Biomedical subjects
Publications and source records attributed to J M Roberts.
Three cases of Capgras' syndrome were identified in one psychiatric hospital within a 1-year period. These are presented and their psychopathology discussed. The traditional assumption that this is a rare syndrome is challenged.
To document patterns of intestinal parasitism in the United States, we analyzed results of 216,275 stool specimens examined by the state diagnostic laboratories in 1987; parasites were found in 20.0%. Percentages were highest for protozoans: Giardia lamblia (7.2%), Entamoeba coli and Endolimax nana (4.2% each), Blastocystis hominis (2.6%), and Entamoeba histolytica (0.9%). The most commonly identified helminths were nematodes: hookworm (1.5%), Trichuris trichiura (1.2%), and Ascaris lumbricoides (0.8%). Identifications of G. lamblia increased broadly from the 4.0% average found in 1979, with 40 states reporting increases and seven reporting decreases. Seasonally, Giardia identifications increased in the summer and fall, especially in the Midwest. Nine states reported hookworms in more than 2% of specimens; none were states with indigenous transmission. We analyzed similar, but abbreviated, data for 1991; parasites were found in 19.7% of the 178,786 specimens and Giardia was found in 5.6%. States reporting percentages of Giardia identification in the highest quartile for both 1987 and 1991 were located in the Midwest or in the Northwest. Cryptosporidium was identified in both the 1987 and 1991 surveys; it had not been identified in a previous survey. For each year, Cryptosporidium was reported from 25 states across the country (for both years in 17 states). We conclude that intestinal parasitism should not be overlooked as a cause of gastrointestinal illness in the United States and that the prevalence of Giardia may be increasing.
Cell adhesion has an essential role in regulating proliferation during the G1 phase of the cell cycle, and loss of this adhesion requirement is a classic feature of oncogenic transformation. The appearance of cyclin A messenger RNA and protein in late G1 was dependent on cell adhesion in both NRK and NIH 3T3 fibroblasts. In contrast, the expression of Cdc2, Cdk2, cyclin D1, and cyclin E was independent of adhesion in both cell lines. Transfection of NRK cells with a cyclin A complementary DNA resulted in adhesion-independent accumulation of cyclin A protein and cyclin A-associated kinase activity. These transfected cells also entered S phase and complete multiple rounds of cell division in the absence of cell adhesion. Thus, cyclin A is a target of the adhesion-dependent signals that control cell proliferation.
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Transforming growth factor-beta (TGF-beta) is a naturally occurring growth inhibitory polypeptide that arrests the cell cycle in middle to late G1 phase. Cells treated with TGF-beta contained normal amounts of cyclin E and cyclin-dependent protein kinase 2 (Cdk2) but failed to stably assemble cyclin E-Cdk2 complexes or accumulate cyclin E-associated kinase activity. Moreover, G1 phase extracts from TGF-beta-treated cells did not support activation of endogenous cyclin-dependent protein kinases by exogenous cyclins. These effects of TGF-beta, which correlated with the inhibition of retinoblastoma protein phosphorylation, suggest that mammalian G1 cyclin-dependent kinases, like their counterparts in yeast, are targets for negative regulators of the cell cycle.
Eukaryotic cells become committed to proliferate during the G1 phase of the cell cycle. In budding yeast, commitment occurs when the catalytic subunit of a protein kinase, encoded by the CDC28 gene (the homolog of the fission yeast cdc2+ gene), binds to a positively acting regulatory subunit, a cyclin. Related kinases are also required for progression through the G1 phase in higher eukaryotes. The role of cyclins in controlling G1 progression in mammalian cells was tested by construction of fibroblasts that constitutively overexpress human cyclin E. This was found to shorten the duration of G1, decrease cell size, and diminish the serum requirement for the transition from G1 to S phase. These observations show that cyclin levels can be rate-limiting for G1 progression in mammalian cells and suggest that cyclin synthesis may be the target of physiological signals that control cell proliferation.
