[This corrects the article DOI: 10.1016/j.chmed.2022.08.005.].

BACKGROUND/AIMS: Anti-thymocyte globulin (ATG) treatment for acute T-cell mediated rejection (TCMR) can increase the risk of cytomegalovirus (CMV) infection. We aimed to evaluate the effect of valacyclovir prophylaxis against CMV infection after ATG administration as anti-rejection therapy. METHODS: We retrospectively analyzed 55 kidney transplant recipients (KTRs) receiving ATG for steroid resistant TCMR. In all KTRs, we used intravenous ganciclovir during ATG injection. In 34 KTRs treated before July 2013, we performed preemptive therapy for CMV infection after ATG therapy. They were regarded as the historic control group (CONT). After July 2013, we used valacyclovir maintenance for 1 month after ATG therapy in 21 patients (VAL). The primary outcome was the incidence of CMV infection, and the secondary outcomes were subsequent acute rejection, and graft and patient outcome. RESULTS: Valacyclovir prophylaxis significantly reduced the incidence of CMV infection (VAL, 9.6% vs. CONT, 67.6%; p < 0.001), and CMV-free survival rate was higher in the VAL group compared to the CONT group (p = 0.009). In the VAL group, two cases of CMV infection were limited to CMV viremia, but CMV disease or syndrome (n = 3) was detected in the CONT group. There was no difference in graft failure (CONT, 70.5% vs. VAL, 47.6%; p = 0.152), incidence of subsequent rejection after ATG treatment (CONT, 41.1% vs. VAL, 33.3%; p = 0.776), and graft or patient survival between the two groups. There were no major adverse events associated with valacyclovir prophylaxis. CONCLUSIONS In conclusion, valacyclovir prophylaxis is effective in the prevention of CMV infection after ATG treatment for steroid resistant TCMR.

BACKGROUND AND PURPOSE: Although sleep disturbances are common and considered a major burden for patients with Alzheimer's disease (AD), the fundamental mechanisms underlying the development and maintenance of sleep disturbance in AD patients have yet to be elucidated. The aim of this study was to examine the correlation between regional cerebral blood flow (rCBF) and sleep disturbance in AD patients using technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT). METHODS: A total of 140 AD patients were included in this cross-sectional study. Seventy patients were assigned to the AD with sleep loss (SL) group and the rest were assigned to the AD without SL group. SL was measured using the sleep subscale of the Neuropsychiatric Inventory. A whole-brain voxel-wise analysis of brain SPECT data was conducted to compare the rCBF between the two groups. RESULTS: The two groups did not differ in demographic characteristics, severity of dementia, general cognitive function, and neuropsychiatric symptoms, with the exception of sleep disturbances. The SPECT imaging analysis displayed decreased perfusion in the bilateral inferior frontal gyrus, bilateral temporal pole, and right precentral gyrus in the AD patients with SL group compared with the AD patients without SL group. It also revealed increased perfusion in the right precuneus, right occipital pole, and left middle occipital gyrus in the AD with SL group compared with the AD without SL group. CONCLUSIONS: The AD patients who experienced sleep disturbance had notably decreased perfusion in the frontal and temporal lobes and increased rCBF in the parietal and occipital regions. The findings of this study suggest that functional alterations in these brain areas may be the underlying neural correlates of sleep disturbance in AD patients.
Alzheimer Disease* ; Brain* ; Cerebrovascular Circulation ; Cognition ; Cross-Sectional Studies ; