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Biomedical subjects

Shinji Takahashi

Publications and source records attributed to Shinji Takahashi.

At least 19 recordsLinked to original sources

Effects of 3-methyl-4-nitrophenol in diesel exhaust particles on the regulation of reproductive function in immature female Japanese quail (Coturnix japonica).

In a previous study, we found that 3-methyl-4-nitrophenol (PNMC), a component of diesel exhaust particles and also a degradation product of the insecticide fenitrothion, exhibits reproductive toxicity in the adult male Japanese quail. The present study investigated the toxicity of PNMC in the female Japanese quail and its ability to influence reproduction in immature females. The quail (21-day-old) were injected intramuscularly (im) with PNMC at doses 0.1, 1 or 10 mg/kg body weight daily for 3 days. There was no significant difference in body growth between the PNMC-administered and control birds. However, the weights of the oviducts were significantly lower in the PNMC-treated birds at all doses. Furthermore, the plasma concentrations of luteinizing hormone (LH) and estradiol-17 beta were significantly decreased with 1 and 10 mg/kg of PNMC. These findings suggest that PNMC might influence the hypothalamo-pituitary-gonadal axis with decreasing in secretion of GnRH, LH and ovarian steroid hormones and subsequently disturb growth of the reproductive organs of immature female quail. This study indicates that PNMC induces reproductive toxicity at the central level and disrupts reproductive function in the immature female quail.

Air Pollutants↗

In ovo exposure quail assay for risk assessment of endocrine disrupting chemicals.

Although there are in vivo assays using various organisms for the risk assessment of chemicals with endocrine disrupting properties, effective experimental methods for avian species are still under debate. We have developed an in ovo exposure assay using Japanese quail eggs, aimed at assessing disrupting effects on avian reproductive development and function. Hybrid eggs from Brazilian Brown male and White Egg female quails, which can be genetically sexed by their plumage color after hatching, were prepared, and test materials dissolved in olive oil were injected into the air-chamber on day 10 of incubation. After sexual maturation of hatched chicks, we observed egg production by females and the egg quality and male-typical reproductive behavior, and then examined reproductive system morphology and serum steroid concentrations in both sexes. Treatment with a synthetic estrogen, diethylstilbestrol (DES, 0.5-50 ng/g egg), dose-dependently reduced the eggshell thickness and strength of eggs. A few females treated with 5 ng/g DES per egg produced soft-shelled/ unmarked eggs, and all laying females treated with 50 ng/g egg produced eggs completely lacking shells. DES also induced shortening of the left oviduct and abnormal development of the right oviduct in a dose-dependent manner, while testis weight was reduced symmetrically. In addition, 2,2',4',6'-tetrachlorobiphenyl-4-ol (10-1,000 ng/g egg), which previously showed relatively high estrogenic activity in vitro, caused dose-dependent shortening of the left oviduct and reduction in testis weight. The methods for evaluating endocrine disrupting effects and preparing experimental birds proposed in the present study are expected to facilitate assays for avian reproductive toxicology.

Animals↗

Avian transgenerational reproductive toxicity test with in ovo exposure.

Ecological risk assessment of environmental pollutants requires effective laboratory assays and extrapolation of the resultant data to wild species. Because avian reproductive disorder and accumulation of persistent compounds in wild birds and their eggs have long been observed in polluted regions, we have developed an assay for investigating whether pollutants accumulated in eggs impair the reproduction of the exposed birds and the survival of the next generation using the Japanese quail. A typical estrogenic compound, diethylstilbestrol (DES), dissolved in olive oil was injected into the air-chamber of fertilized eggs on day 10 of incubation. After sexual maturation of hatched chicks, we mated pairs of male and female quails following an observation period of egg production and collected their eggs. The collected eggs were incubated and checked for the fertility and hatchability, and then the hatchlings were raised and observed in growth for 3 weeks. A dosage of 5 ng/g per egg of DES caused eggshell thinning in eggs laid by exposed females and reduction in eggshell strength. DES also induced shortening of the left oviduct and unexpected development of the right oviduct, while testis weight was reduced symmetrically. The ability of quail pairs to produce offspring was significantly diminished by exposure of females to DES independently of exposure of males, which mainly arose from production of abnormal and inviable eggs. Fertility of normal-shelled eggs and hatchability of fertilized eggs were unchanged regardless of treatments. External morphological abnormalities, which were mostly unopened toes of the foot, were frequently observed in hatchlings from exposed males independently of exposure of females. Additionally, we attempted to extrapolate the experimental results to the northern bobwhite and to predict population trends for quails in a polluted habitat using a population projection model composed of a combination of a Leslie matrix and the logistic equation. In the event of accumulation of an estrogenic compound equivalent to a dosage of 5 ng/g DES in quail eggs, the average population size was predicted to decrease by 20.2% after 1 year, to approximately half after 4 years, and to a fifth after 14 years. When observed weakening of individuals and the risk of egg breakage are taken into consideration, the decline in population was further accelerated. The proposed assay appears to be suitable not only for assessing adverse effects of chemicals on avian reproduction but for population projection of affected wild birds.

