Stability, delay, and chaotic behavior in a lotka-volterra predator-prey system.

We consider the following Lotka-Volterra predator-prey system with two delays: x '( t ) = x ( t ) [ r(1) - ax ( t - tau(1) ) - by( t ) ] y '( t ) = y ( t ) [ - r(1) + cx ( t ) - dy( t - tau(2) ) ] ( E ) We show that a positive equilibrium of system ( E ) is globally asymptotically stable for small delays. Critical values of time delay through which system ( E ) undergoes a Hopf bifurcation are analytically determined. Some numerical simulations suggest an existence of subcritical Hopf bifurcation near the critical values of time delay. Further system (E) exhibits some chaotic behavior when tau(2) becomes large.

Immunohistochemical analysis of midkine expression in human prostate carcinoma.

Midkine (MK) is a growth/differentiation factor frequently expressed at high levels in some types of human malignancies. To investigate whether MK is a useful marker in prostate carcinogenesis, immunohistochemical analysis was performed on samples of both latent and clinical prostate cancers of various stages, as well as on specimens of normal gland and prostatic intraepithelial neoplasia (PIN). Of the 80 clinical cancers examined, 69 specimens (86.3%) were immunoreactive for MK, with metastatic lesions generally showing higher expression than the corresponding primaries; normal prostate tissues were negative or showed only weak staining. Midkine was also detected in 12 of 15 latent cancers (80%) and in 12 of 16 cases of PIN (75%). In sections of whole prostate, MK showed variable expression through tumorous sections, probably in reflection of heterogeneous cell populations. The results demonstrate the possible value of MK as a marker for early and latent disease, as well as for more advanced clinical stages of prostate cancer.

Expression of pepsinogen II with androgen and estrogen receptors in human prostate carcinoma.

The expression of pepsinogen II (PG II), an aspartyl proteinase usually involved in the digestion of proteins in the stomach, was immunohistochemically investigated in conjunction with androgen (AR) and estrogen receptor (ER) status in prostate adenocarcinomas. Of a total of 38 samples obtained from radical prostatectomies, 23 tumors (60.5%) were positive for PG II and there was a significant positive correlation to the expression of AR but not to ER. Cells positive for PG II were localized mainly to the peripheral zones of tumorous glands which, in normal prostate, are negative, and in areas also expressing AR. In addition, a significant correlation between AR and ER was detected in the prostate carcinomas examined, which suggests a hormone-dependent status. On the basis of these results, PG II expression might be closely related to hormonal alterations associated with the development of prostate tumors.

[Newly developed detection system for serum Helicobacter pylori antibodies using ELISA and its clinical significance].

Using ELISA, a specific and sensitive system that detects serum immunoglobulin G antibodies against all soluble antigens of Helicobacter pylori (Hp) has been developed. This system is used at three different concentrations of Hp antigens coated on the solid phase of the ELISA. Anti-Hp antibodies were judged positive when the difference in the ELISA values between high and middle or middle and low concentrations of antigen were over the specific values. For the ELISA system, called the three point antigen method, sensitivity and specificity of urease activity were 86.9% and 70.8%, respectively. Positive rate for antibodies to serum Helicobacter pylori in dyspeptic patients was higher than that in healthy subjects.

Antigen immunohistochemistry of renal cell adenomas in autopsy cases: relevance to histogenesis.

Eighty-three kidneys from autopsy cases, all more than 60 years of age, were used in the present studies. Three millimeter-thick step slices from all kidneys were embedded in paraffin, and serial sections from all blocks used for the immunohistochemical demonstration of Leu M1 (leukocyte membrane antigen) and LTA (Lotus tetragonolobus agglutinin) in cells of proximal convoluted tubular origin, and PNA (peanut agglutinin) and EMA (epithelial membrane antigen) in cells of distal convoluted tubular origin. The ABC staining method was used in all cases. A total of 65 renal cell adenomas found in 31 of the 83 kidneys consisted of 40 papillary, 20 tubular and 5 solid type lesions. The sizes of these renal cell adenomas were from 0.6 to 5 mm in diameter and compression of neighboring tissues was characteristic. Papillary renal cell adenomas were positive in their cytoplasms for Leu M1 and LTA in 7 cases and at their cell membranes for PNA and EMA in 33 cases. The respective figures for tubular renal cell adenomas were 6 cases for Leu M1 and LTA and 14 cases for PNA and EMA. All solid renal cell adenomas were positive in their cytoplasms for PNA and EMA. The immunohistochemical results thus indicated 13 of 65 lesions to have a proximal convoluted tubular cell origin and 52 to be possibly derived from distal convoluted tubules or collecting ducts. A role for metaplasia, however, could not be ruled out.

