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1.
Fly (Austin) ; 16(1): 24-36, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34609265

RESUMO

Notch signalling is a well-conserved signalling pathway that regulates cell fate through cell-cell communication. A typical feature of Notch signalling is 'lateral inhibition', whereby two neighbouring cells of equivalent state of differentiation acquire different cell fates. Recently, mathematical and computational approaches have addressed the Notch dynamics in Drosophila neural development. Typical examples of lateral inhibition are observed in the specification of neural stem cells in the embryo and sensory organ precursors in the thorax. In eye disc development, Notch signalling cooperates with other signalling pathways to define the evenly spaced positioning of the photoreceptor cells. The interplay between Notch and epidermal growth factor receptor signalling regulates the timing of neural stem cell differentiation in the optic lobe. In this review, we summarize the theoretical studies that have been conducted to elucidate the Notch dynamics in these systems and discuss the advantages of combining mathematical models with biological experiments.

2.
Transl Androl Urol ; 10(10): 3756-3765, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34804819

RESUMO

Background: The treatment of impacted upper ureteral stones with hydronephrosis remains a challenge for urologists. The current study aimed to evaluate the impact of preoperative percutaneous nephrostomy (PNS) as a treatment strategy before flexible ureteroscopy (f-URS) of asymptomatic impacted upper ureteral stones with hydronephrosis. Methods: This multicenter retrospective study included patients who underwent PNS (group A, n=61) and those who did not (group B, n=75) before f-URS for asymptomatic impacted upper ureteral stones with hydronephrosis. Impacted ureteral stones are defined as those that remain in one position for >2 months. Operative outcomes, including stone-free rate, operation time, postoperative hospital days, and complication rate, were evaluated. Results: There were no significant differences in age, sex, and stone size between the two groups except in the grade of hydronephrosis, with group A having more cases of advanced hydronephrosis than group B. The stone-free rate was significantly higher in group A than in group B [95% vs. 77% (P=0.004)]. However, there were no significant differences between the groups in operation time [55 vs. 55 min (P=0.84)], postoperative fever [5% vs. 5% (P=1.00)], and postoperative hospital days [2 vs. 2 days (P=0.44)]. In group A, preoperative PNS placement was performed 4 days before f-URS, and the PNS was removed postoperatively on the same day of the f-URS. Additionally, subgroup analysis was performed in cases of grade 2 and 3 hydronephrosis. A total of 110 patients, 60 who underwent f-URS with PNS and 50 who underwent f-URS without PNS, were included. The stone-free rate was significantly higher in f-URS with PNS than in f-URS without PNS [95% vs. 76% (P=0.005)]. However, no significant differences were found between the groups in operation time, ureteral injury, postoperative fever, and postoperative hospital days. Conclusions: At grade 2 or 3 hydronephrosis, preoperative PNS as a treatment strategy for a few days prior to f-URS for impacted upper ureteral stones improved the stone-free rate without increasing the operation time and postoperative length of hospital stay.

3.
IJU Case Rep ; 4(6): 367-370, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34755058

RESUMO

Introduction: The present study showed the involvement of immunosuppressive myeloid-derived suppressor cells during the disease progression in a 69-year-old man with a prostate cancer. Case presentation: The patient with metastatic PC (cT4N1M1ab) was initially treated with primary androgen deprivation therapy for 5 months and then chemotherapy with docetaxel, but he expired at the 8th month. In order to investigate whether myeloid-derived suppressor cells are implicated in the cancer exacerbation during androgen deprivation therapy, we assessed the long-term changes in peripheral blood myeloid-derived suppressor cell fractions by using flow cytometry. While prostate-specific antigen levels decreased after androgen deprivation therapy, the population of each myeloid-derived suppressor cell subsets increased during disease deterioration. Conclusion: Increase in myeloid-derived suppressor cells populations was correlated with prostate cancer progression.

4.
IJU Case Rep ; 4(6): 371-374, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34755059

RESUMO

Introduction: Surgical resection should be considered for giant adrenal cysts if they are functional, if malignancy cannot be ruled out, or if there is a risk of bleeding. However, preventing cyst damage, including fluid leak, and ensuring a good field of view could be challenging in laparoscopic surgery. We report on our successful use of the SAND balloon catheter in laparoscopic adrenalectomy. Case presentation: The patient was a 40-year-old man with a right adrenal cyst that exhibited growth tendency. We performed laparoscopic adrenalectomy using a SAND balloon catheter through a preexisting port. Use of the catheter allowed for not only aspiration of the cyst fluid without leakage into the operative field but also gentle grasping of the cyst wall, which enabled us to easily remove the adrenal gland, including the cyst. Conclusion: Use of the SAND balloon catheter facilitates safe and easy laparoscopic resection of giant adrenal cysts.

