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1.
Biochem Biophys Res Commun ; 714: 149940, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38677008

ABSTRACT

Orthostatic hypotension (OH) is a common condition. Many potential etiologies of OH have been identified, but in clinical practice the underlying cause of OH is often unknown. In the present study, we identified a novel and extraordinary etiology of OH. We describe a first case of acquired severe OH with syncope, and the female patient had extremely low levels of catecholamines and serotonin in plasma, urine and cerebrospinal fluid (CSF). Her clinical and biochemical evidence showed a deficiency of the enzyme aromatic l-amino acid decarboxylase (AADC), which converts l-DOPA to dopamine, and 5-hydroxytryptophan to serotonin, respectively. The consequence of pharmacologic stimulation of catecholaminergic nerves and radionuclide examination revealed her catecholaminergic nerves denervation. Moreover, we found that the patient's serum showed presence of autoantibodies against AADC, and that isolated peripheral blood mononuclear cells (PBMCs) from the patient showed cytokine-induced toxicity against AADC. These observations suggest that her autoimmunity against AADC is highly likely to cause toxicity to adrenal medulla and catecholaminergic nerves which contain AADC, resulting in hypocatecholaminemia and severe OH. Administration of vitamin B6, an essential cofactor of AADC, enhanced her residual AADC activity and drastically improved her symptoms. Our data thus provide a new insight into pathogenesis and pathophysiology of OH.


Subject(s)
Aromatic-L-Amino-Acid Decarboxylases , Autoimmunity , Hypotension, Orthostatic , Female , Humans , Middle Aged , Aromatic-L-Amino-Acid Decarboxylases/deficiency , Autoantibodies/blood , Autoantibodies/immunology , Catecholamines , Dopamine/metabolism , Hypotension, Orthostatic/etiology , Hypotension, Orthostatic/physiopathology , Serotonin/metabolism
2.
Brain Sci ; 14(3)2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38539591

ABSTRACT

In this scoping review, we aimed to comprehensively clarify the methodology of Mental practice (MP) by systematically mapping studies documenting the application of MP to post-stroke paralytic upper-extremity function. Specifically, when is an MP intervention most commonly applied after stroke onset? What is the corresponding MP load (intervention time, number of intervention days, and intervention period)? What are the most common methods of Motor Imagery (MI) recall and MI tasks used during the application of MP? Is MP often used in conjunction with individual rehabilitation? What are the paralyzed side's upper-limb and cognitive function levels at the start of an MP intervention? The research questions were identified according to PRISMA-ScR. The PubMed, Scopus, Medline, and Cochrane Library databases were used to screen articles published until 19 July 2022. In total, 694 English-language articles were identified, of which 61 were finally included. Most of the studies were conducted in the chronic phase after stroke onset, with limited interventions in the acute or subacute phase. The most common intervention time was ≤30 min and intervention frequency was 5 times/week in MP. An audio guide was most commonly used to recall MI during MP, and 50 studies examined the effects of MP in combination with individual rehabilitation. The Fugl-Meyer Assessment mean for the 38 studies, determined using the Fugl-Meyer Assessment, was 30.3 ± 11.5. Additional research with the aim of unifying the widely varying MP methodologies identified herein is warranted.

3.
Biochem Biophys Res Commun ; 703: 149698, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38382359

ABSTRACT

The gene encoding 5'-nucleotidase domain-containing protein 2 (NT5DC2) has been associated with neuropsychiatric disorders related to the abnormality of dopamine activity in the brain. However, its physiological functions remain unclear. In this study, we analyzed the features of NT5DC2 that influence its binding with tyrosine hydroxylase (TH) and its effects on dihydroxyphenylalanine (DOPA) synthesis, using NT5DC2 overexpressed in PC12D cells by the pCMV vector. Western blot analysis revealed that the purified NT5DC2-DYKDDDDK-tag (NT5DC2-tag) protein can bind with the phosphorylated form of recombinant human TH type 1 (rhTH1), apart from the endogenous TH in PC12D cells. Proteomic analysis by mass spectrometry revealed that the purified NT5DC2-tag protein has the potential to bind to 41 proteins with multiple phosphorylation sites in PC12D cells (NT5DC2 binding proteins: positive, 391 sites/41 proteins; and negative, 85 sites/27 proteins). Overexpression of NT5DC2 in PC12D cells decreased DOPA levels in the medium. When the lysate of PC12D cells overexpressing NT5DC2 was incubated at 37 °C, the phosphorylated form of endogenous TH in PC12D cells decreased. This decrease was also detected when phosphorylated rhTH1 was incubated with purified NT5DC2-tag. Overall, our results suggest that NT5DC2 regulates DOPA synthesis by promoting the dephosphorylation of TH, similar to a phosphatase. Therefore, our study provides useful information for understanding various disorders associated with abnormalities in dopamine levels in the brain.


