Effects of occlusal hypofunction and its recovery on PDL structure and expression of VEGF and bFGF in rats.

OBJECTIVES: The purpose of this study was to clarify whether occlusal hypofunction and its recovery affect the structure of the periodontal ligament (PDL) and expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in rats. MATERIALS AND METHODS: Forty-eight Wistar rats aged 5 weeks were used and randomly divided into three groups: the hypofunctional group (HG), recovery group (RG), and control group (CG). In HG and RG, appliances were attached to the maxillary and mandibular incisors. In HG, appliances were set for 11 weeks. In RG, appliances were set for 7 weeks. Appliances were then removed at 0, 1, 3, 7, 14, and 28 days. Untreated rats served as CG. Histological sections were prepared and immunohistochemically stained for VEGF and bFGF. Three groups were evaluated for PDL area and the number of VEGF and bFGF immunopositive cells in PDL. RESULTS: The number of immunopositive cells and PDL area in CG and RG were significantly larger when compared with HG, and PDL area in RG was similar to that in CG. In the recovery process, PDL area and number of VEGF-positive cells in PDL increased from days 0 to 7 and decreased from days 7 to 28. Conversely, the number of bFGF-positive cells in PDL increased significantly after day 1 and peaked at 28 days. CONCLUSIONS: This study suggests that occlusal stimuli regulate PDL area through expression of VEGF and bFGF in rat PDL. CLINICAL RELEVANCE: Occlusal stimuli are able to regulate the expression of VEGF and bFGF in PDL cells, and these growth factors may lead to alveolar bone remodeling in PDL.

Considerations about L2- and L1-norm regularizations for ultrasound reverberation characteristics imaging and vectoral Doppler measurement.

The L1-norm regularization is applied to ultrasonic reverberation characteristics imaging and vectoral Doppler measurement, of which performances are compared with those of L2-norm regularizations. The L1 regularization yields the sharper image than the L2 regularization. Alternatively, for the Doppler measurement, the L1 regularization yields less accuracy than the L2 regularization. Clinical Relevance- This study will permit us to perform quantitative ultrasonic reverberation characteristics and accurate vectoral Doppler observation.

Deep-Learning for High Quality and High Quantitative Ultrasonic Echo Imaging.

This paper performs in simulations deep learning (DL) for high quality and high quantitative ultrasonic (US) echo imaging: (i) reduction of multiple echoes (multiple reverberations) and (ii) grading lobe echoes, (iii) separation of multiply crossed waves in US echo images, (iv) US attenuation correction imaging and (v) superresolutioned reflection and scattering imaging. In addition, (vi) segmentations of benign and malignant (cancerous) tumors in breast tissues are also performed. Clinical Relevance- This study about DL suggests the possibility of DL US segmentation for the automatic differential diagnosis about the human in vivo breast tumors in conjunction with the surrounding DL models.

The dialectical self-concept: contradiction, change, and holism in East asian cultures.

Naïve dialecticism refers to a set of East Asian lay beliefs characterized by tolerance for contradiction, the expectation of change, and cognitive holism. In five studies, the authors examined the cognitive mechanisms that give rise to global self-concept inconsistency among dialectical cultures. Contradictory self-knowledge was more readily available (Study 1) and simultaneously accessible (Study 2) among East Asians (Japanese and Chinese) than among Euro-Americans. East Asians also exhibited greater change and holism in the spontaneous self-concept (Study 1) and inconsistency in their implicit self-beliefs (Study 3). Cultural differences in self-concept inconsistency were obtained when controlling for alternative explanatory variables, including self-criticism (Study 4) and self-concept certainty (Studies 2 and 3) and were fully mediated by a direct measure of dialecticism (Study 5). Naïve dialecticism provides a comprehensive theoretical framework for understanding these cultural differences and the contradictory, changeable, and holistic nature of the East Asian self-concept.

Inhibition by 3-amino-1H-1,2,4-triazole of hepatic tumorigenesis induced by diethylstilbestrol alone or combined with N-nitrosobutylurea in WF rats.