Abnormalities, Drug-Induced↗

Respiratory failure due to morbid obesity in a patient with Prader-Willi syndrome: an experience of long-term mechanical ventilation.

Prader-Willi syndrome (PWS) is characterized by obesity, mild mental retardation or learning disability, and behavior problems, especially in association with food and eating. A 19 year-old man, 150 cm, 140 kg (body mass index [BMI], 62.2 kg.m(-2)), whose condition had been diagnosed as PWS, received 41-day mechanical ventilation because of respiratory failure, chiefly due to morbid obesity. Because the patient frequently developed bronchoconstriction, metered-dose inhalers of a corticosteroid (beclomethasone dipropionate) and a beta2 agonist (salbutamol) were needed. To achieve adequate sedation, which was also crucial to control the bronchoconstriction, the concurrent use of midazolam, fentanyl, ketamine, and propofol was required. Pressure-control ventilation was useful to avoid high airway pressure due to low respiratory system compliance associated with the morbid obesity. Because it appeared that the basic problem leading to respiratory failure in this patient was morbid obesity, body weight reduction was considered to be mandatory. Thus, caloric intake was limited to 1000 kcal.day(-1), resulting in body weight reduction by 50 kg during the patient's stay in the intensive care unit (ICU). The patient was successfully extubated on ICU day 35.

Adult↗

Phylogenetic lineages of invasive and colonizing strains of serotype III group B Streptococci from neonates: a multicenter prospective study.

This study compares the phylogenetic lineages of invasive serotype III group B streptococci (GBS) to those of colonizing strains in order to determine lineages associated with invasive disease. Isolates from 29 infants with early-onset disease (EOD) and from 196 colonized infants, collected in a prospective, multicenter study, were assigned a sequence type (ST) by multilocus sequence typing. Overall, 54.5% of the isolates were in the ST-19 complex, and 40.4% were in the ST-17 complex. Invasive strains were more likely to be in the ST-17 complex than were colonizing strains (59% versus 38%, P = 0.03). After we adjusted for potential confounders, the ST-17 complex was more likely to be associated with EOD than were other lineages (odds ratio = 2.51, 95% confidence interval = 1.02 to 6.20). These data support the hypothesis that ST-17 complex GBS are more virulent than other serotype III GBS.

Adult↗

Impairment of testicular function in adult male Japanese quail (Coturnix japonica) after a single administration of 3-methyl-4-nitrophenol in diesel exhaust particles.

The effects of 3-methyl-4-nitrophenol (PNMC), a component of diesel exhaust, on reproductive function were investigated in adult male Japanese quail. The quail were treated with a single i.m. dose of PNMC (78, 103 or 135 mg/kg body weight), and trunk blood and testes were collected 1, 2 or 4 weeks later. Various levels of testicular atrophy were observed in all groups treated with PNMC. Sperm formation, cloacal gland area, and plasma LH and testosterone concentrations were also reduced in birds with testicular atrophy. To determine the acute effect of PNMC on gonadotrophin from the pituitary, adult male quail were administrated a single i.m. injection of PNMC (25 mg/kg), and plasma concentrations of LH were measured at 1, 3 and 6 h. This dose significantly lowered plasma levels of LH at all three time points. These results suggest that PNMC acts on the hypothalamus-pituitary axis, by reducing circulating LH within a few hours of administration and subsequently reducing testosterone secretion. In addition, in order to investigate the direct effects of PNMC on the secretion of testosterone from testicular cells in quail testes, cultured interstitial cells containing Leydig cells were exposed to PNMC (10(-6), 10(-5) or 10(-4) M) for 4, 8 or 24 h. These quantities of PNMC significantly reduced the secretion of testosterone in a time- and dose-dependent manner. The present findings also suggest a direct effect of PNMC on the testis to reduce testosterone secretion. This study clearly indicates that PNMC induces reproductive toxicity at both the central and testicular levels, and disrupts testicular function in adult male quail.

