Ovarian Steroid Levels inSalamandra salamandra infraimmaculataduring the Reproductive Cycle

Gonadal steroid levels were determined in the ovary ofSalamandra salamandra infraimmaculataduring the reproductive cycle in populations from a xeric region in northern Israel. Varying proportions of previtellogenic and vitellogenic oocytes were present throughout the year, and mature oocytes were present in winter and spring. The numbers of mature oocytes were greater between December and April, after parturition. The levels of 17β-estradiol and testosterone rose during oocyte vitellogenesis and maturation. Levels of progesterone and 17α-hydroxy progesterone appeared to be related to the level of vitellogenesis. Gravid females contained greater quantities of all four steroids than did nongravid females.     

Diagnosis of scaphoid fractures:A prospective multicenter study of 1,052 patients with 160 fractures

In a prospective multicenter study of 1,052 patients with clinical signs of a scaphoid fracture, mammo-graphic films and fine intensifying screens were used at the radiographic examination. 5 standardized projections including 3 special projections focused on the scaphoid were taken. 150 fractures were diagnosed at the first examination but in 10 cases the fracture was first diagnosed at a second radiographic examination after 10-14 days.

The second examination still seems mandatory despite the use of high quality radiographs with optimal spatial resolution and contrast, and the value of supplementary special projections.     

Prognostic factors in hormone-resistant progressing cancer of the prostate.

In 224 consecutive patients with hormone-resistant prostatic cancer referred to 2 European Cancer Centres for palliation of painful bone metastases the one year survival for all patients was 24% (2-year survival: 7%). The median survival was 8 months. In univariate analyses the following prognostic factors were identified: performance status, serum creatinine, alkaline phosphatase, duration of response to primary hormone treatment, degree of bone scan involvement and hemoglobin. Multivariate analyses confirmed the four first parameters to be independent factors. A prognostic model was established (no or one risk factors vs 2 risk factors vs 3 or 4 risk factors) based on performance status, creatinine, alkaline phosphatase and hormone response duration. The median survival of these groups was 10 months, 6 months and 3 months, respectively. This model proved to be discriminative in an external data set of 214 patients with hormone-resistant prostatic cancer entered in two prospective trials. The above differences in outcome between readily and simply defined prognostic groups are greater than the differences one can realistically hope to produce using new treatment strategies. These prognostic factors should be taken into account both in the design and interpretation of clinical studies dealing with the treatment of hormone-resistant progressing prostatic cancer and painful bone metastases.     

Widespread IgE-mediated hypersensitivity in the Sudan to the 'green nimitti' midge, Cladotanytarsus lewisi (Diptera: Chironomidae) II. Identification of a major allergen.

A major allergen has been identified in an aqueous extract of the 'green nimitti' midge, Cladotanytarsus lewisi (Diptera: Chironomidae). Following chromatography on Sephadex G-100 allergenic activity, as assessed by skin ('prick') testing, eluted as two closely related peaks (pools I and II) at about 50% bed volume. When these pools were applied separately to columns of CM-cellulose, activity in each eluted with 0 . 05 M NaCl. Isoelectric focusing of the unfractionated allergen gave a single peak of activity at pI 4 . 3. By SDS--PAGE, biological activity in the whole 'green nimitti' extract and the material eluting from both pools I and II of the Sephadex G-100 column migrated to the same positions and were associated with a molecular size of 15,000--20,000 daltons. Skin test reactivity of the unfractionated material and the Sephadex G-100 pool I and II eluates were all destroyed following incubation with trypsin, chymotrypsin, thermolysin and neuraminidase. These experiments indicate that a major allergen derived from the 'green nimitti' midge, a cause of widespread and severe immediate-type allergy in the Sudan, is an acidic glycoprotein of 15,000--20,000 molecular weight.     

Nucleotide mutations associated with hepatitis B e antigen negativity

One hundred and forty four patients with chronic hepatitis B were tested to identify new mutations associated with hepatitis B e antigen (HBeAg) negativity, using a full genome sequence analysis. All the patients were Chinese and had hepatitis B virus infection of genotype C. Patients with none of the pre-core or core promoter mutations were significantly (P < 0.001) less common in the group with anti-HBe (13%) than in the group with HBeAg (56%). The complete nucleotide sequence was determined in four anti-HBe-positive patients who had neither pre-core nor core promoter mutations and in five HBeAg-positive patients who also had neither of these mutations (the groups were matched for age and sex). Six mutations were found to be significantly more common in the former group than in the latter: G529A (3/4 vs. 0/5), C934A (4/4 vs. 1/5), A1053G (4/4 vs. 1/5), G1915T/A (4/4 vs. 0/5), T2005C/A (4/4 vs. 0/5), and C3026T (3/4 vs. 0/5). Three of the six mutations were significantly more common in the four anti-HBe-positive patients who had neither pre-core nor core promoter mutations, compared to 11 HBeAg-positive patients who had pre-core and core promoter mutations, and also compared to 15 anti-HBe-positive patients who had pre-core and core promoter mutations, suggesting further the specificity of these mutations. Of the six mutations, two resulted in amino acid substitution in the polymerase protein, and one is located near the enhancer I region. The results suggest that the six newly discovered mutations are associated with HBeAg negativity.     