Eighty-six consecutive patients undergoing spinal surgery were studied with preoperative and postoperative compression ultrasonography of the lower extremities to identify acute deep venous thrombosis. Compression stockings were the only method of prophylaxis. Postoperative deep venous thrombosis developed in five patients (6%). Serial ultrasound scanning revealed propagation of the thrombus proximal to the knee in one patient, who was the only patient to be anticoagulated. There were no statistically significant differences in the incidence of deep venous thrombosis compared to the type of procedure, age, sex, length of operation, or duration of bed rest. In conclusion, deep venous thrombosis distal to the inguinal ligament is unusual after spinal surgery. Given the potential complications of anticoagulation, we recommend only mechanical prophylaxis.
Liver biopsies from 63 patients with hepatitis C virus (HCV) infection have been studied. 31 were asymptomatic and had been detected by a variety of screening programs, and most of the other 32 had complained of vague symptoms only. In 57 patients a confident estimate of the duration of infection was able to be made (ranging from 12 months to over 38 years) and 73% of these had been infected for over 5 years. The most common histological pattern observed was a low-grade panacinar hepatitis. This affected 74.6% of all biopsies, and 43% of this group had been infected for over 10 years. Severe chronic active hepatitis and/or cirrhosis occurred in only 8% of the whole series, and in 16.7% of those infected for over 10 years. This incidence of serious sequelae in chronic HCV infection is much lower than previously reported, probably reflecting the methods of patient selection, and may represent more accurately the natural history of the disease in this community. The occurrence of a number of characteristic histological features (lymphoid follicles and aggregates, steatosis, Kupffer cell prominence, and apoptotic or acidophilic bodies) was confirmed, the constellation of which is highly suggestive of HCV infection. It is suggested that apoptosis may play an important role in the perpetuation of HCV as a chronic infection.
OBJECTIVE: Our purpose was to test a potential role for the endogenous smooth muscle relaxant nitric oxide in the control of gestational uterine activity by quantifying and characterizing its synthetic enzyme, nitric oxide synthase, in uterine tissue at the end of pregnancy. STUDY DESIGN: We measured nitric oxide synthase activity through the conversion of tritiated L-arginine to tritiated L-citrulline in subcellular preparations of decidua and myometrium from pregnant rabbits at 27, 30, and 31 days' (term)gestation. Nitric oxide synthase was characterized by measuring its relative inhibition by arginine analogs and its calcium-calmodulin requirement. Nitric oxide synthase activities were compared by one-way analysis of variance with Fisher's post hoc test. RESULTS: Nitric oxide synthase activity in decidua was high at 27 days' gestation (6.32 +/- 1.10 pmol/mg protein per minute, n = 6), less with the approach of labor (30 days = 3.16 +/- 1.25 pmol/mg per minute, n = 4), and lowest at 31 days (1.07 +/- 0.29 pmol/mg per minute, n = 4, p < 0.05). Decidual nitric oxide synthase was calcium insensitive, and arginine analogs reduced activity with potencies consistent with their effect on the induced form of nitric oxide synthase. CONCLUSION: Decidual nitric oxide synthase activity, which has the characteristics of the inducible isoform of the enzyme, is significantly lower on the last day of gestation. This suggests a role for nitric oxide in the control of uterine contractility during pregnancy.
DNA replication is coupled to cell cycle progression at a major regulatory point in the G1 phase of the cell cycle. At this point, the catalytic subunit of a protein kinase (encoded by the CDC28 gene in budding yeast or the homologous CDC2 gene in other eukaryotes) is activated by binding to a positively acting regulatory subunit, a cyclin. Recent research has revealed evidence for two pathways that might connect these kinases to the proteins that replicate DNA: activation of an essential replication factor, or removal of the block that limits genome duplication to once per cell cycle.
OBJECTIVE: Our purpose was to examine whether care by a certified nurse-midwife, including personal labor support, was associated with a reduced risk of cesarean delivery. STUDY DESIGN: A retrospective cohort study comparing 3551 physician-managed patients with 1056 certified nurse-midwife-managed patients in a university hospital with a mixed socioeconomic and ethnic population was performed. Regression analysis was used to estimate the risk of labor abnormalities, diagnosis of fetal distress, and cesarean delivery in patients delivered by a certified nurse-midwife vs a physician and to control for maternal age, race, parity, fetal size, and delivery year. Subjects included were women having at least five prenatal visits who were delivered of term, singleton, liveborn infants without congenital anomalies with occiput presentation. RESULTS: Odds ratio for cesarean section for women delivered by certified nurse-midwives versus those delivered by physicians was 0.71 (95% confidence interval 0.55, 0.91). Midwifery care was associated with a lower risk of abnormal labor (adjusted odds ratio 0.70, 95% confidence interval 0.60, 0.83) and diagnosis of fetal distress (adjusted odds ratio 0.50, 95% confidence interval 0.32, 0.77). CONCLUSION: This work demonstrates that labor abnormalities and diagnosis of fetal distress are less frequent in patients cared for by nurse-midwives, and there is an association with a lower incidence of cesarean section.
