Analysis of Transmission of Infection in Epidemics: Confined Random Walkers in Dimensions Higher Than One.

The process of transmission of infection in epidemics is analyzed by studying a pair of random walkers, the motion of each of which in two dimensions is confined spatially by the action of a quadratic potential centered at different locations for the two walks. The walkers are animals such as rodents in considerations of the Hantavirus epidemic, infected or susceptible. In this reaction-diffusion study, the reaction is the transmission of infection, and the confining potential represents the tendency of the animals to stay in the neighborhood of their home range centers. Calculations are based on a recently developed formalism (Kenkre and Sugaya in Bull Math Biol 76:3016-3027, 2014) structured around analytic solutions of a Smoluchowski equation and one of its aims is the resolution of peculiar but well-known problems of reaction-diffusion theory in two dimensions. The resolution is essential to a realistic application to field observations because the terrain over which the rodents move is best represented as a 2-d landscape. In the present analysis, reaction occurs not at points but in spatial regions of dimensions larger than 0. The analysis uncovers interesting nonintuitive phenomena one of which is similar to that encountered in the one-dimensional analysis given in the quoted article, and another specific to the fact that the reaction region is spatially extended. The analysis additionally provides a realistic description of observations on animals transmitting infection while moving on what is effectively a two-dimensional landscape. Along with the general formalism and explicit one-dimensional analysis given in Kenkre and Sugaya (2014), the present work forms a model calculational tool for the analysis for the transmission of infection in dilute systems.

A hollow-fibre column system to effectively prepare washed platelets.

BACKGROUND AND OBJECTIVES: We developed a hollow-fibre column system specifically adapted to prepare washed platelet concentrates (WPCs). This study was performed to evaluate the efficacy of the hollow-fibre column system for preparing WPCs. MATERIALS AND METHODS: First, the percentages of platelet (PLT) recovery and remaining plasma proteins were calculated by determining the PLT count, volume and plasma protein levels in both the prewash and postwash. Secondly, washed PLTs and unwashed control PLTs were stored for 5 days, and the changes during this 5-day storage of in vitro PLT characteristics were determined. RESULTS: The hollow-fibre column system effectively removed >98% of plasma in platelet concentrates (PCs), and the PLT recovery was 97% on an average. The CD62P-expression level on washed PLTs immediately after washing was approximately twofold higher than that on prewashed PLTs as well as on PLTs washed via manual methods or cell washing devices. Until day 5 during storage, PLT aggregability, hypotonic shock response and swirling scores of washed PLTs were not significantly different from those of the control PCs. CONCLUSION: Our novel hollow-fibre column system proved valuable in preparing washed PLTs with <2% of residual plasma proteins and high recovery of PLTs.

Theory of the transmission of infection in the spread of epidemics: interacting random walkers with and without confinement.

A theory of the spread of epidemics is formulated on the basis of pairwise interactions in a dilute system of random walkers (infected and susceptible animals) moving in [Formula: see text] dimensions. The motion of an animal pair is taken to obey a Smoluchowski equation in [Formula: see text]-dimensional space that combines diffusion with confinement of each animal to its particular home range. An additional (reaction) term that comes into play when the animals are in close proximity describes the process of infection. Analytic solutions are obtained, confirmed by numerical procedures, and shown to predict a surprising effect of confinement. The effect is that infection spread has a non-monotonic dependence on the diffusion constant and/or the extent of the attachment of the animals to the home ranges. Optimum values of these parameters exist for any given distance between the attractive centers. Any change from those values, involving faster/slower diffusion or shallower/steeper confinement, hinders the transmission of infection. A physical explanation is provided by the theory. Reduction to the simpler case of no home ranges is demonstrated. Effective infection rates are calculated, and it is shown how to use them in complex systems consisting of dense populations.

Reaction-diffusion theory in the presence of an attractive harmonic potential.

