Vulnerability of Forests in India: A National Scale Assessment.

Forests are subjected to stress from climatic and non-climatic sources. In this study, we have reported the results of inherent, as well as climate change driven vulnerability assessments for Indian forests. To assess inherent vulnerability of forests under current climate, we have used four indicators, namely biological richness, disturbance index, canopy cover, and slope. The assessment is presented as spatial profile of inherent vulnerability in low, medium, high and very high vulnerability classes. Fourty percent forest grid points in India show high or very high inherent vulnerability. Plantation forests show higher inherent vulnerability than natural forests. We assess the climate change driven vulnerability by combining the results of inherent vulnerability assessment with the climate change impact projections simulated by the Integrated Biosphere Simulator dynamic global vegetation model. While 46% forest grid points show high, very high, or extremely high vulnerability under future climate in the short term (2030s) under both representative concentration pathways 4.5 and 8.5, such grid points are 49 and 54%, respectively, in the long term (2080s). Generally, forests in the higher rainfall zones show lower vulnerability as compared to drier forests under future climate. Minimizing anthropogenic disturbance and conserving biodiversity can potentially reduce forest vulnerability under climate change. For disturbed forests and plantations, adaptive management aimed at forest restoration is necessary to build long-term resilience.

Cautionary tale of right ventricular perforation during Micra™ leadless pacemaker insertion.

Transcatheter pacing systems are self-contained, leadless, devices that offer the potential benefits of avoiding complications related to pectoral pocket and upper extremity vascular access. These systems in preapproval trials demonstrated excellent safety profile with the incidence of device-related cardiac perforation as low as 1.6% with Micra™ (Medtronic) and 1.3% in Nanostim (Abbott). In post-approval registry of Micra™ TPS, the rate of major complications was even lower than in the investigational study ranging from 0.63% to 0.77%. Recently, published report found much higher rates of need for rescue surgery, shock, tamponade, and death among patients implanted with the Micra™ device when compared with transvenous devices. This case report describes two cases of major right ventricular perforation requiring surgical intervention.

Mitigation co-benefits of carbon sequestration from MGNREGS in India.

Mahatma Gandhi Rural Employment Guarantee Scheme a large social security programme being implemented in India, with an average annual investment of US$ 7 billion. The bulk of the activities under this programme are focused on natural resources such as land, water and trees, which provide adaptation benefits. In this study an attempt is made to estimate the carbon sequestration achieved and future potential, as a co-benefit, from MGNREGS. The total mean carbon sequestered at the national level, considering the cumulative number of natural resource based activities, for the year 2017-18 was estimated to be 102 MtCO2. The annual mean carbon sequestration is projected to increase to about 132 MtCO2 by 2020 and 249 MtCO2 by 2030. Drought proofing is one of the activities implemented under MGNREGS and it includes tree planting, relevant to achieving the NDC carbon sink target. The cumulative carbon sink created by drought proofing activities is projected to be 56 MtCO2 in 2020, 281 MtCO2 in 2025 and 561 MtCO2 in 2030. This study demonstrates the significant carbon sink potential of MGNREGS and highlights the importance of estimation and reporting climate mitigation co-benefits of adaptation actions such as MGNREGS under the Paris Agreement.

Bilateral renal angiomyolipomas with invasion of the renal vein: a case report.

An angiomyolipoma (AML) is usually a benign, rare, and, more commonly, a unilateral renal tumour. Bilateral tumours are very rare, particularly in the absence of tuberous sclerosis complex. Only in a few isolated cases have features of malignancy been associated with an AML. We present a unique case of bilateral AMLs mimicking invasive tumours in the absence of any other features of tuberous sclerosis complex.

Toxicity, bioaccumulation and metabolism of phenol in the freshwater fish Oreochromis mossambicus.

The acute toxicity of phenol was determined to be 35.0 mg/l in Oreochromis mossambicus. The fish were exposed to two sublethal concentrations of phenol (2.3 and 3.5 mg/l) for 30 days. The effects of exposure were studied on the bioaccumulation and elimination of phenol from the kidney and biochemical parameters of liver, gill, and muscle at intervals of 10, 20, and 30 days. A statistically significant increase in phenol concentration was noted in tissues from all treated fish groups. Bioaccumulation and biochemical changes were dose and duration dependant. Recovery in fish after post exposure was observed after transferring these fish to normal tap water for 30 days. Elimination of phenol was noted, although the concentration of phenol remained significantly higher than the control after 30 days of the experiment. Total protein, total carbohydrate, and total lipids in the tissues of liver, gill, and muscle of fish decreased greatly. The longer the exposure time, the greater was the percentage reduction of organic matter of the fish exposed to the sublethal concentration of phenol.

