent mitogen for hepatocytes. Direct evidence of a mitogenic role in vivo was sought by inhibiting HGF activity, using continuous administration of neutralizing antibody to rats which had a stimulus for liver regeneration. Alzet osmotic mini-pumps, administering a constant supply of anti-HGF monoclonal antibody (clone D9), were inserted intraperitoneally into male Wistar rats; an irrelevant isotypical antibody was administered to controls. Forty-five animals received an intragastric bolus of 40 per cent carbon tetrachloride (CCl4) and groups of three test and control animals were killed at 24 h intervals for 7 days. Treatment with anti-HGF monoclonal antibody significantly inhibited the levels of immunodetectable HGF in the sera of rats following CCl4 administration. In comparison with controls, hepatocyte proliferation as assessed by bromodeoxyuridine labelling in anti-HGF-treated animals was significantly inhibited at 24 h (P < 0.001), 48 h (P < 0.001), and 96 h (P < 0.05) post-CCl4 administration. In contrast, sinusoidal cell proliferation was not significantly different from controls at any time point. Inhibition of the parenchymal proliferative response to acute CCl4-induced liver injury by the in vivo neutralization of HGF provides direct evidence that this growth factor plays an important role in liver regeneration following necrosis.
Animals↗
What is a preclinical pregnancy loss?
PURPOSE: To evaluate the contribution of embryo quality to preclinical loss rates after in vitro fertilization (IVF)/embryo transfer (ET) pregnancy, multiple gestation, and clinical loss rates were compared to preclinical pregnancy loss rates over a 3-year period. METHODS: The pregnancy outcomes after 1675 fresh ETs from 1994 to 1997 were studied. While establishment of a clinical pregnancy confirms uterine receptivity, multiple gestation rates reflect embryo quality. Because the majority of clinical losses are chromosomally abnormal, clinical loss rates serve as another indicator of embryo quality. RESULTS: The overall preclinical pregnancy loss rate was 5% (78/1675) of ETs and 17% (78/472) of pregnancies. During the 3-year period the pregnancy rates per ET increased from 19 to 36% (P < 0.0001), multiple gestation rates increased from 21 to 48% (P < 0.008), clinical loss rates decreased from 20 to 6% (P < 0.0001), and preclinical pregnancy loss rates remained unchanged from 13 to 19% (P = 0.1). CONCLUSIONS: Preclinical pregnancy loss more likely reflects abnormalities in uterine receptivity rather than embryo quality. If recurrent preclinical pregnancy loss occurs after IVF/ET, evaluation for abnormalities of uterine receptivity should be performed.
Abortion, Spontaneous↗
A randomized trial of the effect of clodronate on skeletal morbidity in multiple myeloma. MRC Working Party on Leukaemia in Adults.
In patients with multiple myeloma, despite a major reduction of bone pain achieved with chemotherapy, skeletal disease continues to progress. The effects of clodronate, an inhibitor of osteoclastic bone resorption, are evaluated on the natural history of skeletal disease in patients with newly diagnosed multiple myeloma. Within the framework of the VIth MRC Multiple Myeloma Trial, 536 patients (218 women, 318 men) with recently diagnosed multiple myeloma were randomized to receive either clodronate 1600 mg daily (n=264) or an outwardly identical placebo (n=272) in addition to chemotherapy. Treatment with clodronate was associated with a 50% decrease in the proportion of patients with severe hypercalcaemia (5.1% v 10.1%, P=0.06) and a similar reduction in reported non-vertebral fractures (6.8% v 13.2%, P=0.04). Fewer patients receiving clodronate sustained vertebral fractures after entry to the trial (38% v 55%, P=0.01) and patients also lost less height over 3 years compared to those receiving placebo (2.0 v 3.4 cm, P=0.01). Biochemical indices of bone turnover were significantly lower in patients receiving concomitant clodronate, both at plateau and at disease relapse. The frequencies of back pain and poor performance status were significantly lower at 24 months in clodronate than in placebo-treated patients (10.9% v 19.9%, P=0.05, and 18.3% v 30.5% P=0.03 respectively.) There was no statistically significant difference in survival between the clodronate and placebo treated patients. The study indicates that long-term oral clodronate slows the progression of skeletal disease in multiple myeloma and decreases the associated morbidity. Patients without overt skeletal disease at diagnosis were also found to benefit from clodronate, indicating that this treatment should be initiated as early in the course of the disease as possible.
