Hypocomplementemia (C3) as an independent predictor for children with acute post-streptococcal glomerulonephritis: a long-term observation.

OBJECTIVE: The aim of this study was to examine the altering patterns in clinical characteristics and severity of acute post-streptococcal glomerulonephritis (APSGN) in children. PATIENTS AND METHODS: We analyzed the medical records of 119 children who were diagnosed with APSGN from 1987 to 2018, retrospectively. The patients were divided into two groups: Group I (n=72, before 1998) and Group II (n=47, after 1998). Clinical, radiologic, and laboratory findings were compared between the two groups. RESULTS: The clinical manifestations, including vomiting (20.8% vs. 4.3%, p=0.014), oliguria (40.3% vs. 19.1%, p=0.016), and generalized edema (86.1% vs. 63.8%, p=0.005), were statistically less frequent since 1998. Pulmonary edema on chest X-ray (22.7% vs. 4.4%, p=0.014) was less frequent in Group II than in Group I. The level of BUN (23.3±19.3 vs. 18.8±11.2, p=0.009) was lower in Group II than in Group I, while that of creatinine was not significantly different between the two groups. C3 level was an independent factor for predicting the development of edema (odds ratio [OR]: 1.034, 95% CI: 1.010-1.060, p=0.006) and acute nephritic symptoms (≥2) (OR: 0.974, 95% CI: 0.952-0996, p=0.020). It was also negatively correlated with an increasing number of acute nephritic symptoms, including oliguria and edema, in patients with APSGN (R=-0.182, p=0.048). CONCLUSIONS: This study demonstrated that APSGN had favorable clinical manifestations and severity over the past 30 years. The monitoring of C3 levels can be used to assess the disease severity and risk of complications, including edema and oliguria, which are decreasing in South Korean children.

Changes in undergraduate medical education due to COVID-19: a systematic review.

OBJECTIVE: This study aims to provide medical educators with insights into the current status and prospects of undergraduate medical education, which has been affected by the COVID-19 pandemic. MATERIALS AND METHODS: We conducted a database search of PubMed, Embase, and ERIC and identified articles on COVID-19-related undergraduate medical education. We independently reviewed titles and abstracts and extracted data on the geographic location of the study, area of specialty, phase in medical school (preclinical year, clerkship year, etc.), type of paper, and the main content of the study. RESULTS: A total of 49 articles published across multiple countries were included in this study. These were categorized as dealing with either (1) curriculum changes in undergraduate medical education due to COVID-19 or (2) student-led educational activities related to COVID-19. The 41 articles in the first category showed two main trends: replacing in-person lectures with online classes in the preclinical years and adopting various remote educational methods to compensate for the discontinued or truncated clerkship in the clinical years. The eight articles in the second category showcased various student educational activities that were conducted to meet the public's medical needs during the pandemic. CONCLUSIONS: This review summarized the essential changes in undergraduate medical education worldwide and reflected on the various teaching methods adopted by medical schools. In preparation for the post-COVID era, a comprehensive online curriculum and evaluation tools are needed, which require the development of necessary infrastructure and adequate resources. Education aimed at helping students be more socially aware and responsible as medical professionals must be promoted.

Structure-function studies of human 5-alpha reductase type 2 using site directed mutagenesis.

Site directed mutagenesis of human steroid 5alpha-reductase types 1 (5AR1) and 2 (5AR2) has been used to identify residues involved in inhibitor/substrate binding by 5AR2. Replacing residues 21-24 (GALA) in 5AR2 with the analogous residues 26-29 (AVFA) from 5AR1 did not significantly alter either the Km for testosterone or the Ki for the competitive inhibitor Finasteride. Replacement of AVFA in 5AR1 with GALA from 5AR2 however, significantly decreased the Km and increased the resistance to Finasteride. These findings confirm that 5AR1 residues 26-29 are involved in inhibitor/substrate binding but suggest residues 21-24 of 5AR2 are not. Replacing residues 20-29 (QCAVGCAVFA) of 5AR1 with the analogous residues 15-24 (ATLVALGALA) from 5AR2, changed the Km and Ki to values approaching those for wild type 5AR2. Replacing residues VAL in wild type 5AR2 with VGC from 5AR1 did not change Km or Ki but replacing ATL in 5AR2 with QCA from 5AR1 significantly decreased the Km and increased the resistance to Finasteride. Conversely, replacing QCA with ATL in 5AR1 containing GALA in place of AVFA, increased the Km and decreased resistance to Finasteride. These findings indicate residues 15-17 of human 5AR2 participate in inhibitor/substrate binding whereas residues 18-20 do not.