Problems involving the capture of a moving entity by a trap occur in a variety of physical situations, the moving entity being an electron, an excitation, an atom, a molecule, a biological object such as a receptor cluster, a cell, or even an animal such as a mouse carrying an epidemic. Theoretical considerations have almost always assumed that the particle motion is translationally invariant. We study here the case when that assumption is relaxed, in that the particle is additionally subjected to a harmonic potential. This tethering to a center modifies the reaction-diffusion phenomenon. Using a Smoluchowski equation to describe the system, we carry out a study which is explicit in one dimension but can be easily extended for arbitrary dimensions. Interesting features emerge depending on the relative location of the trap, the attractive center, and the initial placement of the diffusing particle.

Quadruplet pregnancy complicated by ovarian hyperstimulation syndrome with spontaneous ovulation.

Ovarian hyperstimulation syndrome (OHSS) commonly occurs as a complication of ovarian stimulation with gonadotrophins. Spontaneous OHSS is an extremely rare event, but can occur as a result of stimulation with pregnancy-derived hCG. We herein report a case of quadruplet pregnancy complicated by OHSS with spontaneous ovulation. The patient had previously undergone ovarian stimulation with clomiphene citrate plus FSH. After that, she conceived spontaneously and developed OHSS after three weeks of amenorrhea. The OHSS was managed by conservative treatment and improved at six weeks of gestation. However, a quadruplet pregnancy became apparent on ultrasound examination. The patient therefore elected to have an induced abortion. Besides the conception in the cycle without administration of exogenous gonadotrophins, the symptoms in this case had the same kinetics as iatrogenic OHSS caused by ovarian stimulation.

A case of polycystic ovary syndrome conceived by intracytoplasmic sperm injection following laparoscopic ovarian drilling.

Polycystic ovary syndrome (PCOS) is a disease in which an ovulation disorder is the main cause of infertility. Clomifene citrate (CC) is the treatment of first choice for ovulation induction in PCOS. If ovulation cannot be induced by CC, then either laparoscopic ovarian drilling (LOD) or gonadotropin therapy is selected as a subsequent treatment. Assisted reproductive technology (ART) is indicated for women with PCOS, similar to other infertility patients, when pregnancy is not achieved by intrauterine insemination (IUI). In this study, we experienced a case of PCOS in which pregnancy was achieved by ART following LOD. The case pertains to a 26-year-old patient. She consulted our hospital with a chief complaint of primary infertility. IUI with administration of CC plus recombinant follicle-stimulating hormone (rFSH) was carried out; however, pregnancy was not achieved. Subsequently, ART was carried out. In the first attempt, the development of several follicles was observed under the gonadotropin releasing hormone (GnRH) agonist long protocol. However, a fertilized oocyte was not obtained. In the second attempt, an ovum could not be collected after CC-rFSH ovarian stimulation. In the third attempt, a good quality embryo could not be obtained under the GnRH antagonist protocol, and therefore pregnancy could not be achieved. We performed LOD using a harmonic scalpel for the purpose of preventing severe OHSS and improving the quality of embryos. Following the operation, ovarian stimulation was performed under the CC-rFSH-antagonist protocol. Eighteen follicles were aspirated, six oocytes were picked-up, and five oocytes were normally fertilized. As a result, four embryos from day 2 culture were cryopreserved. Cryopreserved-thawed embryo transfer was thereafter performed, and a single pregnancy was achieved. LOD is a clinically effective treatment for PCOS requiring ART.

Severe Asherman's syndrome complicated with placenta increta conceived by intracytoplasmic sperm injection following hysteroscopic surgery.

Although severe Asherman's syndrome is a disease that may cause infertility, pregnancy and childbirth are possible by performing hysteroscopic surgery. However, the obstetrical outcome is not always satisfactory. We report a case where severe Asherman's syndrome occurred following a cesarean section. Hysteroscopic surgery was performed due to secondary infertility, and pregnancy was achieved through a subsequent intracytoplasmic sperm injection. At 23 weeks of gestation, the patient was hospitalized due to the threat of premature labor, and a cesarean section was performed at 29 weeks of gestation after pregnancy-induced hypertension occurred. It was determined to be abnormal adherent placentation such as placenta increta through intraoperative findings, and a cesarean hysterectomy was performed. The pathological diagnosis of the uterus was placenta increta. Due to the risk of complications from placenta increta in pregnancies following hysteroscopic surgery in patients with severe Asherman's syndrome, it is important to realize the high risk involved in such cases during the pregnancy course, and careful perinatal management should be required.