Outcome of inguinal hernia repair at two rural hospitals in northern Scotland.

INTRODUCTION: Audit of inguinal hernia repair is important in view of the magnitude of the problem and the fact that it is a common operation often performed by surgical trainees. Due to the disparity of the results of various workers with regard to the rate of complications, individual surgeons have been advised to audit their patients' outcomes. METHOD: Retrospective audit was performed, of all the inguinal hernias repaired between 1997 and 2003 inclusive, at two rural hospitals in northern Scotland, under a single consultant. Data were gathered from a hospital database and by means of postal questionnaire specifically aimed at wound complications, recurrence and chronic groin pain. RESULTS: One hundred and sixty-three inguinal hernias were repaired during this period. One hundred and fifty-eight questionnaires were sent to patients ascertained to be living at the time of audit initiation with a response from 129 (86%). At a mean follow-up of 4.34 years, no recurrences were noted and eight patients complained of chronic groin pain of whom only three (1.5%) were experiencing moderate to severe pain. The results achieved by senior house officers were comparable to those obtained by the senior surgeon. CONCLUSION: The incidence of recurrence of hernia after open mesh repair of inguinal hernias is very low. Excellent outcomes can be obtained for inguinal hernia even at remote and rural hospitals in the hands of both experienced and trainee surgeons

Effect of phenol on the metabolism and biochemical composition of the freshwater fish Cyprinus carpio.

The effect of phenol on the fish Cyprinus carpio and the metabolic changes in oxygen consumption and total carbohydrate, total protein and total lipids in the tissues of liver, gills, muscle, brain, and intestine were investigated for sublethal exposure. The oxygen consumption decreased significantly in both toxicants exposed to acute toxicity. Following sublethal exposure to phenol total protein, total carbohydrate, and total lipids in the tissues of liver, gills, muscle, brain and intestine of the fish decreased greatly. The longer the exposure time, the greater was the percentage reduction of organic matter of the fish exposed to sublethal concentration of phenol. Lipid content was not reduced much in exposure when compared with the control.

Clerodane diterpenoids from Pulicaria wightiana.

Five clerodane diterpenoids have been isolated from the aerial parts of Pulicaria wightiana along with 3'5,6-trihydroxy-3,4',7-trimethoxyflavone and 2-methyl-5-hydroxy-chroman-4-one. The structures and stereochemistry of the compounds were established from spectral (mainly 1D and 2D NMR) studies. The last two compounds were not reported earlier from this plant. The antibacterial activity of the diterpenoids were studied.

Loss of telomerase activity during male germ cell differentiation.

Although the activity of telomerase, an enzyme which synthesizes telomeres de novo and stabilizes telomere length has been demonstrated in the testis, the precise expression of activity in different germ cell types is not known. We examined telomerase activity using a PCR-based telomeric repeat amplification protocol during development of the rat testis from birth to adulthood. Telomerase activity was relatively high from birth to the 4th week of age, and then low between the 5th to 10th week, suggesting that the type A spermatogonial stem cells may be the population which is expressing the highest levels of telomerase activity. To ascertain which germ cells expresses the telomerase activity, purified populations of type A spermatogonia from 9-day old rats, and pachytene spermatocytes, round spermatids and epididymal spermatozoa from adult rats were isolated. While type A spermatogonia expressed very strong telomerase activity, the fractions containing pachytene spermatocytes and round spermatids also expressed telomerase activity, but at comparatively lower levels. Telomerase activity was totally absent in epididymal spermatozoa. Thus, it appears that the telomerase activity is expressed at high levels in the type A spermatogonial stem cells, is down-regulated during spermatogenesis, and is absent in the differentiated spermatozoa.

Evidence that basement membrane prevents apoptosis of Sertoli cells in vitro in the absence of known regulators of Sertoli cell function.

