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Biomedical subjects

J R Mann

Publications and source records attributed to J R Mann.

At least 91 records · Page 5Linked to original sources
PubMed1991

Congenital mesoblastic nephroma: possible prognostic and management value of assessing DNA content.

The case records and pathology of all children with kidney tumours treated in the West Midlands Health Authority Region (WMHAR) from 1957 to 1986 were reviewed. The histology was reviewed by a panel of three paediatric pathologists. Thirteen (6%) out of 211 cases were considered to have congenital mesoblastic nephroma (CMN). Nine were of the conventional type, three of the atypical cellular type, and one mixed. DNA ploidy was investigated and showed two of the tumours to be aneuploid and nine diploid (tissue was not available in the two other cases). The two aneuploid tumours were of atypical cellular and mixed histology, respectively; the diploid tumours were of the conventional type in eight cases and atypical cellular in one. The atypical cellular type has been reported to behave more aggressively, but the benefit of additional treatment after surgery to prevent recurrence remains unclear. Measurement of DNA content by flow cytometry, together with histological subclassification, may be useful in selecting patients who will benefit from further treatment after surgery.

DNA, Neoplasm↗
PubMed1991

Development to term of mouse androgenetic aggregation chimeras.

Diploid androgenetic eggs contain two sperm-derived genomes, and only rarely develop to the early somite stage. Also, previous studies have indicated that androgenetic eggs cannot be rescued in aggregation chimeras beyond embryonic stages. Paradoxically, in blastocyst injection chimeras made with androgenetic embryonic stem (ES) cells of the 129/Sv strain, we previously obtained considerable improvement in developmental potential. Although considerable death occurred in utero, overtly normal chimeric fetuses and occasional postnatal chimeras that developed skeletal abnormalities were observed. Consequently, we have re-evaluated the developmental potential of androgenetic aggregation chimeras utilizing androgenetic eggs of the 129/Sv strain, and of the BALB/c and CD-1 strains for comparison. Regardless of strain, androgenetic aggregation chimeras were generally more inviable than previously observed with androgenetic ES cell chimeras, and often the embryoproper was abnormal even when an androgenetic contribution was detected only in the extra-embryonic membranes. This is at least a partial explanation of the greater viability of androgenetic ES cell chimeras, as ES cells do not colonize significantly certain extra-embryonic tissues. Nevertheless, in the 129/Sv strain, occasional development of chimeras to term was obtained, and one chimera that survived postnatally developed identical skeletal abnormalities to those observed previously in androgenetic ES cell chimeras. This result demonstrates that at least one example of paternal imprinting is faithfully conserved in androgenetic ES cells. Also, the postnatal chimerism shows that androgenetic eggs can give rise to terminally differentiated cell types, and are therefore pluripotent. In contrast, only possibly one BALB/c and no CD-1 androgenetic aggregation chimeras developed to term. Therefore, the developmental potential of androgenetic aggregation chimeras is to some extent dependent on mouse strain.

Animals↗
PubMed1990

Androgenetic mouse embryonic stem cells are pluripotent and cause skeletal defects in chimeras: implications for genetic imprinting.

The inviability of diploid androgenetic and parthenogenetic embryos suggests imprinting of paternal and maternal genes during germ cell development, and differential expression of loci depending on parental inheritance appears to be involved. To facilitate identification of imprinted genes, we have derived diploid androgenetic embryonic stem (ES) cell lines. In contrast to normal ES cells, they form tumors composed almost entirely of striated muscle when injected subcutaneously into adult mice. They also form chimeras following blastocyst injection, although many chimeras die at early postnatal stages. Surviving chimeras develop skeletal abnormalities, particularly in the rib cartilage. These results demonstrate that androgenetic ES cells are pluripotent and point to stage- and cell-specific expression of developmentally important imprinted genes.

Animals↗
PubMed1990

A promoter that drives transgene expression in cerebellar Purkinje and retinal bipolar neurons.

