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Biomedical subjects
Publications and source records attributed to J Williams.
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Second-passage rat embryo cells were transfected with a neomycin resistance gene and the activated form of the c-Ha-ras I gene, or with these two genes plus the adenovirus type 2 E1a gene. Foci of morphologically transformed cells were observed in both cases; however, the frequency of transformation was at least ten times higher with two oncogenes than with the ras gene alone. All the transformed cell lines gave rise to rapidly growing tumors when injected subcutaneously into nude mice. All but one of the cell lines transformed by the ras oncogene alone formed metastatic nodules in the lungs of animals that had been injected subcutaneously with transformed cells. When transformed cells were injected intravenously, all the ras single-gene transformants gave rise to many metastatic lung nodules. In contrast, cell lines transformed with ras and E1a did not generate metastases after subcutaneous injection and gave rise to very few metastatic lung nodules after intravenous injection. These data demonstrate that a fully malignant cell with metastatic potential, as measured in an immunodeficient animal, can be obtained from early passage embryo cells by the transfection of the ras oncogene alone.
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The authors studied in vitro immune function as measured by lymphocytic proliferative response to mitogen stimulation in 36 patients with agoraphobia and panic attacks who were participating in a double-blind placebo-controlled psychopharmacological study of anxiety disorder. No significant difference in immune status was observed between panic patients and healthy controls.
Investigations resulting from the isolation of Pseudomonas paucimobilis from the atomizer units of paediatric cool mist tents implicated the hospital water supply as the potential source of contamination. The pathogenic potential of the organism and its role in nosocomial infection is discussed.
Milk samples were obtained in early and/or late lactation from Przewalski horses, Hartmann's zebras, Grant's zebras, domestic horses, ponies and a mule mare made pregnant by embryo transfer. Samples were compared for their content of total solids, ash, calcium, phosphorus, magnesium, sodium, potassium, copper, zinc and iron. Milk from the Przewalski horses, Hartmann's zebra and the domestic horse had similar mineral composition and the content of minerals was higher in early than in late lactation. Milk from the domestic mule contained the lowest concentration of calcium, phosphorus and zinc but the highest concentration of magnesium, sodium and potassium. Milk from the Grant's zebras contained more sodium than potassium, unlike milk from Przewalski horses, Hartmann's zebras or domestic horses in which there was more potassium than sodium.
It has been suggested recently that use of a transport medium (Michel's medium) satisfactorily preserves the antigenicity of surface markers on lymphocytes for immunologic evaluation. Transport medium has been reported to be especially useful when immediate preparation of a specimen for immunologic study is not possible. Because adverse conditions such as changes in temperature during the transport of fresh-frozen tissue may markedly alter immunologic markers, it is desirable to transport fresh tissue in a medium that does not adversely affect the immunoreactivity of the tissue antigens. Therefore, we undertook a comparative study in which we compared cryostat-cut, fresh-frozen sections and tissues fixed in transport medium. The specimens were obtained from 56 consecutive patients who had various malignant lymphomas and benign lymphoid disorders. The results of our study indicate that the morphologic and immunologic findings obtained from the frozen sections that had been maintained in the transport medium (Michel's) may be confusing and may be interpreted inaccurately. This study also confirms our previous observation that the inconclusive or spurious results occasionally obtained with cell suspension technics can be avoided if the immunohistochemical technics are applied to cryostat-cut, fresh-frozen sections. We conclude that immunohistochemical study of cryostat-cut fresh-frozen sections remains the technic of choice for the identification and evaluation of both the morphologic and immunologic characteristics of tissues involved by lymphoproliferative diseases.
