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Purpose: The aim of this study was to find out the role and mechanism of action of neem oil as a postcoital fertility blocker in mouse., Methods: Female mice were injected with neem oil (20 or 40 microliters) surgically into each uterine horn on day 2 postcoitum (pc). Both the uterine horns of each mouse were injected. Arachis oil served as vehicle control. Pregnancy success was determined by the number of implanted embryos on day 8 pc and the number of live fetuses in the uteri on day 18 pc. Transforming growth factor-alpha (TGF alpha), epidermal growth factor (EGF), and epidermal growth factor receptor (EGFR) were immunolocalized in the paraffin-embedded sections of the uteri at 0600 hr on day 5 pc. The unimplanted embryos were assessed in the uteri at 2000 hr on day 5 pc. Uterine secretions were assessed for the leukocytes infiltration on day 4 through day 8 pc., Results: The number of implantation sites on day 8 pc and the number of live fetuses on day 18 pc were lower in the neem oil-treated animals compared to their respective control animals at both the concentrations of neem oil (20 and 40 microliters/uterine horn). Neem oil also caused resorption of some embryos between day 8 pc and day 18 pc. In neem oil-treated mice, EGFR immunostaining decreased in the luminal and glandular epithelium and increased in the stroma as determined at 0600 hr on day 5 pc. Uterine secretions on day 4 through day 6 pc from the neem oil-treated mice showed massive leukocyte infiltration. Unimplanted preimplantation embryos, underdeveloped, degenerated, or at blastocyst stage, were recovered from the uteri after flushing at 2000 hr on day 5 pc from the neem oil-treated animals. A number of retrieved unimplanted embryos showed the direct attachment of the leukocytes to their zona pellucida. It is believed that the secretions of these leukocytes might be responsible for the underdevelopment of the early embryos and hence inhibition of implantation. The exact interaction of these leukocytes and their secretions with the early embryos is under investigation., Conclusions: Postcoital intrauterine treatment of neem oil during preimplantation period causes fertility block in mouse by lowering the EGFR localization in the luminal and glandular epithelium, by causing massive leukocytes infiltration into the uteri, by degenerating the early embryos, and by causing the postimplantation embryonic resorptions in the uteri. The possible mechanism of action of neem oil is discussed.

Purpose: The in vitro effect of anordrin and anordiol on the development of mouse two-cell embryos was studied., Method: Female mice were primed with gonadotropins for superovulation and caged with male mice. Preimplantation embryos, at the two-cell stage, were recovered from the oviducts at 40 hr post-hCG. In the first experiment, two-cell embryos were exposed to culture medium containing different concentrations of anordrin for 3, 12, 24, and 80 hr and then grown in the anordrin-free culture medium and assessed for the formation of total and hatching blastocysts at 80 hr. In the second experiment, two-cell embryos were grown in culture medium containing different concentrations of anordiol and assessed for the formation of total and hatching blastocysts at 80 hr in vitro., Results: Exposure of two-cell embryos to anordrin concentrations of 2.5-7.5 micrograms/ml for 12 hr, 2.5-5.0 micrograms/ml for 24 hr, and 2.5 micrograms/ml for 80 hr caused significant inhibition of the formation of total blastocysts and to 2.5-7.5 micrograms/ml for 12 hr, 1.0-2.5 micrograms/ml for 24 hr, and 1.0 micrograms/ml for 80 hr caused significant inhibition of the formation of hatching blastocysts, in a exposure time-dependent and dose-dependent manner. Exposure of two-cell embryos to anordiol concentrations of 15-25 micrograms/ml for 80 hr caused significant inhibition of the formation of total blastocysts and to 15-20 micrograms/ml for 80 hr caused significant inhibition of the formation of hatching blastocysts in a dose-dependent manner., Conclusion: Anordrin and its metabolite anordiol inhibit the development of two-cell embryos in vitro.

We describe the occurrence of acquired Pelger-Huet anomaly (APHA) in 23 patients treated with paclitaxel (13) or docetaxel (10). A consistent peak of Pelger-Huet cells (PHC) within a range of 3-9 d after treatment with taxoids was noted. The APHA generally disappeared by day 21 after treatment. Peak PHC values for the first course were significantly different in paclitaxel versus docetaxel versus control groups (P < 0.0001) with the maximum PHC counts being significantly higher for docetaxel compared with paclitaxel (P < 0.001) and for paclitaxel compared with controls (P = 0.007). We conclude that taxoid therapy produces transient APHA which peaks between days 3 and 9 and is more pronounced with docetaxel than with paclitaxel.