OBJECTIVE: Human amnion is important in the initiation of labor. Ritodrine, when administered as a tocolytic, is found unchanged in amniotic fluid. We characterized effects of ritodrine binding to beta-adrenergic receptors in amnion and amniocytes. STUDY DESIGN: Iodine 125-iodopindolol, beta-adrenergic receptor agonists, and beta-adrenergic receptor antagonists were used to describe binding characteristics. Experiments were designed with and without isoproterenol and ritodrine to study intracellular cyclic adenosine 3'5'-monophosphate and prostaglandin E2 release. RESULTS: Scatchard analysis revealed a single class of saturable binding sites, with maximum binding capacity of 70.0 +/- 17.2 fmol/mg protein (n = 12) and with high-affinity dissociation constant of 458.9 +/- 72.1 pmol/L. Agonists and antagonists competed for the 125I-iodopindolol binding site consistent with a beta 2-adrenergic receptor. Hill coefficients were 0.6 to 0.8 for agonist competition and 1.0 for antagonist competition and ritodrine. Stimulation with isoproterenol resulted in dose-dependent increases in cyclic adenosine 3'5'-monophosphate and prostaglandin E2. Ritodrine failed to stimulate cyclic adenosine 3'5'-monophosphate and inhibited isoproterenol-stimulated cyclic adenosine 3'5'-monophosphate and prostaglandin E2 production. CONCLUSION: In human amnion binding of ritodrine to beta 2-adrenergic receptors and lack of ritodrine-mediated postreceptor effects are characteristic of a beta 2-adrenergic antagonist.
Because of the potent mitogenic and vasoactive properties of endothelin-1 (ET-1) and the presence of its receptor in third trimester placenta, we postulated that ET-1 might be involved in human placental growth and vascularization during development. As an initial approach to test this hypothesis, placental ET receptors were characterized and quantified in each trimester of pregnancy. Membrane-rich particulates were prepared from first-, second-, and third-trimester villous human placenta obtained immediately after pregnancy termination or delivery. ET receptors were characterized by radioligand saturation analysis, ligand competition, and reverse transcription-polymerase chain reaction (RT-PCR) to determine the concentration, affinity, and specificity of ET binding sites, and to document the presence of specific ET-receptor subtype mRNA transcripts in placentas from each trimester. Kinetic determinations of 125I-labeled ET-1 binding yielded a Kd = 61 pM, consistent with the equilibrium determinations of 34 +/- 6 pM (n = 11). The concentration of ET receptors decreased significantly from 682 +/- 94 fmol/mg protein (n = 4) in the first trimester to 266 +/- 89 fmol/mg protein (n = 4) in the third trimester. Competition studies with unlabeled ET-1 indicated a single class of binding sites with a Ki = 49 +/- 5 pM (n = 9), whereas competition with ET-3 demonstrated binding sites with two affinities. The predominant sites had a Ki = 84 +/- 14 pM, similar to that for ET-1. The RT-PCR data confirmed that both ETA and ETB receptors mRNA transcripts are expressed in human placenta.(ABSTRACT TRUNCATED AT 250 WORDS)
In normal human pregnancy, invasion of the uterus and its arterial system by cytotrophoblasts extends through the entire decidua and the adjacent third of the myometrium. Our previous work showed that during the first trimester of pregnancy, invasion is accompanied by a marked change in the expression of cell adhesion molecules by invasive cytotrophoblasts. In the pregnancy disorder preeclampsia, cytotrophoblast invasion is limited to the superficial decidua, and few arterioles are breached. The purpose of this study was to determine whether cytotrophoblast expression of adhesion molecules in this disorder is also abnormal. Placental bed biopsy specimens from normal pregnancies and those complicated by preeclampsia were stained with anti-integrin antibodies. The results showed that adhesion molecule switching by invasive cytotrophoblasts is abnormal in preeclampsia, which suggests that this subpopulation of trophoblast cells fails to differentiate properly. A likely result is that the delicate balance of adhesive interactions that normally permit cytotrophoblast invasion is tipped in favor of those which restrain this process, with the net effect of shallow uterine invasion.