In 1980-1983 members of IRESCC interviewed parents of 555 children with newly diagnosed cancer on topics of possible aetiological significance. Identical questions were asked of the parents of 1100 control children chosen from hospital admissions and general practitioner lists. Medical information was confirmed whenever possible by cross-checking with NHS records. Data for the 41 children with germ cell tumours and their 82 controls are reported here. The cases had more major congenital malformations than controls, including one neural tube defect. More case than control mothers and fathers reported occupational exposure to chemicals. Nine close relatives of cases had multiple primary tumours, which were often benign or of low-grade malignancy, compared with 1 hospital control and 3 general practitioner control relatives. Cases and controls differed with respect to birth weight and paternal age. No case-control differences were shown for: birth rank, maternal age, chronic illnesses and smoking, mothers' reproductive histories and oral contraceptive usage. In index pregnancies there were no case-control differences for maternal illness, infections, alcohol intake and X-ray and ultrasound exposure. There was no difference between cases and controls for the frequency of twinning the families.
Changes in the mineral composition of mare milk during lactation were studied. Milk samples were obtained from five Thoroughbred mares one to three times weekly from the first to the eighth week of lactation and from two of the mares for an additional 8 wk. Samples averaging 500 mL were obtained after oxytocin was administered to the mares. Each sample was analyzed for total solids, ash, calcium, phosphorus, magnesium, sodium, potassium, copper and zinc. The concentration of all constituents except sodium and potassium decreased throughout lactation. The rates of decline of ash, calcium, phosphorus and magnesium concentration were similar, but the rates of decline of the other elements differed. Thus, the mineral composition of mare milk should be described in terms of the stage of lactation of the mare. The total solids and ash content of mare milk were 12 and 0.61% respectively, at the end of the first week of lactation, 10.5 and 0.45% at 4 wk, 10 and 0.38% at 8 wk and 10.2 and 0.32% at 16 wk. The calcium, phosphorus and magnesium concentrations at the end of the same periods were 1345, 943 and 118 micrograms/g of milk at 1 wk; 1070, 659 and 86 at 4 wk; 831, 574 and 58 at 8 wk and 700, 540 and 43 micrograms/g of milk at 16 wk. Copper and zinc concentrations were 0.85 and 3.1, 0.55 and 2.2, 0.29 and 1.9 and 0.28 and 1.8 microgram/g of milk at 1, 4, 8 and 16 wk, respectively.
The prenatal diagnosis of 4q deletion was made as a result of amniocentesis for high serum alphafetoprotein.
A syndrome of Duchenne muscular dystrophy (DMD), adrenal hypoplasia, glycerol kinase deficiency, and mental retardation has been recognised. We report a further case ascertained from a history of DMD, severe mental retardation, and an Addison-like disorder. Cytogenetic analysis of the proband revealed an interstitial deletion of the short arm of the X chromosome. from Xp21.1 to Xp22.11, comprising about 9% of the length of the normal X chromosome. His mother was heterozygous for the deletion, but his maternal grandmother and sister both had two normal X chromosomes. DNA probe analysis confirmed the existence of a deletion in the affected boy, as probes 754, C7, XJ1-1, and pERT87 consistently failed to hybridize to his DNA. His sister was heterozygous for the RFLP associated with 754, thus confirming that she had two normal X chromosomes. There was no evidence of chronic granulomatous disease, other immunological defect, or retinitis pigmentosa in this case. Biochemical studies revealed gross glyceroluria and hyperglycerolaemia, indicating glycerol kinase deficiency which has been confirmed enzymatically. We have subsequently screened 21 other boys with DMD for glyceroluria and found one other case. Cytogenetic analysis has also been performed in nine other families, where a boy with DMD has been shown to have a deletion of DNA sequences localised to the region Xp21. None of these cases demonstrated any cytogenetic abnormality, nor has their clinical course been unusual.