5.
J Biosci Bioeng ; 132(5): 531-536, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34474981

RESUMO

We have constructed a new bioreactor with reciprocal mixing that is better suited for the cultivation of delicate animal cells. In-silico simulation (computational fluid dynamics) suggested both maximum and average shear stresses in the bioreactor with reciprocal mixing to be remarkably lower than in a conventional bioreactor with rotary mixing. Although we could not find any difference in growth speed and cell density between the bioreactors with reciprocal and rotary mixing, we did find cell viability in the reciprocal-mixing bioreactor to be retained longer than in the rotary-paddle bioreactor. This implied that cell culture in a bioreactor with reciprocal mixing could be prolonged for the production of target proteins. Leakage of lactate dehydrogenase activity into the culture medium was suppressed much more in the reciprocal-mixing bioreactor than in the rotary-paddle one. Production of human tissue plasminogen activator in the former system was also observed to be much higher than in the latter. Therefore, a bioreactor with reciprocal mixing was concluded to be better suited for the cultivation of animal cells and efficient production of proteins, such as antibody drugs and various growth factors.


Assuntos
Reatores Biológicos , Ativador de Plasminogênio Tecidual , Animais , Células CHO , Técnicas de Cultura de Células , Cricetinae , Cricetulus , Humanos
6.
J Neurochem ; 159(4): 778-788, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34490902

RESUMO

Corticosteroids are stress-related hormones that maintain homeostasis. The most effective corticosteroids are corticosterone (CORT) in rodents and cortisol in primates. 11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1; EC 1.1.1.146), encoded by Hsd11b1, is a key regulator of the local concentration of CORT/cortisol. Hsd11b1 expression in layer 5 of the primary somatosensory cortex has been shown in adult mice. However, its localization in the entire neocortex, especially during development, has not been fully addressed. Here, we established robust and dynamic expression profiles of Hsd11b1 in the developing mouse neocortex. Hsd11b1 was found mostly in pyramidal neurons. By retrograde tracing, we observed that some Hsd11b1-positive cells were projection neurons, indicating that at least some were excitatory. At postnatal day 0 (P0), Hsd11b1 was expressed in the deep layer of the somatosensory cortex. Then, from P3 to P8, the expression area expanded broadly; it was observed in layers 4 and 5, spanning the whole neocortex, including the primary motor cortex (M1) and the primary visual cortex (V1). The positive region gradually narrowed from P14 onwards and was ultimately limited to layer 5 of the somatosensory cortex at P26 and later. Furthermore, we administered CORT to nursing dams to increase the systemic CORT level of their pups. Here, we observed a reduced number of Hsd11b1-positive cells in the neocortex of these pups. Our observation suggests that Hsd11b1 expression in the developing neocortex is affected by systemic CORT levels. It is possible that stress on mothers influences the neocortical development of their children.

7.
Clin Case Rep ; 9(8): e04691, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34466249

RESUMO

In the cases of rapid obstruction of urethral catheter, resulting in urinary retention, due to excessive floating material, such as a large number of spherical masses, fungus balls of Candida may be present.

8.
Cereb Cortex ; 31(11): 5225-5238, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34228058

RESUMO

Association projections from cortical pyramidal neurons connect disparate intrahemispheric cortical areas, which are implicated in higher cortical functions. The underlying developmental processes of these association projections, especially the initial phase before reaching the target areas, remain unknown. To visualize developing axons of individual neurons with association projections in the mouse neocortex, we devised a sparse labeling method that combined in utero electroporation and confocal imaging of flattened and optically cleared cortices. Using the promoter of an established callosal neuron marker gene that was expressed in over 80% of L2/3 neurons in the primary somatosensory cortex (S1) that project to the primary motor cortex (M1), we found that an association projection of a single neuron was the longest among the interstitial collaterals that branched out in L5 from the earlier-extended callosal projection. Collaterals to M1 elongated primarily within the cortical gray matter with little branching before reaching the target. Our results suggest that dual-projection neurons in S1 make a significant fraction of the association projections to M1, supporting the directed guidance mechanism in long-range corticocortical circuit formation over random projections followed by specific pruning.

