Catabolic effect in premature infants with early dexamethasone treatment

To evaluate the catabolic effects of dexamethasone therapy on protein metabolism, amino acid concentrations and urinary 3-methylhistidine (3MH) were measured in 28 premature infants who were included in a double-blind controlled study using early dexamethasone therapy in the prevention of bronchopulmonary dysplasia. Fifteen infants received dexamethasone (0.5mg/kg/day i.v.) and 13 infants received normal saline as control. Heparinized venous blood samples for amino acid analysis were obtained before the study and again at day 5 after starting the study. Urinary 3MH was measured on days 1, 3, 5, 7, 14, 21, and 28 of treatment. A substantial increase in amino acid concentrations was observed in infants receiving dexamethasone. Alanine, glutamine, citrulline, ornithine and cystine concentrations increased twofold or more. The 3MH:creatinine ratio was increased in the treated group. These metabolic effects were most likely due to an increase in protein catabolism.     

The possible role of stromal cell stimulation in worsening the prognosis of a subset of patients with breast cancer

This review examines the evidence that a subset of patients with breast cancer have tumors that are stimulated to grow by host cells in the tumor stroma. The search for such a minority group was prompted by the following observations. Adjuvant chemotherapy which is immunosuppressive improves disease-free interval and survival, whereas non-specific immunostimulation worsens the prognosis. Intrinsic immune reactivity is associated with a poor prognosis. A subset of tumors with a bad prognosis has anaplastic cells, dermal lymphatic invasion and a moderate to intense lymphoplasmacytic stromal infiltrate. Evidence is reviewed that adjuvant chemotherapy may be beneficial by virtue of its immunosuppressive effects in addition to tumor kill of minimal residual disease.     

The effects of vandellia cordifolia on renal functions and arterial blood pressure

Vandellia cordifolia (COLSM) G. DON of Scrophulariaceae (V. cordifolia) is an annual wild herb indigenous to Taiwan. It can be found in plains, low altitudes, swampy places, and paddy fields. Taiwanese folk physicians use it in "nephritis, uremia, furnucle, carbuncle." The LD50 (95% confidence limit) of the crude extract of V. codifolia given by the oral route was more than 10 g/kg in rats. By the intraperitoneal route, it was 4.6 g/kg (4.35-4.93). The extraction rate was 16.6%. We studied its effects on renal functions and blood pressure and found that (1) it had diuretic effect on normal rats, (2) it decreased glomerular filtration rate and renal blood flow on normal kidneys in rabbits, (3) it had no effects on glomerular filtration rate and renal blood flow on glycerin-induced insufficient kidneys in rabbits, (4) it had diuretic effects on both normal and glycerin-induced insufficient kidneys in rabbits, (5) it could inhibit Na+ and K+ reabsorption on normal and glycerin-induced insufficient kidneys in rabbits, (6) it had hypertensive effect and this effect could be blocked by phenoxybenzamine. From the above facts, we conclude that V. cordifolia has diuretic effect and it may act on renal tubules to inhibit Na+ and K+ reabsorption.     

Cardio-respiratory measures following isocapnic voluntary hyperventilation

In some individuals, breathing is greater than at rest following voluntary hyperventilation. Most previous investigations have employed short hyperventilation periods; here we examine the time course of cardio-respiratory measures before, during, and after a 5-min voluntary hyperventilation, maintaining isocapnia throughout. We examined the possible co-involvement of the cardiovascular system; hypothesising that post-hyperventilation hyperpnoea results from an increase in autonomic arousal. In four subjects (two males, two females) of 18 (nine males, nine females) we observed a post-hyperventilation hyperpnoea, characterised by a slow decline of ventilation toward resting levels with a time constant of 109.0 +/- 16.1s. By contrast, heart rate, and systolic and diastolic blood pressure were unchanged from rest during and after voluntary hyperventilation for all subjects. We concluded that males and females were equally likely to exhibit post-hyperventilation hyperpnoea, and suggest that they may be characterised by an increased resting heart rate and the choice of breathing frequency to increase ventilation during the voluntary hyperventilation. We further concluded that post-hyperventilation hyperpnoea is rare, but when present is a strong and lasting phenomenon, and that it is not the result of an increased autonomic arousal.     