Air Pollutants↗

Effects of hypothyroidism on gonadal function after transition of short day photoperiod in male golden hamsters (Mesocricetus auratus).

Thyroid hormones permit the annual reproductive transition of seasonal breeders. Although, precise function of thyroid hormones in seasonal breeding is not well understood. In the present study, we examined effects of hypothyroidism on the hypothalamus-pituitary-gonadal axis in adult male golden hamsters after transition of the short-day photoperiod (SD; 8 h light: 16 h dark) condition. We confirmed that hypothyroid, which had been induced by administration of thiouracil in drinking water for 4 weeks, did not have direct effects on testes in male hamsters under the long-day photoperiod. Plasma concentrations of free T3 and T4 decreased 15 weeks after transition of SD condition. Plasma concentrations of testosterone in the hypothyroid group decreased earlier than in the control group after the transition from LD to SD. In animals treated with testosterone after castration, plasma concentrations of LH in the hypothyroid group decreased earlier than in the control group after the transition of SD. On the other hand, pituitary response to GnRH for LH release did not change in castrated hamsters as a result of hypothyroidism. These results suggest that thyroid hormones act the hypothalamus and might be required to maintain GnRH secretion in male golden hamsters.

Androgens↗

Role of L-ficolin/mannose-binding lectin-associated serine protease complexes in the opsonophagocytosis of type III group B streptococci.

Serotype III group B streptococci (GBS) are a common cause of neonatal sepsis and meningitis. Although deficiency in maternal capsular polysaccharide (CPS)-specific IgG correlates with susceptibility of neonates to the GBS infection, serum deficient in CPS-specific IgG mediates significant opsonophagocytosis. This IgG-independent opsonophagocytosis requires activation of the complement pathway, a process requiring the presence of both Ca(2+) and Mg(2+), and is significantly reduced by chelating Ca(2+) with EGTA. In these studies, we defined a role of L-ficolin/mannose-binding lectin-associated serine protease (MASP) complexes in Ca(2+)-dependent, Ab-independent opsonophagocytosis of serotype III GBS. Incubation of GBS with affinity-purified L-ficolin/MASP complexes and C1q-depleted serum deficient in CPS-specific Ab supported opsonophagocytic killing, and this killing was inhibited by fluid-phase N-acetylglucosamine, the ligand for L-ficolin. Binding of L-ficolin was proportional to the CPS content of individual strains, and opsonophagocytic killing and C4 activation were inhibited by fluid-phase CPS, suggesting that L-ficolin binds to CPS. Sialic acid is known to inhibit alternative complement pathway activation, and, as expected, the bactericidal index (percentage of bacteria killed) for individual strains was inversely proportional to the sialic acid content of the CPS, and L-ficolin-initiated opsonophagocytic killing was significantly increased by addition of CPS-specific IgG2, which increased activation of the alternative pathway. We conclude that binding of L-ficolin/MASP complexes to the CPS generates C3 convertase C4b2a, which deposits C3b on GBS. C3b deposited by this lectin pathway forms alternative pathway C3 convertase C3bBb whose activity is enhanced by CPS-specific IgG2, leading to increased opsonophagocytic killing by further deposition of C3b on the GBS.

Animals↗

Cyclic changes in messenger RNAs encoding inhibin/activin subunits in the ovary of the golden hamster (Mesocricetus auratus).