10.
J Neurosci ; 41(22): 4795-4808, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-33906900

RESUMO

Coordination of skilled movements and motor planning relies on the formation of regionally restricted brain circuits that connect cortex with subcortical areas during embryonic development. Layer 5 neurons that are distributed across most cortical areas innervate the pontine nuclei (basilar pons) by protrusion and extension of collateral branches interstitially along their corticospinal extending axons. Pons-derived chemotropic cues are known to attract extending axons, but molecules that regulate collateral extension to create regionally segregated targeting patterns have not been identified. Here, we discovered that EphA7 and EfnA5 are expressed in the cortex and the basilar pons in a region-specific and mutually exclusive manner, and that their repulsive activities are essential for segregating collateral extensions from corticospinal axonal tracts in mice. Specifically, EphA7 and EfnA5 forward and reverse inhibitory signals direct collateral extension such that EphA7-positive frontal and occipital cortical areas extend their axon collaterals into the EfnA5-negative rostral part of the basilar pons, whereas EfnA5-positive parietal cortical areas extend their collaterals into the EphA7-negative caudal part of the basilar pons. Together, our results provide a molecular basis that explains how the corticopontine projection connects multimodal cortical outputs to their subcortical targets.SIGNIFICANCE STATEMENT Our findings put forward a model in which region-to-region connections between cortex and subcortical areas are shaped by mutually exclusive molecules to ensure the fidelity of regionally restricted circuitry. This model is distinct from earlier work showing that neuronal circuits within individual cortical modalities form in a topographical manner controlled by a gradient of axon guidance molecules. The principle that a shared molecular program of mutually repulsive signaling instructs regional organization-both within each brain region and between connected brain regions-may well be applicable to other contexts in which information is sorted by converging and diverging neuronal circuits.


Assuntos
Orientação de Axônios/fisiologia , Efrina-A5/metabolismo , Neocórtex/embriologia , Vias Neurais/embriologia , Ponte/embriologia , Receptor EphA7/metabolismo , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neocórtex/metabolismo , Vias Neurais/metabolismo , Ponte/patologia
11.
Nat Commun ; 12(1): 2083, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33828096

RESUMO

While Delta non-autonomously activates Notch in neighboring cells, it autonomously inactivates Notch through cis-inhibition, the molecular mechanism and biological roles of which remain elusive. The wave of differentiation in the Drosophila brain, the 'proneural wave', is an excellent model for studying Notch signaling in vivo. Here, we show that strong nonlinearity in cis-inhibition reproduces the second peak of Notch activity behind the proneural wave in silico. Based on this, we demonstrate that Delta expression induces a quick degradation of Notch in late endosomes and the formation of the twin peaks of Notch activity in vivo. Indeed, the amount of Notch is upregulated and the twin peaks are fused forming a single peak when the function of Delta or late endosomes is compromised. Additionally, we show that the second Notch peak behind the wavefront controls neurogenesis. Thus, intracellular trafficking of Notch orchestrates the temporal dynamics of Notch activity and the temporal patterning of neurogenesis.


Assuntos
Encéfalo/metabolismo , Proteínas de Drosophila/metabolismo , Transporte Proteico/fisiologia , Receptores Notch/metabolismo , Animais , Diferenciação Celular , Drosophila melanogaster , Endossomos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neurogênese , Transporte Proteico/genética , Transdução de Sinais , Fatores de Transcrição , Proteínas rab de Ligação ao GTP/genética , Proteínas rab4 de Ligação ao GTP/genética
12.
Artigo em Inglês | MEDLINE | ID: mdl-33801068

RESUMO

The aim of the present study was to investigate the association among lunar cycle, menstrual cycle onset, and subjective sleep quality. Menstrual cycle onset data from the six most recent menstrual cycles were obtained for 529 women (aged 25-39 years) using the smartphone app Luna Luna. We also collected questionnaire survey data on sleep quality from each participant. Overall, there was no association between the onset of menstrual cycle and lunar phase. Interestingly, the proportion of good sleepers with menstrual cycle beginning during the light period was significantly higher than that during the dark period, while the proportion of poor sleepers with menstrual cycle beginning during the dark period was significantly higher than that during the light period. When participants were categorized by the combination of lunar phases (light, dark, neutral periods) in the two most recent menstrual cycle onsets, the "both dark period" group and the "other (light and dark) period" group showed the lowest proportion of good sleepers. Menstrual cycle onset in the dark period was associated with a deterioration in subsequent subjective sleep quality, which was more apparent with consecutive onsets in the dark period or at a rapidly changing lunar phase.