The effects of salicylate on bacteria.

Salicylate and related compounds, such as aspirin, have a variety of effects in eucaryotic systems and are well known for their medicinal properties. Salicylate also has numerous effects on bacteria, yet only a handful of individuals within the scientific community appreciate these findings. From a bacterial viewpoint, growth in the presence of salicylate can be both beneficial and detrimental. On one hand, growth of certain bacteria in the presence of salicylate can induce an intrinsic multiple antibiotic resistance phenotype. On the other hand, growth in the presence of salicylate can reduce the resistance to some antibiotics and affect virulence factor production in some bacteria. This review provides an overview of the effects salicylate has on various bacterial species.

Acyl-CoA:Cholesterol Acyltransferase Inhibitory Activity of Lignans Isolated from Schizandra, Machilus and Magnolia Species.

Fifteen lignans were isolated from the fruits of SCHIZANDRA CHINENSIS, the leaves of MACHILUS THUNBERGII, and the flower buds of MAGNOLIA DENUDATA. They were identified as gomisins, schizandrin, wuweizisu, schizantherin, licarins, and machilin, which inhibited rat liver ACAT with IC (50) values of 25-200 microM. Comisin N is the most potent inhibitor with IC (50) value of 25 microM in these lignans.

Acidic polysaccharide from Panax ginseng, ginsan, induces Th1 cell and macrophage cytokines and generates LAK cells in synergy with rIL-2.

We previously reported that an acidic polysaccharide from Panax ginseng named ginsan inhibits the incidence of benzo[a]pyrene-induced autochthonous lung tumors in mice. To elucidate the mechanism of antineoplastic activity, ginsan was tested for its ability to generate LAK cells and to produce cytokines. Spleen cells became cytotoxic to a wide range of tumor cells after 5 days of culture with ginsan in a non-major histocompatibility restricted manner and the activity of ginsan was 12 times higher than that of lentinan. The generation of killer cells by rIL-2 was neutralized only in the presence of anti-IL-2, whereas by ginsan it was neutralized in the presence of anti-IL-2 as well as anti-IFN gamma, or anti-IL-1 alpha. It was confirmed that ginsan induces the expression of mRNA for IL-2, IFN gamma, IL-1 alpha, and GM-CSF. Depletion of AsGM1+ cells from spleen cells reduced the generation of LAK by rIL-2. In contrast, depletion of AsGM1+ as well as Thy1+ cells, CD4+ cells, or DC8+ cells reduced the generation of LAK cells by ginsan. The serologic phenotype of rIL-2 induced LAK cells was CD8- cells, whereas the ginsan induced LAK cells, were CD8+ cells. Ginsan synergized with rIL-2 to generate LAK cells (2.0-15 fold) and the most dramatic synergy was seen at rIL-2 concentrations below 3 U/ml. Ginsan alone inhibited pulmonary metastasis of B16-F10 melanoma cells and enhanced the inhibition of lung colonies by rIL-2. These findings demonstrate that ginsan generates LAK cells from both NK and T cells through endogeneously produced multiple cytokines. This property may contribute to its effectiveness in the immunoprevention and immunotherapy of cancer.

A novel nortriterpene fromHedera rhombea.

A new nortriterpene, rhombenone (1) was isolated from the leaves ofHedera rhombea Bean (Araliaceae). The structure of this compound was established as 27-demethyl-20(S)-dammar-23-ene-6alpha,20-diol-3,25-dione on the basis of spectral analysis including HMQC and HMBC techniques. Rhombenone (1) was the first 27-demethyl nortriterpene of dammarance type isolated from natural sources.

