2{alpha} 3{alpha}-Epithio-5{alpha}-androstan-17{beta}-ol in Treatment of Gynecomastia

1. 1. The clinical effect of epitiostanol, a new anti-estrogenagent (2,3-epithio-5a-androstan-17ß-ol) against gynecomastiawas studied in comparison with dromostanolone propionate infifty-four patients ranging from twenty to fifty years in agewithout previous history of hormone therapy and with normalliver function. The experiment was performed for eight weeksby double blind methods in three dosage groups, epithiostanol10 mg, and 20 mg and dromostanolone propionate 50 mg.
2. 2. Epithiostanol20 mg was most effective with regards to effecton mass sizeand tenderness, (effective in 96%, 20/21), followedby 10 mgepitiostanol (effective in 89%, 16/18) and dromostanolonepropionate50 mg (effective in 89%, 16/18) in descending order.No sideeffects were observed in any of the three groups.
3. 3. Basedon the results of the present study, epitiostanol isconcludedto be at least as effective as dromostanolone propionateagainstgynecomastia and to be safe from the viewpoint of sideeffects.A satisfactory therapeutical effect on gynecomastiacan be expectedwith a weekly dosage of 20 mg of epitiostanolfor an administrationperiod of between five to eight weeks.

Present Address: Department of Surgery, Keio University Hospital,Shinanomachi, Shin-juku-ku, Tokyo, Japan.     

Antibodies Against the β-Subunit of Ovine Luteinizing Hormone Can Decrease the Clearance of Human Chorionic Gonadotropin in Rhesus Monkeys*

ABSTRACT: Contraceptive vaccines based on active immunization against gonadotropic hormones are being investigated in humans and other primates. Immunization against the β-subunit of ovine luteinizing hormone (oLHβ) reduces fertility in rhesus monkeys by inducing inadequate luteal phases and preventing corpus luteum rescue by rhesus chorionic gonadotropin (rhCG). These effects result from the cross-reactions of the oLHβ-antibodies with rhCG and rhLH. We used human CG (hCG), which also cross-reacts strongly with anti-oLHβ to examine how the circulating oLHβ-antibodies affect the metabolic clearance rates (MCR) of hCG in rhesus monkeys. ¹²⁵I-hCG was injected into four nonimmunized and seven immunized monkeys and blood was collected at frequent intervals over 7 days. Total and immunoprecipitable radioactivity did not differ significantly, suggesting that the radioactivity in the plasma consisted almost entirely of ¹²⁵I-hCG. This was confirmed by column chromatography. The MCR (mean ± SE) was significantly lower (p < 0.001) in six immunized monkeys (0.35 ± 0.06 liters/day) as compared to controls (1.19 ± 0.09 liters/day). The hCG disappearance curve in control monkeys was best described by a two-compartmental system (slow and fast) while an additional third (intermediate) compartment of distribution was typical for immunized animals. The half-lives of hCG for the two exponentials corresponding to the slow and fast components of distribution were not significantly different between the two groups. One immunized monkey had a MCR (1.44 liters/day) that was much greater than the MCR of the other six. This monkey cleared a significantly smaller proportion of hCG in the slow and a higher proportion in the intermediate compartment and unlike the others, formed a circulating immune complex capable of binding hCG that was significantly larger than the antibody-hCG complexes found in the other six immunized animals. We conclude that circulating antibodies to oLHβ reduced the MCR of hCG in six of seven monkeys. The decreased MCR found in immunized monkeys is associated with a shift in clearance from the “fast” to the “slow” compartment as well as the addition of an intermediate compartment of distribution. Plasma disappearance rates of hCG depend on the size of the antibody hCG complex.     

Immunologic, Clinicopathologic and Prognostic Features of Lymphoma of the Gastrointestinal Tract

The lymphoma cells of 32 patients with histopathologically provenmalignant lymphomas with gastrointestinal (G-I) tract involvementwere examined for their surface marker characteristics. Twelvecases were diagnosed as primary lymphoma of the G-I tract and20 cases as secondary lymphoma of the G-I tract according toclinical and autopsy findings. Only one of the primary G-I tractlymphomas was identified as T-cell type, seven as B-cell typeand four as surface immunoglobulin (S-Ig)-negative non-T type(defective B-cell type). Ten of the 11 cases of non-T cell typewere histopathologically diagnosed as diffuse large lymphoidlymphoma, and one as diffuse medium-sized or poorly differentiatedlymphocytic lymphoma. This suggests that most primary G-I tractlymphoma would be large lymphoid lymphoma, even if it couldbe found at an early stage. The histopathological diagnosisof one case of T-cell type was controversial lymphocyte depletionof Hodgkin's disease or pleomorphic lymphoma is most probable. Three of the 20 secondary G-I tract lymphomas were identifiedas T-cell type, eight as B-cell type, five as defective B-celltype and four as S-Ig-undetermined non-T cell type. In contrastwith the primary G-I tract lymphomas, all histologic types wereincluded in the secondary G-I tract lymphomas. The period fromonset to G-I tract involvement ranged from four to 88 mo withan average of 32.6 mo. The tumor mass in the G-I tract in B-celllymphoma was usually large enough to be able to be detectedclinically, while a large proportion of the G-I tract lesionsin defective B-cell lymphoma and T-cell lymphoma were so smallthat they were detected only at autopsy. These results suggestthat B-cell lymphoma has a higher incidence of G-I tract involvementand a more pronounced capacity to proliferate in the G-I tractthan defective B-cell lymphoma and T-cell lymphoma. The prognosis for the patients with G-I tract lymphoma variedaccording to the stage at the time of the first examination.All three patients with stage I primary lymphoma of the G-Itract are surviving, while only three of nine patients withstage II or higher are still alive. In the case of secondaryG-I tract lymphoma, although the median survival time of stageI patients was fairly long (66 mo). more than 80% of the patientsdied of the disease. Half of the patients with stage I diseasedied within 6 mo and about 40% of the patients died within 1mo after G-I tract involvement. This indicates that secondaryG-I tract involvement of lynaphoma is a poorer risk factor forprognosis than is primary G-I tract lymphoma.     

