Biomedical subjects
Publications and source records attributed to M Gibson.
Ovarian cysts of clinical significance are uncommon in the fetus and neonate. The authors diagnosed a large fetal cyst prenatally by ultrasound scan and removed it in the neonatal period. Analysis of the fluid obtained from the cyst demonstrated a capacity of the fetal ovary to synthesize estrogen and progesterone.
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The red cells of a normal male blood donor, K.S., were first grouped as B but he was found to lack anti-A in his serum. Closer investigation revealed that his red cells had very weak A activity, demonstrable only by absorption and elution of anti-A. He is a non-secretor of ABH and a secretor of Lea. Blood group A-, B and H-gene specified glycosyltransferases were detected in his serum. In contrast to the finding of a B antigen of normal strength on his red cells, the B transferase in his serum was only about 30% of the normal level and, despite the very weak A activity of K.S's red cells, the A transferase level was about 50% of that found in the serum of group A individuals with normal strength of A antigen. Moreover, the A transferase on the basis of its pH optimum, Km values for donor and acceptor substrates, activation by divalent cations, isoelectric focusing profile and capacity to convert O to A-active cells, was characterized as the product of an A1 gene. A family study showed that K.S's wife is group A2 and that they have two sons, one group A2 and the other group B. The group B son is assumed to have inherited a B gene from the propositus but the level of B transferase in the son's serum is three times as high as that in his father's serum. The wife of the propositus and his group A2 son have normal A2 transferases in keeping with their A2 red cell status. The A2 son therefore appears to have inherited an A2 gene from his mother but neither the A1 nor the B gene shown to be carried by his father. The distribution of transferase activities in K.S's red cells differs from that in his serum. A level of B transferase within the normal range was found in his red cell membranes but a very low level of A transferase was detected. The discrepancies between the serum transferases and ABO red cell group, together with the pattern of inheritance within the family, led to a suspicion of chimaerism. This was confirmed by the finding of fibroblasts with the female 46XX karyotype in cultures of the propositus' skin. These results suggest that K.S. is a dispermic chimaera with two different cell lines of the genotypes BO and A1O or A1A1. The group A2 son is assumed to have inherited an O gene from his father. It seems probable that K.S.'s bone marrow and reproductive organs are comprised predominantly of the XY cell line which carried the blood group BO genotype whereas his skin and other tissues which contribute the A1 transferase to his plasma, are partly made up of the XX cell line which carries the blood group A1O or A1A1 genotype.
We constructed lambda recombinants containing the Harvey murine sarcoma virus genome and the thymidine kinase (tk) gene of herpes simplex virus type 1 linked to each other. The tk gene was located in a position downstream from both the long terminal repeat and the src gene of Harvey murine sarcoma virus. The DNAs of the lambda recombinants were used to transfect NIH3T3 mouse fibroblasts in order to obtain Harvey murine sarcoma virus DNA-induced foci of transformed cells. The transformed foci were superinfected with a helper-independent retrovirus, and new individual retrovirus were isolated from the superinfected foci. The new viruses could induce focus formation on NIH3T3 cells and could convert NIH3T3(TK-) cells into TK+ cells by carrying the herpes simplex virus type 1 tk gene into the TK- cells. From virus-infected cells, we isolated nonproducer foci on NIH3T3 cells and TK+ transformants on NIH3T3(TK-) cells containing one such new viral genome coding for the dual properties. The new retroviral sequence in the nonproducer cells could be rescued into virus particles at high titers by superinfection with a helper-independent retrovirus. A hybridization analysis indicated that the recombinant virus contained both the Harvey murine sarcoma virus src sequence and the tk gene sequence in a single RNA species approximately 4.9 kilobases long. We concluded that retroviruses can be used as true vectors for genes other than genes that lead to oncogenesis.
A 23-year-old woman had endometritis due to Chlamydia trachomatis infection. Chlamydia trachomatis was cultured from endometrial tissue obtained by biopsy, and elevated levels of serum antibodies, including IgM antibodies, to C. trachomatis were found. Cervical secretions were also positive for antibody. After treatment with tetracycline, endometrial cultures for C. trachomatis were negative and endometrial inflammation disappeared. Chlamydia trachomatis has been implicated in salpingitis, cervicitis, urethritis, and peritonitis, This case shows that endometritis may also result from C. trachomatis infection and in such instances may be a contributing factor in infertility.