Activation of multiple effector pathways of immune system by the antineoplastic immunostimulator acidic polysaccharide ginsan isolated from Panax ginseng.

In the present study an acidic polysaccharide ginsan, with a molecular weight of 150,000, devoid of lectin properties, was purified from Panax ginseng C.A. Meyer (Araliaceae). Ginsan induced the proliferation of T cells and B cells. Spleen cells became cytotoxic to a wide range of tumor cells without major histocompatibility complex-restriction after 4 or 5 days culture in vitro with ginsan. For the generation of these ginsan-activated killer (AK) cells adherent macrophages and CD4+ cells were needed as accessory cells. The generation of ginsan-AK cells was blocked in the presence of anti-IL-2, anti-IFN gamma, anti-IL-1 or anti-TNF alpha antibodies, showing the importance of these cytokines in the process. The surface phenotypes of the 4 day-cultured ginsan-AK cells was Thy1+, AsGM1+, CD8+, which is distinct from rIL-2 induced lymphokine activated killer (LAK) cells that were CD8. The ginsan also activated macrophages to produce reactive nitrogen intermediates and become tumoricidal. It also exhibited significant in vivo antitumor activity against B16 melanoma cells lines, and in the benzo(a)pyrene-induced autochthonous lung tumor model, at much lower doses than the maximum tolerate doses. Indeed, no mice died, which injected with ginsan at 1g/kg body weight intraperitoneally. In conclusion, 'ginsan' could potentially be an ideal nontoxic antineoplastic immunostimulator by activating multiple effector arms of the immune system.

Acyl-CoA : cholesterol acyltransferase inhibitors from Magnolia obovata.

In the course of a search for acyl-CoA : cholesterol acyltransferase (ACAT) inhibitors from natural sources, new types of ACAT inhibitors were isolated from the extract of Magnolia obovata leaves, and identified as obovatol, honokiol, and magnolol. The active compounds inhibit rat liver ACAT with IC50 values of 42, 71, and 86 microM, respectively.

Polyacetylene analogs, isolated from hairy roots of Panax ginseng, inhibit Acyl-CoA : cholesterol acyltransferase.

In the course of our screening program for acyl-CoA : cholesterol acyltransferase (ACAT) inhibitors from Korean herbal medicines, ACAT inhibitors were isolated from the hairy roots of Panax ginseng (Araliaceae) and identified as panaxynol, panaxydol, panaxydiol, and panaxytriol. These active compounds inhibit rat liver ACAT with IC50 values of 94, 80, 45 and 79 microM, respectively.

2'-Hydroxycinnamaldehyde from stem bark of Cinnamomum cassia.

2'-Hydroxycinnamaldehyde, which inhibits farnesyl-protein transferase (FPTase), has been isolated from the stem bark of Cinnamomum cassia Blume. The biologically active agent in the extract has been purified by silica column chromatography and HPLC. The structure of the isolated compound was elucidated on the basis of 500 MHz NMR experiments.

Phenolic compounds from Duchesnea chrysantha and their cytotoxic activities in human cancer cell.

Five phenolic compounds were isolated from 80% aq. acetone extract of Duchesnea chrysantha. Their cytotoxicities were screened by the colorimetric tetrazolium assay (MTT assay). Gallic acid, methyl caffeate, protocatechuic acid and pedunculagin mildly inhibited the survival of PC14 and MKN45 human cancer cell. Brevifolin carboxylic acid showed a strong cytotoxic activity.

Particle-enhanced turbidimetric immunoassay of sex-hormone-binding globulin in serum.