High-dose cytarabine (ara-c) may overcome cytarabine resistance in leukemic blasts. It has been used as a successful salvage and in postremission therapy but not as initial induction treatment. Patients aged 15 to 60 years, presenting with newly diagnosed acute myeloid leukemia (AML) were randomized to receive either high-dose cytarabine, 3 g/m2 12 hourly on days 1, 3, 5, and 7 for 8 doses, daunorubicin 50 mg/m2 days 1 to 3, etoposide 75 mg/m2 days 1 to 7, (HIDAC-3-7) or standard dose cytarabine 100 mg/m2 continuous intravenous infusion for 7 days with daunorubicin and etoposide at the same dose and schedule as above (7-3-7). Patients could receive a second or third induction course if complete remission (CR) was not achieved. All patients received the same postinduction consolidation therapy (5-2-5) for 2 courses. Eligible patients had no prior chemotherapy or myelodysplastic disease. Patients have been followed for a median of 4.5 years. Of 301 patients treated, complete response (CR) was achieved in 71% with HIDAC-3-7 and 74% with 7-3-7. For patients in CR, the estimated median remission duration was 45 months with HIDAC-3-7 and 12 months with 7-3-7 (P = .0005 univariate analysis, P = .0004 multivariate analysis). The estimated percentage of patients relapse free 5 years after achieving a CR was 49% on HIDAC-3-7 and 24% on 7-3-7. Patients in CR tended to survive longer with HIDAC-3-7 but there were no overall survival differences between the two arms. HIDAC-3-7 was associated with significantly more toxicity in induction with more leukopenia, thrombocytopenia, nausea, and vomiting and eye toxicity (all P < .001) but a similar incidence of severe central nervous system and cerebellar toxicity compared to 7-3-7. The consolidation treatment was the same in both arms but caused significantly more leukopenia and thrombocytopenia in patients previously treated with HIDAC-3-7 induction (P < .0001). We conclude that a dose-effect exists for cytarabine in AML and that HIDAC-3-7 prolongs remission duration and disease-free survival and is tolerable when used as initial induction therapy in patients with de novo AML.

Fifteen prepubertal rats were divided into 3 groups of 5 each: (1) hyperthyroid group (TH), the rats were treated with thyroxine (T4) (25 micrograms/100g body weight/day) for 60 days from the age of day 31 to day 90; (2) T4-withdrawal group (TH-T4), the rats were given T4 for 30 days from the age of day 31 to day 60 and then the T4 treatment was withdrawn for the following 30 days from the age of day 61 to day 90 and the animals were given vehicle during this period; and (3) control group, the rats were given vehicle for 60 days from the age of day 31 to day 90. All were killed at the age of day 91. Serum levels of testosterone, T4 and triiodothyronine increased in the TH group (P < 0.001). The levels decreased to the euthyroid status in the TH-T4 group. Hyperthyroidism caused various changes in the levels of epididymal lipids. The levels changed further or were restored differentially in the TH-T4 group. The number of spermatozoa decreased, in caput epididymis (CpE) as well as in cauda epididymis (CdE), in the TH group (P < 0.001). The number was not restored in the TH-T4 group. The forward motility of the spermatozoa, determined in CdE, decreased in the TH group (P < 0.001) and was not restored in the TH-T4 group. The study showed that chronic hyperthyroidism, induced at the prepubertal age, causes various changes in epididymal lipid composition and sperm parameters. The study may be helpful in revealing the reasons for male infertility in hyperthyroid patients.

Gap junctions are made up of connexin proteins, which comprise a multigene family in mammals. Targeted mutagenesis of connexin43 (Cx43), one of the most prevalent connexin proteins, showed that its absence was compatible with survival of mouse embryos to term, even though mutant cell lines showed reduced dye coupling in vitro. However, mutant embryos died at birth, as a result of a failure in pulmonary gas exchange caused by a swelling and blockage of the right ventricular outflow tract from the heart. This finding suggests that Cx43 plays an essential role in heart development but that there is functional compensation among connexins in other parts of the developing fetus.

