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We describe interstitial pneumonitis induced by bicalutamide prescribed to treat prostate cancer. A 78-year-old man with severe lower paralysis and a bladder/rectal disorder was referred to our hospital. Prostate-specific antigen was elevated to 1418 ng/mL at that time and magnetic resonance imaging revealed multiple bone metastases. A rectal examination revealed hard nodules in the bilateral lobes of the prostate. We diagnosed prostate cancer without a biopsy, and then maximally blockaded androgens by castration and bicalutamide administration. Eight months later, he was admitted to a local hospital with breathing difficulties, and a computed tomography scan revealed interstitial pneumonitis. A physician concluded that the cause of the interstitial pneumonitis was bicalutamide, which was immediately withdrawn and replaced with prednisolone. The patient recovered over a period of 3 months. Bicalutamide-induced interstitial pneumonitis is quite rare. However, adverse reactions to maximal androgen blockade therapy should be considered and appropriate treatment for interstitial pneumonitis should be promptly initiated, as this condition is reversible.

We report a case of primary mucosa-associated lymphoid tissue (MALT) lymphoma of the prostate. A 57-year-old man complained of dysuria, nocturia, and sensation of residual urine for 3 years. The laboratory data showed that the serum prostate-specific antigen (PSA) level was 5.2 ng/mL. A physical examination revealed mild prostate enlargement and no lymphadenopathy. Magnetic resonance imaging (MRI) suggested benign prostatic hyperplasia. A transrectal ultrasound-guided prostate needle biopsy was performed and the prostatic tissues of the biopsy showed the features of MALT lymphoma. And then complete clinical investigation, including bone marrow biopsy and positron emission tomography (PET), did not show any other involved site. The patient was diagnosed as having extranodal marginal zone B cell MALT-type lymphoma of the prostate, low grade and stage I. He received external beam radiation therapy to the prostate with a total dose of 44 Gy in 22 fractions. A follow-up biopsy of the prostate was performed 12 months after the radiation therapy. The immunohistochemical analysis showed no evidence of disease. He became free of disease within the following 24 months.

This retrospective study was designed to examine the applicability of in situ hybridization to the study of numeric chromosome aberrations in conventionally fixed, embedded tissue sections of human prostate cancers. By use of in situ hybridization with chromosome-specific DNA probes, the copy number of pericentromeric sequences on chromosomes 7, 11, 17 X, and Y was detected within interphase nuclei in formalin-fixed and paraffin-embedded tissue specimens from 21 patients with adenocarcinoma of the prostate. The percentage of hyperdiploid cells (3 or more spots) was estimated by using light microscopy. The percentage of hyperdiploid cells for chromosomes 7 and 17 was highly correlated with increasing tumor Mostofi grade (P<0.05, Spearman rank correlation) or increasing Gleason score (P<0.05). The percentage of hyperdiploid cells for chromosome 11 was not correlated with either tumor Mostofi grade or Gleason score (P>0.05). Since high tumor grade is indicative of more aggressive tumor behavior and a worse prognosis, these findings suggest that the percentage of hyperdiploid cells may be highly predictive of prostate tumor aggressiveness. Our preliminary results suggest that measurement of numeric chromosome aberrations using in situ hybridization in prostate cancer may serve as a predictive factor for the prognosis of prostate cancer.[PUBLICATION ABSTRACT]

In service engineering,a service is represented as a functional structure that satisfies customer requirements.Specific entities and their activities are associated with a functional structure as a way to accomplish a goal.In this phase,it is important for service designers to have broad knowledge,since entities that construct a service include both human and physical products.Therefore,the extent of the designer＇s knowledge is the key to the enhancement of design solutions.However,few tools to support designers in the embodiment phase have been proposed.In this paper,for the purpose of constructing a function embodiment knowledge base in service design,the representational form of knowledge is proposed,and a prototype system of function embodiment knowledge base is established.Then function embodiment knowledge is collected from multiple service cases using the prototype system,and the effectiveness of knowledge base is discussed.

Elucidation of neural circuit functions requires visualization of the fine structure of neurons in the inner regions of thick brain specimens. However, the tissue penetration depth of laser scanning microscopy is limited by light scattering and/or absorption by the tissue. Recently, several optical clearing reagents have been proposed for visualization in fixed specimens. However, they require complicated protocols or long treatment times. Here we report the effects of 2,2'-thiodiethanol (TDE) solutions as an optical clearing reagent for fixed mouse brains expressing a yellow fluorescent protein. Immersion of fixed brains in TDE solutions rapidly (within 30 min in the case of 400-µm-thick fixed brain slices) increased their transparency and enhanced the penetration depth in both confocal and two-photon microscopy. In addition, we succeeded in visualizing dendritic spines along single dendrites at deep positions in fixed thick brain slices. These results suggest that our proposed protocol using TDE solution is a rapid and useful method for optical clearing of fixed specimens expressing fluorescent proteins.