The plasma concentrations of testosterone (T), dehydroepiandrosterone (D), androstenedione (A), pregnenolone (delta 5P), progesterone (P), 17-hydroxypregnenolone (17-delta 5P), 17-hydroxyprogesterone (17-P), 11-deoxycortisol (S), and cortisol (F) were measured before, and 30 and 60 minutes after, a bolus intravenous injection of 25 units of adrenocorticotropic hormone (ACTH) in nine normal women and in fifteen patients with a variety of manifestations of androgen excess. Patients with androgen excess demonstrated significantly higher mean baseline levels of T, D, A, delta 5P, 17-delta 5P, and 17-P. After a bolus intravenous injection of 25 units of ACTH, higher-than-normal increments were noted for the following steroids: delta 5P (one patient), 17-delta 5P (one patient), D (two patients), P (one patients), 17-P (two patients), and S (two patients). Following ACTH injections, the ratios of increments in plasma steroid pairs were computed to estimate the efficiency of several adrenal enzymes, and evidence suggesting partial deficiency of 3 beta-hydroxysteroid dehydrogenase delta 4-5 isomerase (five patients) and 11 beta-hydroxylase (five patients) was found. In addition, 6 of the 15 patients with androgen excess exhibited an abnormally high increment in D relative to the increment in F. The data show that apparent abnormalities in adrenal steroid biosynthesis are a frequent occurrence in patients with hyperandrogenism.
The characterization of the hyperandrogenism of two sisters with type A insulin-resistant diabetes and hirsutism is presented. Testosterone (T) and androstenedione levels were elevated in peripheral serum. These were not markedly affected by infusion of adrenocorticotropic hormone. In patient 1 glucocorticoid suppression decreased T levels by 50% and androstenedione levels by 30% but had no effect on them in patient 2. Estrogen-progestin suppression markedly reduced testosterone levels in both patients. The blood production of T in patient 1 was 0.8 mg/day and in patient 2 was 4.5 mg/day, both of which are elevated. Selective venous catheterization in patient 2 revealed markedly elevated testosterone levels in the ovarian veins, and polycystic ovaries were found at subsequent laparotomy. These endocrine studies have shown that the source of excessive testosterone in these patients is excessive production by the ovaries, and it can be suppressed by oral contraceptives.
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Another example of haemopoietic chimaerism in dizygotic twins is described. Each twin had two distinct blood cell populations. The red cell populations differed in three blood group systems and in other genetic characters, and the white cell population in HLA types and in XX/XY karyotypes. The biological significance of these findings is discussed with special reference to the relative proportions of the two red and white cell populations, the ABH blood group gene-specified glycosyltransferase levels, and the HLA types.
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UNLABELLED: A rat model to study the local effects of testicular vein ligation is described. One hour after unilateral testicular vein ligation, the testicular concentration of testosterone was significantly greater (P less than 0.01) on the side that was ligated than in the contralateral testis (177.1 +/- 19.7 [SEM] ng/gm of tissue as compared with 108.8 +/- 11.8 ng/gm of tissue, respectively). This effect was not seen 1 week after the testicular vein ligation. The testosterone concentration in the ligated testis was also higher than that in sham-operated animals. These differences in testicular testosterone concentration were not associated with changes in peripheral serum testosterone levels. CONCLUSION: ligation of the testicular vein causes an acute rise in the testicular concentration of testosterone and may thus mediate changes in testicular function.
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Prematurity and premature rupture of the membranes present major obstetric problems. When associated with amnionitis, the result may be disastrous. A case of Haemophilus influenzae aminionitis in association with premature rupture of the membranes is presented. The rarity of this organism as a causative agent in amnionitis and its possible causative role in premature membrane rupture are considered in review of the scant relevant literature.
The automated assay of maternal anit-D levels has been compared with manual methods and correlated with the severity of haemolytic disease of the newborn using discriminant analysis. The automated assay of anti-D proved to be marginally better than manual techniques in predicting the need for amniocentesis. The level at which amniocentesis should be considered has been calculated to be 4IU/ml of maternal serum.