Physical and biological properties of U.S. standard endotoxin EC after exposure to ionizing radiation.

Techniques that reduce the toxicity of bacterial endotoxins are useful for studying the relationship between structure and biological activity. We used ionizing radiation to detoxify a highly refined endotoxin preparation. U.S. standard endotoxin EC. Dose-dependent changes occurred by exposure to 60Co-radiation in the physical properties and biological activities of the endotoxin. Sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis showed gradual loss of the polysaccharide components (O-side chain and R-core) from the endotoxin molecules. In contrast, although endotoxin revealed a complex absorption pattern in the UV range, radiation treatment failed to modify that pattern. Dose-related destruction of the primary toxic component, lipid A, was suggested by the results of activity tests: both the pyrogenicity and limulus reactivity of the endotoxin were destroyed by increasing doses of radiation. The results indicate that the detoxification is probably due to multiple effects of the ionizing radiation on bacterial lipopolysaccharides, and the action involves (i) the destruction of polysaccharide moieties and possibly (ii) the alteration of lipid A component of the endotoxin molecule.     

Inherited chondrodysplasia punctata due to a deletion of the terminal short arm of an X chromosome

We studied two families with an inherited deletion of the short arm of an X chromosome (Xp) in which affected male offspring have epiphyseal stippling in infancy (chondrodysplasia punctata), nasal hypoplasia, ichthyosis, and mental retardation. The presence of ichthyosis and the apparent pattern of X-linked recessive inheritance prompted investigation of the short arm of the X chromosome through studies of genetic markers and focused cytogenetic analysis. Biochemical studies suggested that there was a deletion of three genes previously mapped to the X-chromosome short arm, including the steroid sulfatase locus, the Xg locus, and the M1C2X locus. Prometaphase chromosomes demonstrated a deletion of Xp at p22.32 in the affected boys, in their obligate-carrier mothers, and in 11 of 25 women at risk as potential carriers. The women carrying the Xp deletion had normal gonadal function and fertility but were shorter than the noncarriers in their families (P less than 0.00001). These findings have implications for the genetic organization of this portion of the human X chromosome and demonstrate that small cytogenetic abnormalities may account for disorders with apparent mendelian patterns of inheritance.     

Immunotopographic assessment of lymphoid and plasma cell malignancies in the bone marrow

To determine the utility of tissue section immunochemistry in the evaluation of bone marrow involved by lymphoid and plasma cell malignancies, snap-frozen, undecalcified bone marrow core and aspirate samples from 23 patients with these disorders were studied with a battery of monoclonal antibodies. With techniques that preserve architecture, difficult diagnostic cases characterized by core but not aspirate involvement, or the reverse, were resolved. By means of an extensive battery of monoclonal antibodies applied to serial sections, complex tumor cell phenotypes were established in all 23 cases. In addition to the identification of straightforward monoclonal surface immunoglobulin expression in small cleaved cell lymphomas (four cases), the battery approach added immunologic certainty in malignancies with unusual or difficult phenotypes: peripheral T-cell lymphomas with idiosyncratic antigen expression, and chronic lymphocytic leukemias and small cell lymphomas with faint surface immunoglobulin expression (four cases). For the chronic lymphocytic leukemias and the small cell lymphomas, the combined IgD+, B2+, B1+, Ia+, Leu-1+ phenotype taken as a whole had greater utility than any isolated marker. The acute lymphocytic leukemias and the myelomas studied demonstrate the wide range of B-cell antigens that must be detected to account for the variety of B-cell neoplasms encountered. Additionally, the previously undescribed phenotypic subset of CALLA+ myelomas, which is of prognostic relevance, was identified. Marrow frozen section immunotyping is a major asset in the evaluation of patients with lymphoma, leukemia, and myeloma when special care is accorded to tissue handling and to treatment of endogenous peroxidase/pseudoperoxidase and interstitial immunoglobulin.     

Humoral and cellular immune response after measles vaccination in Taiwan.