Although the role of basement membrane in the morphological and functional differentiation of Sertoli cells has been well characterized, very little is known about its involvement in Sertoli cell survival and maintenance throughout life. When cultured on laminin or Matrigel, 80-90% of Sertoli cells retained their viability. Sertoli cells prevented from attachment and basement membrane deposition by plating on plastic surfaces coated with polyhydroxyethylmethacrylate (poly-HEMA) exhibited a loss of viability by approximately 50% within 24 h. Addition of soluble laminin did not prevent the loss of viability of Sertoli cells, whereas soluble Matrigel enhanced the survival significantly when added at a concentration of 100 micrograms/ml or more. The addition of FSH, epidermal growth factor, testosterone, retinoic acid, or a mixture of insulin, transferrin, and selenium had no significant effect on the viability of Sertoli cells cultured on polyHEMA for up to 72 h. When all of these hormones and factors were added together, a significantly higher percentage of cell survival was observed at 24, 48, and 72 h, but the percent survival was significantly lower than that seen on either laminin or Matrigel. The nature of cell death occurring in the Sertoli cells plated on polyHEMA was determined by agarose gel analysis that revealed a ladder of approximately 200-base pair DNA multiple fragments. Flow cytometric analysis of propidium iodide-stained cells indicated that most of the cells were apoptotic. Freshly isolated Sertoli cells and adherent cells on basement membrane did not show internucleosomal DNA breakdown or an apoptotic peak in the flow cytometric analysis. These results suggest that basement membrane plays a crucial role in Sertoli cell survival in vitro when it is used as a solid substratum for culture, and in the absence of basement membrane, FSH and other regulators of Sertoli cell function cannot prevent Sertoli cell apoptosis.

Role of luteinizing hormone in the expression of cholesterol side-chain cleavage cytochrome P450 and 3 beta-hydroxysteroid dehydrogenase, delta 5-4 isomerase messenger ribonucleic acids in the primate corpus luteum.

It is well established that LH has an obligatory role in the acute production of progesterone by the primate corpus luteum in vivo because interruption of LH support to the corpus luteum at any time during the luteal phase is accompanied by an immediate and sustained fall in serum progesterone concentrations. However, recent studies have demonstrated that maximal steroidogenic capacity of cultured human luteal cells and maximal levels of messenger RNAs (mRNAs) for cholesterol side chain cleavage cytochrome P450 (P450scc) and 3 beta-hydroxysteroid dehydrogenase, delta 5-4 isomerase (3 beta-HSD) in luteal tissue are observed shortly after luteinization and decline thereafter throughout the remainder of the luteal phase. These findings would suggest that the role of LH in the acute regulation of progesterone production may differ from its role in the expression of mRNAs for steroidogenic enzymes. We initiated the current studies to define the role of LH upon the expression of mRNAs for P450scc and 3 beta-HSD by the primate corpus luteum. For this purpose, we treated cynomolgus monkeys with a potent GnRH antagonist for 1, 2, and 3 days during the luteal phase of the menstrual cycle and measured levels of mRNAs for P450scc and 3 beta-HSD in corpora lutea. Treatment of monkeys with the GnRH antagonist reduced bioactive LH concentrations to less than 5 ng/ml by 48 h of treatment, and LH concentrations remained less than 5 ng/ml thereafter. Serum progesterone concentrations were reduced by 74% after 1 day of antagonist treatment, 88% after 2 days of antagonist treatment, and by more than 95% after 3 days of GnRH antagonist treatment. Although progesterone secretion was markedly diminished after 24 h of antagonist treatment, there were no differences in mRNAs for P450scc and 3 beta-HSD between antagonist-treated and control animals. However, mRNAs for P450scc and 3 beta-HSD were significantly (P < 0.05) reduced after 2 days of antagonist treatment and were nearly nondetectable after 3 days of antagonist treatment. These results demonstrate a temporal dissociation of the effects of LH on the acute regulation of progesterone secretion and the maintenance of specific mRNAs involved in progesterone production. Nonetheless, the results clearly show that LH is required for the continued expression of mRNAs for P450scc and 3 beta-HSD by the primate corpus luteum.

Vascular endothelial growth factor messenger ribonucleic acid expression in the primate ovary.