Six groups of inbred male WF rats were castrated at 40 days of age. Group 1 was given no further treatment; groups 3-6 received sc implantations of 5.0 mg diethylstilbestrol [(DES) CAS: 56-53-1]. At 50-55 days of age, groups 5 and 6 were given drinking water containing 5.0 mg N-nitrosobutylurea [(NBU) CAS: 869-01-2] per day for 30 days. After the termination of NBU treatment, groups 2, 4, and 6 were given 3-amino-1H-1,2,4-triazole (AT), considered an inhibitor of hydroperoxidases, in the drinking water throughout the experiment. Castrated male rats or rats castrated and treated with AT alone developed neither hepatic tumors nor pituitary tumors. The hepatic tumor incidence, the size and total number of hepatic tumors, and the mean liver weight were significantly reduced in rats given the DES-NBU combination and slightly reduced in rats given DES alone when AT was administered. In contrast, AT treatment did not change the pituitary tumor incidence and the mean pituitary weight. The thyroid gland weights were approximately 7-44 times greater in AT-treated groups than those in each corresponding control group. These data indicate that AT inhibited hepatic but not pituitary tumorigenesis and caused enlargement of the thyroid gland. The present study, therefore, provides evidence that the metabolic activation of DES by oxidation is involved in rat liver carcinogenesis.

Induction of hepatic tumors by diethylstilbestrol alone or in synergism with n-nitrosobutylurea in castrated male WF rats.

Inbred male WF rats were castrated at 40 days of age and divided into 5 groups. Group I was given no further treatment. Groups III, IV, and V received pellet implants of 5.0 mg diethylstilbestrol (DES) concurrently with castration. At 50-55 days of age, groups II, IV, and V were given drinking water containing 5.0 mg N-nitrosobutylurea (NBU) per day for 30 days (subthreshold dose). At the termination of NBU treatment, group V further received daily sc injections of 2-bromoergocryptine (CB-154; 0.4 mg/100 g body wt) four times a week throughout the experiment. None of castrated rats or rats castrated and treated with NBU alone developed hepatic tumors (HT) and pituitary tumors (PT). Incidences of HT and PT in groups III, IV, and V were 4/9 (44%) and 7/9 (78%), 15/17 (88%) and 12/17 (71%), and 17/20 (85%) and 4/20 (20%), respectively. The treatment of DES alone resulted in the concurrent development of HT and PT in castrated male rats (group III), and further NBU treatment significantly increased the incidence of HT (group IV). CB-154 treatment did not change the incidence of HT, the number of HT per rat, and the liver weight, although it significantly reduced the incidence of PT, the pituitary weight, and the serum prolactin level in castrated male rats given DES and NBU (group V). These results indicate that DES itself had a direct carcinogenic effect on the liver; this effect was not mediated by prolactin, and NBU increased the effect of DES in this process.

Effects of 17 beta-estradiol and diethylstilbestrol on concurrent development of hepatic, mammary, and pituitary tumors in WF rats: evidence for differential effect on liver.

17 beta-Estradiol [(E2) CAS: 50-28-2; estradiol] and diethylstilbestrol [(DES) CAS: 56-53-1; alpha-alpha'-diethyl-4,4'-stilbenediol] were compared to determine their tumor-inducing abilities in tissue. After castration at 40 days of age, inbred male WF rats received a pellet of either 5.0 mg DES or 5.0 mg E2. Approximately half of the rats that had been given DES or E2 were further given at 50-55 days of age 5.0 mg N-nitrosobutylurea [(NBU) CAS: 869-01-2; 1-butyl-1-nitrosourea] in their drinking water each day for 30 days. None of the castrated rats given E2 alone developed hepatic tumors (HT). Even further addition of NBU did not elicit any HT. Conversely, E2 treatment as well as DES treatment, whether administrated alone or in combination with NBU, resulted in an increase in the incidence of pituitary tumors (PT) and in the mean pituitary weight. The data indicate that E2 was ineffective in inducing HT in castrated male rats, whereas E2 showed an ability to induce PT similar to that of DES. In addition, E2 was not as able to induce as many mammary tumors as DES was able to induce. There was no significant synergism between E2 and NBU in contrast to that between DES and NBU in mammary tumorigenesis, whereas these two estrogens had a similar effect in causing an increase in the pituitary weight. This study, therefore, suggests that the carcinogenic effect of estrogens may not always correlate with their estrogenic effect and further confirms the noninvolvement of prolactin in hepatic tumorigenesis.