Although the in vivo effect of estrogen on myometrial differentiation is well documented, estrogen effects on primary myocytes in vitro have been difficult to demonstrate. To construct a stable uterine myocyte system, capable of direct estrogen responsiveness, we used a transformed hamster myometrial cell line. Since these cells expressed a low level of estrogen receptors (ERs), we have stably transfected them with a vector for the human ER. After transfection, ER concentration increased from less than 300 sites per cell to 17,000 +/- 2,000 sites per cell (mean +/- SEM). To test the functional integrity of the transfected receptors, a chloramphenicol acetyltransferase gene linked to an estrogen response element upstream of thymidine kinase promoter was transiently transfected, and the amount of chloramphenicol acetyltransferase activity, an indicator of estrogen responsiveness, was found to increase 20-fold in response to 17 beta-estradiol (1 nM for 48 h). Furthermore, we tested the ability of estrogen to activate endogenous genes by measuring progesterone receptor (PR) induction. PR concentration in the transfected cells was 3,700 +/- 800 and increased 9-fold to 33,000 +/- 6,000 with 17 beta-estradiol (2 nM). This receptor density increase was confirmed by immunoblotting. PR induction was maximal at 16 h, was concentration dependent, and was not elicited by tamoxifen or ICI 164,384. We conclude that transformed hamster myocytes transfected with an ER gene are capable of estrogen-dependent PR expression in vitro and may serve as a useful system to study estrogen effect on myocytes.
We performed a retrospective study of 564 vaginal occiput posterior (OP) deliveries to investigate the influence of this position on maternal and fetal morbidity. The cases were compared to 1,068 controls matched for race, parity and delivery method. The OP group had a higher incidence of severe perineal laceration and episiotomy than the occiput anterior (OA) group. Within the OP group, operative delivery was associated with a higher incidence of severe perineal laceration, vaginal laceration and episiotomy than was spontaneous delivery. Similarly, the OP group delivered by forceps had a higher incidence of severe perineal lacerations, vaginal lacerations and episiotomy than those delivered by vacuum extraction. Mediolateral episiotomy was associated with a lower incidence of severe perineal lacerations than median episiotomy during delivery from the OP position. The infants delivered from the OP position had a higher incidence of Erb's and facial nerve palsy than did those delivered from the OA position. All these injuries occurred following forceps delivery. Vaginal delivery from the persistent OP position is associated with increased maternal morbidity, and operative vaginal delivery from this position is associated with increased neonatal morbidity.
We describe several characteristics of a novel smooth muscle cell line, SHM (Syrian hamster myometrium) derived from a primary uterine leiomyosarcoma which was induced by chronic estrogen plus androgen treatment of a female Syrian (golden) hamster. To determine the usefulness of the SHM cell line as a model for understanding myometrial function and its regulation, we have examined the morphologic and immunocytochemical properties of these cells, and the ability of uterotonic agonists to activate transmembrane signaling via phosphoinositide hydrolysis. The SHM cells exhibited a spindle-shape, smooth musclelike morphology when subconfluent, and a more compact, stellate shape at confluence. Like primary myocytes, SHM cells expressed the intermediate filament desmin and the contractile protein alpha smooth muscle actin, but not the epithelial antigen cytokeratin. Norepinephrine and bradykinin, which stimulate contraction and inositol polyphosphate production in the uterus, also stimulated inositol polyphosphate production in SHM cells. The maximal phosphoinositide signaling responses were lower in SHM cells compared with primary hamster uterine myocytes. We conclude that the SHM cell line exhibits primary uterine myocyte characteristics, and may therefore be a useful system for examining the mechanisms through which myometrial functions are regulated.