Aged↗
Insight into the origin and clonal history of B-cell tumors as revealed by analysis of immunoglobulin variable region genes.
Recombination of VH, DH and JH genes is a unique first step in normal B-cell development. Subsequent differentiation to a mature plasma cell is accompanied by further events in the Ig genes, including VL-JL joining, somatic hypermutation and isotype switching. Chromosomal changes leading to B-cell tumors can occur at many points in this sequence, and may be partly a consequence of the genetic mobility and mutability permitted in order to generate a diverse antibody repertoire. V genes of neoplastic B cells may reflect the point of maturation reached by the B cell of origin, prior to transformation. Analysis of tumors therefore provides useful information on V-gene patterns in normal B cells, and may add another dimension to classification of B-cell tumors. Transformation may also preserve cell populations normally destined to die by apoptosis. Tumor cells arrested in the site where somatic hypermutation and isotype switch are occurring can still be subject to these processes, and could be influenced by persisting antigen. However, mutation is silenced at the point of exit to the periphery, leading to fixed mutational patterns in tumors of mature B cells. V-gene analysis provides an invaluable tool for understanding the genesis of neoplastic change. It also has a clear clinical relevance in tracking tumor cells, measuring residual disease, and finally in offering the opportunity of developing vaccines for treatment.
Amino Acid Sequence↗
A survey of current United Kingdom practice for antenatal screening for inherited disorders of globin chain synthesis. UK Forum for Haemoglobin Disorders.
AIMS: To document current United Kingdom practice for antenatal screening for inherited disorders of globin chain synthesis and to compare such practice with guidelines published by the British Committee for Standards in Haematology and the Standing Committee on Sickle Cell, Thalassaemia and other Haemoglobinopathies (SMAC). METHODS: The members of the UK Forum on Haemoglobin Disorders were surveyed about their current practice for antenatal haemoglobinopathy screening. The UK Forum is a national group of haematologists, paediatricians, laboratory scientists, and counsellors working in the field of diagnosis and management of disorders of haemoglobin synthesis; such disorders including the alpha and beta thalassaemias, sickle cell disease, and other haemoglobinopathies. RESULTS: Completed questionnaires from 38 hospitals (or cooperating groups of hospitals) were analysed. The great majority of hospitals were applying appropriate laboratory methods, but problems were commonly encountered in ensuring that appropriate testing of antenatal patients and, when necessary, of their partners, was carried out early in pregnancy. When screening was selective there was quite often a failure to identify all women in whom testing was indicated, and cut off points used as an indication for further testing were sometimes inappropriate. CONCLUSIONS: Many practical problems are still encountered in following guidelines for the antenatal diagnosis of haemoglobinopathies. A need for improved administrative procedures and increased funding was identified. In addition there is a need for agreed guidelines giving more specific advice on technical aspects of laboratory practice.
Female↗
Feto-maternal alloimmune thrombocytopenia: antenatal therapy with IVIgG and steroids.
Explore the source record for details and available documents.
Adult↗
NEAR's flyby of 253 mathilde: images of a C asteroid
On 27 June 1997, the Near Earth Asteroid Rendezvous (NEAR) spacecraft flew within 1212 kilometers of asteroid 253 Mathilde. Mathilde is an irregular, heavily cratered body measuring 66 kilometers by 48 kilometers by 46 kilometers. The asteroid's surface is dark (estimated albedo between 0.035 and 0.050) and similar in color to some CM carbonaceous chondrites. No albedo or color variations were detected. The volume derived from the images and the mass from Doppler tracking of the spacecraft yield a mean density of 1.3 +/- 0.2 grams per cubic centimeter, about half that of CM chondrites, indicating a porous interior structure.
Journal Article↗
Are Melnick-Needles syndrome and oto-palato-digital syndrome type II allelic? Observations in a four-generation kindred.
Melnick-Needles syndrome (MNS) is a female-limited skeletal dysplasia inherited in a X-linked dominant pattern. Males born to women with MNS may exhibit lethal multiple congenital anomalies, but recurrence of this phenotype within one family has not been reported. Males with oto-palato-digital syndrome type II (OPD II) also demonstrate a multiple congenital anomalies phenotype that includes skeletal dysplasia but the maternal phenotype includes only mild craniofacial anomalies. These two syndromes have been suggested as being allelic despite differences in the described maternal phenotypes. We present a four-generation kindred in which four males had a consistent multiple congenital anomalies phenotype. The females in this family have skeletal changes characteristic of MNS but have only mild craniofacial anomalies and also deafness attributable to ossicular deformity, traits more commonly found in OPD II. The expression of manifestations of MNS and OPD II in males and females in this kindred further suggest that these syndromes are allelic.