Exposure of mouse spermatozoa and oocytes duringin vitro fertilization (IVF) to lipopolysaccharide (LPS) and phorbol myristate acetate (PMA) activated macrophages (U937 cell line), but not unactivated macrophages cultureconditioned medium or control medium (RMPI+DMEM with 0.5% FBS) resulted in inhibition of IVF (87.2%), first cleavage (90.8%) and total blastocyst formation 97.5%). The direct coculture of the activated macrophages with 2-cell stage embryos resulted in arrested development (91.2%), an effect that was significantly diminished in the presence of monolayer of human endometrial stromal cells in the coculture (58.3%). In contrast, the majority of 2-cell embryos developed to blastocysts when exposed to unactivated macrophages, or macrophage-stromal cell cocultures (94.1%). The majority of 2-cell embryos cultured in control medium (DMEM/Ham's F12 with 2% FBS) developed to morulae (96.2%), then underwent growth arrest and degeneration. Furthermore, culturing blastocyst stage embryos in the above groups resulted in a significant enhancement of trophoblast outgrowth, particularly in coculture with activated macrophages as compared to any other group (P<0.005). There was a significant increase in the levels of TGF-β, GM-CSF, IL-1α, IL-1β, TNF-α, PGE(2), TXB(2) and LTB(4) released into the culture conditioned medium of activated macrophages compared to unactivated macrophages (P<0.001). These results suggest that the secretory products of activated macrophages, among them those determined in this study, in a stage-specific manner can directly effect sperm-egg interaction, early embryonic development and trophoblastic outgrowth. This data provides further support for the hypothesis that in endometriosis-associated infertility, continuous exposure of spermatozoa, oocytes and early embryos to activated macrophage-derived factors may play a vital role in their survival during transportation and fertilization as well as development during early embryonic stage.

In this study, the effect of preovulatory treatment with RU486, for different lengths of time and combinations of days, was shown in terms of the ova recovery, in vitro fertilization of recovered ova, in vivo fertilization and quality of fertilized ova in PMSG/hCG-primed mice. Female mice were injected with PMSG followed 48 h later by hCG to induce superovulation. Mice received RU486 (20 mg kg-1 body wt) for 1, 2, 3 and 4 preovulatory days (in different combinations). Ovulation, as judged by the number of ova recovered at 14 to 14.5 h post-hCG, was depressed (P < 0.001), and the total number of embryos recovered at 40 h post-hCG was low (P < 0.001), in mice receiving a minimum of two consecutive days' treatment (day before PMSG + day of PMSG; or day before hCG + day of hCG) of RU486 under study. Quality of ova recovered from RU486-treated animals was not affected as determined by their ability to become fertilized in vitro. In vivo fertilization, as determined by the recovery of 2-cell embryos, was suppressed significantly in mice treated with RU486 for four consecutive preovulatory days (P < 0.001). A varied degree of premature compaction was observed in 2-cell embryos immediately upon retrieval from the oviduct of RU486-treated animals, the effect being most marked in mice receiving RU486 for a minimum of two consecutive preovulatory days under study. It is suggested that premature compaction of early embryos was under the continuous influence of the luminal environment of treated animals and might be the reason for their degeneration at later stages in the reproductive tract and for a low pregnancy rate as shown by other studies. Compacted embryos decompacted within 15-30 min in vitro and led to normal blastocyst formation in vitro in RU486-free culture medium.

Purpose: The in vitro effect of neem oil was studied on the development of mouse two-cell embryos and trophectodermal cell attachment and proliferation., Method: Female mice were primed with gonadotropins for superovulation and caged with male mice. Early embryos, at the two-cell and the blastocyst stages, were recovered at 40 and 88 hr post-hCG from the oviducts and the uteri, respectively. In the first experiment, two-cell embryos were exposed to culture medium containing different concentrations of neem oil for 1, 12, and 24 hr and then grown in neem oil-free culture medium and assessed for the formation of total and hatching blastocysts at 96 hr. In the second experiment, partially hatching blastocysts were cocultured with human endometrial stromal cell monolayers in culture medium containing different concentrations of neem oil and assessed for the attachment and proliferation of trophectodermal cells at 96 hr., Results: Exposure of two-cell embryos to neem oil concentrations of 0.050-0.500% for 1 hr, 0.010-0.250% for 12 hr, and 0.005-0.100% for 24 hr caused significant inhibition of the formation of total and hatching blastocysts, in a dose-dependent manner. Neem oil at 0.050-0.100% concentrations inhibited, in a dose-dependent manner, the in vitro attachment and proliferation of trophectodermal cells of partially hatching blastocysts cocultured with human endometrial stromal cells monolayers., Conclusion: Neem oil inhibits the development of two-cell embryos and attachment and proliferation of the trophectodermal cells of partially hatching blastocysts in vitro. The study encourages the use of this herbal product as a postcoital contraceptive that warrants further research.