Progressive activity in latent prostate carcinoma defined by argyrophilic staining of the nucleolar organizer regions (AgNOR).

Argyrophilic staining of the nucleolar organizer regions (AgNOR) was studied in 30 cases of benign prostatic hyperplasias (BPH), 17 cases of latent prostate carcinomas, 50 cases of clinical carcinomas and seven cases of metastatic lesions from prostate carcinomas. The criteria for these comparisons were the number of positive-staining dots per nucleus, the area of the dots, and a relative score determined by multiplying the number of positive-staining dots in the nuclei by the areas of the dots. Overall, there were no significant differences in these three parameters between BPH and latent carcinomas. Among latent carcinomas, however, significantly higher AgNOR scores were observed for infiltrative lesions than for non-infiltrative lesions. AgNOR dot number, area and score increased as tumors became less differentiated, with no significant differences detected in metastatic versus non-metastatic carcinomas. These results suggest that some latent tumors are similar in biological behavior, such as cell proliferation, to clinical carcinoma.

Expression of nm23-H1 and nm23-H2 proteins in prostate carcinoma.

The nm23 gene products/nucleoside diphosphate (NDP) kinase expression in prostate carcinomas and benign hyperplasias was evaluated immunohistochemically. Monoclonal antibodies against nm23-H1 and nm23-H2 proteins were prepared using the corresponding proteins fused with glutathione S-transferase as immunogens. Of the 80 cases of nonmetastatic prostate carcinoma examined, 74% (59/80) and 60% (48/80) were immunoreactive for nm23-H1 or nm23-H2 protein, respectively. Negative staining for nm23-H1 occurred in 83% of metastatic lesions, while 34% were negative for nm23-H2. All primary tumors corresponding to the metastases examined showed positive immunostaining for nm23-H1, indicating an inverse relationship between expression of this protein and metastatic status. nm23-H2 protein was detected in 83% of primary tumors and its expression appeared to be significantly correlated to the degree of histological differentiation. In contrast, all cases of benign prostatic hyperplasia showed elevated levels of both nm23-H1 and nm23-H2 expression. These data suggest that the nm23/NDP kinase may play a role in suppressing the expression of malignant potential in prostate carcinomas.

Immunohistochemical evaluation of estrogen receptor status in benign prostatic hypertrophy and in prostate carcinoma and the relationship to efficacy of endocrine therapy.

The levels of estrogen receptors in human benign prostatic hypertrophy and in various pathological classifications of prostate carcinoma were assessed using immunohistochemical methods. All cases of benign hypertrophy showed elevated levels of estrogen receptor, while receptor-positive cells were detected in only 48% of carcinomas, indicating a negative correlation between receptor status and malignancy. Furthermore, the prognosis for effective endocrine therapy was poor in cases where tissues demonstrated low or negative receptor levels. In addition, the estrogen receptor status was compared to cell kinetic index such as proliferating cell nuclear antigen and argyrophilic staining of the nuclear organizer region.

Immunohistochemical analysis of estrogen receptors in 313 paraffin section cases of human thyroid tissue.

