[Treatment of repeated spontaneous miscarriages by intravenous immunoglobulins].
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Abortion, Habitual↗
Biomedical subjects
K Thomas
Publications and source records attributed to K Thomas.
The C. elegans genome sequencing project: a beginning.
The long-term goal of this project is the elucidation of the complete sequence of the Caenorhabditis elegans genome. During the first year methods have been developed and a strategy implemented that is amenable to large-scale sequencing. The three cosmids sequenced in this initial phase are surprisingly rich in genes, many of which have mammalian homologues.
Animals↗
Topical glucocorticoids inhibit activation by allergen in the upper respiratory tract.
We have studied the effect of a topically administered glucocorticoid, fluticasone propionate (FP), on infiltration and activation of eosinophils in the nasal mucosa after provocation with allergen. Forty-four patients with seasonal allergic rhinitis entered a double-blind, crossover study in which they underwent treatment with either FP (200 micrograms once daily) or identical placebo for 2 weeks. Patients then underwent nasal-allergen provocation followed by nasal lavage and biopsy at one of several time points between 0 and 8 hours. Patients subsequently received the alternate treatment for 2 weeks before repeat allergen provocation, nasal lavage, and biopsy, as before. Biopsy specimens of nasal mucosa obtained during the immediate allergic response demonstrated an influx of eosinophils (stained by monoclonal antibody EG1) of similar magnitude during both FP and placebo treatment. Significantly, fewer eosinophils in these biopsy specimens were activated (stained by monoclonal antibody EG2) after treatment with FP compared with that after placebo treatment (median values, 8.8 and 36.6 cells per square millimeter, respectively; p less than 0.02). The concentration of eosinophil cationic protein in nasal lavage fluid was significantly elevated above baseline from 2 to 8 hours after allergen, and this increase was abolished by treatment with FP. These results suggest that topical glucocorticoids inhibit allergen-induced activation of eosinophils in allergic rhinitis.
Administration, Topical↗
Circhoral fluctuations of serum total renin, inhibin and related hormones around the mid-cycle in normal human females.
Total renin and inhibin are secreted by the ovary. Although luteinizing hormone (LH) and/or follicle stimulating hormone (FSH) may stimulate their secretion, the close relationship between fluctuations of gonadotrophins, oestradiol, progesterone, renin and inhibin during the cycle is still conjectural. To investigate the temporal relationship between the short-term fluctuations in the circulating concentrations of LH and FSH and the ovarian hormones (oestradiol, progesterone, renin and inhibin), blood samples were collected at 15-min intervals for 6 h from 15 normal women in the late follicular (n = 4), early luteal (n = 5) or luteal (n = 6) phases of the menstrual cycle. LH levels showed the well-known pulsatile secretion with decreasing frequency and increasing relative amplitude from the late follicular to the luteal phase. Progesterone and oestradiol serum levels were pulsatile, 25% and 35-50% of which were linked to LH pulses, with time lags of 30 and 12-15 min respectively. Renin levels presented significant pulses, 26% of which were related to LH pulses with a time lag of less than 10 min; no coincidence was found between renin and oestradiol pulses. Inhibin levels presented only scattered pulses of small amplitude, which were unrelated to LH or FSH. These results show that, besides the LH-related pulses, pulsatile secretion of some ovarian hormones (oestradiol, progesterone and renin) may also occur independently of LH pulses and may be unrelated to one another. Moreover, contrary to the other ovarian hormones, inhibin seems to follow a tonic, not a pulsatile type of secretion around the mid-cycle.
Adult↗
Phosphodiesterase inhibition in ventricular cardiomyocytes from guinea-pig hearts.