A particle-enhanced turbidimetric immunoassay (PETIA) for human sex-hormone-binding globulin (SHBG) is described. The method involves use of antibody covalently coupled to latex particles and is almost fully automated, with sample processing being complete in less than 20 min. The working reagents are stable for at least three months, and full calibration of the assay each day is not essential. A particular advantage is that pretreatment of samples is rarely required because the working range of the assay is from 2.0 to 320 nmol/L for nondiluted serum. Intra- and interassay CVs were less than 4.5% and 8.5%, respectively, and mean analytical recovery was 101.5%. SHBG concentrations of 129 serum samples determined by this method and by a commercially available immunoradiometric assay correlated highly.

Purification and characterisation of ovine C4: evidence for two molecular forms in ovine plasma.

A relatively rapid procedure is described for the isolation of the fourth component of complement (C4) from ovine plasma. The method, which recovers approximately 30% C4, is based upon DEAE Sephacel anion exchange chromatography of PEG precipitated plasminogen depleted plasma followed by cation exchange chromatography on CM Sepharose and finally gel filtration. SDS-PAGE of purified ovine C4 under reducing conditions revealed a complex pattern of bands which was interpreted on the basis of a three polypeptide chain structure for each of two distinct species, or isotypes, of C4 molecule herein termed C4A and C4B. Each isotype differs in the mol. wt of the alpha chain--108 and 95 K respectively. Nucleophilic substitution of immunoprecipitated ovine C4 with radiolabelled methylamine revealed that both C4 species contained a reactive thiol ester site and that each could be cleaved into an activated form (presumably C4b) characterised by a truncated alpha' chain some 8 K lower in mol. wt. A comparison of the isotype composition of purified C4 with that of immunoprecipitated C4 from the same animal indicated that the purification procedure favoured isolation of the C4B isotype. The mol. wts of both the alpha and beta chains were lowered following digestion of ovine C4 with neuraminidase.

Sex hormone-binding globulin secretion by human hepatocarcinoma cells is increased by both estrogens and androgens.

The secretion of sex hormone-binding globulin (SHBG) by the human hepatocarcinoma cell line Hep G2 was increased significantly not only by estradiol (E2) but also by testosterone (T), dihydrotestosterone, and the synthetic androgen danazol in the presence, but not the absence, of fetal calf serum. The secretion of SHBG also was stimulated by the antiestrogen tamoxifen, although this required the use of longer incubation periods and higher concentrations than were required for the steroids. The antiandrogen cyproterone acetate and cortisol (5 microM) decreased SHBG secretion. Pregnanediol (5 microM) had no discernible effect. These changes were considered specific as none of the compounds altered either the secretion of total protein by the cells or their total protein content. Cells incubated with a mixture of E2 (0.5 microM) and T (0.5 microM) secreted significantly more SHBG than did cells incubated with E2 (1.0 microM), indicating these steroids exert their effects through different mechanisms. The increases with E2 and T were reduced significantly by tamoxifen and cyproterone acetate, respectively, suggesting receptor mediation of the steroid effects. The E2-related increase was abolished by cycloheximide, indicating that the changes were due to alterations in the synthesis of SHBG rather than to alterations in the release of previously synthesized protein. These findings suggest the T-related decrease in plasma SHBG levels may be due to causes other than a decrease in the hepatic synthesis of the protein. Additionally, they indicate that Hep G2 cells may prove suitable for examining the regulation of the SHBG gene by a variety of compounds.

Purification and characterisation of the fourth component of bovine complement.

A relatively rapid method for the isolation of complement protein C4 from bovine plasma is described. The method consists of DEAE Sephacel anion exchange chromatography of plasminogen-depleted bovine plasma followed by cation exchange chromatography on CM Sepharose and finally gel filtration on a TSK G3000 SW column. A yield of approximately 20% was obtained. Conventional SDS-PAGE of purified bovine C4 showed the presence of alpha, beta and gamma polypeptide chains, the molecular weights of which were determined from Ferguson plots to be 95,000 +/- 2,500, 80,500 +/- 2,000 and 30,000 +/- 500 daltons, respectively. SDS-PAGE of C4 immunoprecipitated from the plasma of individual cattle in gels with a reduced proportion of crosslinker showed size polymorphism of the alpha chain. The presence of dual alpha chains was confirmed by radiolabelling their reactive thiol ester moiety with 14C methylamine. The difference in size of the two bovine alpha chains is approximately 1,800 daltons. On activation of bovine C4 both alpha chains were cleaved into alpha' chains (87,000 and 85,000 daltons) characteristic of C4b.

