Primary orbital angiosarcoma: a case report

PURPOSE: The pathogenesis, natural history, histopathology, and recommended treatment for orbital angiosarcoma are illustrated and reviewed. METHODS: Case report. RESULTS: A 71-year-old white male presented with bluish discoloration and swelling of the left medial canthal area. A fine needle aspiration and excisional biopsy with histopathologic examination was performed, which showed angiosarcoma. Pattern of growth was demonstrated radiographically and histopathologically, confirming primary orbital angiosarcoma. Subsequent wide surgical resection was carried out, with substantial reconstruction of the left orbital and periorbital area. The patient responded well to the surgery, and was free of tumor after six years of follow-up. CONCLUSION: Angiosarcoma is a rare and highly malignant tumor of epithelial origin. The aggressive nature of this tumor usually results in a high mortality rate despite treatment. However, early diagnosis and wide surgical excision has resulted in successful treatment of these tumors.     

Effects of estrogen on autotomy in normal and ovariectomized rats.

Gonadal hormones may modulate analgesia responses induced by acute stress in humans and rats. To evaluate the effects of gonadal hormones in modifying neuropathic pain, we measured autotomy changes following sciatic nerve resection in ovariectomized rats and in the presence of estrogen replacement. Two groups of female rats were subjected to ovariectomy and sham surgery. Each group was then divided into two subgroups receiving subcutaneously sesame oil with or without estradiol benzoate (5 microg/day/rat). All rats then underwent sciatic nerve resection in one hindlimb. Degree of self-mutilation was measured daily for 8 weeks. Estradiol treatment resulted in significantly lower autotomy scores in ovariectomized rats (3.6 +/- 0.6 vs. 5.5 +/- 0.3, p < 0.01) and in sham-operated rats (3.4 +/- 0.7 vs. 5.1 +/- 0.4, p < 0.05). The results of this study indicate that estrogen can modify the autotomy behavior, an indicator of neuropathic pain, in rats after nerve injury.     

The Effectiveness of the Gene Which Slows the Rate of Wallerian Degeneration in C57BL/Ola Mice Declines With Age

The rate of Wallerian degeneration is unusually slow in severed axons of mice of the C57BL/Ola strain. Within mice of that strain we have now found that the rate of degeneration increases with the age of the animal. In 4-week-old mice nerve stimulation evokes muscle contractions even 5 days after sciatic nerve section and compound action potentials can be recorded in the distal nerve stump up to 3 weeks after section. In 1-year-old animals no action potentials can be excited 5 days after nerve section. Heterozygous mice carrying only one copy of the dominant gene show the same age-related decline in viability of the distal nerve stump after axotomy, and the rate of decline is no greater than for homozygous mice. The more rapid rate of degeneration of severed axons of mice of the C57BL/6J strain was affected in the opposite way by age, degeneration occurring more slowly in older animals.     

Structural changes and alteration in expression of TGF-beta1 and its receptors in prostatic intraepithelial neoplasia (PIN) in the ventral prostate of noble rats

BACKGROUND: Prostatic intraepithelial neoplasia (PIN) is the most likely pre-cancereous lesion and represents the major target for chemoprevention of prostate cancer. The multi-functional role of TGF-beta1, together with its receptors, in normal prostate and development of prostatic neoplasia remains controversial and requires further investigation. METHODS: Ventral prostates were removed from Noble rats treated with a combination of testosterone (T) and estradiol (E(2)) for various periods of time, and processed for ultrastructural examination and histopathological grading. To evaluate the role of TGF-beta1 and TGFbeta receptor types I and II in normal prostate and high-grade PIN development, expression pattern of TGF-beta1 and TGFbeta-RI and TGFbeta-RII were studied on prostate samples with PIN lesions. RESULTS: Pathologically, low-grade PIN (LGPIN) and high-grade PIN (HGPIN) were observed in ducts or alveoli after three and five months of T + E(2) treatment, respectively. EM study revealed that HGPIN cells were characterized by a reduction in abundance of secretory apparatus and the nucleus with highly irregular and undulated membrane and often with inclusion bodies although the basal lamina remained largely normal. This was associated with a high level of expression of TGF-beta1 in stromal tissue subjacent to foci of HGPIN. No definite positive reactivity of TGF-beta1 was identified in glandular epithelial cells of HGPIN. These results implicated that the major site for the TGF-beta1 production remained to be restricted to stromal compartment at the stage of HGPIN, and a paracrine regulation of TGF-beta1 might be involved in the development of HGPIN. Positive staining for the TGFbeta-RI was found in the cytoplasm of luminal epithelial cells of normal ventral prostate. The intense positive reactivity for TGFbeta-RI was also identified in prostates with HGPIN lesions. Similar expression pattern of TGFbeta-RII was also observed. CONCLUSIONS: Based on the EM study, we concluded that HGPIN in ventral prostate was accompanied with alterations in nuclear morphology together with a change in secretory activity. The over expression of TGFbeta-RI and RII in HGPIN cells as well as TGF-beta1 in stromal tissue subjacent to HGPIN implicated a growth-stimulating role instead of inhibiting role of this peptide growth factor during the early stage of prostatic neoplasia.     