We studied the distribution of messenger RNA (mRNA) that encodes for vascular endothelial growth factor (VEGF) within the primate ovary by in situ hybridization and Northern analysis to determine if the presence of mRNA for this angiogenic factor is associated with structures within the ovary in which angiogenesis is thought to play a role in development and/or function. In situ hybridization to sections of cynomolgus ovaries with a 35S-labeled antisense RNA probe revealed specific tissue localization within the follicle as well as the corpus luteum, but not stromal tissue. Intense expression of mRNA for VEGF during the late follicular phase was confined to the maturing follicle which, we presume, was destined for ovulation. Hybridization within the corpus luteum exhibited a punctate pattern suggesting that there may be specific cells within the corpus luteum that express mRNA for VEGF. The expression of mRNA for VEGF during the early and late luteal phase of the menstrual cycle was studied by Northern analysis. Messenger RNAs were detectable at approximately 3.7 and 5.0 kb positions in corpora lutea collected during the early luteal phase of the menstrual cycle (days 3-5 postovulation). No hybridization signals were observed with RNA prepared from regressing corpora lutea (1-2 days following the onset of menses). The gonadotropic regulation of the expression of mRNA for VEGF in the corpus luteum was studied by treating monkeys with a potent GnRH antagonist during the midluteal phase of the menstrual cycle. Administration of the antagonist for 1 or 2 days did not alter the expression of mRNA for VEGF in comparison to corresponding controls. However, a 3-day treatment regimen brought about a significant reduction in the levels of mRNA for VEGF (P less than 0.01). These studies demonstrate a development-related expression of mRNA for VEGF in the ovary during the menstrual cycle and are consistent with the hypothesis that VEGF may play important roles in follicle selection and corpus luteum function in primates.

Characterization of the levels of messenger ribonucleic acid that encode for luteinizing hormone receptor during the luteal phase of the primate menstrual cycle.

The present study was designed to characterize the expression of LH receptor messenger RNA (mRNA) in the primate corpus luteum throughout the luteal phase of the menstrual cycle. We obtained corpora lutea from cynomolgus monkeys at defined stages of the luteal phase. LH receptor mRNA was demonstrated in monkey ovarian sections by in situ hybridization with a 35S-labeled antisense RNA probe derived from rat LH receptor complimentary DNA. The hybridization signals were confined to thecal layers of antral follicles and corpus luteum. Using the same LH receptor cDNA, the pattern of expression of mRNA encoding for LH receptor during the luteal phase was determined by Northern blot analysis. Four species of mRNA migrating at 1.0, 4.0, 7.5, and 8.0 kilobase (kb) were identified; the 4.0 kb size mRNA species was more abundant than the other three species. Quantitative analysis of the 4.0 kb band of mRNA throughout the luteal phase by densitometry revealed that the levels of LH receptor mRNA were low during the early luteal phase (days 3-5 of the luteal phase). A progressive increase in the message levels was observed from the early luteal phase to the end of the luteal phase. By days 11-12, there was a significant increase in the message levels (less than 0.05) which further increased during the late luteal phase (days 13-15). After menstruation, the levels became undetectable. In contrast, mRNA levels for 3 beta-hydroxysteroid dehydrogenase, a key enzyme involved in luteal steroidogenesis, were high shortly after ovulation and declined throughout the remainder of the luteal phase. These results indicate that after ovulation and luteinization, the expression of mRNAs that encode for specialized luteal cell proteins is differentially regulated.

Effect of altering endogenous gonadotrophin concentrations on the kinetics of testicular germ cell turnover in the bonnet monkey (Macaca radiata).

The role of FSH and diurnal testosterone rhythms in specific germ cell transformations during spermatogenesis were investigated using DNA flow cytometry and morphometry of the seminiferous epithelium of the adult male bonnet monkey (Macaca radiata), the endogenous hormone levels of which were altered by two different protocols. (1) Active immunization of five monkeys for 290 days using ovine FSH adsorbed on Alhydrogel resulted in the neutralization of endogenous FSH, leaving the LH and diurnal testosterone rhythms normal. (2) Desensitization of the pituitary gonadotrophs of ten monkeys by chronically infusing gonadotrophin-releasing hormone analogue, buserelin (50 micrograms/day release rate), via an Alzet pump implant (s.c.) led to a 60-80% reduction in LH and FSH as well as total abolition of testosterone rhythms. The basal testosterone level (3.3 +/- 2.0 micrograms/l), however, was maintained in this group by way of an s.c. testosterone silicone elastomer implant. Both of the treatments caused significant (P < 0.01) nearly identical reduction in testicular biopsy scores, mitotic indices and daily sperm production rates compared with respective controls. The germ cell DNA flow cytometric profiles of the two treatment groups, however, were fundamentally different from each other. The pituitary-desensitized group exhibited a significant (P < 0.001) increase in 2C (spermatogonial) and decrease in 1C (round spermatid) populations while S-phase (preleptotene spermatocytes) and 4C (primary spermatocytes) populations were normal, indicating an arrest in meiosis caused presumably by the lack of increment in nocturnal serum testosterone. In contrast, in the FSH-immunized group, at day 80 when the FSH deprivation was total, the primary block appeared to be at the conversion of spermatogonia (2C) to cells in S-phase and primary spermatocytes (4C reduced by > 90%). In addition, at this time, although the round spermatid (1C) population was reduced by 65% (P < 0.01) the elongate spermatid (HC) population showed an increase of 52% (P < 0.05). This, taken together with the fact that sperm output in the ejaculate is reduced by 80%, suggests a blockade in spermiogenesis and spermiation. Administration of booster injections of oFSH at time-points at which the antibody titre was markedly low (at days 84 and 180) resulted in a transient resurgence in spermatogenesis (at day 180 and 228), and this again was blocked by day 290 when the FSH antibody titre increased.(ABSTRACT TRUNCATED AT 400 WORDS)