Three hundred and thirteen cases of human thyroid tissues, comprising 39 nodular goiters from 34 females and 5 males, 130 adenomas from 93 females and 37 males, and 144 carcinomas from 99 females and 45 males were used for the present immunohistochemical assessment of estrogen receptor (ER) expression. Thirty-three cases of follicular carcinoma, 115 cases of papillary carcinoma and 6 cases of anaplastic carcinoma were included in the malignant tumor group. Incidences of ER-positive cases were 23/39 (58.9%) for nodular goiter, 44/130 (33.8%) for adenoma and 26/144 (18.0%) for cancer. In the individual carcinoma categories, 7/23 (30.4%) follicular, 19/115 (16.5%) papillary and 0/6 (0%) anaplastic lesions were judged as positive cases. Thus, the incidence of ER-positive cases tended to decrease with the degree of malignancy; this trend being similar in both sexes. Moreover, the average ages of ER-positive cases were lower than those of ER-negative cases for all types of thyroid carcinoma except the follicular variety in males. It was thus suggested that ER expression may be related to prognosis and tumor growth at early stage. Since the incidence of ER does not significantly differ between females and males, the observed sex differences regarding thyroid tumor incidence may reflect the higher estrogen serum content in females.

Primary malignant melanoma of the female urethra: a case report.

A case of primary malignant melanoma of the female urethra is presented. A 65-year-old Japanese woman was referred with dysuria and urethral bleeding. A hemorrhagic blue-black tumor, 3 cm in diameter, was diagnosed as a malignant melanoma by urinary cytology and biopsy. In spite of radical surgery followed by adjuvant immunochemotherapy with beta interferon, dacarbazine, nimustine and vincristine (IFN beta-DAV), the patient died of the disease one year after surgery because of lung metastasis which developed six months after diagnosis. The regional lymph nodes were not involved. In the present paper, we have briefly discussed the diagnostic value of cytological examination for this condition, as well as biopsy, with regard to the risk of hematogeneous tumor spread.

Inhibitory effect of potassium citrate on rat renal tumors induced by N-ethyl-N-hydroxyethylnitrosamine followed by potassium dibasic phosphate.

Potassium dibasic phosphate (PDP) was administered at a concentration of 10% by weight in basal diet to unilaterally nephrectomized Wistar rats previously given 1000 ppm N-ethyl-N-hydroxyethyl-nitrosamine (EHEN) in the diet for 2 weeks. To study the effect of alkalinization on renal mineralization, some animals concomitantly received 5% potassium citrate (PC). Feeding PDP alone promoted adenomatous hyperplasias, which were regarded as preneoplastic lesions, as well as renal cell tumors in EHEN-initiated rats, whereas the addition of PC to PDP diets reduced the promoting effect. Histopathology, serum biochemistry and urinalysis indicated retardation of renal calcium crystallization by PC. Two other phosphate salts, sodium phosphate (SP) and calcium phosphate (CP), were also administered. SP showed a slight promoting effect on adenomatous hyperplasias and a 2-fold increase in the yield of renal cell tumors, while CP induced a clear reduction of both lesions, over EHEN alone. The promoting effects of both PDP and SP and the inhibitory effect of PC were somewhat correlated to 5-bromo-2'-deoxyuridine labeling indices, the degree of nephropathy, and mineralization in the kidney. Immunohistochemically, the nephropathy induced by phosphate salts was not linked to alpha 2u-globulin. A pathogenesis for renal carcinogenesis is suggested in which nephropathy associated with mineralization enhances the development of renal cell tumors.

Promoting effects of potassium dibasic phosphate on early-stage renal carcinogenesis in unilaterally nephrectomized rats treated with N-ethyl-N-hydroxyethylnitrosamine.

The effects of potassium dibasic phosphate (PDP), potassium aluminum sulfate (PAS) and copper sulfate (CS) on early-stage renal carcinogenesis were investigated in unilaterally nephrectomized male Wistar rats after N-ethyl-N-hydroxyethylnitrosamine (EHEN) administration. After feeding 1,000 ppm EHEN, or basal diet for 2 weeks and removal of the left kidney at week 3, male Wistar rats were divided into 8 groups of 20 rats each. These groups received the following dietary treatments: 50,000 ppm PDP, 50,000 ppm PAS, 5,000 ppm CS or basal diet, respectively, for 18 weeks from weeks 3 to 20. The average numbers of adenomatous hyperplasias counted as preneoplastic lesions in the EHEN with 50,000 ppm PDP group were significantly higher than in the EHEN alone group or the EHEN followed by 50,000 ppm PAS or 5,000 ppm CS group. The treatment with 50,000 ppm PDP induced renal calcification and promoted the development of preneoplastic lesions in unilaterally nephrectomized rats treated with EHEN, but that with 50,000 ppm PAS or 5,000 ppm CS did not.