Subject(s)
Mixed Function Oxygenases , Tyrosine 3-Monooxygenase , Humans , Tyrosine 3-Monooxygenase/genetics , Tyrosine 3-Monooxygenase/metabolism , Phosphorylation , Mixed Function Oxygenases/metabolism , Dopamine , Carrier Proteins/metabolism , Proteomics , Dihydroxyphenylalanine/metabolism
4.
Endocr J ; 70(11): 1077-1085, 2023 Nov 28.
Article in English | MEDLINE | ID: mdl-37704414

ABSTRACT

Residual pancreatic endocrine function is important for maintaining metabolic status after pancreatectomy and is closely related to patient nutritional status and prognosis. In contrast to insulin secretion, the significance of glucagon secretion following pancreatectomy remains unclear. In this study, we assessed the changes in pancreatic glucagon secretion during pancreatectomy to determine their pathophysiological significance. We evaluated glucagon and insulin secretion using a liquid meal tolerance test before and after pancreatectomy in patients scheduled to undergo pancreaticoduodenectomy (PD) or distal pancreatectomy (DP). After pancreatectomy, fasting plasma glucagon levels were significantly decreased in both the PD (n = 10) and DP (n = 5) groups (PD: from 18.4 to 10.5 pg/mL, p = 0.037; DP: from 21.0 to 12.1 pg/mL, p = 0.043), whereas postprandial plasma glucagon levels were not changed. In the liquid meal tolerance test after pancreatectomy, 60-min plasma glucagon levels and the area under the curve (AUC) for 0-120 min of PD were significantly higher than those for DP (60-min plasma glucagon: PD 49.0 vs. DP 21.7 pg/mL, p = 0.040; AUC0-120min: PD 4,749 vs. DP 3,564 µg min/mL, p = 0.028). Postoperative plasma glucose, serum insulin, and serum C-peptide levels during the liquid meal tolerance test were not significantly different between the two groups. Although fasting plasma glucagon levels decreased, postprandial glucagon responses were maintained after both PD and DP. The difference in residual meal-stimulated glucagon response between PD and DP suggests that a relative excess of postprandial glucagon is involved in the postoperative nutritional status after PD through its impact on systemic metabolic status.


Subject(s)
Glucagon , Pancreatectomy , Humans , Pancreatectomy/adverse effects , Blood Glucose/metabolism , Pancreas/metabolism , Insulin Secretion , Insulin , Postprandial Period/physiology
5.
Acta Obstet Gynecol Scand ; 102(7): 914-920, 2023 07.
Article in English | MEDLINE | ID: mdl-37194424