Calcium confusion--is the variability in calcium response by Sertoli cells to specific hormones meaningful or simply redundant?

When results of more than ten different studies on hormone-induced calcium signals in Sertoli cells are taken together, a wide variety of responses emerges. The reported changes range from increased concentrations, via no response at all, to decreased calcium concentrations. Minor variations in cell isolation techniques, culture conditions, or techniques for measuring the intracellular calcium could explain some of these differences. However, erratic variations in response are also observed within research groups under very similar experimental conditions. Such 'negative' findings are mainly reported orally and do not further penetrate the scientific community. As hormone-dependent calcium responses evidently may depend very much on the context of the cells, calcium transients would appear to be unreliable bioassay principles with which to detect the primary actions of FSH and effectors such as androgens on Sertoli cells. A more important biological question is whether these sometimes opposed calcium transients are connected with a particular cellular response. To date there is no evidence for such a tight coupling in Sertoli cells, implying that, at least under in vitro conditions, calcium signals might even be redundant altogether. Such calcium variability is probably not unique to Sertoli cells, and the aim of this commentary is to promote an open debate that may help to transform the current state of 'calcium confusion' into a better understanding of the intracellular calcium language.

Cytotoxic activity of lutropin-gelonin conjugate in mouse Leydig tumor cells: potentiation of the hormonotoxin activity by different drugs.

A hormonotoxin preparation composed of gelonin, a basic protein of 30,000 Da isolated from the plant Gelonium multiflorum and the luteinizing hormone (LH, lutropin) isolated from the sheep pituitary has been studied for its cytotoxic action on mouse testicular Leydig tumor cells (MA-10 cells). Gelonin modified with 2-iminothiolane and conjugated with hormone modified by N-succinimidyl-3-2-pyridyl dithiopropionate was able to inhibit protein synthesis in Leydig tumor cells. An enhancement of the cytotoxicity of the hormonotoxin was obtained in the presence of drugs like quinacrine, chloroquine, verapamil and monensin. We report that the cytotoxicity of hormonotoxin was enhanced 10-15 times with quinacrine (7.6 microM), chloroquine (29 microM), verapamil (40 microM) and monensin (0.29 microM). While quinacrine, chloroquine and verapamil were not cytotoxic to MA-10 cells for up to 48 h, monensin alone reduced protein synthesis significantly in 48 h. All the drugs studied here inhibited steroidogenic action of the native hormone even at concentrations which were not detrimental to protein synthesis. On the basis of the above studies, we suggest that it may be feasible to develop combination strategies to destroy gonadal cells bearing gonadotropin (LH) receptors. In cells not bearing LH receptors (COS-7 cell line) there was no cytotoxicity either with hormonotoxin alone or in combination with the drugs, suggesting specificity of action.

Molecular cloning and expression of the ovine testicular follicle stimulating hormone receptor.

A sheep testicular cDNA library constructed in pcDNA1 vector was screened with a probe generated by polymerase chain reaction (PCR) and corresponding to a 1.6 kb fragment of the rat luteinizing hormone receptor cDNA. Several clones hybridizing to the rat probe at low stringency were sequenced to obtain 95% of the putative full-length ovine follicle-stimulating hormone receptor (oFSH-R) cDNA. The missing 5' region was obtained by PCR amplification of the cDNA library. Sequencing revealed a 2085 nucleotide open reading frame encoding a mature protein of 678 amino acids (74,580 daltons). The oFSH-R is remarkably similar (> 90%) to the human and rat FSH receptors, has a structural motif like the G protein-coupled family of receptors and contains 3 potential sites for N-linked glycosylation. RNA blot analysis revealed two major transcripts of 2.6 kb and 6.7 kb in size and a smaller transcript of about 1 kb in the sheep testis. A 53 residue segment in the extracellular domain unique to the receptor contains more than 50% of residues bearing functional side chains that could participate in ligand (FSH) interaction and/or signal transduction. Transfection of human fetal kidney cell line (293) with the cloned oFSH receptor cDNA based in pcDNA1/Neo vector revealed functional expression. Labeled oFSH bound to receptor expressed on the membrane with high affinity and specificity. In stably transfected 293 cells, purified oFSH and hFSH but not oLH stimulated cyclic AMP accumulation. Chemically deglycosylated oFSH (DG-oFSH) was inactive in these cells but it effectively blocked the action of native hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of a specific estrogen antibody on pregnancy establishment in the bonnet monkey (Macaca radiata).