Analysis of C3 and C4 in ovine plasma.

The distributions of plasma concentrations of complement proteins C3 and C4 were studied in sample populations of merino and Suffolk sheep. No differences between the breeds or the sexes were observed. The distribution for ovine C4 was polymodal and very disperse relative to that for C3. It was found, however, that C3 concentrations were elevated in specimens from 20 merino sheep bred as high responders to a Trichostrongylus vaccine. Significantly decreased plasma C4 concentrations were observed in representatives of both merino and merino X Border Leicester cross-bred sheep affected with congenital progressive ovine muscular dystrophy. Agarose gel electrophoretic variants of ovine C3 were not detected. Evidence for electrophoretic variants of ovine C4 in agarose gels was found although individual allotypes could not be reliably identified. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) did not reveal size heterogeneity for the alpha and beta chains of immunoprecipitated ovine C3. Analysis of reduced immunoprecipitated ovine C4 by SDS-PAGE revealed considerable size heterogeneity in the alpha chain consistent with isotypic and/or allotypic variability. The data presented strongly suggest the presence of two C4 loci in sheep, each of which exhibits polymorphism.

Plasma sex hormone binding globulin concentration and binding capacity in children before and during puberty.

The steroid binding capacity and concentration of plasma sex hormone binding globulin have been compared in 116 children aged between 2 and 14 years. Concentration was measured by electroimmunodiffusion standardised with reference to the mass of the pure protein and binding capacity by quantitating the binding of radiolabelled 5 alpha-dihydrotestosterone. Binding capacity correlated highly with concentration in all subjects and neither differed significantly between the sexes before or during puberty. However, both were significantly lower in pubertal than in pre-pubertal children. These findings suggest the metabolism of the protein is similar in boys and girls and that the fall in its steroid binding capacity at puberty in fact is due to a fall in its concentration rather than to changes in its physicochemical properties.

Distribution of complement protein C4 concentrations in bovine plasma.

Complement component C4 concentrations were measured in 40 pure bred Hereford cattle and 40 cattle from a mixed breed herd. Significant differences were not observed between the two groups studied nor between bulls and cows. However, the distribution of C4 concentrations was relatively disperse and appeared polymodal suggesting the presence of two isotypes of C4. Polyacrylamide gel electrophoresis of immunoprecipitated bovine C4 showed many samples to have two C4 alpha chains differing in relative molecular mass by about 1800. Isoelectric focusing of bovine plasma in agarose gels followed by immunofixation with specific anti-C4 antisera revealed two populations of native C4 differing in pI by about 0.3 pH unit. An association between the type of C4 alpha chain present and the pI of the native C4 molecule was observed. Collectively these findings indicate the presence of two structural C4 genetic loci in cattle.

Comparative measurements of plasma binding capacity and concentration of human sex hormone binding globulin.

Comparisons are made of the plasma binding capacity and concentration of sex hormone binding globulin. Concentration was measured by electroimmunodiffusion standardised in terms of mass of the protein and binding capacity by two methods measuring the binding of 5 alpha-dihydrotestosterone. Isolation of steroid bound by SHBG was by either ammonium sulphate precipitation or cellulose filter discs. Both binding methods correlate highly with electroimmunodiffusion indicating they respond similarly to changes in the plasma concentration of the protein. However, they do not equally reflect the actual concentration. Estimates of the molecular mass of the protein of 188000 and 100000 from the precipitation and disc methods respectively, suggest the former measures less of the protein present than does the latter. A parallel reduction in binding capacity and concentration is seen in obese post-menopausal females. This previously unreported finding suggests that the reduced plasma binding capacity of sex hormone binding globulin in obesity is not due to altered or impaired steroid binding.