The concentration of 25-hydroxyvitamin D3-binding protein (DBP) was measured, by immunodiffusion, in the blood of chickens from embryonic stages to sexual maturity. Low levels of DBP and 1,25-(OH)2D3 were detectable in the blood of chick embryos from the 12th and 17th day of incubation respectively and stayed at the same low levels until hatching. The blood concentration of DBP doubled between the 1st and 5th days of life, then increased slowly and reached the mean level of the adult male at 7-8 weeks of age. The concentration of DBP was independent of vitamin D status in growing chickens. A large increase was observed in DBP blood levels in hens just before sexual maturity. This change, and those observed in moulting hens, followed the variations in plasma concentrations of oestradiol more closely than those of progesterone or testosterone. Moreover, a large increase in plasma DBP levels was induced in immature chickens by oestradiol (0.5 mg/day), but not by testosterone or progesterone. Finally, the experimental suppression of egg shell formation and the associated decrease in 1,25-(OH)2D3 plasma levels had no effect on plasma DBP concentrations. However, 1,25-(OH)2D3 and DBP levels were higher in hens laying shell-less eggs than in immature pullets. The increases in DBP levels at hatching, in immature pullets treated with oestrogens, in hens laying uncalcified eggs and at the onset of egg production were associated with increases in 1,25-(OH)2D3, suggesting a relationship between the levels of DBP and 1,25-(OH)2D3 in the blood.
The production of shell-less eggs was induced in hens to measure the effects of the high demands made by shell formation on the blood minerals and hormones whose concentrations change during egg formation. In control hens laying hard-shelled eggs, the concentration of ionized calcium in plasma decreased at the onset of shell formation, but no change was found in hens laying shell-less eggs. Total calcium concentrations in plasma decreased slightly throughout the ovulation cycle in both groups. Concentrations of inorganic phosphorus in the plasma were increased in the control group during the period of shell formation and decreased when calcification was suppressed. Finally, the concentrations of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) in plasma were significantly increased 16 and 20 h following an ovulation compared with 4 h after ovulation, or compared with the concentrations observed in hens laying shell-less eggs. The variations in the plasma concentrations of ionized calcium, inorganic phosphorus and 1,25-(OH)2D3 associated with egg formation were therefore absent in hens laying shell-less eggs demonstrating their direct link with shell calcification. On the other hand, suppression of shell production had no influence on the changes in the plasma concentrations of progesterone, oestradiol and testosterone which are associated with the normal ovulatory cycle. It is concluded that the increases in intestinal and uterine calcium transport and in 1,25-(OH)2D3 production which occur at the onset of egg production in hens are mainly controlled by factors involved in maintaining calcium homeostasis rather than by gonadal hormones.
We report the case of a pre-term infant who developed severe hyponatremia and water retention associated with the ingestion of an overdose of the non-steroid anti-inflammatory drug naproxen eight hours before delivery. Recovery was complete and subsequent development unimpaired.
An experiment was conducted to investigate possible differences in plasma hormone levels between females of two lines of chickens selected for high (FL) or low (LL) abdominal fat content. Blood was taken at weekly intervals from 6 weeks of age to sexual maturity, and assays were performed for luteinizing hormone (LH), growth hormone (GH), and estradiol (E2). Age-related increases in the plasma titers of LH and estradiol were found while GH remained low apart from initial and final fluctuations. There was no difference between the strains in plasma E2, only minor differences in plasma GH, but a clear-cut difference was observed in plasma LH during the prepubertal period. Plasma LH tended to be higher in the LL, but the reason for this remains unclear.
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A modification of the method of Carr et al. [1976] for the ultrasonic assessment of liver volume was devised for use with a UI Octoson water delay B mode echoscope, and 32 subjects without clinical history or signs of liver disease were examined. In 9 subjects the measurements were repeated by a separate observer. Comparison of the variance between observers and that between subjects showed that the precision of the method is within acceptable limits, the variance ratio (F) being 13.7 (p less than 0.001). The mean liver volume was 1,545.4 +/- (SD) 255 ml. This finding is in close agreement with previously published data. The liver volume was correlated with body weight, height, body surface area, and body mass index. The liver volume was found to correlate best with body weight using partial correlation analysis. This was in accordance with previously published data, with the exception of that of Koischwitz [1979]. However, variations in weight could only account for 0.43 of the variation in liver volume.