We report two cases of secondary myelodysplastic syndrome (SMDS) which followed successful treatment of a primary malignancy with high-dose chemotherapy supported by reinfusion of autologous stem cells. The SMDS was diagnosed 24 months and 40 months, respectively, following autografting. Both patients lived for 7 months after the diagnosis of SMDS. Our cases support the view that there is an increased risk of SMDS/acute leukemia following autologous marrow transplantation.

This study was designed to investigate the changes in the murine bone marrow microvasculature following treatment with 5-fluorouracil (5-FU) or total-body irradiation (TBI). Seventy 8- to 12-week-old C3H male mice received either 5-FU at a dose of 150 mg/kg intravenously (i.v.) or TBI at a dose of 8 Gy in two fractions 4 hours apart. Femurs from the treated mice were studied by vascular casting, using mercox, and by routine histology at days 5, 21, and 90. On day 5, the sinusoids were markedly swollen, and many were fused with one another. This was accompanied by significant reduction in the bone marrow cellularity. The central sinus was grossly dilated in both TBI- and 5-FU-treated groups. The pronounced sinusoidal dilatation on day 5 appears to be a mechanical effect due to hematopoietic cell loss resulting in relative negative pressure outside the sinusoids. On day 21, the sinusoidal swelling had subsided, and the overall vascular volume appeared to be restored to normal. However, there was a large variation in the shape and size of the sinusoids, and those present were not uniformly distributed. This may be due to the result of mechanical pressure from the reconstituted hematopoietic cells. Whether these changes in the shape and distribution of sinusoids have functional significance--for instance, release of the hematopoietic cells into the circulation--remains to be established.

This paper reports the successful pregnancy in rats with only 10-20% of ovarian tissue. Sprague-Dawley female rats of breeding age were divided into five groups: group 1 (completely ovariectomized), the ovaries from both the sides of the rats were removed completely; group 2 (partially ovariectomized, 80-90% of the ovary of each side was removed leaving the remaining tissue in place; group 3 (ovariectomized with flank transplant), the ovary of each side was removed from the ovarian stalk and inserted into a subcutaneous pocket made surgically in the flank on the respective side of the same rat; group 4 (partially ovariectomized with flank transplants), 80-90% of the ovarian mass was removed from the ovarian stalk and put back in the flank position in the subcutaneous pocket on the same side; group 5 (control), rats with intact ovaries. Estrous cyclicity, mating behavior and pregnancy rate were recorded in the animals. Percent rats cycled were 0.00, 80.00, 80.00, 70.00 and 100 in groups 1-5 respectively; percent cycled rats mated were 86.27, 100, 71.42 and 100 in groups 2-5 respectively; and percent mated rats reaching successful pregnancy were 36.36, 0.00, 100 and 100 in groups 2-5 respectively. Pregnancy rate in the mated rats in group 2 was lower than that of groups 4 (P < 0.01) and 5 (P < 0.01), whereas, it did not differ among groups 4 and 5.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To present a case of adult T cell leukaemia lymphoma (ATLL) in a non-Aboriginal Australian woman with no apparent risk factor., Clinical Features: A 43-year-old Australian woman of European descent presented with a febrile illness associated with generalised lymphadenopathy and splenomegaly., Investigations: There was lymphocytosis in the peripheral blood with a T helper cell phenotype. There were also lytic bone lesions with associated hypercalcaemia. HTLV-1 antibody was detected by agglutination assay and confirmed by western blot test., Treatment and Outcome: After initial response to CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone), she relapsed and died with central nervous system involvement eight months after the initial diagnosis., Conclusion: To our knowledge this is only the third case of ATLL in a non-Aboriginal person in Australia.