Assuntos
Menstruação , Lua , Adulto , Feminino , Humanos , Ciclo Menstrual , Reprodução , Sono
13.
BMC Health Serv Res ; 21(1): 274, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33766027

RESUMO

BACKGROUND: This study aimed to explore associations between various elements of primary care, patient satisfaction, and loyalty. METHODS: This cross-sectional study used a modified version of the Primary Care Assessment Tool (PCAT), which was adapted for Japan. We distributed the PCAT questionnaire to patients aged 20 years or older at five rural primary care centres in Japan. We confirmed the validity and reliability of the measure for our study. Next, we examined which elements of primary care were related to patient satisfaction and loyalty using Spearman's correlation and structural equation modelling. RESULTS: Of 220 eligible patients, 206 participated in this study. We developed nine component scales: first contact (regular access), first contact (urgent access), longitudinality, coordination, comprehensiveness (variety of care), comprehensiveness (risk prevention), comprehensiveness (health promotion), family-centeredness, and community orientation. Longitudinality and first contact (urgent access) were related with patient satisfaction. Longitudinality, first contact (regular access), and family-centeredness were related to patient loyalty. In the structural equation modelling analysis, two variables were significantly related to loyalty, namely a combined variable including longitudinality and first contact (regular access), along with family-centeredness. CONCLUSIONS: While a patient satisfaction model could not be distilled from the data, longitudinality, first contact (urgent access), and family-centeredness were identified as important elements for the cultivation of patient loyalty. This implies that primary care providers need to develop a deep understanding of patients' contexts and concerns and pay attention to their level of access to cultivate greater patient loyalty.


Assuntos
Satisfação do Paciente , Atenção Primária à Saúde , Adulto , Estudos Transversais , Humanos , Japão , Qualidade da Assistência à Saúde , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto Jovem
14.
Transl Androl Urol ; 10(2): 775-784, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33718079

RESUMO

Background: Holmium laser enucleation of the prostate (HoLEP) has been a widely utilized minimally invasive surgical procedure for benign prostate hyperplasia. The current study aimed to compare surgical outcomes and King's Health Questionnaire (KHQ) assessment scores following HoLEP between younger men and those aged ≥75 years. Methods: This prospective single-center study compared perioperative complications, postoperative urinary conditions, and KHQ scores (nine categories) between men aged ≥75 years (group A) and men aged <75 years (group B) before and 1, 3, and 6 months after surgery. Results: A total of 100 patients were included for analysis (group A, n=38 and group B, n=62). No differences in patient backgrounds, perioperative complications, such as perioperative decrease in hemoglobin, postoperative fever, postoperative indwelling catheterization duration, or postoperative hospitalization duration, and KHQ were observed between both groups. Both groups showed significantly better International Prostate Symptom Scores, quality of life, maximum urinary flow rate, and postvoid residual volume 1, 3, and 6 months after HoLEP compared to their respective preoperative levels (P<0.01). Regarding KHQ categories, both groups showed significantly better general health perceptions, impact on life, emotions, and sleep/energy 1 month after HoLEP; role limitations, physical limitations, and social limitations 3 months after HoLEP; and personal relationships and incontinence severity measures 6 months after HoLEP compared to their respective preoperative levels (P<0.05). Conclusions: HoLEP could be safe and effective even for men aged ≥75 years, comparing complications, urinary condition, and KHQ scores.

15.
Elife ; 102021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33666170

RESUMO

Transmembrane protein Golden goal (Gogo) interacts with atypical cadherin Flamingo (Fmi) to direct R8 photoreceptor axons in the Drosophila visual system. However, the precise mechanisms underlying Gogo regulation during columnar- and layer-specific R8 axon targeting are unknown. Our studies demonstrated that the insulin secreted from surface and cortex glia switches the phosphorylation status of Gogo, thereby regulating its two distinct functions. Non-phosphorylated Gogo mediates the initial recognition of the glial protrusion in the center of the medulla column, whereas phosphorylated Gogo suppresses radial filopodia extension by counteracting Flamingo to maintain a one axon-to-one column ratio. Later, Gogo expression ceases during the midpupal stage, thus allowing R8 filopodia to extend vertically into the M3 layer. These results demonstrate that the long- and short-range signaling between the glia and R8 axon growth cones regulates growth cone dynamics in a stepwise manner, and thus shapes the entire organization of the visual system.