1. The present study compared the cyclic nucleotide phosphodiesterase (PDE) activities in cardiomyocytes and ventricular cardiac tissue from guinea-pigs. The aim of the study was to determine whether PDE activities in ventricular tissue accurately reflect the isoenzymes present in cardiomyocytes. 2. In homogenates of cardiomyocytes and multicellular ventricular tissue, four distinct soluble PDE activities could be separated by DEAE-sepharose chromatography. 3. In multicellular cardiac tissue as well as in cardiomyocyte preparations, adenosine 3':5'-cyclic monophosphate (cyclic AMP) PDE isoenzymes I-IV were comparable in terms of substrate affinities, and inhibition or stimulation by guanosine 3':5'-cyclic monophosphate (cyclic GMP). However, in cardiomyocytes the Vmax values of PDE I-IV were lower by a factor of about 2 to 7 and the basal activities were lower by a factor of about 3 to 5 as compared to multicellular cardiac tissue. 4. To investigate whether the PDE I-IV activities were similarly inhibited by PDE inhibitors in both preparations, we studied the effects of 3-isobutyl-1-methylxanthine (IBMX), UD-CG 212 Cl (2-(4-hydroxy-phenyl)-5-(5-methyl-3-oxo-4, 5-dihydro-2H-6-pyridazinyl)benzimidazole HCl) and rolipram. UD-CG 212 Cl was a selective PDE III inhibitor in cardiomyocytes (IC50 0.3 mumol l-1) and in ventricular tissue (IC50 value 0.1 mumol l-1). Rolipram selectively inhibited PDE IV in cardiomyocytes (IC50 1.4 mumol ml-1) and in ventricular tissue (IC50 1.1 mumol l-1) whereas IBMX was a nonselective PDE inhibitor in both preparations.5. It is concluded that the PDE isoenzymes I-IV from multicellular ventricular tissue can be used as a representative system for investigating PDE inhibiting properties of PDE inhibitors in the myocardium since comparable PDE isoenzymes I-IV exist in guinea-pig ventricular cardiomyocytes and multicellular ventricular tissue.
1-Methyl-3-isobutylxanthine↗
Regulation of skeletal muscle dihydropyridine receptor gene expression by biomechanical unloading.
Biomechanical unloading of the rat soleus by hindlimb unweighting is known to induce atrophy and a slow- to fast-twitch transition of skeletal muscle contractile properties, particularly in slow-twitch muscles such as the soleus. The purpose of this study was to determine whether the expression of the dihydropyridine (DHP) receptor gene is upregulated in unloaded slow-twitch soleus muscles. A rat DHP receptor cDNA was isolated by screening a random-primed cDNA lambda gt10 library from denervated rat skeletal muscle with oligonucleotide probes complementary to the coding region of the rabbit DHP receptor cDNA. Muscle mass and DHP receptor mRNA expression were assessed 1, 4, 7, 14, and 28 days after hindlimb unweighting in rats by tail suspension. Isometric twitch contraction times of soleus muscles were measured at 28 days of unweighting. Northern blot analysis showed that tissue distribution of DHP receptor mRNA was specific for skeletal muscle and expression was 200% greater in control fast-twitch extensor digitorum longus (EDL) than in control soleus muscles. A significant stimulation (80%) in receptor message of the soleus was induced as early as 24 h of unloading without changes in muscle mass. Unloading for 28 days induced marked atrophy (control = 133 +/- 3 vs. unweighted = 62.4 +/- 1.8 mg), and expression of the DHP receptor mRNA in the soleus was indistinguishable from levels normally expressed in EDL muscles. These changes in mRNA expression are in the same direction as the 37% reduction in time to peak tension and 28% decrease in half-relaxation time 28 days after unweighting. Our results suggest that muscle loading necessary for weight support modulates the expression of the DHP receptor gene in the soleus muscle.
Animals↗
Effect of epidermal growth factor on inhibin secretion in human placental cell culture.
The effect of epidermal growth factor (EGF) on inhibin secretion was investigated in a primary culture of human placental cells. Dissociated cells were cultured with EGF, FSH, 8-Br-cAMP, and two agents known to increase intracellular cAMP. Inhibin level in the culture medium was measured by immunoenzymatic assay. Addition of EGF (0.1-1000 ng/ml) in the cell culture induced a dose-dependent increase of inhibin levels in the medium after 2 days of culture. Greater response of placental cells to EGF in the inhibin secretion occurred at the doses of 10-1000 ng/ml, where inhibin levels in the medium increased by 84.9-111.5% compared to the control (P < 0.01). FSH stimulated the inhibin secretion in the placental cells. EGF combined with FSH resulted in a greater response of placental cells in inhibin secretion. Addition of FSH (30 ng/ml) and EGF (0.1-1000 ng/ml) in the culture induced inhibin levels significantly higher than that of either FSH alone or EGF alone (P < 0.01). The effect of EGF on inhibin secretion was closely correlated with the seeding density of trophoblasts and the time course of culture. Obvious effect of EGF was found at the number of 1-2 x 10(6) cells per well and after 36-48 h of culture. Addition of 8-Br-cAMP, cholera toxin, or forskolin in the culture increased the inhibin levels more than 6-fold, 5-fold, and 2-fold, compared to the controls, respectively. When EGF combined with one of these agents was added in the culture, the inhibin in the medium increased to a level higher than those with the individual agents alone. EGF resulted in an increase in basal and cAMP induced human CG secretions in the trophoblasts in a similar manner as in the inhibin secretion. However, the effect of EGF on the proliferation of trophoblasts was not observed by measurements of the cell growth with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and DNA content in the cells with fluorescence spectrophotometry. Morphological study showed that EGF induced trophoblasts to differentiate and form syncytium. These data suggest that EGF stimulates inhibin secretion in human placental cells in vitro. EGF and its interaction with other hormones or growth factors may play an important role in the complicated hormonal regulation during human pregnancy.