In vivo two-photon microscopy utilizing a nonlinear optical process enables, in living mouse brains, not only the visualization of morphologies and functions of neural networks in deep regions but also their optical manipulation at targeted sites with high spatial precision. Because the two-photon excitation efficiency is proportional to the square of the photon density of the excitation laser light at the focal position, optical aberrations induced by specimens mainly limit the maximum depth of observations or that of manipulations in the microscopy. To increase the two-photon excitation efficiency, we developed a method for evaluating the focal volume in living mouse brains. With this method, we modified the beam diameter of the excitation laser light and the value of the refractive index in the immersion liquid to maximize the excitation photon density at the focal position. These two modifications allowed the successful visualization of the finer structures of hippocampal CA1 neurons, as well as the intracellular calcium dynamics in cortical layer V astrocytes, even with our conventional two-photon microscopy system. Furthermore, it enabled focal laser ablation dissection of both single apical and single basal dendrites of cortical layer V pyramidal neurons. These simple modifications would enable us to investigate the contributions of single cells or single dendrites to the functions of local cortical networks.

Glucose is a significant energy resource for maintaining physiological activities, including body temperature homeostasis, and glucose homeostasis is tightly regulated in mammals. Although ambient temperature tunes glucose metabolism to maintain euthermia, the significance of body temperature in metabolic regulation remains unclear owing to strict thermoregulation. Activation of Qrfp neurons in the preoptic area induced a harmless hypothermic state known as Q-neuron–induced hypothermia and hypometabolism (QIH), which is suitable for studying glucose metabolism under hypothermia. In this study, we observed that QIH mice had hyperinsulinemia and insulin resistance. This glucose hypometabolic state was abolished by increasing the body temperature to euthermia. Moreover, QIH-mediated inappetence and locomotor inactivity were recovered in euthermia QIH mice. These results indicate that body temperature is considerably more powerful than ambient temperature in regulating glucose metabolism and behavior, and the glucose hypometabolism in QIH is secondary to hypothermia rather than modulated by Qrfp neurons. QIH is a hibernation-like state characterized by hypothermia and hypometabolism, yet its glucose metabolic profile remains unclear. In this study, the authors used the QIH model and discovered that a diabetes-like state is induced by hypothermia.

The suprachiasmatic nucleus (SCN) of the hypothalamus is the master circadian clock in mammals. SCN neurons exhibit circadian Ca 2+ rhythms in the cytosol, which is thought to act as a messenger linking the transcriptional/translational feedback loop (TTFL) and physiological activities. Transcriptional regulation occurs in the nucleus in the TTFL model, and Ca 2+ -dependent kinase regulates the clock gene transcription. However, the Ca 2+ regulatory mechanisms between cytosol and nucleus as well as the ionic origin of Ca 2+ rhythms remain unclear. In the present study, we monitored circadian-timescale Ca 2+ dynamics in the nucleus and cytosol of SCN neurons at the single-cell and network levels. We observed robust nuclear Ca 2+ rhythm in the same phase as the cytosolic rhythm in single SCN neurons and entire regions. Neuronal firing inhibition reduced the amplitude of both nuclear and cytosolic Ca 2+ rhythms, whereas blocking of Ca 2+ release from the endoplasmic reticulum (ER) via ryanodine and inositol 1,4,5-trisphosphate (IP 3 ) receptors had a minor effect on either Ca 2+ rhythms. We conclude that the in-phasic circadian Ca 2+ rhythms in the cytosol and nucleus are mainly driven by Ca 2+ influx from the extracellular space, likely through the nuclear pore. It also raises the possibility that nuclear Ca 2+ rhythms directly regulate transcription in situ.

Jasmonates regulate plant defense and development. In Arabidopsis (Arabidopsis thaliana), JASMONATE-ASSOCIATED VQMOTIF GENE1 (JAV1/VQ22) is a repressor of jasmonate-mediated defense responses and is degraded through the ubiquitin-26S proteasome system after herbivory. We found that JAV1-ASSOCIATED UBIQUITIN LIGASE1 (JUL1), a RING-type E3 ubiquitin ligase, interacted with JAV1. JUL1 interacted with JAV1 in the nucleus to ubiquitinate JAV1, leading to proteasomal degradation of JAV1. The transcript levels of JUL1 and JAV1 were coordinately and positively regulated by the CORONATINE INSENSITIVE1-dependent signaling pathway in the jasmonate signaling network, but in a manner that was not dependent on CORONATINE INSENSITIVE1-mediated signaling upon herbivory by Spodoptera litura. Gain or loss of function of JUL1 modulated the expression levels of the defensin gene PDF1.2 in leaves, conferring on the plants various defense properties against the generalist herbivore S. litura. Because neither the JUL1 mutant nor overexpression lines showed any obvious developmental defects, we concluded that the JAV1/JUL1 system functions as a specific coordinator of reprogramming of plant defense responses. Altogether, our findings offer insight into the mechanisms by which the JAV1/JUL1 system acts specifically to coordinate plant defense responses without interfering with plant development or growth.