Cytomorphometric analysis of vaginal cells during normal cycle, under oral contraceptive therapy or in-vitro fertilization stimulation protocol

A cytomorphometric analysis of superficial vaginal cells inwomen in three groups of different types of hormonal concentrationwas made. There were 15 women in each group. Group I was studiedduring a natural cycle, group II under oral contraceptive therapyand group III during an in-vitro fertilization (IVF) stimulationprotocol. Morphometric parameters were measured on an imageanalyser. The area, perimeter and several form factors weremeasured separately for nuclei and cytoplasm. The nucleus:cytoplasmicratio was also determined. The cytoplasmic area was significantlyreduced in group II and was associated with a statisticallysignificant reduction of the nuclear area. The nucleus:cytoplasmicratio appeared significantly increased in group II and reducedin group III. Low oestradiol impregnation obtained with an oralminidosed contraceptive interfered with vaginal cell maturation.High oestradiol concentrations obtained during IVF protocolsinduced marked nuclear pycnosis but did not induce supra-physiologicalcell enlargement. Maximal cell size is genetically regulatedaccording to Driesch's law of volume invariance and hormonalover-stimulation has no effect on cell size. The nucleus:cytoplasmicratio appears to be a powerful parameter reflecting the oppositeeffects of hormones on cell compartments.     

Biochemical evidence for the involvement of central serotonergic neurotransmission in the action of the antidepressant drug Medifoxamine

Medifoxamine, an antidepressant agent which has an original chemical structure, has been shown through in vitro studies, utilising radioligand binding in tissue homogenates, to bind with moderately high affinity to 5-HT_1c and 5-HT₂ receptor subtypes and to 5-HT uptake sites (IC₅₀ 950, 980, and 1,500 nM, respectively). It has been shown to bind in vivo to rat brain 5-HT₂ receptors after acute treatment with high dose (50 mg/kg, i.e., 133.9 μmol/kg). After 14 days continuous treatment with low dose (20 mg/kg, 53.6 μmol/kg), a decrease in the capacity of [³H]-5-HT uptake and a dose-dependent down-regulation of 5-HT₂ receptors in rat cerebral cortex were observed. These results indicate that medifoxamine, which has been shown previously to act through dopaminergic systems, interacts also with central serotonergic neurotransmission and particularly with the 5-HT₂ receptors, which could contribute to its antidepressant effect.     

Male pseudohermaphroditism due to Leydig cell agenesia and absence of testicular LH receptors

OBJECTIVE: The aim of our study was to establish the definitive diagnosis in an adult patient with male pseudohermaphroditism in whom testicular feminization syndrome had been suspected at the age of 8, based on genetic, clinical and pathological studies. DESIGN: Hypothalamo-hypophysio-testicular function was assessed in vivo. Androgen mechanism of action and testicular gonadotrophin binding were studied in vitro. PATIENT: At the age of 33 the phenotype was almost completely feminine except for slight clitoral enlargement and posterior labial fusion. Internal genital duct derivatives were masculine except for a short vagina. Both testes were cryptorchid. MEASUREMENTS: LH and FSH were determined pre- and post-gonadectomy. Progesterone, 17-OH-progesterone, androstenedione, dehydroepiandrosterone testosterone (T) and oestradiol were determined basally in peripheral and spermatic blood post-hCG stimulation, and in peripheral blood after orchidectomy. Dihydrotestosterone (DHT) receptors and 5 alpha-reductase activity were determined in genital skin fibroblasts. Receptors for LH and FSH were determined in membrane preparations from both testes. RESULTS: LH was high (31 IU/l) and FSH (8 IU/ml) normal. T or steroid precursors were detected basally or after hCG stimulation in peripheral blood showing absence of testicular production. Spermatic venous blood steroid concentrations were consistent with slight T production, in accordance with testis histology which showed few Leydig-like cells among fibroblasts in the interstitial space. DHT specific binding capacity and affinity and 5 alpha-reductase activity were normal in genital skin fibroblasts. Gonadotrophin binding studies in testicular membranes confirmed the absence of LH specific binding, whereas FSH binding was higher than normal when expressed per mg of protein (27.0 vs 9.4 +/- 0.6 fmol/mg protein in controls), and lower than normal in both testes since patient's testicular weights were abnormally low. CONCLUSIONS: The patient was considered to have an almost complete form of Leydig cell agenesia/hypoplasia in which absence of specific LH binding correlated with total absence of differentiated Leydig cells and insensitivity of undifferentiated interstitial cells to LH stimulation.     

Tuberculosis in healthcare workers caring for a congenitally infected infant.

OBJECTIVE: To assess the extent of nosocomial transmission of tuberculosis among infants, family members, and healthcare workers (HCWs) who were exposed to a 29-week-old premature infant with congenital tuberculosis, diagnosed at 102 days of age. DESIGN: A prospective exposure investigation using tuberculin skin test (IST conversion was conducted. Contacts underwent two skin tests 10 to 12 weeks apart. Clinical examination and chest radiographs were performed to rule out disease. Isoniazid prophylaxis was administered to exposed infants at higher risk. SETTING: A neonatal intensive care unit in an urban hospital in Brussels, Belgium. PARTICIPANTS: Ninety-seven infants, 139 HCWs, and 180 visitors. RESULTS: Newly positive TST results occurred in HCWs who had been in close contact with the infant. Six (19%) of 32 primary care nurses and physicians had TST conversions and received treatment. Among the 97 exposed infants, 85 were screened and 34 were identified as at higher risk of infection. Of these, 27 received preventive isoniazid. None of the infants and none of the 93 other infants' family members evaluated were infected. CONCLUSIONS: Congenital tuberculosis in an infant poses a risk for nosocomial transmission to HCWs. Delayed diagnosis of this rare disease and close proximity are the most important factors related to transmission.     