The effect of tyrphostin AG-556 on intimal thickening in a mouse model of arterial injury

BACKGROUND: Inflammation has been shown to play an important role in promoting the response to arterial injury and proinflammatory cytokines, such as tumor necrosis factor (TNF) alpha, are candidate mediators. AG-556 is a tyrosine kinase inhibitor proven to be effective in a model of multiple sclerosis-like syndrome in mice due to its immunomodulating effect. In the current study, we investigated the effect of the tyrphostin AG-556 on neointimal thickening and cytokine profile in a model of arterial injury in the mouse. METHODS: Injury was induced by external cuff placement on the left femoral artery of wild-type C57BL/6 mice. AG-556 dissolved in DMSO was injected intraperitoneally daily to the injured mice in a dosage of 2 mg/mouse. Control mice received DMSO injections. Histological analysis was carried out to assess neointimal formation. Splenocytes were cultured in the absence and presence of a mitogen for evaluation of thymidine incorporation and cytokine production. RESULTS: AG-556 treatment significantly attenuated intimal thickening (43,000+/-17,000 microm2; n=11) when compared to DMSO administration (286,000+/-127,000 microm2; n=10; P<0.05). Basal interferon-gamma production by splenocytes from AG-556-treated mice was increased by approximately 20-fold in comparison with levels in DMSO-treated animals, whereas Con-A induced secretion of the cytokine was similar between both groups. Levels of TNF-alpha, IL-4 and IL-10 in the culture supernatant from treated and non-treated animals did not differ significantly. CONCLUSION: The tyrosine kinase inhibitor AG-556 may have a role in the reduction of intimal thickening. The effect could be mediated via an immune modulating effect involving a significant increase in the smooth muscle cell inhibitory cytokine IFN-gamma.     

Placental site trophoblastic tumor of the mediastinum

Choriocarcinoma has been described as the most frequent subtype of mediastinal germ cell tumors showing trophoblastic differentiation. We report a unique case of a placental site trophoblastic tumor, which developed in the mediastinum of a 14-year-old boy 2 years after the resection of a mature teratoma. The recurrent tumor was composed of a grossly hemorrhagic and necrotic mass. Histologically, diffusely infiltrating large polygonal cells with focal nodular growth and a teratomatous part containing mature intestinal, respiratory, and squamous epithelium with adjacent cutaneous adnexal structures were found. The typical morphologic features included vessel wall infiltration by the neoplastic cells with fibrinoid deposits and geographic necroses within the tumor masses. Characteristic diffuse positivity for melanoma cell adhesion molecule and human leucocyte antigen G was found on immunohistochemical investigation, confirming the diagnosis of placental site trophoblastic tumor. The patient died 1 year later after polychemotherapy. The outcome of this rare tumor is similar to the reported poor clinical outcome in patients with mediastinal choriocarcinomas.     

Involution and regeneration of the thymus in mice,induced by bacterial endotoxin and studied by quantitative histology and electron microscopy

Lipopolysaccharide from S. typhosa, injected intraperitoneally into Swiss albino mice, produced acute thymic involution—maximal at 48 hours after injection, followed by regeneration that was complete within 5 to 7 days. Using tissues fixed and embedded for electron microscopy, cell counts were made with the light microscope and cytological details were examined in electron micrographs. The cellular events of involution and regeneration were similar to those produced by injection of adrenal glucocorticoids, but it remains to be determined whether or not endotoxin acts on the thymus by inciting adrenal cortical secretion. Involution appeared to be the result of both the death of small lymphocytes and reduced lymphopoiesis in the thymus. Within 48 hours, macrophages had cleared away the cellular debris and medullary epithelial cells showed signs of hypertrophy and increased putative secretory activity. Subsequently, large lymphocytes proliferated at an accelerated rate in the subcapsular cortex, the cortex grew in width by the accumulation of small lymphocytes, and regeneration ceased when the thymus had reached its former size. These observations provide circumstantial evidence for the hypothesis that in regeneration, medullary epithelial cells increase their production of a lymphopoietic hormone which stimulates mitotic proliferaton of cortical lymphocytes.     

Accumulation of exogenous polyamines in gerbil brain after ischemia

Regionally selective delayed neuronal degeneration is a characteristic sequel of cerebral ischemia. Recent evidence indicates that changes in brain polyamine metabolism may be critical for nerve cell survival after ischemia. Within hours after ischemia, intracellular putrescine levels are greatly increased and remain elevated for days, whereas only minor changes are noted in the levels of the polyamines spermine and spermidine. In contrast, the extracellular levels of all polyamines are low after ischemia. Injections of polyamines following ischemia, however, can protect neurons in the gerbil brain from delayed cell death, with spermine being the most potent of the polyamines. In the present study, therefore, we sought to determine if increased polyamine uptake occurs in the brain after ischemia. In the hippocampal slice preparation, temperature-dependent uptake was unique for spermine, but not for spermidine or putrescine. Uptake of [¹⁴C]spermine was transiently increased after ischemia, peaking at 150% of control by 12–13 h and subsiding by 24 h. Intravenous injections of [³H]spermidine resulted in a postischemic accumulation of this polyamine throughout the forebrain parenchyma. We conclude that:

1. Active cellular uptake of spermine is transiently increased early after ischemia;
2. A nonspecific accumulation of exogenous polyamines occurs early after ischemia probably owing to a compromised blood-brain barrier, and
3. The findings indicate that exogenous polyamines can exert their effect directly in the brain after ischemia.