Cell Differentiation↗
Changes in bioactive and immunoactive inhibin levels around human labor.
The changes in bioinhibin (B-inhibin) and immunoinhibin (I-inhibin) levels were studied in the serum of healthy term pregnant women by ovine pituitary cell culture and immunoenzymatic assay systems before and 24 h after delivery. In the maternal serum, a sharp decline in both B-inhibin and I-inhibin levels was observed within first 6 h after delivery. B-inhibin and I-inhibin in maternal serum were 3.45 +/- 0.25 and 3.77 +/- 0.43 U/mL, respectively, before labor and decreased by 35.82% and 38.89% 30 min after labor. One hour after delivery, B-inhibin and I-inhibin were reduced by 56.74% and 61.48%, respectively. After 6 h, B-inhibin and I-inhibin levels were lowered by 93.86% and 78.90%, respectively. Twenty-four hours later, both inhibins were nearly undetectable. In the retroplacental serum, B-inhibin and I-inhibin were 4.92 +/- 0.34 and 10.13 +/- 1.16 U/mL, respectively, i.e. 42.48% and 168.60% higher than the levels of B-inhibin (P less than 0.05) and I-inhibin (P less than 0.001) in maternal serum before delivery. In the umbilical cord serum, the B-inhibin concentration was 0.75 +/- 0.16 U/mL, whereas the I-inhibin concentration was 9.58 +/- 0.75 U/mL, which was much higher than that of B-inhibin (P less than 0.001). No difference was found in B-inhibin or I-inhibin levels in the serum samples collected separately from umbilical arteries and veins (P greater than 0.05). In addition, inhibin levels were measured in amniotic fluid and placental extract. In amniotic fluid, B-inhibin and I-inhibin concentrations were 2.37 +/- 0.35 and 8.01 +/- 0.55 U/mL, respectively. In the comparison, B-inhibin in amniotic fluid was 31.3% lower than that in maternal serum before delivery (P less than 0.05), but I-inhibin was 112.5% higher than that in the maternal serum (P less than 0.001). In the placental extract, the B-inhibin concentration was 12.80 +/- 0.35 U/g tissue, while the I-inhibin concentration was 33.86 +/- 2.93 U/g tissue, which was more than twice as high as the B-inhibin level (P less than 0.001). Our data provide further evidence that inhibin may be mainly produced in the placenta during pregnancy.
Adult↗
Growth requirements and expression of LDL receptor and HMG-CoA reductase in Hep G2 hepatoblastoma cells cultured in a chemically defined medium.
A serum-free chemically defined medium (CDM) has been developed which sustains the growth in culture of the highly differentiated human hepatoma cell line Hep G2. Unlike rodent hepatoma lines, Hep G2 cells in serum-free medium have an absolute requirement for lipoprotein lipids (either low density lipoprotein (LDL) or high density lipoprotein (HDL)) for growth. In the presence of LDL (or HDL) growth was further enhanced by insulin, triiodo-L-thyronine, 17 alpha-ethinylestradiol but not by epidermal growth factor (EGF). On type I collagen gels cells cultured in CDM were contact inhibited and formed monolayers. This contrasted with the pattern of growth of cells cultured in the presence of serum on type I collagen gels and cells cultured on tissue-culture plastic in either CDM or medium containing serum which formed foci of multilayered cells. Expression of the LDL receptor and HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase genes was comparable in Hep G2 cells cultured in CDM and serum-containing medium. Furthermore, the binding and internalisation of 125I-LDL at 37 degrees C was modulated by hormones that have previously been shown to affect LDL receptor levels in liver in vivo or in hepatocytes cultured in serum-containing medium in vitro. The culture system described provides a basis for studying the regulation of hepatocyte-specific functions by soluble factors (either plasma- or cell-derived) and cell-substratum interactions in a human liver cell line.
Carcinoma, Hepatocellular↗
Evaluating the new Medigap standardization regulations.
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Data Collection↗
Hearing impairments in middle age: the acceptability, benefit and cost of detection (ABCD).