A genomic clone encoding the Purkinje cell-specific L7 protein has been isolated and utilized to drive the expression of beta-galactosidase in mice. Three independent transgenic lines, germ line transformed with an L7-beta-galactosidase fusion gene, exhibit beta-galactosidase expression in both cerebellar Purkinje cells and retinal bipolar neurons. This distribution is the same as that previously determined for the L7 protein by immunohistochemistry. The transgenic murine lines can be used to obtain populations of marked Purkinje and bipolar neurons. Similar L7 promoter constructs can be used to express other foreign genes specifically in these two classes of neurons.

Animals↗
PubMed1990

The UK Children's Cancer Study Group: testicular malignant germ cell tumours 1979-1988.

The United Kingdom Children's Cancer Study Group (UKCCSG) malignant germ cell tumour (MGCT) studies were undertaken to establish standard protocols of investigation, staging, and treatment. The efficacy of new drug combinations and the value of serial measurements of serum alphafetoprotein (AFP) and human chorionic gonadotrophin (HCG) were evaluated. Following the initial surgery, staging of the tumour was performed using a variety of investigative approaches. In stage 1 testicular tumours, orchidectomy was performed. In more advanced tumours, and in stage 1 tumours that failed to show the expected decline in AFP or recurred, chemotherapy was used after appropriate surgery. Seventy-three boys, under 14 years of age, with testicular MGCTs have been entered into the UKCCSG studies since 1979. Serum AFP was measured preoperatively, or within 2 weeks of operation, in 70 boys. It was unequivocally elevated in 69. Monitoring by serial AFP measurement proved valuable in assessing response and in early detection of recurrence. HCG was measured in 46 boys, and was raised in three. Sixty-seven (91%) of the tumours were yolk sac (Teilum) tumours, four were immature teratoma, and two were mixed MGCTs. The only non-AFP producing tumour was an immature polydermal teratoma in a 1-year-old boy. Serum HCG was raised in three boys with yolk sac tumours, one with a mixed teratoma, and one 14-year-old boy who had a mixed MGCT. The results of treatment were assessed on April 1, 1989 (median time from diagnosis, 3 years 4 months). Seventy-one boys were alive, 48 of whom had been cured by orchidectomy alone. The remaining 25 patients received chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

'Clustering'--real or apparent? Probability maps of childhood cancer in the West Midlands Health Authority region.

The West Midlands Regional Children's Tumour Registry collects detailed information on all cases of childhood cancer in the West Midlands Health Authority Region (WMHAR). The distribution by electoral ward of all cases diagnosed in the WMHAR between 1980 and 1984 has been determined. Analysis has also been performed for leukaemias/non-Hodgkin's lymphomas alone. We suggest that this latter grouping should be universally employed, owing to the difficulty of accurately separating out cases of leukaemia. Both spatial analyses showed several wards with significantly excessive rates on the basis of their cumulative Poison probability. Observed/expected ratios of 3-35 were seen for cases in significant wards, which are similar to the ratios seen in analysis of incidence around nuclear installations. However, further detailed consideration of these individual significance levels in the light of the number of statistically significant wards which would occur by chance alone, due to the multiple use of the test, accounted completely for the number of wards obtained in each of the groups considered. Thus, apparent 'clustering' of cases could be mere statistical artefact. In the WMHAR, therefore, using the technique of probability mapping, no true spatial pattern of incidence was found, other than that which would occur by chance alone. This, in a large area without nuclear installations and an even mix of rural and industrialised regions, could be seen as control data for those studies which have considered cases of childhood leukaemia around nuclear facilities, where the observation of single point clusters associated with suspected sites restricts assessments of spatial pattern in the rest of the area.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Malignant hepatic tumours in children: incidence, clinical features and aetiology.