Comparative effects of ischemia and acute hypoxemia on muscle afferents from tibialis anterior in cats

Comparative effects of ischemia and acute hypoxemia (PaO₂ = 24 mm Hg) were studied in anesthetized cats on afferents from the tibialis anterior limb muscle. Metaboreceptors (groups III and IV fibers) and mechanoreceptors were identified by their activation by an intraarterial injection of lactic acid (LA) or high-frequency vibrations (HFV) applied to the extremity of the muscle tendon, respectively. Ischemia and hypoxemia exerted opposite influences on the two categories of muscle afferents: they depressed the response of mechanoreceptors to HFV, but markedly enhanced the spontaneous tonic activity of metaboreceptors. The effects of hypoxamia were delayed but slightly greater and lasted longer during the recovery period than those exerted by ischemia. The inhibitory action on mechanoreceptors exerted by a reduced oxyden supply to muscle is interpreted as a result from local acidosis. Indeed, under normoxic conditions, a LA bolus injection during the HFV test also reduced the firing rate of these receptors. © 1993 John Wiley & Sons, Inc.     

The siderophore iron transporter of Candida albicans (Sit1p/Arn1p) mediates uptake of ferrichrome-type siderophores and is required for epithelial invasion

The human fungal pathogen Candida albicans contains a close homologue of yeast siderophore transporters, designated Sit1p/Arn1p. We have characterized the function of SIT1 in C. albicans by constructing sit1 deletion strains and testing their virulence and ability to utilize a range of siderophores and other iron complexes. sit1 mutant strains are defective in the uptake of ferrichrome-type siderophores including ferricrocin, ferrichrysin, ferrirubin, coprogen, and triacetylfusarinine C. A mutation of FTR1 did not impair the use of these siderophores but did affect the uptake of ferrioxamines E and B, as well as of ferric citrate, indicating that their utilization was independent of Sit1p. Hemin was a source of iron for both sit1 and ftr1 mutants, suggesting a pathway of hemin uptake distinct from that of siderophores and iron salts. Heterologous expression of SIT1 in the yeast Saccharomyces cerevisiae confirmed the function of Sit1p as a transporter for ferrichrome-type siderophores. The sit1 mutant was defective in infection of a reconstituted human epithelium as a model for human oral mucosa, while the SIT1 strain was invasive. In contrast, both sit1 and SIT1 strains were equally virulent in the mouse model of systemic infection. These results suggest that siderophore uptake by Sit1p/Arn1p is required in a specific process of C. albicans infection, namely epithelial invasion and penetration, while in the blood or within organs other sources of iron, including heme, may be used.     

Dissection of seroreactivity against the tryptophan-rich motif of the feline immunodeficiency virus transmembrane glycoprotein

Immunogenicity of the tryptophan-rich motif (TrpM) in the membrane-proximal ectodomain of the transmembrane (TM) glycoprotein of feline immunodeficiency virus (FIV) was investigated. Peptide 59, a peptide containing the TrpM of the TM of FIV, was covalently coupled to Qbeta phage virus-like particles (Qbeta-59) in the attempt to induce potent anti-TrpM B cell responses in cats. All Qbeta-59 immunized cats, but not cats that received a mixture of uncoupled Qbeta and peptide 59, developed antibodies that reacted with a same epitope in extensive binding and binding competition assays. The epitope recognized was composed of three amino acids, two of which are adjacent. However, Qbeta-59-immune sera failed to recognize whole FIV in all binding and neutralization assays performed. Furthermore, no reactivity against the TrpM was detected by screening sera from FIV-infected cats that had reacted with TM peptides, confirming that this epitope does not seem to be serologically functional in the FIV virion. The data suggest that TrpM may not be a suitable target for antiviral vaccine design.     

Promotion of U937 cell adhesion on polypropylene surfaces bearing phosphorylcholine functionalities

Phosphorylcholine (PC) groups were grafted onto ammonia plasma-treated biaxially-oriented polypropylene (BOPP) surfaces, via (a) reductive amination of phosphorylcholine glyceraldehyde and (b) a two-step procedure involving the chemical amplification of surface amine groups with tris(2-aminoethyl amine) and subsequent reductive amination of phosphorylcholine glyceraldehyde. The occurrence of grafting was ascertained by X-ray photoelectron spectroscopy (XPS) and attenuated total reflectance Fourier-transform infrared (ATR-FT-IR) spectroscopy. The wettability of PC-modified surfaces was assessed by dynamic contact-angle measurements using the Wilhelmy plate method. Human U937 macrophages adhered and proliferated to a significantly larger extent on PC-modified surfaces, compared to unmodified or ammonia plasma-modified BOPP.