To elucidate changing patterns of inhibin/activin subunit mRNAs in the ovary of the golden hamster (Mesocricetus auratus) during the oestrous cycle, inhibin/activin subunit cDNAs of this species were cloned and ribonuclease protection assay and in situ hybridization were carried out. Inhibin alpha-subunit mRNA was localized in granulosa cells of primary, secondary, tertiary and atretic follicles throughout the 4-day oestrous cycle. It was also expressed in luteal cells on days 1 (oestrus), 2 (metoestrus) and 3 (dioestrus). betaA-subunit mRNA was localized in granulosa cells of large secondary (>200 microm) and tertiary follicles throughout the oestrous cycle. betaB-subunit mRNA was confined to granulosa cells of large secondary and tertiary follicles. Both alpha- and betaA-subunit mRNAs were also found in ovarian interstitial cells and theca interna cells of tertiary and atretic follicles in the evening of day 4 (pro-oestrus). A striking increase in betaA-subunit mRNA levels was also observed during the preovulatory period. The expression pattern of betaA-subunit mRNA during the preovulatory period is unique and not found in other species. An i.v. injection of anti-luteinizing hormone-releasing hormone (LHRH) serum before the LH surge abolished the expression of alpha- and betaA-subunit mRNAs in ovarian interstitial cells and theca interna cells. The treatment also abolished the preovulatory increase in betaA-subunit mRNA. Furthermore, administration of human chorionic gonadotrophin (hCG), which followed the injection of anti-LHRH serum, restored the expression patterns of alpha- and betaA-subunit mRNAs. The present study revealed that the golden hamster showed a unique expression pattern of betaA-subunit mRNA in response to the LH surge.

Activins↗

Gene expression of sex-determining factors and steroidogenic enzymes in the chicken embryo: influence of xenoestrogens.

Many genes involved in gonadal development have been proposed for mammals. To elucidate if those genes play any critical role in sexual differentiation of the avian gonad, we have examined expressions of the genes for proposed sex-determining factors (SF1, Sox9, DMRT1, Wpkci, and AMH), steroidogenic enzymes (P-450scc, 3beta-HSD, P-450c17, 17beta-HSD and aromatase) and the estrogen receptor in the urogenital system during chicken embryogenesis (days 4-16 of incubation), using a semi-quantitative reverse transcription-polymerase chain reaction. Transcripts of the genes for sex-determining factors except Wpkci and AMH were detected in both sexes but had no sexual dimorphism. Wpkci expression was female specific and constantly high throughout incubation. AMH was expressed in both sexes from the earliest stages but was higher in males than in females after the onset of gonadal differentiation. Expressions of the genes for more downstream enzymes in a steroidogenic pathway, such as P-450c17, 17beta-HSD and aromatase, were clearly higher in females than in males. In particular, 17beta-HSD expression increased in the course of gonadal development in females, whereas it was constantly low in males. Aromatase was highly expressed in females during gonadal differentiation but not in males over the period. In addition, to elucidate the relationship between gene activation during embryogenesis and reproductive abnormalities in wild birds, we examined expressions of these genes in embryos treated with various doses of diethylstilbestrol (DES), as a representative estrogenic compound. DES had no effect on the expressions of all the genes in either sex during the periods of gonadal differentiation (days 8, 12, and 16). Sexual dimorphism of the gene expression for steroidogenic enzymes appeared to be closely related to gonadal development in the chicken embryo, especially in the female. However, all the genes examined here seem unlikely to respond to xenoestrogens.

Animals↗

MHC class IIB gene sequences and expression in quails (Coturnix japonica) selected for high and low antibody responses.

Two quail lines, H and L, which were developed for high (H) and low (L) antibody production against inactivated Newcastle disease virus antigen, were used to examine differences in the organization, structure and expression of the quail Mhc class IIB genes. Four Coja class IIB genes in the H line and ten Coja class IIB genes in the L line were identified by gene amplification using standard and long-range PCRs and sequencing of the amplified products. RFLP analysis, sequencing and gene mapping revealed that the H line was fixed for a single class IIB haplotype, which we have designated CojaII-02HL- CojaII-01HL. In contrast, evidence was found for two class IIB haplotypes segregating in the L line. Some individuals were found to be homozygous for haplotype CojaII-08L- CojaII-07L and others were found to be heterozygous CojaII-08L- CojaII-07L/ CojaII-02HL- CojaII-01HL. However, expression of CojaII-02HL- CojaII-01HL was not detected in the L line. SRBC immunization induced a measurable antibody response in the serum and a line-specific class IIB gene expression in the peripheral white blood cells. CojaII-01HL was expressed at the highest level in the H line and CojaII-07L in the L line. The expression of the class IIB mRNA reached the highest level at approximately 1 week after the primary antibody response and then declined exponentially. The antibody and class IIB gene expression data obtained in response to SRBC immunization provide further evidence that quails within the L line had reduced immunocompetence compared with those in the H line.