Adenosine Deaminase and Purine Nucleoside Phosphorylase Activities of Various Cultured Cell Lines Derived from Human Hematologic Malignancies

The activities of adenosine deaminase (ADA) and purine nucleosidephosphorylase (PNP) in the cytoplasmic fraction of various culturedcell lines derived from human leukemias and malignant lymphomaswere measured and compared in terms of cell lineage and differentiationof these cultured cell lines as based on cell surface markers.Generally, T-cell lines had higher ADA activity. Above all,two lines (P12/1chikawa and MOLT-3) which had the same differentiationmarkers as common thymocyte showed the highest ADA activity.There were no differences in the ADA activity among five non-Tnon-B cell lines, five B-cell lines and five normal B-cell lines.The ADA activity was lower in myeloid cell lines. No significantdifferences in PNP activity among all these cell lines wereobserved. ADA activity may be useful as a differentiation marker of T-celllineage.     

Anti-ATLA (Antibody to the Adult T-Cell Leukemia Cell-Associated Antigen)-Positive Hematologic Malignancies in the Kanto District

Serum or plasma specimens from 278 patients having various hematologicmalignancies or some other diseases were screened for reactivitywith adult T-cell leukemia cell-associated antigen (ATLA). Antibodiesagainst ATLA in cultured MT-1 cells, a line derived from adultT-cell leukemia (ATL), were found in 18 (6.5%) of the total278 patients, but in 10 (34.5%) of 29 patients born in the ATL-endemicarea. The antibodies were also detected in eight (80%) of 10patients with ATL or adult T-cell leukemia/lymphoma (ATLL),and most of them were born in the ATL-endemic area. The antibodies were detected in only eight (3.2%) of 249 patients whowere born in an ATL nonendemic area, but six of the eight patientswere ones with acute leukemia, and they were found to have hadmassive blood transfusions in cluding platelet or granulocytetransfusions. Generally, the patients who received transfusionswere found to have a higher incidence of anti-ATLA than thosewithout transfusions. In particular, in acute leukemia in anATL-nonendemic area, the antibodies were detected in six (21.4%)of the 28 patients who had previous transfusions, but in noneof the 16 not given transfusions. Further more, ATLA reactivityof the sera from the two patients was found to change from negativeto positive in one to three months. During that period, bothpatients had massive platelet or granulocyte transfusions. Theseresults not only confirm Hinuma's initial report on anti-ATLA,but also indicate the rare existence of anti-ATLA-negative patientswho have ATL or ATLL. These facts also suggest that massiveblood transfusions are one of the possible causes of the generationof anti-ATLA in the patients. However, direct evidence to provethis possibility must be sought.     

Inoculation of Rhesus Monkeys with Human Helicobacter pylori: A Long-term Investigation on Gastric Mucosa by Endoscopy

Abstract: To study the pathogenetic role of Helicobacter pylori, colonization of this organism was attempted in conventional rhesus monkeys. After inoculation of human H. pylori to the gastric mucosa of four 10-year-old monkeys, endoscopical and histological examinations were repeated for 10 weeks. The organisms were recovered bacteriologically from all 4 monkeys at the first week, from 3 animals at the 2nd, and from 2 animals at the 6th to 10th week. The endoscopical examination showed only minimum changes in the mucosal appearance such as erythema and erosion due to H. pylori colonization throughout the study. In contrast, the histological examination revealed prominent polymorphonuclear cell infiltration, edema of the mucosa and dissected epithelium at the earlier periods and mononuclear cell infiltration afterwards. The maximum lymphocyte reaction such as clusters or the formation of a thick layer at the bottom of the lamina propria was observed at the 8th week. These results indicated that rhesus monkeys can be infected by human H. pylori resulting in similar pathologic changes in the human stomach, and that this animal model may be useful for future studies.