ABSTRACT

INTRODUCTION: We aimed to describe physiological changes in endometrial blood flow (minute arterioles running through the endometrium) from ovulation to the mid-luteal phase using superb microvascular imaging. MATERIAL AND METHODS: The study involved 17 women (median age, 32.5 years; first to third interquartile range, 29.8-40.0 years) with regular menstrual cycles who were managed in our institute from 2020 to 2021. The uterus was delineated at the sagittal section using transvaginal ultrasonography incorporated with superb microvascular imaging. For each participant, a total of 28 cycles were observed; 17 cycles observed within one day of ovulation and the implantation period, 5-7 days (D5-7) after ovulation in the same cycle, and nine cycles in which only ovulation was observed, and two cycles in which only D5-7 was observed. Therefore, 26 and 19 images at ovulation and D5-7, respectively, were acquired. Endometrial blood flow was evaluated by depth of the vascular signal in the endometrium and categorized as follows: signals only in the basal layer of the endometrium (grade 1), reaching up to half the endometrium (grade 2), and covering the whole endometrium (grade 3). Changes in the grade of endometrial blood flow from ovulation to D5-7 after ovulation, and the relationship between the grade of endometrial blood flow and the endometrial thickness on ovulation and D5-7 after ovulation, were analyzed. Statistical significance was set at p < 0.05. RESULTS: The endometrial blood flow from ovulation to D5-7 after ovulation during the same menstrual period showed a downgrade in 14 of 17 cycles (82.3%) and no change in the remaining three cycles (17.6%), indicating a decrease in the endometrial blood flow from ovulation to D5-7 after ovulation (p = 0.001). There were differences between the grade of endometrial blood flow and median endometrial thickness on ovulation (grade 1: 5.9 mm, grade 2: 9.1 mm, and grade 3: 11.2 mm); however, no differences in the endometrial thickness were found between the grades on D5-7 after ovulation. CONCLUSIONS: In the normal menstrual cycle, endometrial blood flow decreased from ovulation to the mid-luteal phase, and the endometrial thickness in the ovulatory phase was related to the endometrial perfusion.


Subject(s)
Endometrium , Luteal Phase , Female , Humans , Adult , Endometrium/diagnostic imaging , Ovulation/physiology , Menstrual Cycle/physiology , Uterus/blood supply
6.
Surg Case Rep ; 9(1): 61, 2023 Apr 18.
Article in English | MEDLINE | ID: mdl-37071261

ABSTRACT

BACKGROUND: Rectovaginal fistula (RVF) is a troublesome and refractory complication after low anterior resection (LAR) for rectal cancer. An omental flap repair was performed for the RVF caused due to Crohn's disease and childbirth trauma. However, there are few cases of an omental flap repair for RVF after LAR. Herein, we present a successfully repaired case of RVF by omental flap coverage after LAR for rectal cancer. CASE PRESENTATION: A 50-year-old female patient with advanced rectal cancer underwent laparoscopic LAR with double-stapling technique anastomosis and achieved curative resection. She complained of a stool from the vagina and was diagnosed with RVF on the postoperative day (POD) 18. Conservative therapy was ineffective. We performed laparoscopic fistula resection and direct closure of the vagina and rectum, designed the omentum that could reach the pelvis, repaired RVF by omental flap coverage, and performed transverse colostomy on POD 25. She was discharged on initial POD 48. Seven months after the initial operation, colostomy closure was administered. There was no recurrence of RVF found 1 year after the initial operation. CONCLUSIONS: The patient achieved an omental flap coverage for RVF. We successfully performed the omental flap coverage repair in patients with RVF after the leakage of LAR. An omental flap may become an alternative treatment for muscle flap or an effective treatment for RVF.

7.
J Neural Transm (Vienna) ; 130(5): 611-625, 2023 05.
Article in English | MEDLINE | ID: mdl-36939908

ABSTRACT

The dark pigment neuromelanin (NM) is abundant in cell bodies of dopamine (DA) neurons in the substantia nigra (SN) and norepinephrine (NE) neurons in the locus coeruleus (LC) in the human brain. During the progression of Parkinson's disease (PD), together with the degeneration of the respective catecholamine (CA) neurons, the NM levels in the SN and LC markedly decrease. However, questions remain among others on how NM is associated with PD and how it is synthesized. The biosynthesis pathway of NM in the human brain has been controversial because the presence of tyrosinase in CA neurons in the SN and LC has been elusive. We propose the following NM synthesis pathway in these CA neurons: (1) Tyrosine is converted by tyrosine hydroxylase (TH) to L-3,4-dihydroxyphenylalanine (L-DOPA), which is converted by aromatic L-amino acid decarboxylase to DA, which in LC neurons is converted by dopamine ß-hydroxylase to NE; (2) DA or NE is autoxidized to dopamine quinone (DAQ) or norepinephrine quinone (NEQ); and (3) DAQ or NEQ is converted to eumelanic NM (euNM) and pheomelanic NM (pheoNM) in the absence and presence of cysteine, respectively. This process involves proteins as cysteine source and iron. We also discuss whether the NM amounts per neuromelanin-positive (NM+) CA neuron are higher in PD brain, whether NM quantitatively correlates with neurodegeneration, and whether an active lifestyle may reduce NM formation.


