Schistosoma mansoni: autoradiographic tracking studies of isotopically-labelled challenge parasites in naive and vaccinated CBA/Ca mice

The migration of isotopically-labelled challenge parasites of Schistosoma mansoni in naive CBA/Ca mice, and CBA/Ca mice vaccinated 4 weeks previously with about 600 radiation-attenuated cercariae, has been followed by means of compressed organ autoradiography. In naive mice, only 16% of the challenge parasites failed to migrate from the skin to the lungs, whereas up to half of the individuals that succeeded in reaching the pulmonary vasculature did not move on to the liver. The tracking technique thus revealed a total loss of 58% of the challenge parasites, which correlated well with the fact that only 50% of the challenge was recovered as adult worms by retrograde perfusion of the hepatic portal system. Challenge migration in vaccinated mice initially proceeded more slowly than in naive mice, but peak numbers of foci were eventually recorded in the lungs on the same day in both groups of individuals. We did not therefore recognize a delay in parasite migration in vaccinated mice. In the present experiments, 58.5% of the challenge failed to reach the lungs of vaccinated rodents, and 25% of those parasites that did attain the pulmonary vasculature were not recruited to the liver. The tracking technique thus accounted for a total loss of 83.5% of the parasites, which again correlated well with the fact that we recovered only 22% of the challenge as adult worms at portal perfusion. The data presented here prove conclusively that the major phase of immune-dependent challenge elimination in vaccinated CBA/Ca mice occurs in the cutaneous tissues, and that only a small proportion of the parasites are lost in the lungs. These data are entirely consistent with those we have published elsewhere for the CBA/Ca mouse using a multiplicity of different techniques; they differ however, from results reported by others for the C57 Black strain of mouse. Possible reasons for these discrepancies are discussed.     

Immune response to food antigens: Kinetics of food-specific antibodies in the normal population

The role of food-specific antibodies in the pathogenesis of food allergy is controversial. The first step in solving this controversy may be the assessment of antibody response to food antigens in the normal population. Most of the existing data in this field come from studies that used assays of different standards. This study investigated food-specific antibodies in the normal population using standardized assays. Normal levels of antibody titers were also derived for use as reference. Two hundred and eight individuals from different age groups participated. Immunoglobulin G (IgG) antibodies to cow's milk and its component proteins, and to hen's egg ovalbumin, IgA and IgM antibodies to β-lactoglobulin and ovalbumin were measured by enzyme-linked immunosorbent assay. The sepharose-radioallergosorbent test was used to measure IgE antibodies to cow's milk and ovalbumin. Titers of IgG antibodies to cow's milk and its component proteins revealed an age-related trend, peaking in the 5 months-1 year age group and then decreased to negligible values in adults. A similar trend was observed with IgG anti-ovalbumin antibodies. Temporal association was less evident for antibodies of other classes. Only six subjects had positive IgE antibodies to cow's milk, while none had positive IgE anti-ovalbumin antibody. The prevalences of IgG antibodies to cow's milk, its component proteins, and ovalbumin are influenced by age and feeding habits. Cross-reactivity to related food antigens is common. The presence of IgE antibodies to food antigens is not a physiological phenomenon.     

Transrectal ultrasound-guided transperineal 14-core systematic biopsy detects apico-anterior cancer foci of T1c prostate cancer