[Effects of sex hormones and propylthioracil on growth of transplantable rat thyroid tumor with estrogen receptor (ER)].

UNLABELLED: Effects of hormones (E2: estradiol, TP: testosterone) and propylthiouracil (PTU) on the growth of transplantable rat thyroid tumor (F2D1) having estrogen receptors were studied. Rat thyroid neoplasms, induced by N-bis (2-hydroxypropyl) nitrosamine, were inoculated subcutaneously from donor to recipient rats, in order to establish 16 transplantable rat thyroid tumor lines. The grafts were used for histological studies and for the assay of estrogen receptor (ER) and androgen receptor (AR). Of these lines, we designated papillary carcinoma, which was positive for ER (N: 12.5fmol/mg protein, Kd: 0.4nM) but negative for AR, as F2D1. For studies on the effects of sex hormones and PTU on the growth of transplantable tumors, the rats which had been inoculated with tumors were divided into the following 8 groups; (1) Intact, (2) PTU, (3) ovariectomy (OV), and (4) OV + E2 for female, and (5) Intact, (6) PTU, (7) castration (CA), and (8) CA + TP for male. RESULTS: The growth rate of F2D1 in female rats was decreased by OV, but no change was observed in OV + E2 as compared with Intact. CA and CA + TP in male rats did not influence the growth rate. PTU produced a significant increase in the growth rate in both sexes. These results demonstrate that estrogen and PTU act on the growth of ER-positive rat thyroid tumors.

Carcinogenicity study in rats of phytic acid 'Daiichi', a natural food additive.

The carcinogenicity of phytic acid 'Daiichi' (PA), a natural food additive, was examined in Fischer 344 rats of both sexes. PA was added to the drinking-water of groups of 60 male and 60 female rats at levels of 1.25 or 2.5% for 100-108 wk. There was a dose-dependent reduction in the mean final body weights of rats treated with PA. Necrosis and calcification of the renal papillae were observed in PA-treated rats, but not in the controls. The incidences of necrosis (calcification) were as follows: one (three) out of 57 males given 2.5% PA; one (none) out of 59 males given 1.25% PA; 10 (17) out of 55 females given 2.5% PA; six (six) out of 58 females given 1.25% PA. Renal papillomas occurred in three of the high-dose male rats, four of the high-dose female rats, and three of the low-dose female rats. The development of papillomas seemed to be related to calcification and necrosis of the renal papillae induced by PA. While many other tumours developed in all groups, including the controls, the organ distribution of these neoplasms and their histological characteristics did not differ significantly from those known to occur spontaneously in this strain of rats.

Possible application to medium-term organ bioassays for renal carcinogenesis modifiers in rats treated with N-ethyl-N-hydroxyethylnitrosamine and unilateral nephrectomy.

The effects of the renal tumor promoters; beta-cyclodextrin (beta-C), DL-serine (DL-S), basic lead acetate (LA), trisodium nitrilotriacetate monohydrate (NTA) and potassium bromate (KB), and diethylene glycol (DEG) as a negative control, on early stage of renal carcinogenesis were investigated in unilaterally nephrectomized male Wistar rats after N-ethyl-N-hydroxyethylnitrosamine (EHEN) administration. Wistar male rats were fed 1000 ppm EHEN diet for 2 weeks and the left kidney was removed at week 3, then the animals were divided into 7 groups of 15 rats each. These groups received the following treatments: 1000 ppm LA, 10000 ppm NTA or 500 ppm KB diet for 18 weeks from week 3; 45 mg/100 g body wt./day of beta-C injected sc for 7 days; 100 mg/100 g body wt. of DL-S injected sc biweekly for 6 weeks; 5% DEG in drinking water as a negative control for two days. Five rats in each group were killed at weeks 8, 12 and 20 and their kidneys were examined histologically. At week 20, the average numbers of adenomatous hyperplasias seen as preneoplastic lesions in the beta-C, DL-S, LA, NTA or KB groups were significantly higher than those in the DEG or control groups. Thus within a relatively short period of 20 weeks, promoting effects of chemicals can be detected as a significant increase of adenomatous hyperplasias in this model.