Subject(s)
Parkinson Disease , Humans , Parkinson Disease/metabolism , Tyrosine 3-Monooxygenase/metabolism , Cysteine/metabolism , Melanins/metabolism , Catecholamines/metabolism , Norepinephrine/metabolism , Substantia Nigra/metabolism , Dopaminergic Neurons/metabolism
8.
Front Hum Neurosci ; 17: 1313835, 2023.
Article in English | MEDLINE | ID: mdl-38298203

ABSTRACT

Introduction: Concerns regarding the ecological validity of movement-related cortical potential (MRCP) experimental tasks that are related to motor learning have recently been growing. Therefore, we compared MRCP during real movement task (RMT) and simulated movement task (SMT) from an ecological validity perspective. Methods: The participants performed both RMT and SMT, and MRCP were measured using electroencephalogram (EEG). EEG was based on the 10-20 method, with electrodes placed in the motor cortex (C3 and C4) and supplementary motor cortex (FCz [between Fz and Cz] and Cz) areas. This experiment examined the MRCP using Bereitschaftspotential (BP) and negative slope (NS') onset times, and BP, NS', and motor potential (MP) amplitudes during the task. Results: The results revealed that the SMT exhibited later BP and NS' onset times and smaller BP, NS', and MP amplitudes than the RMT. Furthermore, in RMT, the onset time of MRCP was delayed, and the amplitude of MRCP was smaller in the second half of the 200 times task than in the first half, whereas in SMT, there was no change in onset time and amplitude. The SMT showed a different MRCP than the RMT, suggesting that the ecological validity of the task should be fully considered when investigating the cortical activity associated with motor skill learning using MRCP. Conclusion: Ecological validity of the study should be fully considered when investigating the cortical activity associated with motor skill learning using MRCP. Moreover, it is important to understand the differences between the two methods when applied clinically.

9.
Front Neurol ; 14: 1298291, 2023.
Article in English | MEDLINE | ID: mdl-38259644

ABSTRACT

Introduction: Virtual reality-based mirror therapy (VRMT) has recently attracted attention as a novel and promising approach for treating upper extremity dysfunction in patients with stroke. However, the clinical efficacy of VRMT has not been investigated. Methods: This study aimed to conduct a meta-analysis to evaluate the effects of VRMT on upper extremity dysfunction in patients with stroke. We screened articles published between January 2010 and July 2022 in PubMed, Scopus, MEDLINE, and Cochrane Central Register of Controlled Trials. Our inclusion criteria focused on randomized controlled trials (RCTs) comparing VRMT groups with control groups (e.g., conventional mirror therapy, occupational therapy, physical therapy, or sham therapy). The outcome measures included the Fugl-Meyer assessment upper extremity test (FMA-UE), the box and block test (BBT), and the manual function test (MFT). Risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool 2.0. We calculated the standardized mean differences (SMD) and 95% confidence intervals (95% CI). The experimental protocol was registered in the PROSPERO database (CRD42022345756). Results: This study included five RCTs with 148 stroke patients. The meta-analysis showed statistical differences in the results of FMA-UE [SMD = 0.81, 95% CI (0.52, 1.10), p < 0.001], BBT [SMD = 0.48, 95% CI (0.16, 0.80), p = 0.003], and MFT [SMD = 0.72, 95% CI (0.05, 1.40), p = 0.04] between the VRMT and the control groups. Discussion: VRMT may play a beneficial role in improving upper extremity dysfunction after stroke, especially when combined with conventional rehabilitation. However, there were differences in the type of VRMT, stage of disease, and severity of upper extremity dysfunction. Multiple reports of high-quality RCTs are needed to clarify the effects of VRMT. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022345756.