Pregnancy following calcium ionophore oocyte activation in an oligozoospermia patient with repeated failure of fertilization after ICSI.

A successful pregnancy outcome after calcium ionophore A23187 oocyte activation in an infertile couple with a repeated failure of achieving fertilization after ICSI is reported. The secondary infertility couple with oligozoospermia underwent ICSI two times. However, none of the oocytes were fertilized. In the third ICSI attempt, three oocytes after ICSI were activated using calcium ionophore for five minutes. Two of three oocytes thus became fertilized. A successful pregnancy outcome was thereafter achieved with the delivery of a healthy infant without congenital abnormalities. Oocyte activation using calcium ionophore was thus found to be a useful method in a case of repeated failure of fertilization after ICSI.

Twin pregnancy after in vitro fertilization in a woman with a unicornuate uterus.

A unicornuate uterus is a rare congenital uterovaginal anomaly. A unicornuate uterus is associated with infertility, cervical incompetence, and premature labor. A case of a 32-year-old null gravid female with a unicornuate uterus who had wished to bear a child for five years is reported. After undergoing insemination treatment with the husband's semen, in vitro fertilization was performed and a twin pregnancy occurred. A successful outcome was achieved with the delivery of viable infants following intensive obstetric management.

Endoscopic in vivo evaluation of tissue atypia in the esophagus using a newly designed integrated endocytoscope: a pilot trial.

BACKGROUND AND STUDY AIMS: A newly designed magnifying endoscope featuring an endocytoscopy function provided by ultrahigh magnification was evaluated in a pilot study in patients with various types of benign and malignant pathology in the esophagus. PATIENTS AND METHODS: Seventy-five consecutive patients were included in the study from 15 March to 21 December 2005. Twenty-nine patients with specific esophageal lesions that had been detected by regular or narrow-band imaging, or both, were further evaluated using endocytoscopy, followed by tissue biopsy or resection. During the endocytoscopic examinations, the esophageal mucosa was stained with 0.5 % methylene blue. The endocytoscopic findings were graded from 1 to 5 in an endocytoscopic atypia (ECA) classification. The final histopathological diagnoses based on biopsies or resected specimens were as follows: category 1 in the Vienna classification, n = 4; category 2, n = 6; category 3, n = 1; category 4, n = 10; and category 5, n = 7. The endocytoscopic diagnoses were compared with the histopathological diagnoses. RESULTS: Clear endocytoscopic images were obtained in all cases. In definitely malignant lesions, the cell nuclei had an enlarged and irregularly arranged appearance (grade ECA 5). The positive predictive value for malignancy (grades ECA 4 and 5) was 94 %; the false-negative rate was 16.7 %, and the false-positive rate was 6.3 %. The overall accuracy of endocytoscopy for differentiating between nonmalignant tissue (categories 1 - 3 in the Vienna classification) and malignant tissue (categories 4 and 5) was 82 %. CONCLUSIONS: These preliminary results suggest that incorporating endocytoscopy facilities into a standard endoscope may be helpful in characterizing tissue in a variety of esophageal lesions. The potential clinical impact of this method in relation to other gastrointestinal organs requires further study.

Involvement of LEU13 in interferon-induced refractoriness of human RSa cells to cell killing by X rays.