Relationships between serum thyroid stimulating hormone levels and development of thyroid tumors in rats treated with N-bis-(2-hydroxypropyl)nitrosamine.

Relationships between serum thyroid stimulating hormone (TSH) levels, carcinogen dose and development of thyroid tumors were studied in Wistar rats of both sexes treated with N-bis-(2-hydroxypropyl)nitrosamine (DHPN). DHPN (210 mg/100 g body wt) was injected i.p. weekly. Wistar rats were used, divided into five groups of males (M1-M5) and five groups of females (F1-F5). M1 and F1 received one injection of DHPN, M2 and F2 two injections of DHPN, M3 and F3 three injections of DHPN, M4 and F4 four injections, and M5 and F5 as control rats received saline vehicle. The resultant incidences of total thyroid tumors were 4% in group M1, 24% in M2, 80% in M3, 76% in M4, 0% in F1, 4% in F2, 20% in F3, 17% in F4 and 0% in M5 and F5. Thus dose dependence for DHPN carcinogenesis was found in both sexes for up to at least three injections of DHPN and in all cases males proved more susceptible than females. Similar results were gained for carcinomas treated separately. A sex difference in DHPN induction of thyroid tumor was thus shown for Wistar rats opposite to that reported to exist in humans. However, no clear relationship between dose of DHPN or incidence of thyroid tumors and serum TSH concentration was evident at the end of the experiment (week 30).

Immunohistochemical detection of estrogen receptors in paraffin sections of human thyroid tissues.

The optimal demonstration of estrogen receptor binding in thyroid tissues was made under conditions of 10% protease in 50 mM Tris-HCl buffer (pH 7.6) for 10 min as the pretreatment digestion step, incubation of primary antibody (ER-ICA monoclonal kit; Abbott Laboratories) at 37 degrees C for 2 h and incubation of secondary antibody (ABC kit; Vector) at 37 degrees C for 40 min. Thyroid tissues used for assessing the reaction were 17 cases of goiter, 25 adenoma cases, 27 cases of papillary carcinoma, 14 cases of follicular carcinoma and 10 latent cancer cases. Incidences of positive estrogen receptor reaction were 22% (11/51) for all thyroid cancers, 20% (5/25) for the thyroid adenomas and 59% (10/17) for goiters. 15% (4/27) of papillary carcinomas, 21% (3/14) of follicular carcinomas and 40% (4/10) of latent cancers proved positive, the estrogen receptor reaction being limited to the nuclei of thyroid follicular/papillary type cells.

Greater inhibitory effects for testosterone than castration in rat thyroid tumorigenesis initiated by N-bis(2-hydroxypropyl)nitrosamine.

The effects of testosterone and castration on thyroid tumorigenesis subsequent to initiation by N-bis(2-hydroxypropyl)nitrosamine (DHPN) were investigated in male Wistar rats. Following 2 weekly i.p. injections of DHPN at the dose of 210 mg/100 g body weight, testosterone was administered in the diet at concentrations of 0.15% or 0.03% for 28 weeks. Castration was performed on a separate group of animals 1 week after the final injection of DHPN. The incidence of thyroid adenomas and carcinomas were 69% (9/13) and 15% (2/13), respectively, in rats treated with DHPN alone, 0% (0/15) and 6% (1/15) in rats treated with DHPN and 0.15% testosterone, 13% (2/15) and 13% (2/15) in rats treated with DHPN and 0.03% testosterone and 33% (5/15) and 33% (5/15) in the castrated animals initiated by DHPN. The reduction in adenoma development associated with testosterone treatment was significant at both concentrations. In contrast, only a tendency for decrease of thyroid tumor incidence was observed in rats castrated.