Amino Acid Sequence↗

Equivalence of high-virulence clonotypes of serotype III group B Streptococcus agalactiae (GBS).

Analysis of growth characteristics, multilocus enzyme electrophoresis, restriction digest pattern (RDP) typing and multilocus sequence typing have identified clonotypes of serotype III group B Streptococcus agalactiae (GBS) associated with invasive infection in neonates. This study sought to unify phenotypic and genotypic classifications of type III GBS strains associated with increased virulence in newborns. High-virulence clonotype (HVC) strains possessed the translation initiation factor 2 (infB) C allele, found in RDP type III-3 strains, and hybridized with the RDP type III-3-specific probe AA3.6, whereas non-HVC strains shared the infB A allele and genomic DNA from these strains did not hybridize with the AA3.6 probe. The characteristic growth lag of HVC GBS at 40 degrees C has been attributed to the presence of a heat-labile fructose-1,6-bisphosphate aldolase (Fba) enzyme in these strains. The deduced amino acid sequence of fba genes of both HVC and non-HVC strains, however, were identical. HVC and RDP type III-3 represent the same genetically related group of bacteria. The characteristic growth differences of virulent strains of type III GBS, however, are not directly attributable to differences in fba.

Alleles↗

Expression of nerve growth factor (NGF), and its receptors trkA and p75 in ovaries of the cyclic golden hamster (Mesocricetus auratus) and the regulation of their production by luteinizing hormone.

In the present study, changes in localization of nerve growth factor (NGF) and its receptors, trkA and p75 in the ovary were investigated during the estrous cycle of the golden hamster. The effect of LH surge on changes in localization of NGF, trkA and p75 in the ovary was also investigated. NGF and its receptors trkA and p75 were localized in oocytes, granulosa cells and theca cells of various stages of follicles throughout the estrous cycle. NGF and its two receptors were also present in numerous interstitial cells and luteal cells. The number of interstitial cells staining positively for NGF and its two receptors was greater in ovaries of day 1 (day 1=day of ovulation) than the other days during the estrous cycle. Treatment with the antiserum against luteinizing hormone releasing hormone (LHRH-AS) at 1100 h on day 4 completely blocked ovulation. There were few positive reactions for NGF and its two receptors in interstitial cells 24 hr after LHRH-AS injection. The effect of LHRH-AS treatment was blocked by a single injection of 10 IU human chorionic gonadotropin. The distinct widespread distribution of NGF and its two receptors in the ovary of golden hamsters suggest that NGF may be an important growth factor for regulation of ovarian function. Furthermore, the LH surge may be an important factor for inducing production of NGF and its two receptors in interstitial cells of the cyclic golden hamster.

Animals↗

[Complete neurological recovery in a patient with decerebrate rigidity following cardiac arrest from acute airway obstruction by advanced laryngeal cancer].

A 59-year-old man presented with severe dyspnea caused by advanced laryngeal cancer. As he had disregarded the dyspnea for a month, we did not have enough information about the extent of the tumor. The pulse oximeter showed 88% with oxygen inhalation. Because of severe dyspnea, he could not maintain supine position. Fiberoptic laryngoscopy showed tumor bulk obstructing airway directly. In the operating room, at first, a cricothyroid membrane puncture was attempted under local anesthesia but the procedure was abandoned when the patient became hypoxic and unconscious. Immediately tracheostomy and cardiopulmonary resuscitation were performed. Tumor bulk had displaced the trachea and surrounding structures, making a tracheostomy difficult. Nine min after loss of consciousness, a secure airway was obtained. However, he was still unconscious and developed characteristic decerebrate rigidity. Therefore the patient was treated with infusion of thiamylal and free radical scavenger and mild hypothermia therapy (bladder temperature 34 degrees C). On the fifth day of this treatment, after rewarming and discontinuation of thiamylal, the patient responded to command. He recovered with no neurological deficits. This case suggests that combined treatment with barbiturate, free radical scavenger, and mild hypothermia therapy is effective to minimize ischemic brain damage after cardiopulmonary resuscitation.

Acute Disease↗

[Effect of airway pressure and Trendelenburg position on the cross-sectional area of the internal jugular vein in anesthetized patients].