In vitro evidence is presented showing toxicity of neem oil on sperm-egg interaction in mouse. Cumulus oophorus-enclosed ova, inseminated with capacitated spermatozoa, were cultured in 1 ml of in vitro fertilization (IVF) medium and overlayered by 1 ml of different concentrations of neem oil (1, 5, 10, 25, 50 and 100%) for IVF duration of 4h. At the end of incubation, ova were allowed to grow in neem oil-free culture medium and assessed for fertilization, first cleavage (2-cell formation) and blastocyst formation in vitro at 4-14h, 24h and 108h post-insemination respectively. The study showed that the presence of neem oil at concentrations of 10, 25 and 50% caused inhibition of IVF in a dose-dependent manner. The toxic effect of exposure of 25 and 50% neem oil was further carried over to the first cleavage of the resulting fertilized ova and the toxic effect of 5, 10, 25 and 50% was carried over to the blastocyst formation from the resulting fertilized ova when grown in neem-oil free culture medium. A total of 94.1% inhibition of 2-cell formation and 100% inhibition of blastocyst formation from the inseminated ova was observed in 50 and 25% neem oil-treated groups respectively. Neem oil at 100% concentration caused 100% degeneration of ova at 1h of sperm-ova coculture. The study showed a direct toxic effect of neem oil on sperm-egg interaction in vitro and encourages research investigations of this herbal product as a pre-coital contraceptive.

17 beta-Hydroxy-11 beta(4-dimethylaminophenyl)-17 alpha-(1-propynyl)estra-4, 9-dien-3-one (RU486) inhibited the in vitro development of different stages of mouse preimplantation embryos under study. Two-celled embryos, morulae, and early blastocysts were obtained from B6D2F1 mice. The embryos were grown in Ham F-10 nutrient mixture (with glutamine) supplemented with sodium bicarbonate (2.1 g/L), calcium lactate (282 mg/L), and bovine serum albumin (fraction V, 3 mg/mL) at 37 degrees C in a humidified incubator supplied with 5% CO2 in air. RU486 was added to the culture medium at concentrations of 1, 5, 10, and 20 micrograms/mL. Culture medium with 0.05% ethanol served as the control. In vitro growth of embryos was assessed by the following criteria: (i) two-celled stage embryo development to blastocyst stage after 72 h, (ii) morula stage grown to blastocyst stage after 24 h, and (iii) early blastocyst stage development to hatching blastocyst after 12 h, in culture. RU486 inhibited the in vitro development of two-celled embryos, morulae, and early blastocysts at concentrations of 5, 10, and 20 micrograms/mL culture medium (p less than 0.001). The inhibitory effect of RU486 at these concentrations on the development of all the stages of embryos under study was irreversible. However, RU486 did not affect embryo development at 1 microgram/mL culture medium. The study indicates the direct adverse effect of RU486 at 5 micrograms/mL and higher concentrations in culture medium on the development of mouse preimplantation embryos in vitro, and it encourages its further investigation as a postcoital contraceptive in animal models and humans.

The effect of RU 486 at different concentrations (1, 5, 10, and 20 micrograms/ml) was studied on sperm-egg interaction in vitro in B6D2F1 mice. The in vitro fertilization rate of mouse ova decreased from 77.0% (control) to 50.0%, 28.7%, and 7.5% in the presence of RU 486 concentrations at 5, 10, and 20 micrograms/ml medium, respectively (p less than 0.001). A concentration of 1 microgram/ml did not affect the fertilization rate. A progesterone concentration at equal to or double the concentration RU 486 did not reverse the inhibitory effect of RU 486 on in vitro fertilization, which suggests a progesterone-independent mechanism. Exposure of spermatozoa (for 90 minutes) or ova (for 60 minutes) to RU 486 (20 micrograms/ml) followed by washing with RU 486-free medium before coincubation did not affect the fertilization rate. The presence or absence of cumulus cells did not change the inhibitory effect of RU 486 (20 micrograms/ml) on in vitro fertilization. RU 486 at 5 to 20 micrograms/ml medium was associated with perivitelline polyspermy in nonfertilized ova and enhanced perivitelline polyspermy in fertilized ova.

The examination of sequential karyotypes in hematologic disorders has demonstrated that karyotypic changes are often associated with concurrent changes in clinical behavior. Acquired abnormalities that recur among different patients may also suggest genomic areas important to tumor progression. We therefore examined sequential karyotypes in 21 patients with non-Hodgkin lymphoma (NHL). Sixteen of the 21 karyotypes demonstrated changes, including the majority of 6 small lymphocytic, 11 follicular, and 4 intermediate and high-grade diffuse lymphomas. The t(14;18)(q32;q21) occurred in ten initial karyotypes was retained in all cases. The band most frequently affected by newly acquired abnormalities was 14q32 (n = 5); chromosomes 1 and 2 (n = 5, each), and the 17p arm (n = 4) were also commonly affected. The acquired deletion of all or part of 17p appeared to be associated with a poor prognosis. Histologic transformation and karyotypic change did not correlate. This study of sequential karyotypes in NHL 1) confirms the primary importance of the t(14;18), 2) suggests that the 14q32 band is involved frequently in both primary and secondary cytogenetic events, and 3) suggests other genomic regions of potential significance to progression.