AIM: The optimal biopsy strategy for prostate cancer detection, especially in men with isolated prostate-specific antigen (PSA) elevation, remains to be defined. We evaluated diagnostic yield and safety of transrectal ultrasound (TRUS)-guided transperineal systematic 14-core biopsy and compared the spatial distribution of cancer foci detected with this technique in men with and without abnormality on digital rectal examination (DRE). METHODS: In a prospective study, 289 men aged between 50 and 87 years (median age, 70 years) underwent TRUS-guided transperineal systematic 14-core prostate biopsy because of elevated PSA and/or abnormal DRE findings. Using the fan technique, 12 cores from the peripheral zone and two cores from the transition zone were obtained systematically. To characterize the spatial distribution of cancer positive cores, site-specific overall and unique cancer detection rates were compared between stage T1c and T2 cancers. RESULTS: Prostate cancer was detected in 105 of the 289 patients (36%). Major complications requiring prolonged hospital stay or re-hospitalization during a 4-week postbiopsy period were rare (1.4%). Sixty-seven stage T1c cancers were identified. These cancers were associated with significantly lower PSA and a smaller number of cancer positive cores when compared with stage T2 cancers (n= 38). The overall cancer detection rate was highest at the anterior peripheral zone and the posterior peripheral zone in stage T1c and stage T2 cancers, respectively. The unique cancer detection rate at the anterior peripheral zone was significantly higher in stage T1c cancers than in stage T2 cancers. Therefore, when the prostate is extensively biopsied using the transperineal approach, cancer positive cores are characteristically distributed anteriorly in stage T1c cancers and posteriorly in stage T2 cancers. CONCLUSIONS: TRUS-guided transperineal systematic 14-core biopsy showed an apico-anterior distribution of cancer foci in stage T1c prostate cancers.     

Evaluation of the effectiveness of sildenafil using questionnaire methods versus audio-visual sexual stimulation

AIM: In the present study, an audio-visual sexual stimulation (AVSS) test was used to evaluate the effectiveness of sildenafil, and the AVSS test was coevaluated with the international index of erectile function (IIEF) questionnaire. METHODS: Forty-two patients with erectile dysfunction (ED) were examined (age range, 28-73 years; mean, 51.9 +/- 11.4 years). Each patient answered the IIEF questionnaire and underwent laboratory tests and the AVSS test before administration of sildenafil. The IIEF questionnaire and AVSS test (1 h after administration of 25 mg or 50 mg sildenafil) were re-evaluated in the outpatient clinic 4 weeks later. Questions 3 and 4 of the IIEF test were used to evaluate the effectiveness of sildenafil. Sildenafil was determined to be effective if each score totalled four or five after administration. RESULTS: The rate of effectiveness of sildenafil was 52.4%, and the mean score of the IIEF 5 improved from 7.2 to 15.4 following treatment with sildenafil. The maximum and mean rigidity of the penile tip improved after the sildenafil treatment (36.1%vs 57.7% and 14.2%vs 35.8%, respectively). The maximum and mean rigidity of the penile base rose (42.4%vs 57.7% and 17.9%vs 36.8, respectively). Similarly, following treatment with sildenafil, the penile tumescence increased from 6.6 cm to 7.6 cm at the penile tip and from 7.5 cm to 8.5 cm at the penile base. CONCLUSIONS: In some ED patients the results of the IIEF questionnaire are not always consistent with those of objective evaluation, including AVSS. In these patients, combined assessment using the IIEF and AVSS might be more useful to evaluate the precise effectiveness of sildenafil, rather than relying on the IIEF results alone.     

CASE REPORT: Fibrosing cholestatic hepatitis after living related-donor renal transplantation

A 43-year-old man underwent living related-donor renal transplantation because of chronic renal failure in 1991. During the transplant period, both donor and recipient were seronegative for hepatitis B surface antigen (HBsAg). The donor was seropositive for antibody to hepatitis B surface antigen (anti-HBs) due to hepatitis B virus (HBV) vaccination. After transplantation, FK506 and methylprednisolone had been administered to the patient as immunosuppressants. In 1993, HBsAg appeared in his serum. His alanine aminotransferase level elevated gradually during 1995 and then in 1996, general fatigue, ascites and jaundice developed. At this time his serum was positive for hepatitis B e antibody, contained more than 100000 Meq/mL HBV-DNA and 100% precore mutant. Despite subsequent intensive therapy, liver dysfunction progressed and this patient died of hepatic failure 2 months following admission. At autopsy, the liver exhibited cholestasis, fibrosis extending from the portal tracts, mild inflammation and hepatocytes with a ground-glass appearance. In addition, HBsAg and hepatitis B core antigens had accumulated in the hepatocytes. Consequently, the final diagnosis was fibrosing cholestatic hepatitis (FCH) due to precore mutant HBV infection contracted after renal transplantation. It is unclear when and where the recipient liver became HBV infected. Nevertheless, after renal transplantation, while receiving immunosuppressive drugs, HBV appeared to have the potential to cause hepatic failure and FCH may have been a fatal complication for the recipient.     