10.
Gan To Kagaku Ryoho ; 50(13): 1548-1550, 2023 Dec.
Article in Japanese | MEDLINE | ID: mdl-38303337

ABSTRACT

The patient was a 72-year-old female. She had been taking rivaroxaban for chronic atrial fibrillation; however, she stopped taking it due to anemia and was hospitalized urgently. A contrast-enhanced computed tomography(CT)scan showed a 30 mm mass in the ascending colon, and a colonoscopy revealed ascending colon cancer(cT3, cN0, cM0, cStage Ⅱa). The tumor was hemorrhagic and was thought to have caused the anemia. On day 6 of hospitalization, another contrast- enhanced CT scan showed a poorly contrast-enhanced area in the left atrium, and transesophageal echocardiography revealed 2 left atrial thrombi(27 mm and 17 mm). Since early induction of anticoagulation therapy was considered, an emergency open right colectomy was performed to remove the cause of the bleeding. Intravenous heparin therapy was started the day after surgery and was switched to oral apixaban therapy on the fourth postoperative day. The postoperative course was good, and she was discharged home on the 17th postoperative day. This patient had conflicting clinical problems simultaneously; however, immediate decision-making and initiation of treatment were effective.


Subject(s)
Anticoagulants , Colonic Neoplasms , Heart Diseases , Hemorrhage , Thrombosis , Aged , Female , Humans , Anemia/etiology , Anticoagulants/therapeutic use , Atrial Fibrillation/drug therapy , Colonic Neoplasms/complications , Colonic Neoplasms/surgery , Heart Diseases/diagnosis , Hemorrhage/etiology , Thrombosis/diagnosis
11.
PLoS One ; 17(11): e0276694, 2022.
Article in English | MEDLINE | ID: mdl-36356043

ABSTRACT

The hypothalamus is comprised of heterogenous cell populations and includes highly complex neural circuits that regulate the autonomic nerve system. Its dysfunction therefore results in severe endocrine disorders. Although recent experiments have been conducted for in vitro organogenesis of hypothalamic neurons from embryonic stem (ES) or induced pluripotent stem (iPS) cells, whether these stem cell-derived hypothalamic neurons can be useful for regenerative medicine remains unclear. We therefore performed orthotopic transplantation of mouse ES cell (mESC)-derived hypothalamic neurons into adult mouse brains. We generated electrophysiologically functional hypothalamic neurons from mESCs and transplanted them into the supraoptic nucleus of mice. Grafts extended their axons along hypothalamic nerve bundles in host brain, and some of them even projected into the posterior pituitary (PPit), which consists of distal axons of the magnocellular neurons located in hypothalamic supraoptic and paraventricular nuclei. The axonal projections to the PPit were not observed when the mESC-derived hypothalamic neurons were ectopically transplanted into the substantia nigra reticular part. These findings suggest that our stem cell-based orthotopic transplantation approach might contribute to the establishment of regenerative medicine for hypothalamic and pituitary disorders.


Subject(s)
Hypothalamus , Mouse Embryonic Stem Cells , Animals , Mice , Hypothalamus/physiology , Axons/physiology , Neurons/physiology , Supraoptic Nucleus , Paraventricular Hypothalamic Nucleus
12.
Brain Sci ; 12(8)2022 Aug 16.
Article in English | MEDLINE | ID: mdl-36009150

ABSTRACT

Continuous repetition of motor imagery leads to mental fatigue. This study aimed to examine whether fatigue caused by motor imagery training affects improvement in performance and the change in corticospinal excitability. The participants were divided into "physical practice training" and "motor imagery training" groups, and a visuomotor task (set at 50% of maximal voluntary contraction in participants) was performed to assess the training effect on fatigue. The measurements were recorded before and after training. Corticospinal excitability at rest was measured by transcranial magnetic stimulation according to the Neurophysiological Index. Subjective mental fatigue and muscle fatigue were assessed by using the visual analog scale and by measuring the pinch force, respectively. Additionally, the error area was evaluated and calculated at pre-, mid-, and post-terms after training, using a visuomotor task. After training, muscle fatigue, subjective mental fatigue, and decreased corticospinal excitability were noted in both of the groups. Moreover, the visuomotor task decreased the error area by training; however, there was no difference in the error area between the mid- and post-terms. In conclusion, motor imagery training resulted in central fatigue by continuous repetition, which influenced the improvement in performance in the same manner as physical practice training.