Abnormalities, Multiple↗
Use of phage expression to analyze regions of a human V4-34(VH4-21)-encoded IgG autoantibody required for recognition of DNA. No involvement of the 9G4 idiotope.
Explore the source record for details and available documents.
Antibodies, Antinuclear↗
Differences in mutational patterns between rheumatoid factors in health and disease are related to variable heavy chain family and germ-line gene usage.
The sequences of the heavy chain variable (V(H)) segment and dissociation constants (Kd) of 14 IgM rheumatoid factors (RF) derived from 11 different germline gene segments from five healthy immunized donors (HID) are described. We extend a previous analysis of two clones from one donor using only the germline segment DP-10. In the present study, the mutation patterns of these new RF and the two earlier reported HID RF clones are analyzed in relation to V(H) family, germ-line origin, and Kd. The panel of HID RF is further compared with 33 previously described IgM RF from patients with rheumatoid arthritis (RA). There is a high rate of mutation in the panel of HID RF (mean of ten mutations/V(H)). RF originating in RA patients have a comparable mutation rate (mean of 11 mutations/V(H)), suggesting that hypermutation of IgM RF is not disease related. The HID RF have, however, a significantly lower affinity for IgG than the RA RF. We found that the structural basis of the differences between HID and RA RF is related to V(H) family usage. RF of the V(H)1 family use very similar germ-line genes in HID and RA patients. HID RF of the V(H)1 family have, however, a low ratio of replacement-to-silent (R:S) mutations of only 0.41 in the heavy chain complementarity region (CDR(H))1 and 2. This is statistically significantly lower than the corresponding ratio of 3.14 in the V(H)1 RA RF. In contrast, RF of the V(H)3 family from HID and RA patients have very similar R:S ratios of 1.75 and 1.71 in CDR(H)1 and 2, respectively. The V(H)3 RA RF are, however, predominantly encoded by genes not encoding any HID RF. Thus, both repertoire differences and hypermutation resulting in significantly lower R:S ratios can be observed in RF from HID compared with RA RF.
Amino Acid Sequence↗
Umbilical cord blood collection and separation for haematopoietic progenitor cell banking.
Cord blood transplantation has been proven to be a suitable form of treatment for a variety of diseases in childhood and more recently in an increasing number of adult patients. Banks of cord blood cryopreserved after HLA testing are required in order to provide various HLA types for unrelated transplantation. To optimize storage space cord blood needs to be stored as a separated product. Several early methods of cord blood separation resulted in a significant loss of progenitor cells. We used a separation procedure where the donation was separated by centrifugation into a buffy coat fraction, a red cell fraction, and a plasma fraction. Twenty-five samples, (mean initial volume 81 ml) were assessed. Nucleated cells were recovered in the buffy coat fraction. Recoveries of nucleated cell count, total progenitors and CD34-positive cells in the buffy coat were 90%, 88% and 100%, respectively. The buffy fraction was tested for sterility by aerobic and anaerobic culture. Using this closed bag system, volume reduction was achieved while maintaining sterility and retaining progenitor cells in a final mean buffy coat volume of 44 ml. Red cell and plasma fractions were available for ABO grouping, virology testing and cryopreservation. The results show that cord blood can be effectively volume-reduced using simple and readily available blood banking techniques.
Adult↗
Profile of monoamine and excitatory amino acid release in rat supraoptic nucleus over parturition.