The major epidemiological investigations of hearing impairment, disability and handicap show that the elderly are the group most disabled by their hearing impairment. There is considerable debate concerning the most efficient way of reducing this inevitable burden of age-related hearing impairments in the next generation. Early fitting of 'targeted' individuals with hearing aids may help but there are a large number of methodological problems associated with conducting and evaluating such a programme of research (especially retrospectively). The logical prerequisite to early fitting as a means of reducing later disability is to ascertain the acceptability of and benefit given by intervention at this early stage. This study therefore set out to investigate the age/sex register provided by the primary physician (GP) as an appropriate base to identify candidates for early aid fitting among a sample of middle-aged patients (50-65 years) living in Roath, Cardiff. Of the 662 who replied to an initial contact letter (1050 were on the age/sex register), 21 already possessed hearing aids. After screening and examination 66 people were offered some form of management which was accepted by 43 during the course of the study. Aid use thereby increased from about 3% to over 9% in this middle-aged group. A 2 year follow-up indicated continued use of the aids, and benefit on a speech reception task was measured. The cost of detecting those who might benefit was calculated using a two-question 'paper and pencil' screen as the first step. A national programme for Wales would cost at least 188,000 pounds per annum at 1990 prices over an initial 5 year span if a criterion which aimed to find at least 45 dB HTL impairments over mid-frequencies was implemented. For a criterion of 35 dB the cost would be 378,000 pounds pa.
Auditory Threshold↗
Posttraumatic cerebral arterial spasm: transcranial Doppler ultrasound, cerebral blood flow, and angiographic findings.
Thirty patients admitted after suffering closed head injuries, with Glasgow Coma Scale scores ranging from 3 to 15, were evaluated with transcranial Doppler ultrasound monitoring. Blood flow velocity was determined in the middle cerebral artery (MCA) and the intracranial portion of the internal carotid artery (ICA) in all patients. Because proximal flow in the extracranial ICA declines in velocity when arterial narrowing becomes hemodynamically significant, the extracranial ICA velocity was concurrently monitored in 19 patients. To assess cerebral perfusion, cerebral blood flow (CBF) measurements obtained with the intravenous 133Xe technique were completed in 16 patients. Vasospasm, designated as MCA velocity exceeding 120 cm/sec, was found in eight patients (26.7%). Severe vasospasm, defined as MCA velocity greater than 200 cm/sec, occurred in three patients, and was confirmed by angiography in all three. Subarachnoid hemorrhage (SAH) was documented by computerized tomography in five (62.5%) of the eight patients with vasospasm. All cases of severe vasospasm were associated with subarachnoid blood. The time course of vasospasm in patients with traumatic SAH was similar to that found in patients with aneurysmal SAH; in contrast, arterial spasm not associated with SAH demonstrated an uncharacteristically short duration (mean 1.25 days), suggesting that this may be a different type of spasm. A significant correlation (p less than 0.05) was identified between the lowest CBF and highest MCA velocity in patients during the period of vasospasm, indicating that arterial narrowing can lead to impaired CBF. Ischemic brain damage was found in one patient who had evidence of cerebral infarction in the territories supplied by the arteries affected by spasm. These findings demonstrate that delayed cerebral arterial spasm is a frequent complication of closed head injury and that the severity of spasm is, in some cases, comparable to that seen in aneurysmal SAH. This experience suggests that vasospasm is an important secondary posttraumatic insult that is potentially treatable.
Adolescent↗
Betamethasone in tetanus patients: an evaluation of its effect on the mortality and morbidity.
The effect of betamethasone on the outcome in moderate to severe tetanus was studied in a randomised, double blind, placebo controlled study in 22 patients. The mortality rate was reduced by 36.1% with the addition of corticosteroids to the regime of treatment. Betamethasone did not alter the duration of intensive care in those requiring it, but reduced the need for tracheostomy and ventilation. The mean daily dose of diazepam required was not significantly different between the two groups and there was no increase in the incidence of infections in the betamethasone group.
Adult↗
Effect of three antibacterial drugs in lowering blood & stool ammonia production in hepatic encephalopathy.