13.
Front Endocrinol (Lausanne) ; 13: 941166, 2022.
Article in English | MEDLINE | ID: mdl-35903276

ABSTRACT

Human stem cell-derived organoid culture enables the in vitro analysis of the cellular function in three-dimensional aggregates mimicking native organs, and also provides a valuable source of specific cell types in the human body. We previously established organoid models of the hypothalamic-pituitary (HP) complex using human pluripotent stem cells. Although the models are suitable for investigating developmental and functional HP interactions, we consider that isolated pituitary cells are also useful for basic and translational research on the pituitary gland, such as stem cell biology and regenerative medicine. To develop a method for the purification of pituitary cells in HP organoids, we performed surface marker profiling of organoid cells derived from human induced pluripotent stem cells (iPSCs). Screening of 332 human cell surface markers and a subsequent immunohistochemical analysis identified epithelial cell adhesion molecule (EpCAM) as a surface marker of anterior pituitary cells, as well as their ectodermal precursors. EpCAM was not expressed on hypothalamic lineages; thus, anterior pituitary cells were successfully enriched by magnetic separation of EpCAM+ cells from iPSC-derived HP organoids. The enriched pituitary population contained functional corticotrophs and their progenitors; the former responded normally to a corticotropin-releasing hormone stimulus. Our findings would extend the applicability of organoid culture as a novel source of human anterior pituitary cells, including stem/progenitor cells and their endocrine descendants.


Subject(s)
Induced Pluripotent Stem Cells , Pituitary Hormones, Anterior , Pluripotent Stem Cells , Biomarkers/metabolism , Epithelial Cell Adhesion Molecule/metabolism , Humans , Organoids/metabolism , Pituitary Gland/metabolism , Pituitary Hormones, Anterior/metabolism
14.
Int J Mol Sci ; 23(8)2022 Apr 10.
Article in English | MEDLINE | ID: mdl-35456994

ABSTRACT

Parkinson's disease (PD) is an aging-related disease and the second most common neurodegenerative disease after Alzheimer's disease. The main symptoms of PD are movement disorders accompanied with deficiency of neurotransmitter dopamine (DA) in the striatum due to cell death of the nigrostriatal DA neurons. Two main histopathological hallmarks exist in PD: cytosolic inclusion bodies termed Lewy bodies that mainly consist of α-synuclein protein, the oligomers of which produced by misfolding are regarded to be neurotoxic, causing DA cell death; and black pigments termed neuromelanin (NM) that are contained in DA neurons and markedly decrease in PD. The synthesis of human NM is regarded to be similar to that of melanin in melanocytes; melanin synthesis in skin is via DOPAquinone (DQ) by tyrosinase, whereas NM synthesis in DA neurons is via DAquinone (DAQ) by tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC). DA in cytoplasm is highly reactive and is assumed to be oxidized spontaneously or by an unidentified tyrosinase to DAQ and then, synthesized to NM. Intracellular NM accumulation above a specific threshold has been reported to be associated with DA neuron death and PD phenotypes. This review reports recent progress in the biosynthesis and pathophysiology of NM in PD.


Subject(s)
Neurodegenerative Diseases , Parkinson Disease , Dopamine/metabolism , Humans , Melanins/metabolism , Monophenol Monooxygenase/metabolism , Neurodegenerative Diseases/metabolism , Parkinson Disease/metabolism , Substantia Nigra/metabolism , Tyrosine 3-Monooxygenase/metabolism
15.
eNeuro ; 9(2)2022.
Article in English | MEDLINE | ID: mdl-35437265

ABSTRACT

Hypothalamic melanin-concentrating hormone (MCH) neurons are important regulators of multiple physiological processes, such as sleep, feeding, and memory. Despite the increasing interest in their neuronal functions, the molecular mechanism underlying MCH neuron development remains poorly understood. We report that a three-dimensional culture of mouse embryonic stem cells (mESCs) can generate hypothalamic-like tissues containing MCH-positive neurons, which reproduce morphologic maturation, neuronal connectivity, and neuropeptide/neurotransmitter phenotype of native MCH neurons. Using this in vitro system, we demonstrate that Hedgehog (Hh) signaling serves to produce major neurochemical subtypes of MCH neurons characterized by the presence or absence of cocaine- and amphetamine-regulated transcript (CART). Without exogenous Hh signals, mESCs initially differentiated into dorsal hypothalamic/prethalamic progenitors and finally into MCH+CART+ neurons through a specific intermediate progenitor state. Conversely, activation of the Hh pathway specified ventral hypothalamic progenitors that generate both MCH+CART- and MCH+CART+ neurons. These results suggest that in vivo MCH neurons may originate from multiple cell lineages that arise through early dorsoventral patterning of the hypothalamus. Additionally, we found that Hh signaling supports the differentiation of mESCs into orexin/hypocretin neurons, a well-defined cell group intermingled with MCH neurons in the lateral hypothalamic area (LHA). The present study highlights and improves the utility of mESC culture in the analysis of the developmental programs of specific hypothalamic cell types.