The requirement for estrogen for pregnancy establishment has not been conclusively demonstrated in primates. Selective neutralization of estrogens was achieved in mated female monkeys during preimplantation and postimplantation periods by injecting characterized estrogen antiserum from either day 14 to 18 or day 28 to 32 of cycle. While estrogen deprivation during preimplantation period in 5 animals exposed to 14 ovulatory cycles resulted in only one pregnancy, only 3 of 13 monkeys treated during postimplantation period continued pregnancy to term. In comparison with controls (4 of 5 monkeys becoming pregnant), the percent protection against pregnancy in animals treated during preimplantation period was 93. The pregnancy termination in 10 of 13 monkeys treated during postimplantation period when compared with normal postimplantation pregnancy wastage in our colony (2%) is also highly significant (P less than 0.01). The present study demonstrates a critical need for estrogen during the peri-implantation period for a successful pregnancy establishment in primates.

Chronic suppression of testicular function by constant infusion of gonadotropin-releasing hormone agonist and testosterone supplementation in the bonnet monkey (Macaca radiata).

OBJECTIVE: To study the efficacy of long-term buserelin acetate infusion to desensitize pituitary and block testicular function in adult male monkeys (Macaca radiata). ANIMALS: Proven fertile male monkeys exhibiting normal testicular function. PROTOCOL: Each of the control (n = 5) and experimental monkeys (n = 10) received a fresh miniosmotic pump every 21 days, whereas pumps in controls delivered vehicle of experimentals released 50 micrograms buserelin acetate every 24 hours. On day 170 (renewed every 60 days) a silastic capsule containing crystalline testosterone (T) was implanted in the experimental monkeys. At the end of 3 years, treatment was stopped, and recovery of testicular function and fertility monitored. RESULTS: (1) Treatment resulted in marked reduction of nocturnal but not basal serum T; (2) the pituitary remained desensitized to buserelin acetate throughout the 3-year period; (3) animals were largely azoospermic with occasional oligospermia exhibited by two monkeys; and (4) withdrawal of treatment restored testicular function, with 70% of animals regaining fertility. CONCLUSION: Long-term infertility (but restorable) can be induced in male monkeys by constant infusion of buserelin acetate and T.

Epidermal growth factor modulates the expression of vascular endothelial growth factor in the human prostate.

The growth and dissemination of tumors in the body has been associated with angiogenesis. Vascular endothelial growth factor (VEGF) is an angiogenic factor that stimulates endothelial cell growth and enhances vascular permeability. VEGF exerts its action by binding to specific cell surface receptors. Three receptors, VEGFR-1 (flt-1), VEGFR-2 (flk-1), and VEGFR-3 (flt-4) have been identified. Very little information on the coordinated expression of VEGF and its receptors in normal prostate, benign prostatic hyperplasia (BPH), and prostate carcinoma is available. Therefore, we examined the immunohistochemical localization of VEGF and its receptors in tissues derived from normal human prostate, BPH, and prostatic carcinoma. Immunostaining for VEGF was absent in the normal prostate. Epithelium lining the glands of prostate derived from patients with BPH exhibited strong immunostaining. The intensity of staining was relatively less in prostate carcinoma. It is interesting that VEGFR-1 and VEGFR-3 were strongly expressed in both stromal and epithelial tissues in normal prostate, BPH, and carcinoma. In comparison, VEGFR-2 was not localized to normal prostate and its expression in the stroma of BPH and epithelium of carcinoma was very weak. Because progression of prostate cancer is accompanied by altered expression of epidermal growth factor (EGF) and its receptor (EGFR) in malignant cells, we investigated the effect of EGF on VEGF gene expression by Northern blot analysis in 2 human prostate cancer cell lines that express EGFR. EGF greatly enhanced the expression of VEGF messenger RNA in DU145 and PC3 cell lines in a dose-dependent manner. The EGF induction of VEGF gene expression suggests a mechanism by which angiogenesis could be accelerated in BPH and prostate carcinoma.