Inhibitory effect of antiestrogen on hepatic tumorigenesis in WF rats treated with diethylstilbestrol alone or in combination with N-nitrosobutylurea.

Four groups of inbred male WF rats were castrated and received sc implantations of diethylstilbestrol [(DES) CAS: 56-53-1; alpha,alpha'-diethyl-4,4'-stilbenediol] at 40 days of age. Group I was given no further treatment; groups II and IV were treated with antiestrogen (AntiE) clomiphene citrate simultaneously with DES treatment. At 50-55 days of age, groups III and IV were given drinking water containing N-nitrosobutylurea [(NBU) CAS: 869-01-2; 1-butyl-1-nitrosourea] for 30 days. Castrated male rats or rats castrated and treated with NBU alone developed neither hepatic tumors (HT) nor pituitary tumors (PT). When AntiE was administered, incidences of HT and PT, size and the total number of HT, and mean pituitary weight were significantly reduced in rats given DES alone and in rats given DES with NBU. AntiE treatment changed the distribution in the histologic classification of hepatocellular lesions: Neoplastic nodules, instead of hepatocellular carcinomas, were predominant. The results indicate that AntiE was effective in the inhibition of hepatic and pituitary tumorigenesis associated with DES treatment. Our previous study has shown that prolactin was not involved in this hepatic tumorigenesis. Therefore, these studies provide evidence that the carcinogenic effect of DES on the liver cell is direct and that HT are regulated in development and growth by AntiE treatment.

Synergism of diethylstilbestrol and other carcinogens in concurrent development of hepatic, mammary, and pituitary tumors in castrated male rats.

Castrated male WF rats, given implants of pellets containing 5.0 mg diethylstilbestrol (DES), were given N-butyl-N-nitrosourea (NBU) in small amounts, which alone produced no mammary tumors in intact female rats. Treatment resulted in the high yield of hepatic tumors (HT), mammary tumors (MT), and pituitary tumors (PT) concurrently in each rat. If animals were further treated with prolactin, the development of HT and MT was accelerated, whereas that of PT was suppressed. None of the intact or castrated rats receiving NBU and/or prolactin developed tumors in any tissues if DES treatment was omitted. Exposure of male rats, preconditioned similarly to NBU treatment, to 200 rads of 14.1-MeV fast-neutron radiation also elicited HT, MT, and PT with an efficiency comparable to that of NBU-treated rats. These findings indicate that DES played an essential role in the whole carcinogenic process in each tissue and that castrated male rats, if conditioned properly with estrogens, are useful for the study of the carcinogenesis mechanism in these tissues.

Mammary carcinogenic effect of low-dose fission radiation in Wistar/Furth rats and its dependency on prolactin.

The mammary carcinogenic effect in rats of low-dose fission radiation and its dependency on prolactin were studied. A total of 141 female W/Fu rats were exposed to 4.8, 8.9, or 19.5 rads of fission radiation that had both fision neutrons of 2.0 million electron volts (MeV) and gamma ray components similar to those produced by the Hiroshima bomb. Only 1 of 48 rats (2.0%) developed mammary tumor (MT) after irradiation alone, whereas 20 of 48 rats (41.6%) developed MT's if prolactin was supplied shortly after irradiation by means of grafting of the prolactin-secreting pituitary tumor. Furthermore, MT's occurred in 11 of 45 rats (24.4%) treated with prolactin as late as 12 months after irradiation, which suggested the long-term survival of radiation-induced dormant MT cells. A correlation was found between the development of MT and the elevation of serum prolactin level; most MT's appeared shortly after the grafted mammotropic pituitary tumor became palpable. The growth of MT's appeared to be promoted by prolactin in collaboration with ovarian hormones; the growth of adenocarcinomas was dependent on prolactin and ovarian hormones, whereas the growth of fibroadenomas appeared to be less hormone-dependent. Much higher biologic effectiveness, especially in the low-dose range, was found with 2.0-MeV fission neutrons compared with 14.1-MeV fast neutrons or 180-kilovolt peak X-rays in rat mammary carcinogenesis.