Subject(s)
Hypothalamic Hormones , Mouse Embryonic Stem Cells , Animals , Hedgehog Proteins/metabolism , Hypothalamic Hormones/metabolism , Hypothalamus/metabolism , Melanins/metabolism , Mice , Mouse Embryonic Stem Cells/metabolism , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neurons/physiology , Orexins/metabolism , Pituitary Hormones/metabolism
16.
Support Care Cancer ; 30(6): 4981-4992, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35188584

ABSTRACT

PURPOSE: Previous evidence regarding the impact of exercise interventions on chemotherapy-induced peripheral neuropathy often focuses on lower-extremity functions, such as muscle strength and balance ability, while their effects on upper extremities remain unknown. We aimed to evaluate the efficacy of combined hand exercise intervention on upper-extremity function, symptoms, and quality-of-life in patients with chemotherapy-induced peripheral neuropathy (CIPN). METHODS: After screening 341 patients, 42 were randomly assigned to either the intervention (n = 21) or control (n = 21) group. Participants were evaluated at baseline (T0) and after one (T1) and two (T2) chemotherapy cycles. The primary outcome was upper-extremity function measured using the Michigan Hand Outcomes Questionnaire (MHQ) at T2. The intention-to-treat and as-treated populations were compared using a mixed-effect model. RESULTS: In the intention-to-treat analysis, the decline in activities of daily living of MHQ was significantly suppressed in the intervention group compared with that in the control group at T2 (difference: 7.23; 95% confidence interval: 0.35-14.10). Similarly, in the as-treated analysis, the decline in activities of daily living of MHQ was significantly suppressed in the intervention group compared with that in the control group at T2 (difference: 13.09; 95% confidence interval: 5.68-20.49). Pain also significantly improved in the intervention group compared with that in the control group at T2 (difference: 13.21; 95% confidence interval: - 22.91 to - 3.51). CONCLUSION: The combined hand exercise intervention may improve upper-extremity function, such as by suppressing decline in ADL, and reduce pain in patients with CIPN.


Subject(s)
Antineoplastic Agents , Peripheral Nervous System Diseases , Activities of Daily Living , Antineoplastic Agents/adverse effects , Exercise Therapy , Humans , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/therapy , Pilot Projects , Quality of Life , Upper Extremity
17.
Medicine (Baltimore) ; 100(45): e27738, 2021 Nov 12.
Article in English | MEDLINE | ID: mdl-34766584

ABSTRACT

OBJECTIVES: In the present study, the effect of attentional bias modification (ABM) on older outpatients, with chronic low back pain, was examined. DESIGN: This was a single-center, randomized, single-blinded, crossover trial and patients were randomly divided in a 1:1 allocation ratio into two groups: an ABM Leading group and an ABM Trailing group. PARTICIPANTS: Forty-three outpatients with chronic low back pain participated. INTERVENTIONS: Patients were evaluated four times and the treatments were ABM + Normal intervention or Normal intervention only. OUTCOMES: Outcome measures included pain intensity on the Numerical Rating Scale, the Pain Catastrophizing Scale, Fear-Avoidance Beliefs Questionnaire, Hospital Anxiety and Depression Scale, Somatic Symptom Scale-8, and EuroQol 5 Dimension-3 levels questionnaire. In addition, we performed the 30-second Chair-Stand test and the Timed Up & Go test for physical function evaluations. RESULTS: There was no change in pain intensity due to ABM. However, the total Pain Catastrophizing Scale score was significantly decreased, and the EuroQol 5 Dimension-3 levels questionnaire and 30-second chair-stand test were significantly improved (P <.05). TRIAL REGISTRATION: The Health Science Ethics Committee, Graduate School of Biomedical Sciences, Nagasaki University (permit number: 17060861), and the clinical trial was registered with UMIN (UMIN000029424).