Regulation and targeting of antiapoptotic XIAP in acute myeloid leukemia.

XIAP is a member of the inhibitors-of-apoptosis family of proteins, which inhibit caspases and block cell death, with prognostic importance in AML. Here we demonstrate that cytokines regulate the expression of XIAP in leukemic cell lines and primary AML blasts. Inhibition of phosphatidylinositol-3 kinase (PI3K) with LY294002 and of the mitogen-activated protein kinase (MAPK) cascade by PD98059 resulted in decreased XIAP levels (34+/-8.7 and 23+/-5.7%, respectively). We then generated OCI-AML3 cells with constitutively phosphorylated Akt (p473-Akt) by retroviral gene transfer. Neither these nor Akt inhibitor-treated OCI-AML3 cells showed changes in XIAP levels, suggesting that XIAP expression is regulated by PI3K downstream effectors other than Akt. The induction of XIAP expression by cytokines through PI3K/MAPK pathways is consistent with its role in cell survival. Exposure of leukemic cells to chemotherapeutic agents decreased XIAP protein levels by caspase-dependent XIAP cleavage. Targeting XIAP by XIAP antisense oligonucleotide resulted in downregulation of XIAP, activation of caspases and cell death, and sensitized HL-60 cells to Ara-C. Our results suggest that XIAP is regulated by cytokines through PI3K, and to a lesser degree through MAPK pathways. Selective downregulation of XIAP expression might be of therapeutic benefit to leukemic patients.     

Human papillomavirus, cytomegalovirus and herpes simplex virus infections for cervical cancer in Taiwan

Previously, we had reviewed 43 cases of invasive cancers, adenosquamous cell carcinoma and adenocarcinoma for HPV type infections. With the same cases we extended the investigation to cytomegalovirus (CMV) and herpes simplex virus (HSV) infections. Results show that the prevalence of CMV and HSV infections from these cases of cervical carcinoma was 67 and 76%, respectively, by polymerase chain reaction. The results of the analysis of the association of HPV, CMV and HSV with various clinical characteristics of cervical cancer patients indicated that the correlation between HSV infections and clinical stages of squamous carcinoma was marginally significant (P=0.068). HSV infections seemed to have a higher association with cell keratinization pattern as compared with the other two viral infections.     

Paracrine effects of hepatocyte growth factor/scatter factor on non-small-cell lung carcinoma cell lines.

We have studied the mitogenic, motogenic and morphogenic effects of hepatocyte growth factor (HGF), also known as scatter factor (SF), on 15 non-small-cell lung carcinoma (NSCLC) cell lines that have had their ras genotype determined. HGF/SF stimulated proliferation in only three cell lines and exerted no mitogenic activity on six lines. The growth of the remaining six lines was inhibited. The mitogenic effects were not related to the ras genotype of these cell lines, but the inhibitory effect was more commonly observed in cell lines with relatively high levels of Met/HGF receptor (HGFR) expression. HGF/SF induced or enhanced both scatter activity on monolayer culture and single-cell invasion in collagen gels in approximately half of these cell lines. Although the ras genotype of tumour cells did not influence the HGF/SF-induced motogenic activity, cell lines with the mutant ras genotype more commonly demonstrated a spontaneous motogenic activity than those with the wild-type ras genotype. When tumour cells were grown in collagen gels, HGF/SF induced irregular branching extensions of cell aggregates formed by five out of eight adenocarcinoma cell lines, but significant lumen morphogenesis was distinctly absent. The presence of autocrine HGF/SF loop in these tumour cell lines did not influence their spontaneous or HGF/SF-induced mitogenic, motogenic or morphogenic activities. Overall, our data suggest that stimulation of cell motility, rather than proliferation or differentiation, is the predominant paracrine effect of HGF/SF on NSCLC cells in vitro.     