Suppression of diethylstilbestrol and N-nitrosobutylurea-induced mammary and pituitary tumorigenesis in rats by prolonged treatment with 2-bromoergocryptine.

Inbred male W/Fu rats were castrated at 40 days of age (24) and divided into five groups. Group I was given no further treatment. Groups II, IV, and V received pellet implants of 5.0 mg diethylstilbestrol (DES) concurrently with the castration. At 50 to 55 days of age, Groups II, IV, and V were given drinking water containing 5.0 mg N-nitrosobutylurea (NBU)/day for 30 days. This amount does not induce mammary tumors (MTs) in castrated male rats (24) or in female rats (31). At the termination of NBU treatment, Group V received further daily s.c. injections of 2-bromoergocryptine (CB-154; 0.4 mg/100 g body weight) four times/week throughout the experiment. None of the castrated rats or rats castrated and treated with NBU alone developed MT or pituitary tumors (PTs). Incidences of MT and PT in Groups III, IV, and V were three of nine (33%) and seven of nine (78%), 15 of 17 (88%) and 12 of 17 (17%), and three of 20 (15%) and four of 20 (20%), respectively. The treatment with DES alone resulted in the concurrent development of MT and PT in castrated male rats (Group III), and further NBU treatment markedly accelerated the development and growth of MT (Group IV). CB-154 treatment profoundly reduced the incidences of both MT and PT in castrated male rats given DES and NBU (Group V). This treatment also depressed the increase in the number of MT per rat with MT, the pituitary and epididymis weights, and the serum prolactin levels caused by DES treatment. These results indicate that prolonged treatment with CB-154 was effective in the suppression of the concurrent tumorigenesis of mammary and pituitary glands, and the elevation of circulating prolactin levels, by counteracting the continuous stimulatory action of DES. In addition, CB-154 was able to reverse DES-enhanced growth of the epididymis in castrated male rats, suggesting a direct action of prolactin.

Inhibition of a transplantable pancreatic carcinoma by castration and estradiol administration in rats.

Influence of sex steroids on the growth of an azaserine-induced transplantable rat pancreatic carcinoma, DSL-2, was studied. This established transplantable tumor has been maintained in syngeneic rats. Inbred male Lewis rats were pretreated with castration and s.c. implantation of 1.0-mg 17 beta-estradiol (CAS: 50-28-2; estradiol) pellets at 7 weeks of age. Tumor cells were inoculated s.c. on the back of intact male, castrated male, or 17 beta-estradiol-treated castrated male rats. Additional male rats served as non-tumor-bearing controls. There was no difference in the body weight between tumor-bearing and non-tumor-bearing male rats. A distinct difference in the tumor growth was observed in variously conditioned recipients. In castrated male hosts, the serum testosterone levels and the epididymis weights were significantly decreased, and the tumor weights were significantly less as compared to intact control hosts. Additional pretreatment with 17 beta-estradiol caused a markedly slower growth of tumors and increases of the serum 17 beta-estradiol levels and the pituitary weights in castrated male recipients. The remarkable response of tumor growth to castration was also observed in a fast-growing tumor derived from DSL-2. Moreover, close positive relationships between tumor weights and the activities of both serum amylase and lipase were observed. Results showed that the pretreatment with castration alone or in combination with 17 beta-estradiol treatment was able to inhibit the growth of the transplantable tumor. In addition, tumor cells had an ability to produce amylase and lipase, and the amount of enzymic activity was related to the tumor volume. Thus, these data indicate that the transplantable rat pancreatic carcinoma retains physiological function. Our previous study has shown the modulation by sex steroids of azaserine-induced preneoplastic lesions of pancreas in rats. Therefore, androgens and estrogens may play key roles as promoters and inhibitors during the process of pancreatic carcinogenesis.