Subject(s)
Attentional Bias , Behavior Therapy , Low Back Pain , Aged , Cross-Over Studies , Humans , Low Back Pain/therapy , Outpatients , Pilot Projects
18.
Int J Surg Case Rep ; 85: 106183, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34252642

ABSTRACT

INTRODUCTION: A decompensated cirrhosis sometimes develops collateral circulation due to severe fibrosis. Rupture of this collateral circulation can induce a fatal situation. CASE PRESENTATION: A 59-year-old man with alcoholic cirrhosis was admitted to our emergency department with a chief complaint of impaired consciousness. The patient had hypotension upon arrival, and enhanced computed tomography (CT) revealed a massive hemoperitoneum. Imaging examinations, including interventional radiography, could not identify the source of bleeding preoperatively; therefore, emergency surgery was performed. Intraoperatively, a collapsed small vessel connecting liver segment 4 and the expanded umbilical vein as collateral circulation due to portal hypertension was detected as the source of bleeding. Ligating the stump of the small vessel and postoperative intensive care saved the patient's life. The patient was discharged from our hospital 14 days after the surgery. CLINICAL DISCUSSION: A rupture of the umbilical vein associated with cirrhosis is rare and causes a critical situation because of the fast blood flow in the collateral circulation caused by portal hypertension. Moreover, the amount of bleeding tends to increase since the abdominal cavity is a free space and patients with cirrhosis have coagulopathies, including thrombocytopenia and prolonged prothrombin time. Although a retrospective review of the enhanced CT image could identify the minute findings, arterial portography was insufficient to detect bleeding from the umbilical vein. Therefore, emergency exploratory laparotomy was required for the diagnosis and treatment. CONCLUSION: Rupture of the reopened umbilical vein can cause idiopathic spontaneous hemoperitoneum in patients with decompensated cirrhosis.

19.
Nutrients ; 13(7)2021 Jun 22.
Article in English | MEDLINE | ID: mdl-34206490

ABSTRACT

Dietary content during pregnancy is important because it is necessary for the growth of the fetus. With the assumption that the nutritional status of the fetus can be monitored by measuring amino acid concentrations in the amniotic fluid, we investigated whether the habitual dietary intake of pregnant women affected the composition of the amniotic fluid and the significance of performing amniotic fluid analysis. The subjects were 34 mothers who delivered full-term babies by cesarean section. Three biological samples were collected from the mothers: blood, cord blood, and amniotic fluid. At the same time, the mothers' prenatal nutritional intake information was also recorded. When the amino acid contents of the samples were compared with the mothers' nutrient intake, many amino acids in the amniotic fluid were positively correlated with lipid intake, but not with protein intake. There was a negative correlation between lipid intake and carbohydrate intake, and the amino acid contents of the amniotic fluid were also negatively correlated with carbohydrate intake. The results of this study were consistent with those found in animal models, suggesting that the analysis of amniotic fluid may be a useful method to investigate the effects of habitual diet during human pregnancy on the fetus.


Subject(s)
Amino Acids/analysis , Amniotic Fluid/chemistry , Dietary Carbohydrates/analysis , Dietary Fats/analysis , Eating/physiology , Fetal Blood/chemistry , Adult , Diet/statistics & numerical data , Diet Surveys , Female , Fetal Development/physiology , Humans , Maternal Nutritional Physiological Phenomena , Nutrition Assessment , Pregnancy , Prenatal Care/statistics & numerical data , Reproducibility of Results
20.
ANZ J Surg ; 91(12): 2824-2826, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34180573

ABSTRACT

To decrease complications associated with the treatment of coeliac axis (CA) stenosis due to median arcuate ligament (MAL) syndrome in pancreaticoduodenectomy, we performed combined preoperative endovascular stenting and intraoperative MAL resection. This technique can secure the CA blood flow to the hepatic artery before surgery in one stage and prevent CA restenosis and stent dislocation because there is no extrinsic compression of the CA after MAL resection.


Subject(s)
Median Arcuate Ligament Syndrome , Constriction, Pathologic/surgery , Humans , Ligaments/surgery , Median Arcuate Ligament Syndrome/surgery , Pancreaticoduodenectomy/adverse effects , Stents
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