Culture of human cells with human interferon alpha and beta (IFNA and IFNB) results in increased resistance of the cells to cell killing by X rays. To identify candidate genes responsible for the IFN-induced X-ray resistance, we searched for genes whose expression levels are increased in human RSa cells treated with IFNA, using an mRNA differential display method and Northern blotting analysis. RSa cells, which showed increased survival (assayed by colony formation) after X irradiation when they were treated with IFNA prior to irradiation, showed increased expression levels of LEU13 (IFITM1) mRNA after IFNA treatment alone. In contrast, IF(r) and F-IF(r) cells, both of which are derived from RSa cells, showed increased X-ray resistance and high constitutive LEU13 mRNA expression levels compared to the parental RSa cells. Furthermore, the IFNA-induced resistance of RSa cells to killing by X rays was suppressed by antisense oligonucleotides for LEU13 mRNA. LEU13, a leukocyte surface protein, was previously reported to mediate the actions of IFN such as inhibition of cell proliferation. The present results suggest a novel role of LEU13 different from that in the inhibition of cell proliferation, involved in IFNA-induced refractoriness of RSa cells to X rays.

Increased and decreased expression of CD69 and CD23, respectively, in gravity-stressed lymphocytes.

BACKGROUND: Recent studies have shown that gravity-changing stress modulates expression levels of cell surface molecules on human lymphocytes. However, previous in vitro microgravity studies have been performed with lymphocytes treated with mitogenic agents. HYPOTHESIS: The aim of the study was to test if exposure of cells to gravity-changing stress alone alters the expression levels of cell surface molecules. Specifically, we examined whether the expression of activation markers is altered after exposure of lymphocytes to combinations of microgravity and hypergravity. METHODS: We used free-fall in parabolic flight for human subjects and a drop-shaft to expose peripheral blood mononuclear cells (PBMC) to gravity-changing stress. After such exposure, PBMC were isolated, and expression levels of CD69, CD23 and CD38 were estimated using three-color flow cytometry. RESULTS: Increased percentages of CD69-positive cells were observed with PBMC from 3 of 4 volunteers who undertook 10 parabolic flights. Exposure of blood to gravity-changing stress in the drop-shaft increased both ratios of CD69-positive cells and levels of CD69 expression on T and B cells. In contrast, the percentages of CD23-positive B cells was decreased. However, gravity-changing stress was not always followed by significant alteration in CD38 expression. CONCLUSIONS: Our findings suggest that CD69 and CD23 might be useful markers that are up- and down-regulated, respectively, after exposure of lymphocytes to gravity-changing stress.

Cyst-associated renal cell carcinoma: clinicopathologic characteristics and evaluation of prognosis in 27 cases.

BACKGROUND: No consistent clinicopathologic characteristics of cyst-associated renal cell carcinoma (CRCC) have previously been determined. METHODS: In total, 768 patients with renal cell carcinoma (RCC) underwent radical or partial nephrectomy. Renal cell carcinoma was classified as CRCC in 27 of these patients (3.5%, subdivided into RCC originating in a cyst and cystic RCC), clear-cell RCC in 662 patients (86.2%), chromophobe cell renal carcinoma in 36 patients (4.7%) and papillary RCC in 43 patients (5.6%) according to the criteria of the World Health Organization. RESULTS: The pathologic stage and nuclear grade were usually lower in those with CRCC (low stage/low grade; 89%/96%) or chromophobe cell renal carcinoma (low stage/low grade; 89%/80%) than in those with clear-cell RCC (low stage/low grade; 59%/65%) or papillary RCC (low stage/low grade; 53%/69%). Of the 27 CRCC patients, only 19 (70%) could be diagnosed through preoperative imaging studies. Patients with CRCC showed a favorable prognosis (survival rate: 95% at 1 year, 89.7% at 3 years and 84.4% thereafter) and, especially among the patients with RCC originating in a cyst, no cancer-related death was observed. Comparing the survival among four types of RCC, a favorable outcome was observed in cases of CRCC or chromophobe cell renal carcinoma compared with clear-cell RCC or papillary RCC (clear vs chromophobe: P = 0.002; chromophobe vs papillary: P = 0.019; clear vs cyst-associated: P = 0.001; papillary vs cyst-associated: P = 0.00079). CONCLUSIONS: In cases of CRCC, the disease was usually detected at lower stages and grades and therefore the prognosis was better than in cases of other types of RCC. Preoperative diagnosis of this disease was very difficult, especially in cases of RCC originating in a cyst.