Long-term ovariectomized rabbits were given injections of progesterone and prolactin in an alternating sequence (progesterone for 5 days, prolactin for 4 days and progesterone for 5 days) to test the hypothesis that each of these hormones acts to increase the other's receptor, resulting in a positive feedback process whereby prolactin augments the progesterone-dependent increase in the mRNA for the uterine protein, uteroglobin. The results of this study support the hypothesis, in that the experimental rabbits produced exceptionally large concentrations of uteroglobin.

The clinical, pathological and immunological features of a case of mantle zone lymphoma are described. The patient presented at the age of 16 with a history of painless enlargement of the inguinal lymph nodes, biopsy of which revealed a nodular small cell lymphoma. During the course of 11 yr he was treated with total nodal irradiation, splenectomy and combination chemotherapy at different times. A recent lymph node biopsy reviewed along with the previous node biopsies was diagnosed as mantle zone lymphoma. At this stage, the immunological studies showed that the neoplastic lymphoid cells had characteristic markers of mantle zone lymphocytes. He is asymptomatic with mild generalized lymphadenopathy 11 yr after the initial diagnosis. This case illustrates the diagnostic and therapeutic problems which may be encountered. Detailed immunological marker studies with an extended panel of monoclonal antibodies are described.

A 36 year old woman presented with a nasopharyngeal tumour which was diagnosed and treated as diffuse large cell lymphoma. Twelve mth later the patient developed acute myeloid leukemia. At this stage, the original biopsies were reviewed and considered in retrospect to be granulocytic sarcoma on the basis of staining for chloracetate esterase and lysozyme. She achieved and maintained marrow and peripheral blood remission with chemotherapy, but developed several cutaneous nodules and 2 breast lumps. One breast lump was excised and was found, by the use of monoclonal antibodies, to carry myeloid markers. Thus monoclonal antibodies provided additional confirmatory evidence for the diagnosis of granulocytic sarcoma.

Two patients with an initial diagnosis of a poorly differentiated lymphocytic lymphoma suffered a pathological rupture of the spleen in association with the histological transformation of the disease to a large cell lymphoma and the development of a leukaemic phase. The value of computerized tomographic scanning of the upper abdomen in confirming the diagnosis of splenic rupture is demonstrated.

The effect of tick infestation on reproductive success of mammals was studied by using rabbits bred after they had served as hosts for Dermacentor variabilis . Mating success, pregnancy incidence, litter size and neonatal viability were reduced in tick-exposed rabbits, and the proportional number of abnormalities found in preimplantation-stage embryos was much higher than in unexposed controls. Fecundity was restored by prolonging the interval between tick exposure and breeding or by treatment with an acaricide.

Ovariectomized rabbits from different breeders were treated at different times of the year with prolactin alone or with progesterone and the production of uteroglobin by the uterus was studied. There were seasonal, strain and dose variables in the uterine response to prolactin and progesterone. Treatment with prolactin (at 1 mg/day) plus progesterone generally induced higher levels of uteroglobin production than did treatment with progesterone alone. The differences were greatest in the winter for Tennessee animals and in the spring for animals from the New Mexico and North Carolina colonies. Ovariectomy produced a decrease (P less than 0.01) in the concentration of cytosolic oestrogen and progesterone receptors, and prolactin treatment restored the concentration to oestrous control values. However, there were no seasonally dependent changes in the concentration of the receptors for any of the treatment groups. Increased doses of prolactin (2 mg/day) induced high levels of uteroglobin production and new proteins to appear in uterine secretions of long-term ovariectomized rabbits but much lower levels (10-11%) when given to pregnant does. Additional ovulations were also noted plus adverse effects on the embryos.

We report a case of acute nonlymphocytic leukemia, type M4 according to the FAB classification, whose cytogenetics showed trisomy 4 and multiple double minute chromosomes. The patient gave no history of exposure to toxic or carcinogenic substances.