Congenital defects and other disorders have been reported in association with malignant liver tumours. In order to assess their significance, a population-based survey was undertaken on children aged less than 15 years diagnosed with malignant liver tumours during the 30 years 1957-1986. The cases were identified from information collected by the West Midlands Regional Children's Tumour Registry. Pertinent data were extracted from their clinical records, and the original biopsy and any necropsy material were reviewed by a panel of three paediatric pathologists. Of the 50 eligible cases registered, eight were excluded because histology review showed that they had non-malignant conditions (3) or malignancies of extrahepatic origin (4) or because no pathological material was available (1). The diagnoses in the remaining 42 cases were hepatoblastoma (27), hepatocellular carcinoma (3), rhabdomyosarcoma (6), rhabdoid tumour (3) and yolk sac tumour (3). The incidence of primary malignant liver tumours was 1.20 per 10(6) person years and that of the hepatoblastoma sub-group was 0.77 (average childhood population of the West Midlands for the time period being 1,166,500). The presenting clinical, radiological and biochemical features were similar to those reported in other series and the ethnic and social class distributions were unremarkable compared with the local population. Congenital defects or other possibly related features were present in nine (21%) patients. Our results, taken with other reports, suggest that hepatoblastoma is a malignant tumour related to maldevelopment, possibly associated with 11p or 5q mutations, whereas hepatocellular carcinoma is more usually a complication of metabolic and other disorders which lead to cirrhosis.

Child↗
PubMed1990

The inter-regional epidemiological study of childhood cancer (IRESCC): case-control study of children with central nervous system tumours.

Tumours of the central nervous system comprise 23% of all childhood cancers and form the most common group of solid malignancies. Little is know about their aetiology. The present report concerns the results of a case-control study of 78 incident cases of central nervous system tumours in children. No case-control differences were detected for the following: pre-natal diagnostic X-rays, general anaesthetics during pregnancy, pregnancy infections, pregnancy drugs (including sedatives, tranquillizers and anti-convulsants), alcohol consumption in pregnancy, child's birthweight, breast-feeding, childhood illnesses, previous medication in the child. A significant excess of case mothers had suffered from diseases of the nervous system (RR 2.6). There was a deficit of children who had been immunised among the case children which approached significance, and an excess of congenital abnormalities among cases which also approached significance. There was a small excess of neoplastic disease among case parents. The results of this study suggest that in our patients genetic rather than environmental factors are more important, but the small numbers included in the present study meant that no definite conclusions could be reached.

Abnormalities, Multiple↗
PubMed1989

Results of the United Kingdom Children's Cancer Study Group's malignant germ cell tumor studies.

The United Kingdom Children's Cancer Study Group's malignant germ cell tumor studies were undertaken to establish standard protocols for investigating, staging, and treating children, and to study the efficacy of new drug combinations and the value of serial measurement of serum alphafetoprotein (AFP) and human chorionic gonadotrophin (HCG). Boys with Stage I testicular tumors were treated by orchidectomy alone, whereas, after appropriate surgery, chemotherapy was recommended for children with more advanced testicular tumors or with tumors at other sites. From 1979 to 1987, 126 children aged 0 to younger than 16 years with malignant germ cell tumors were registered. They were similar to patients in other large pediatric series with respect to sites of origin, age at presentation in relationship to primary site, histology, female predominance for sacrococcygeal site, and presence of associated malformations (present in 17%). Serum AFP was measured in 123 patients and was elevated in 115, whereas HCG was raised in 19 of 77. Monitoring by serial AFP measurement proved valuable in assessing response to therapy and in early detection of tumor recurrence. When treatment results were assessed in February 1988, 101 of 122 patients were alive (four who received nonprotocol chemotherapy were excluded). Forty-four patients had been cured by surgery alone (41 with testicular tumors, two with ovarian tumors, and one with sacrococcygeal tumor). All of the remaining 78 children received chemotherapy. The initial low dose vincristine, actinomycin, and cyclophosphamide (LDVAC) regimen proved ineffective, actuarial survival at 5 years followup being 8% (12 patients), and a regimen of cisplatin, vinblastine, and bleomycin (PVB) caused unacceptable toxicity, with actuarial survival at 5 years follow-up being 67% (nine patients). Five-year actuarial survival was 87% for 17 children given high dose VAC with or without doxorubicin and 84% for 33 given bleomycin, etoposide, and cisplatin (BEP). All 7 children given various combinations of these regimens survived. Excluding the 12 LDVAC cases, patient survival by site was as follows: testis (59 patients, 100%); vagina, uterus, and prostate (four patients, 100%); ovary (25 patients, 88%); thorax (five patients, 40%), and other (four patients, 67%). Similarly, patient survival by stage was Stage I (62,97%), Stage II (14,86%); Stage III (18,83%); and Stage IV (16,72%). Survival by histology was analysed only in cases for which histologic review had been done the LDVAC cases were excluded.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1988

Evaluation of eight and a half years of neonatal screening for haemoglobinopathies in Birmingham.