Mutagenicity of bisphenol A and its suppression by interferon-alpha in human RSa cells.

Bisphenol A is used as a monomer in the production of polycarbonate plastic products. The widespread use of bisphenol A has raised concerns about its effects in humans. Since there is little information on the mutagenic potential of the chemical, the mutagenicity of bisphenol A was tested using human RSa cells, which has been utilized for identification of novel mutagens. In genomic DNA from cells treated with bisphenol A at concentrations ranging from 1x10(-7) to 1x10(-5)M, base substitution mutations at K-ras codon 12 were detected using PCR and differential dot-blot hybridization with mutant probes. Mutations were also detected using the method of peptide nucleic acid (PNA)-mediated PCR clamping. The latter method enabled us to detect the mutation in bisphenol A-treated cells at a dose (1x10(-8)M) equivalent to that typically found in the environment. Induction of ouabain-resistant (Oua(R)) phenotypic mutation was also found in cells treated with 1x10(-7) and 1x10(-5)M of bisphenol A. The induction of K-ras codon 12 mutations and Oua(R) mutations was suppressed by pretreating RSa cells with human interferon (HuIFN)-alpha prior to bisphenol A treatment. The cells treated with bisphenol A at the concentration of 1x10(-6)M elicited unscheduled DNA synthesis (UDS). These findings suggested that bisphenol A has mutagenicity in RSa cells as well as mutagens that have been tested in these cells, and furthermore, that a combination of the PNA-mediated PCR clamping method with the human RSa cell line may be used as an assay system for screening the mutagenic chemicals at very low doses.

Study on glutathionesulphonic acid as biodistribution promoter: concomitant use effect on verapamil hydrochloride and tegafur.

The effect of glutathionesulphonic acid (N-(N-gamma-L-glutamyl-L-beta-sulphoalanylglycine, GSO3H), which is one of the minor metabolites of glutathione (GSH), on the pharmacokinetics of verapamil hydrochloride (verapamil x HCl) and tegafur was investigated in rats. GSO3H was concomitantly used as sodium salt (GSO3Na). No significant change by the concomitant use of GSO3Na was recognized in the pharmacokinetics parameters of verapamil x HCl and tegafur, and plasma elimination of both substances was not affected by GSO3Na. The tissue-to-plasma concentration ratio (Kp) of verapamil x HCl in the lung 5 min after its administration under concomitant use of GSO3Na rose significantly, however, this effect disappeared 120 min after administration. No significant change was recognized in other organs. On the other hand, a significant difference of Kp of tegafur under a steady state concentration of GSO3Na was not recognized in any organs. It seemed that the elevation of a lipid solubility (oil water partition coefficient) of verapamil x HCl by the concomitant use of GSO3Na was related to the increase of the Kp value of verapamil x HCl in the lung. The partition coefficient of GSO3Na itself decreased when it was used concomitantly with verapamil x HCl.

Enhancement of protease activity involved in modulation of cell mutability by microgravity stress in UVC-irradiated human cells.

It is an intriguing question whether gravity-changing stress modulates human cell mutability. To resolve this problem, it is necessary to determine the cellular events leading to modulation. We previously detected protease activation just after UV (UVC, principally 254 nm wavelength) irradiation followed by hypomutability in cultured human cells. We here investigated whether UV-activated protease activity is affected in human UVAP-1 cells exposed to gravity-changing stress prior to UV irradiation.

Modification of urinary secretion of 8-hydroxy-2'-deoxyguanosine and serum ACTH concentration following repetitive parabolic flights.

It is important to clarify the molecular mechanisms of physiological responses of the human body to changes in gravity. Previous reports demonstrated that gravity-changing stress increases the human urinary concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG). However, it has yet to be clarified whether repetitive parabolic flight modulates the urinary concentration of 8-OHdG after exposure to gravity-changing stress. In the present study, the effects of the number of previous experiences with parabolic flight on urinary excretion of 8-OHdG and concentration of serum ACTH were examined in 12 healthy volunteers.