Neomycin (700 mg/8 h), ampicillin (500/6 h) and metronidazole (400 mg/8 h), were compared for their effect, on oral administration for 4 days, in reducing blood ammonia in 27 patients with stable chronic liver disease. It was found that there was 38.2, 38.5 and 8.7 m mol/litre mean reduction in blood ammonia in the neomycin, ampicillin and metronidazole treated groups respectively. The difference in blood ammonia was statistically significant for both neomycin (P = 0.01) and ampicillin (P = 0.03) but there was no significant change after metronidazole treatment (P = 0.6). The total stool enzyme activity at optimum pH was maximally reduced by ampicillin and minimally with metronidazole. The reduction was noted to be 3.51 m mol/1 (P = 0.01), 3.87 m mol/1 (P = 0.08) and 2.8 m mol/1 (P = 0.02) of NH3/g dry weight of stool for neomycin, ampicillin and metronidazole respectively. The main bacterial gut enzymes responsible for ammonia production, urease and protease, were found to be very sensitive to stool pH. At pH 6 their activity was around 20 per cent of what was found in optimum pH of 7.4 and at pH 5 it is only about 8 per cent of optimum activity. None of the three antibacterial agents changed the stool pH significantly. It can be concluded that oral neomycin and ampicillin are superior to oral metronidazole in lowering blood ammonia.
Administration, Oral↗
Inhibin production and secretion in human placental cells cultured in vitro.
In this study, human trophoblast cells were isolated from term placentas by trypsin-DNase digestion and Percoll gradient centrifugation. After the cells were cultured in vitro, bioactive inhibin and immunoreactive inhibin were measured in the culture medium and cellular lysate by an ovine pituitary cell culture system and an immunoenzymatic assay. The trophoblast cells were capable of producing inhibin, as indicated by the observation that enhancement of inhibin content and secretion was dependent upon the cell number and time in culture. High levels of inhibin were observed in the culture medium and the cellular lysate with cell numbers of over 1 x 10(6) cells/well, whereas the inhibin levels decreased until they were nearly undetectable when the cell number was less than 0.25 x 10(6) cells/well. In the culture medium, a sharp increase of inhibin levels was observed after 2 days of culture. Bio-inhibin and immuno-inhibin concentrations in the culture medium increased tenfold and fourfold, respectively, from day 2 to day 4. The peak level of bio-inhibin (3.5 U/mL) occurred on day 4 and that of immuno-inhibin (3.55 U/mL) on day 6. In contrast, the maximal level of bio-inhibin (4.45 U/mL) and immuno-inhibin (4.25 U/mL) in the cellular lysate was observed on day 2.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell Separation↗
[Identification of angiotensin II receptor and determination of its subtypes in rabbit and guinea pig fetal tissue].
Membrane angiotensin II receptors were measured in trophoblastic tissues using a 2-step procedure. The first step consisted of the relative measurement performed at a fixed 125I[Sar1 Ile8]AII concentration of 0.15 nM in order to determine which tissues had a sufficient number of binding sites for studying the competition curves. The second consisted of determining the maximal binding (Bmax) and the dissociation constant (Kd) for [Sar1 Ile8] AII and the receptor subtypes in these tissues. The relative binding measurement revealed a significant number of occupied sites in rabbit fetal placenta and chorion (159 +/- 17 and 51 +/- 10 fmol/mg proteins) and in guinea pig chorion (132 +/- 12). The mean values of the other trophoblastic tissues were 3-10-fold lower in the 2 species. The competition curves obtained from tissues with high angiotensin II binding receptors showed the predominance of the AT2 subtype in rabbit fetal placenta (AT1/AT2 = 25/75) and of the AT1 receptor in guinea pig chorion (97/3) and in rabbit chorion (90/10). The [SAR1 Ile8] AII affinity (Kd) obtained from Scatchard plot analysis was 1.2 +/- 0.2 nM (n = 5) in fetal placenta and 1.2 (n = 1) in rabbit chorion and 0.5 +/- 0.1 (n = 3) in guinea pig chorion. In these tissues, the respective Bmax values were 1,281 +/- 115 (n = 5), 263 (n = 1) and 1,188 +/- 134 fmol/mg proteins (n = 3). These findings indicate that rabbit fetal placenta and chorion and guinea pig chorion are the most important sites of action for the renin-angiotensin system present in trophoblastic tissues.
1-Sarcosine-8-Isoleucine Angiotensin II↗
Repair of a ruptured calcaneal tendon by transposition of the tendon of the peroneus longus muscle in a goat.
Traumatic rupture of the calcaneal tendon was diagnosed in a 3-year-old female goat. Clinical features included tarsal hyperflexion and diffuse swelling in the area of the calcaneal tendon. Surgical repair consisted of debridement of devitalized tissue and transposition of the tendon of the peroneus longus muscle to bridge the calcaneal tendon defect. Adequate postoperative immobilization followed by gradual introduction of tendon loading allowed a favorable outcome.
Animals↗