16.
J Toxicol Sci ; 46(1): 31-42, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33408299

RESUMO

Nonalcoholic fatty liver disease, which has been rapidly increasing in the world in recent years, is roughly classified into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis. This study was based on our previous reports that stated that the combination treatment of N1-methylnicotinamide (MNA) and hydralazine (HYD) improves fatty liver in NAFL model rats. This finding was attributed to the MNA metabolism inhibition by HYD, which is a strong inhibitor of aldehyde oxidase (AO); this results in an increase in hepatic MNA and improved fatty liver. We hypothesized that orally administered nicotinamide (NAM), which is the precursor of MNA and is a form of niacin, would be efficiently metabolized by nicotinamide N-methyltransferase in the presence of exogenous S-adenosylmethionine (SAM) in NAFL rats. To address this issue, NAFL model rats were orally administered with NAM, SAM, and/or HYD. As a result, liver triglyceride (TG) and lipid droplet levels were barely altered by the administration of NAM, SAM, NAM+SAM, or NAM+HYD. By contrast, the triple combination of NAM+SAM+HYD significantly reduced hepatic TG and lipid droplet levels and significantly increased hepatic MNA levels. These findings indicated that the combination of exogenous SAM with AO inhibitors, such as HYD, has beneficial effects for improving fatty liver with NAM.


Assuntos
Metionina/metabolismo , Niacinamida/administração & dosagem , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Administração Oral , Aldeído Oxidase/antagonistas & inibidores , Animais , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Hidralazina/administração & dosagem , Hidralazina/farmacologia , Gotículas Lipídicas/metabolismo , Fígado/metabolismo , Masculino , Niacinamida/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ratos Sprague-Dawley , S-Adenosilmetionina/administração & dosagem , Triglicerídeos/metabolismo
17.
Hum Genet ; 140(2): 277-287, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32617796

RESUMO

CRISPR-Cas9 are widely used for gene targeting in mice and rats. The non-homologous end-joining (NHEJ) repair pathway, which is dominant in zygotes, efficiently induces insertion or deletion (indel) mutations as gene knockouts at targeted sites, whereas gene knock-ins (KIs) via homology-directed repair (HDR) are difficult to generate. In this study, we used a double-stranded DNA (dsDNA) donor template with Cas9 and two single guide RNAs, one designed to cut the targeted genome sequences and the other to cut both the flanked genomic region and one homology arm of the dsDNA plasmid, which resulted in 20-33% KI efficiency among G0 pups. G0 KI mice carried NHEJ-dependent indel mutations at one targeting site that was designed at the intron region, and HDR-dependent precise KIs of the various donor cassettes spanning from 1 to 5 kbp, such as EGFP, mCherry, Cre, and genes of interest, at the other exon site. These findings indicate that this combinatorial method of NHEJ and HDR mediated by the CRISPR-Cas9 system facilitates the efficient and precise KIs of plasmid DNA cassettes in mice and rats.


Assuntos
Sistemas CRISPR-Cas/genética , Reparo do DNA por Junção de Extremidades/genética , Técnicas de Introdução de Genes/métodos , Plasmídeos/genética , Reparo de DNA por Recombinação/genética , Animais , DNA/genética , Éxons/genética , Feminino , Edição de Genes/métodos , Genoma/genética , Íntrons/genética , Camundongos , Camundongos Endogâmicos C57BL , Mutação/genética , Ratos , Ratos Long-Evans , Ratos Wistar
18.
Cell Rep ; 33(4): 108305, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33113378

RESUMO

Columns are structural and functional units of the brain. However, the mechanism of column formation remains unclear. The medulla of the fly visual center shares features with the mammalian cerebral cortex, such as columnar and layered structures, and provides a good opportunity to study the mechanisms of column formation. Column formation is initiated by three core neurons in the medulla, namely, Mi1, R8, and R7. The proper orientation of neurons is required for the orientation and arrangement of multiple columns. Their orientations may be under the control of planar cell polarity (PCP) signaling, because it is known to regulate the orientation of cells in two-dimensional tissue structures. In this study, we demonstrate that the ligands DWnt4 and DWnt10 expressed specifically in the ventral medulla and dorsal medulla, respectively, globally regulate the columnar arrangement and orientation of Mi1 and R8 terminals through Fz2/PCP signaling in a three-dimensional space.

19.
IJU Case Rep ; 3(5): 166-169, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32914061

RESUMO

Introduction: Plasmacytoid urothelial carcinoma is a rare and aggressive variant of bladder cancer. Case presentation: A 75-year-old woman presented with plasmacytoid urothelial carcinoma with retroperitoneal dissemination was treated with chemotherapy. After an unsuccessful first-line chemotherapy with gemcitabine and cisplatin, we assessed circulating tumor cells; one such cell was found to be positive for programmed death-ligand 1. The patient received second-line chemotherapy with pembrolizumab. However, the tumor extended to the retroperitoneal organs, and the patient eventually died. Autopsy revealed a widespread diffuse scirrhous infiltration of the carcinoma into the retroperitoneum. However, distant metastasis was not observed. Conclusion: The evaluation of circulating tumor cells and autopsy revealed a disease state of progressive plasmacytoid urothelial carcinoma treated with pembrolizumab.

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