BACKGROUND: Several maneuvers such as, Trendelenburg position or breath holding, are proposed to increase success rate and decrease complications during internal jugular vein cannulation. We investigated the relationship between the cross-sectional area of the right internal jugular vein (RIJV) and several maneuvers in anesthetized patients. METHODS: We studied 18 adult patients (10 males, 8 females) undergoing RIJV cannulation after anesthetic induction and endotracheal intubation. We measured cross-sectional area of the RIJV at the level of the cricoid cartilage using ultrasound imaging and standardized by dividing it with body weight. Measurements were taken at supine position (S), supine plus 20 cmH2O breath hold (SH), 10 degrees Trendelenburg position (T-position) (T), and 10 degrees T-position plus 20 cmH2O breath hold (TH). We also measured blood volume (BV) with pulse dye-densitometry. RESULTS: The standardized cross-sectional areas of the RIJV during S, SH, T and TH maneuvers were 1.92 +/- 1.5, 2.82 +/- 1.8, 2.71 +/- 1.5, 3.51 +/- 1.6 mm2 x kg(-1), respectively. Every maneuver increased significantly the cross-sectional area compared to that of supine position (P < 0.05). The effects of the maneuvers tended to be larger when the BV was smaller. CONCLUSIONS: Breath holding at 20 cmH2O and 10 degrees T-position showed almost the same dilatation effects on RIJV (164%, 159%). Simultaneous performance of the both maneuvers was most effective (222%) in dilating cross-sectional area of RIJV in anesthetized patients.

Airway Resistance↗

Milrinone attenuates the negative inotropic effects of landiolol in halothane-anesthetized dogs.

BACKGROUND: Clinical use of high dose beta-blocker therapy is limited by excessive negative inotropic effects. Previous studies suggest that milrinone may be of utility in limiting the inotropic but not the chronotropic effects of beta blockers. We examined the hemodynamic effects of co-administration of a new potent selective beta(1) blocker, landiolol, and milrinone in halothane-anesthetized dogs. METHODS: Eighteen adult mongrel dogs were anesthetized with 1.2 MAC halothane. Hemodynamic measurements were made at baseline, 30 min after starting the milrinone (0.5 micro g x kg(-1) x min(-1)) or normal saline infusion (n = 9 in each), then 30 min after each change in the dose of landiolol infusion. The tested doses of landiolol were 10, 100, and 1000 micro g x kg(-1) x min(-1). RESULTS: Landiolol (>/= 10 micro g x kg(-1) x min(-1)) has significant and comparable negative chronotropic effects in both groups of dogs. While it also has significant negative inotropic effects in both groups, such effects are significantly attenuated in the dogs treated with milrinone. CONCLUSION: Milrinone is effective to attenuate the negative inotropic effects of landiolol in halothane-anesthetized dogs.

Adrenergic beta-Antagonists↗

Subtractive hybridization identifies a novel predicted protein mediating epithelial cell invasion by virulent serotype III group B Streptococcus agalactiae.

Group B Streptococcus agalactiae bacteria (group B streptococci [GBS]) are the most common cause of serious bacterial infection in newborn infants. The majority of serotype III-related cases of neonatal disease are caused by a genetically related subgroup of bacteria, restriction fragment digest pattern (RDP) type III-3, suggesting that these strains possess unique genes contributing to virulence. We used genomic subtractive hybridization to identify regions of genomic DNA unique to virulent RDP type III-3 GBS strains. Within one of these III-3-specific regions is a 1,506-bp open reading frame, spb1 (surface protein of group B streptococcus 1). A mutant type III GBS strain lacking Spb1 was constructed in virulent RDP type III-3 strain 874391, and the interactions of the wild-type and spb1 isogenic mutant with a variety of epithelial cells important to GBS colonization and infection were compared. While adherence of the spb1 isogenic mutant to A549 respiratory, C2Bbe1 colonic, and HeLa cervical epithelial cells was slightly lower than that of the 874391 strain, invasion of the Spb1(-) mutant was significantly reduced with these cell lines compared to what was seen with 874391. The defect in epithelial invasion was corrected by supplying spb1 in trans. These observations suggest that Spb1 contributes to the pathogenesis of neonatal GBS infection by mediating internalization of virulent serotype III GBS and confirm that understanding of the population structure of bacteria may lead to insights into the pathogenesis of human infections.

Amino Acid Sequence↗