Inhibitory effects of estrogen and castration on the early stage of pancreatic carcinogenesis in Fischer rats treated with azaserine.

Effects of sex steroids on pancreatic carcinogenesis during the early stage were studied in azaserine-treated rats of both sexes. Fischer rats were given weekly i.p. injections of azaserine (30 mg/kg) [CAS:115-02; diazoacetate serine(ester)] at 2 and 3 weeks of age and were divided into six groups. Castration, ovariectomy, and s.c. implantations of either a 0.3-mg or a 1.0-mg 17 beta-estradiol (CAS:50-28.2; estradiol) pellet were performed at 7 weeks of age. The groups were as follows: group 1, intact male; group 2, castrated; group 3, castrated plus 0.3 mg estradiol; group 4, castrated plus 1.0 mg estradiol; group 5, ovariectomized; and group 6, intact female. Rats were killed 4 months after the last injection of azaserine. Azaserine treatment induced atypical acinar cell foci and nodules (AACN) in both sexes. The acidophilic AACN are considered preneoplastic lesions. An apparent sex difference was observed; the number of acidophilic AACN was greater in male rats than in female rats. Castration caused a significant decrease in both the serum testosterone levels and the number of acidophilic AACN, which were comparable to those in ovariectomized female rats. Furthermore, when estradiol treatment was administered to the castrated male rats, a linear decrease in the number of acidophilic AACN and an elevation in the serum estradiol levels were observed and were dose dependent. There were also positive relationships between estradiol treatments and the mean pituitary and pancreas weights. These results showed that estradiol treatment and the drop in testosterone levels caused by castration were highly effective in inhibiting the development and growth of preneoplastic lesions of the pancreas of the rats treated with azaserine. This estradiol effect was dose dependent. The present study, therefore, provides evidence that estrogen may act as an inhibitor and androgen as a promoter in the early stage of pancreatic carcinogenesis in rats.

Plural spectral frequency divisions for ultrasonic tissue displacement vector measurement.

For a human tissue displacement vector or strain tensor measurement, the plural spectral frequency division method (PSFDM) is presented. In this report, the effectiveness of the processing is demonstrated by performing the measurements on an agar phantom interrogated by wideband ultrasonic (US) single beam scanning and compounding of steered plane wave transmissions.

Characterization of histamine release in digitonin-permeabilized rabbit platelets.

To manipulate the intracellular milieu of rabbit platelets, permeabilization was performed using digitonin. Permeabilized platelets showed dose-dependent release of histamine, which was stored in granules of rabbit platelets, in response to extracellular calcium ion. As PMA stimulated the release reaction in digitonin-permeabilized platelets, the protein kinase C system, which regulates metabolic processes and cell reactions in intact platelets, was revealed to be working. Cupric phenanthroline also released histamine from permeabilized rabbit platelets dose-dependently, and dithiothreitol inhibited the release strongly. Since cupric phenanthroline is a mild oxidant which catalyzes the formation of disulfide bridges, as in the case of Ca2+-ATPase of sarcoplasmic reticulum, the results suggested that protein cross-linking is implicated in the regulation of the release reaction in permeabilized rabbit platelets.

The presence of catechol-o-methyltransferase activity in separately cultured cerebromicrovascular endothelial and smooth muscle cells.

The activity of catechol-o-methyltransferase (COMT) was investigated in cultured and propagated cerebromicrovascular endothelial and smooth muscle cells using high performance liquid chromatography and immunocytochemistry. The existence of COMT was detected in both cell types. The demonstration of this enzyme activity in the cerebromicrovascular smooth muscle cells, in addition to the endothelium, indicates that the enzymatic barrier to catecholamine is not limited to capillaries, the main constituents of the blood-brain barrier.