A pilot neonatal screening programme for haemoglobinopathies linked with screening for phenylketonuria and congenital hypothyroidism was reviewed. During 1978 to December 1986 137,000 neonates were tested. There were improvements in the detection rate and accuracy of diagnosis for homozygotes and mixed heterozygotes, mainly associated with the introduction of citrate agarose gel electrophoresis as a follow up procedure on all specimens showing any abnormality on the initial cellulose acetate electrophoresis. We recommend that the programme is continued on a service basis.

Anemia, Sickle Cell↗
PubMed1988

Histologic and immunohistochemical investigation of neuroblastomas and correlation with prognosis.

Forty-one confirmed cases of childhood neuroblastoma diagnosed over a 13-year period were reviewed and reclassified. Most of the tumors were stained using a peroxidase antiperoxidase method for neuron specific enolase (NSE), protein gene product (PGP) 9.5, and S100 protein, all of which have previously been reported to be positive in some neuroblastomas. The relation to prognosis of the histology and immunohistochemistry was studied. There was a significant trend toward improved survival with increasing degree of differentiation, and with decreasing mitosiskaryorrhexis index (MKI) in the stroma-poor group. There was no significant correlation between immunohistochemical staining and survival, although the presence and amount of staining for all three markers tended to increase with tumor differentiation. This study concludes that histologic classification in neuroblastoma is helpful in assessing prognosis but that the clinical features are generally more reliable as indicators of prognosis. The immunohistochemistry of markers used did not contribute towards assessment of prognosis.

Abdominal Neoplasms↗
PubMed1988

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): case control study of children with bone and soft tissue sarcomas.

The Inter-Regional Epidemiological Study of Childhood Cancer included 43 cases of soft tissue and 30 cases of bone sarcomas, together with their 146 matched controls. Analysis of a wide range of aetiological factors revealed few risk factors relating to events during the index pregnancy, the earlier medical experiences of the case child, or parental medical, occupational and smoking history. Associations which did emerge included: lower birth weight in children with Ewing's tumour, an excess of mothers of children with soft tissue sarcoma with symptoms of toxaemia in pregnancy; and more children with rhabdomyosarcoma who received antibiotics soon after birth. There was some evidence that mothers of children with soft tissue sarcoma may have had reduced fertility with a significant excess of the case mothers having no other pregnancies. Slight excesses of congenital malformations in the case children and of malignant and benign/borderline neoplastic disease in the older mothers were consistent with the existence of a degree of genetic predisposition in the development of the tumours in this series.

Adult↗
PubMed1988

Full term development of mouse eggs fertilized by a spermatozoon microinjected under the zona pellucida.

A mature motile mouse spermatozoon was microinjected under the zona pellucida of mouse eggs. Twenty-five percent of eggs were fertilized, and 54% of these developed to normal fetuses or to term after transfer to pseudopregnant recipients. These results provide a quantitative estimate of the minimum proportion of spermatozoa in a population that are able to contribute to normal development--at least 54% of mature individuals that were able to fertilize the egg after microinjection, or at least 13 1/2% (25% of 54%) of the total population of mature sperm. The production of normal young shows that sperm microinjection is a feasible means for the treatment of severe male infertility in the human and in other species.

Animals↗
PubMed1988

Facts for teachers of children with cancer.

As the prospects of cure for children with cancer increase, the long term consequences of treatment and the quality of life experienced by survivors assume greater importance. Strategies to encourage early return to school after diagnosis are of considerable importance both educationally and socially, but teachers require information to help them facilitate the child's return. The extent to which professional contact is fostered between children's cancer centres and the education service is the subject of this short survey.

Child↗