Interspeaker variation in habitual speaking rate: additional evidence.

PURPOSE: The purpose of the present study was to test the hypothesis that talkers previously classified by Y.-C. Tsao and G. Weismer (1997) as habitually fast versus habitually slow would show differences in the way they manipulated articulation rate across the rate continuum. METHOD: Thirty talkers previously classified by Tsao and Weismer (1997) as having habitually slow (n = 15; 7 males, 8 females) and habitually fast (n = 15; 8 males, 7 females) articulation rates produced a single sentence at 7 different rates, using a magnitude production paradigm. Hence, the participants were not randomly assigned to conditions. RESULTS: Quadratic regression functions relating measured to intended articulation rates were all statistically significant, and most important, there were significant differences between the slow and fast groups in the y intercepts of the functions, for both males and females. CONCLUSIONS: This study provides a constructive replication of Tsao and Weismer (1997), showing a difference between slow and fast talkers with a new set of speech materials and in a new task. The findings appear to be consistent with a biological basis for intertalker rate differences.     

Effects of Iron Supplementation on Testicular Function and Spermatogenesis of Iron-Deficient Rats

Iron deficiency is the most common micronutrient deficiency in the world. Previous studies have shown that iron deficiency increases oxidative stress and decreases antioxidant enzymes, and studies of male infertility indicated that oxidative stress may affect male reproductive functions. The aim of this study was to investigate the effects of iron supplementation on spermatogenesis and testicular functions in iron-deficient rats. Three-week-old male Sprague Dawley (SD) rats were randomly divided into two groups: an iron-adequate control (AI group, 35 ppm FeSO₄) and an iron-deficient group (ID group, <5 ppm FeSO₄). After three weeks, the iron-deficient group was divided into an original iron-deficient group and five iron-supplemented groups, the latter fed diets containing different doses of FeSO₄ (6, 12, 18, 24, and 35 ppm). After five weeks, blood and testis tissue were analyzed. We presented as median (interquartile range, IQR) for continuous measurements and compared their differences using the Kruskal–Wallis test followed by the Mann–Whitney U test among groups. The results showed that as compared with the AI group, the ID group had significantly lower serum testosterone and poorer spermatogenesis (The medians (QR) were 187.4 (185.6–190.8) of AI group vs. 87.5 (85.7–90.4) of ID group in serum testosterone, p < 0.05; 9.3 (8.8–10.6) of AI group vs. 4.9 (3.4–5.4) of ID group in mean testicular biopsy score (MTBS], p < 0.05); iron supplementation reversed the impairment of testis tissue. In the testosterone biosynthesis pathway, iron supplementation improved the lowered protein expressions of hydroxysteroid dehydrogenases caused by iron deficiency. Additionally, decreased activities of glutathione peroxidase and catalase, and increased cleaved-caspase 8 and caspase 3 expression, were found in the iron-deficient rats. The iron-supplemented rats that received > 12 ppm FeSO₄ exhibited improvements in antioxidant levels. In conclusion, iron supplementation can abrogate testis dysfunction due to iron deficiency through regulation of the testicular antioxidant capacity.     

Biosynthesis of the ansamycin antibiotic ansatrienin (mycotrienin) by Streptomyces collinus

The biosynthesis of ansatrienin (mycotrienin) has been studied in radioactive and stable isotope feeding experiments with Streptomyces collinus Tü 1892. The m-C7N unit of the ansa ring is efficiently and specifically derived from 3-amino-5-hydroxybenzoic acid; shikimic acid is not incorporated into this part of the molecule but does label the cyclohexanecarboyxlic acid moiety, providing all seven of its carbon atoms. Incorporation of methionine confirms origin of the methoxy group by transmethylation. The D-alanine moiety is derived directly from D-alanine rather than L-alanine. The terminal steps in the conversion of shikimic acid into cyclohexanecarboyxlic acid seem to be sequential reduction of 2,5-dihydrobenzoic acid and cyclohexene-1-carboxylic acid as evidenced by feeding experiments and the detection of a new ansatrienin containing a 1-cyclohexene instead of the cyclohexane moiety.