A robust numerical solution to reconstruct a globally relative shear modulus distribution from strain measurements.

To noninvasively quantify tissue elasticity for differentiating malignancy of soft tissue, we previously proposed a two-dimensional (2-D) mechanical inverse problem in which simultaneous partial differential equations (PDE's) represented the target distribution globally of relative shear moduli with respect to reference shear moduli such that the relative values could be determined from strain distributions obtained by conventional ultrasound (US) or nuclear magnetic resonance (NMR) imaging-based analysis. Here, we further consider the analytic solution in the region of interest, subsequently demonstrating that the problem is inevitably ill-conditioned in real-world applications, i.e., noise in measurement data and improper configurations of mechanical sources/reference regions make it impossible to guarantee the existence of a stable and unique target global distribution. Next, based on clarification of the inherent problematic conditions, we describe a newly developed numerical-based implicit-integration approach that novelly incorporates a computationally efficient regularization method designed to solve this differential inverse problem using just low-pass filtered spectra derived from strain measurements. To evaluate method effectiveness, reconstructions of the global distribution are carried out using intentionally created ill-conditioned models. The resultant reconstructions indicate the robust solution is highly suitable, while also showing it has high potential to be applied in the development of an effective yet versatile diagnostic tool for quantifying the distribution of elasticity in various soft tissues.

An effective ultrasonic strain measurement-based shear modulus reconstruction technique for superficial tissues--demonstration on in vitro pork ribs and in vivo human breast tissues.

An effective shear modulus reconstruction technique is described which uses ultrasonic strain measurements for diagnosis of superficial tissues, i.e. our previously developed ultrasonic strain measurement and shear modulus reconstruction methods are combined and enhanced. The technique realizes very low computational load, yet yields fairly high quantitativeness, high stability and spatial resolution, and large dynamic range. The suitability of the method is demonstrated on in vitro pork ribs and in vivo human breast tissues (fibroadenoma and scirrhous carcinoma).

Estimation of shear modulus distribution in soft tissue from strain distribution.

In order to obtain noninvasively quantitative static mechanical properties of living tissue, we propose a new type of inverse problem by which the spatial distribution of the relative elastic modulus of the tissue can be estimated only from the deformation or strain measurement. The living tissue is modeled as a linear isotropic incompressible elastic medium which has the spatial distribution of the shear modulus, and the deformation or strain is supposedly measured ultrasonically. Assuming that there is no mechanical source in the region of interest, we derive a set of linear equations in which unknowns are the spatial derivatives of the relative shear modulus, and the coefficients are the strain and its spatial derivatives. By solving these equations, the spatial derivatives of the relative shear modulus are determined throughout the region, from which the spatial distribution of the relative shear modulus is obtained by spatial integration. The feasibility of this method was demonstrated using the simulated deformation data of the simple inclusion problem. The proposed method seems promising for the quantitative differential diagnosis on the lesion in the tissue in vivo.

Fine elasticity imaging utilizing the iterative RF-echo phase matching method.

To non-invasively quantify elasticity of soft tissue, we previously developed the iterative two-dimensional (2-D) rf-echo phase matching method for accurately measuring a 2-D displacement vector field generated in vivo in soft tissue during acquisition of two successive rf-echo data frames. We also developed a stable method for uniquely reconstructing a shear modulus distribution using strains derived from the measurement data. However, as in our measurement method a displacement is determined by using the phase characteristics of the finite local echo data as the index to iteratively search for the corresponding local data, change of the local phase characteristics due to tissue deformation deteriorates the accuracy of the determination. Thus, we improve the previous method such that, in principle, the displacement can be determined using an infinitesimal phase characteristics. That is, we incorporate an effective mechanism into the previous iterative phase matching scheme: the local size is made suitably smaller during the iterative phase matching. The demonstrated ability of measurement and reconstruction in simulation, and experiments on in vitro in pork rib and in vivo in breast tissue, shows this refinement allows not only better spatial resolution of the shear modulus image but also improved accuracy, and indicates that the improved method has a high potential to be applied for various soft tissues.