The magnocellular oxytocin neurons of the hypothalamic supraoptic (SON) and paraventricular nuclei play an important role in the initiation and maintenance of parturition in the rat. As little is known about the neural inputs responsible for activating oxytocin neuron activity at this time, we used the technique of microdialysis to examine the profile of monoamine and excitatory amino acid neurotransmitter release within the SON before and during parturition. Microdialysis probes were implanted into the SON of anesthetized pregnant rats (n = 8) on the morning of the day preceding parturition (day 20), and 15-min dialysate samples were collected from freely moving animals over the following 2 days until 3 h after birth of the last pup. On the day of parturition (day 21), dialysate concentrations of norepinephrine were significantly increased (P < 0.05) in the hour leading up to the expulsion of the first pup and, compared with those on the previous day, remained at significantly (P < 0.05) elevated levels throughout the course of parturition. A significant (P < 0.01) increase in glutamate concentrations was also detected, although in this case, it was only elevated transiently in the 15-min period immediately before the onset of pup expulsion. Mean levels of dopamine were not different between days 20 and 21, but a significant increase in dopamine release was detected specifically during the second half of parturition. No significant changes in serotonin and aspartate concentrations were observed on days 20 and 21 or in relation to parturition. This study provides an analysis of neurotransmitter release in the SON over parturition and indicates that norepinephrine concentrations are elevated well in advance of the onset of pup expulsion, whereas a burst of glutamate release occurs immediately before the birth of the first pup. Such changes are likely to reflect activity in afferent inputs to the SON and may represent neurochemical events involved in the initiation and maintenance of parturition.
Animals↗
Anxiety, self-confidence and performance in Tae Kwon-Do.
142 male Tae Kwon-do competitors completed the Competitive State Anxiety Inventory-2 about 1 hr. before competition. Multivariate analysis of variance showed that the players who won reported lower cognitive and somatic anxiety and higher self-confidence than those who lost. Discriminant function analysis indicated that 89 (62.68%) participants could be correctly classified as winners or losers on the basis of their precompetition Competitive State Anxiety Inventory-2 scores. The findings concur with previous research in karate.
Achievement↗
DNA-based diagnostics for adrenoleukodystrophy in a large New Zealand family.
AIM: To develop a DNA-based diagnostic test for adrenoleukodystrophy (ALD) in a large New Zealand family. METHODS: Mutation screening of the X chromosome-linked ALD gene was undertaken by direct sequencing of PCR amplified products encompassing defined exons of the ALD gene. The identification of a mutation led to the development of a simple restriction enzyme digestion protocol of a PCR amplified product to identify those individuals with the mutation. RESULTS: A nonsense mutation, resulting in deduced premature termination of translation of the ALD gene product, was detected in exon 4 of the ALD gene in an affected male. This mutation was found in three obligate gene carriers in the same ALD family. A DNA-based test was established to identify this mutation by Bgl II digestion of a PCR amplified product encompassing exons 3 and 4 of the ALD gene. The DNA-based test was applied to a chorionic villus sampling for prenatal diagnosis. CONCLUSIONS: A simple DNA-based test has been developed for ALD in a large New Zealand family. This test provides a rapid means of determining carrier status and for undertaking prenatal diagnosis for ALD in this family.
Adolescent↗
Transforming growth factor-alpha expression is altered during experimental hepatocarcinogenesis.
In order to characterize the role of transforming growth factor-alpha (TGF alpha) during hepatocarcinogenesis, liver tissue was examined at 10, 16, and 19 weeks following initial 10-week diethylnitrosamine (50 mg l-1 drinking water) exposure in female Wistar rats. Liver tissue protein extracts were electrophoresed and transferred to nitrocellulose filters. Levels of tissue-derived TGF alpha and epidermal growth factor receptor (EGFr) were assessed using an anti-TGF alpha monoclonal antibody (Ab-1) and an anti-EGFr polyclonal antibody (AB-4), coupled with scanning densitometric quantification. Immunolocalization of TGF alpha was performed in Bouin's-fixed, paraffin-embedded liver tissue sections. The distribution and intensity of TGF alpha immunoreactivity varied according to the degree of dysplasia, severely dysplastic cells being strongly immunoreactive. At week 10, mild hepatocyte dysplasia and perivenular inflammation were evident, together with a corresponding increase in perivenular TGF alpha immunoreactivity. By week 16, foci of moderate to severe dysplasia were observed; at this stage, there was a decrease in perivenular immunoreactivity but a further increase in overall liver tissue TGF alpha levels. Some 'altered foci' and dysplastic nodules showed intense immunoreactivity for TGF alpha. At these time points, immunodetectable liver EGFr was found to decrease significantly in comparison with normal control tissue. TGF alpha immunoreactivity was observed in fully developed carcinomas at week 19, although some tumours were negative by immunohistochemistry. The up-regulation of immunodetectable TGF alpha and the concomitant down-regulation of EGFr demonstrated positive (P < 0.01) and negative (P < 0.001) correlations, respectively, with hepatocyte proliferation indices. These findings suggest that the TGF alpha/EGFr ligand receptor system may be important during tumour promotion and in the stimulation of continued proliferation in hepatocellular carcinomas.
Animals↗