In vivo growth and differentiation potential of tracheal basal cells of rabbits in vitamin A deficiency

The growth and differentiation potential of rabbit tracheal basal cells were investigated in vitamin A deficient mice. Denuded rat tracheal grafts were xenotransplanted into nude mice made vitamin A deficient by feeding them retinol-free pellets from mid-gestation. Rabbit tracheal epithelial cells harvested enzymatically or cells derived from a basal-cell-rich fraction obtained by elutriation (purity 93.3%) had previously been inoculated into the grafts ( n  = 8, each). The grafts were implanted into the vitamin A deficient or control mice aged about 10 weeks. Four weeks later, the grafts were retrieved for histological examination.
The graft epithelium established by either basal cells or un-fractionated cells in vitamin A deficient hosts (groups 1 and 2, respectively) was atrophic, whereas grafts repopulated with both cell types in the controls had pseudostratified columnar epithelium. Group 1 and 2 grafts both showed squamous metaplasia; 10 metaplastic foci in 32 tracheal rings in group 1 ( P  < 0.02 or 0.002, compared with values for group 2 or controls, respectively), and 2 foci in 35 rings in group 2 (no statistical difference compared with controls).
In conclusion, during vitamin A deficiency, rabbit tracheal epithelial cells, including the progeny of highly-purified basal cells, lost their potential for establishing a mucociliary epithelium and rather appeared to undergo squamous metaplasia.     

MRP2基因单核苷酸多态性对晚期卵巢癌铂类化疗敏感性的影响

目的 :探讨MRP2基因单核苷酸多态性与晚期卵巢癌对铂类化疗敏感性的关系。方法 :本研究包括 89例晚期卵巢癌患者 ,其中Ⅲ期 77例 ,Ⅳ期 12例。所有患者均行肿瘤细胞减灭术 ,术后常规化疗 6～ 8疗程 ,均用顺铂加紫杉醇及其他药物化疗。 89例患者中 ,完全缓解 (CR)或部分缓解 (PR) 6 2例 ,肿瘤无变化 (NC)或进展 (PD) 2 7例。采用单核苷酸延伸技术 ,检测肿瘤组织中MRP2基因促进子 (C 2 4T)、第 10外显子 (G12 4 9A)及第 2 8外显子 (C3972T)的单核苷酸多态性。观察其对铂类化疗敏感性的影响。结果 :MRP2基因促进子及第 2 8外显子单核苷酸多态性对卵巢癌患者对铂类化疗反应无明显影响 ,而MRP2基因第 10外显子突变型与铂类化疗敏感性密切相关 (P <0 0 5 )。结论 :MRP2基因第 10外显子单核苷酸多态性影响晚期卵巢癌患者对铂类化疗的敏感性     

Hyperbaric oxygen stimulates cell proliferation and normalizes multidrug resistance protein-2 protein localization in primary rat hepatocytes

Hyperbaric oxygen therapy (HBO) has been used for many clinical treatments, including primary liver non-function. However, the cellular mechanism by which HBO treatment ameliorates liver function is not understood. Therefore, the purpose of this study was to elucidate this cellular mechanism using primary cultured rat hepatocytes in in vitro studies. Hepatocytes were treated with HBO at 1 day after plating, and the morphological and functional characteristics of bile canaliculi formed in cultured hepatocytes were observed by time-lapse microscopy. Multidrug resistance protein-2 localization was observed by confocal laser microscopy. In cultured hepatocytes, the labeling index in the HBO group at 2 days after treatment was significantly higher than that in the control group. In addition, the proliferating cellular nuclear antigen level in the HBO group was significantly higher than that in the control group. The contraction of the bile canaliculi in the HBO group was slower than in the control group and the dilatation of bile canaliculi in the HBO group was much larger than in the control group. Multidrug resistance protein-2 in the HBO group was localized at the apical membrane. These results show that HBO stimulates hepatocytes to proliferate and HBO normalizes multidrug resistance protein-2 localization to the apical membrane, which could dilate bile canaliculi.