Antibodies to the serine rich Entamoeba histolytica protein (SREHP) prevent amoebic liver abscess in severe combined immunodeficient (SCID) mice

Amoebic liver abscess caused by Entamoeba histolytica is a major cause of morbidity and mortality worldwide. We used mice with severe combined immunodeficiency (SCID mice) to study the role of antibody in protection from amoebic liver abscess, and to identify protective antigens of E. histolytica. Antisera to recombinant versions of two major surface antigens of E. histolytica, the serine rich E. histolytica protein (SREHP) and the 170 kDa adhesin were used in this study. We found that 100% of SCID mice passively immunized with antiserum to the recombinant SREHP molecule were protected from developing amoebic liver abscess after intrahepatic challenge with virulent E. histolytica trophozoites. In contrast, preimmune serum, antiserum to a portion of the 170 kDa adhesin, and antiserum to the trpE fusion partner of SREHP did not protect SCID mice from amoebic liver abscess. Our study demonstrates that antibodies to a recombinant version of the amoebic SREHP molecule can protect against amoebic liver abscess, and suggest the recombinant SREHP molecule should be considered as a possible vaccine candidate to prevent amoebic liver abscess.     

THYROID DISEASE AND OTHER AUTOIMMUNE PHENOMENA IN A FAMILY STUDY OF PRIMARY SJOGREN'S SYNDROME

Autoimmune diseases and autoantibodies have been documentedin 42 index cases with definite primary Sjögren's syndrome(1° SS), 207 relatives and 39 spouses. The results werecompared with control data from a local population survey. Thyroiddisease, 1° SS and their associated autoantibodies werethe commonest autoimmune abnormalities observed and found predominantlyin older female relatives. The HLA-DR3 phenotype associatedwith 1° SS, antinuclear factor, hypothyroidism, and thyroidmicrosomal antibody. Rheumatoid arthritis and systemic lupuserythematosus were not found in excess in the families. PrimarySjögren's syndrome is frequently associated with thyroiddisease and we suggest that there is a common genetic predispositionbetween these diseases which differs from 2° SS associatedwith rheumatoid arthritis and systemic lupus erythematosus.This includes MHC and non-MHC genes. KEY WORDS: Thyroid disease, Genetics, HLA-DR3, Sjögren's syndrome     

EN BLOC NEPHRECTOMY IN PATIENTS UNDERGOING POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION FOR NONSEMINOMATOUS TESTIS CANCER: INDICATIONS, IMPLICATIONS AND OUTCOMES

Purpose

We review the indications for nephrectomy at post-chemotherapy retroperitoneal lymph node dissection, identify patients at risk for nephrectomy and assess the impact of nephrectomy on outcome.

Materials and Methods

Using a computerized data base and chart review we retrospectively reviewed the records of 848 patients who underwent retroperitoneal lymph node dissection after chemotherapy.

Results

En bloc nephrectomy was performed at retroperitoneal lymph node dissection after chemotherapy in 162 of the 848 patients (19%). The indications for nephrectomy included contiguous involvement of perirenal structures in 73% of the cases, renal vein thrombosis in 6%, a poorly functioning or nonfunctioning renal unit in 5% and a combination of these conditions in 16%. Pathological studies of the hilum revealed cancer in 20% of the cases, teratoma in 49% and fibrosis in 31%. Patients requiring nephrectomy had significantly more advanced disease and larger disease volume at presentation and after chemotherapy. There were no significant differences in perioperative morbidity or mortality compared with patients who did not undergo nephrectomy. Only 3 patients required perioperative dialysis and none required long-term renal support.

Conclusions

These findings support en bloc nephrectomy at post-chemotherapy retroperitoneal lymph node dissection in select patients with large volume perihilar retroperitoneal disease.     

CHARACTERIZATION, LOCALIZATION AND DISTRIBUTION OF alpha1 ADRENOCEPTOR SUBTYPE IN MALE RABBIT URETHRA

Purpose

The subtype specificity, localization and distribution of urethral alpha_{1-adrenoceptors} were studied in the male rabbit urethra.

Materials and Methods

The properties of the urethral alpha_{1-adrenoceptors} were investigated using radioligand receptor binding and light microscopic autoradiography with [(¹²⁵) I]iodo-2-[b-(4-hydroxyphenyl)-ethylaminomethyl]tetralone (HEAT), and immunohistochemistry with monoclonal anti-alpha smooth muscle actin and anti-alpha sarcomeric actin antibodies.

Results

Saturation experiments with [(¹²⁵) I]HEAT demonstrated the presence of significant amounts of a single high affinity binding site for alpha₁ adrenoceptors in the male rabbit urethra. The pharmacological profile of the alpha₁ adrenoceptors in rabbit urethra, determined by inhibition experiments with subtype selective alpha₁ adrenoceptor antagonists, was characterized by the following rank order of potency of inhibition constants (K_i values): prazosin <or= to WB 4101 < spiperone < 5-methylurapidil < BMY 7378. The pKi values for the rabbit urethra were correlated with the pKi values for rat spleen, submaxillary glands, and vas deferens and for those reported for cloned alpha_1d receptors with correlation coefficients of 0.68, 0.929, 0.909, and 0.523, respectively.

Conclusions

The pharmacological characterization demonstrates the predominance of alpha_1A or alpha_1A + alpha_1B adrenoceptor subtype(s) in male rabbit urethral smooth muscle. Furthermore, the autoradiographic and immunohistochemical studies show a heterogeneous distribution of alpha₁ adrenoceptors along the longitudinal axis of the urethra, within the smooth muscle fibers, with the receptors being localized more densely in the proximal than in the distal urethra.     

COMBINED POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION AND RESECTION OF CHEST TUMOR UNDER THE SAME ANESTHETIC IS APPROPRIATE BASED ON MORBIDITY AND TUMOR PATHOLOGY

Purpose

We determine if post-chemotherapy resection of residual retroperitoneal and chest tumor under the same anesthetic is reasonable based on tumor pathology and morbidity, and if the finding of necrosis in the abdomen allows observation of chest tumor.

Materials and Methods

We retrospectively reviewed 143 post-chemotherapy patients who underwent resection of residual retroperitoneal and chest disease under the same anesthetic.

Results

Retroperitoneal pathology was generally predictive of chest pathology. Concordance existed in 77.5% of patients with necrosis, 70% with teratoma and 69% with cancer of the abdomen. However, the correlation was much stronger (86%) in predicting necrosis/fibrosis if cases were categorized as uncomplicated by Indiana University criteria. Although the morbidity of the combined approach is higher than that of standard post-chemotherapy retroperitoneal lymph node dissection, it was acceptable.

Conclusions

The morbidity of post-chemotherapy retroperitoneal lymph node dissection and resection of chest disease under the same anesthetic is acceptable. Retroperitoneal pathology generally predicts chest pathology but this correlation is much stronger if the case is uncomplicated based on our criteria. In an uncomplicated case the discovery of necrosis of the abdomen allows observation of chest tumor.