Measles immunoglobulin G (IgG) seroepidemiologic studies have been widely used to monitor the effectiveness of measles immunization programs in Taiwan. However, studies about cellular immunity against the measles virus have been lacking. This study surveyed cellular immunity after measles, mumps and rubella combined vaccine (MMR) immunization in Taiwan. Seventy six people between 1 and 80 years of age were enrolled. All patients lived in northern Taiwan, and none of them had immunodeficient disease. Every enrolled patient donated a tube of heparinized blood between January 2004 and June 2004 for cross-sectional studies of IgG seroepidemiologic and MMR-specific lymphoproliferative response. The results showed that the current 3-dose (measles x 1 + MMR x 2) measles immunization program induced slightly higher IgG seroprevalence (100% vs 85%, p=0.244) and a higher frequency of significant (stimulation indices > or = 3) MMR-specific lymphoproliferative response (50% vs 15%, p=0.044) than a 2-dose (measles x 1 + MMR x 1) immunization program, although there was no difference in IgG titers and stimulation indices. Furthermore, the population aged older than 36 years (pre-immunization era) had higher IgG titers and seroprevalence, and similar MMR-specific lymphoproliferative responses to that of the population aged younger than 36 years (post-immunization era). In summary, with the limited data, the current 3-dose (measles x 1 + MMR x 2) measles immunization policy probably more effectively induces humoral and cellular immunity than the 2-dose (measles x 1 + MMR x 1) policy. Measles IgG seroprevalence in populations of different age groups exceeds nearly 90%. Measles has been eliminated temporarily in Taiwan. For a better understanding of the durability of vaccine-induced immunity and in order to establish the most appropriate immunization schedule, long-term and large-scale prospective studies of measles-specific seroepidemiology and cellular immunity will be needed.     

Activation of MAP kinases,pp90rsk and pp70-S6 kinases in mouse mast cells by signaling through the c-kit receptor tyrosine kinase or FcϵRI: rapamycin inhibits activation of pp70-S6 kinase and proliferation in mouse mast cells

The high-affinity receptor for IgE, Fc_?RI, represents the major cell surface structure through which mast cells express immunologically specific secretory function. By contrast, the stem cell factor receptor (SCFR), which is encoded by c-kit, is essential for normal mast cell development. The signaling pathways initiated by the stimulation of mast cells through the Fc_?RI, which lacks intrinsic kinase activity, and the SCFR, a member of the receptor tyrosine kinase family, generally have been regarded to be distinct. We report here that mouse mast cells stimulated either with SCF or with IgE and specific antigen exhibit a remarkably similar pattern of activation of mitogen-activated protein kinases (MAPK), 90 kDa-S6 kinases (pp90^rsk), and pp70-S6 kinases (pp70-S6K). These results indicate that all three families of protein kinases are associated with the cell surface receptor-dependent activation of secretion, as well as proliferation, in mast cells. We also show that the immunosuppressant rapamycin, but not FK506, can inhibit both SCF-dependent pp70-S6 kinase activation and SCF-dependent proliferation in mouse mast cells, without suppressing IgE- and antigen-dependent mediator release. These findings suggest that the activation of pp70-S6 kinase represents an important link in the stimulation of cell proliferation by SCF. Our results also indicate that the intracellular signaling pathways initiated by stimulation of mast cells through the Fc_?RI or the SCFR exhibit more overlap than has previously been appreciated.     

Detection of St. Louis encephalitis virus antigen in mosquitoes by capture enzyme immunoassay.

Surveillance methods that measure St. Louis encephalitis (SLE) virus activity in nature may provide forewarning of its epidemic occurrence in humans. An antigen capture enzyme immunoassay was developed to detect SLE virus in infected mosquitoes. The assay detected purified SLE viral antigen at a concentration of 62 pg/0.1 ml when antigen was incubated overnight; 250 pg/0.1 ml was detected in a single-day assay (antigen incubated for 3 h). The assay detected 67.9 and 70.8% of laboratory-prepared pools of infected mosquitoes after 3 h and overnight incubation, respectively. The sensitivity of the procedure was 90.5% in identifying pools with infectious titers greater than dex 3.0. The specificity of the assay was controlled by retesting positive pools preincubated with SLE virus and normal antibodies, which led to a diminution of signal in the pools containing viral antigen. The procedure was suitably specific in discriminating between SLE and related flaviviruses, detecting only high infectious doses of heterologous antigens.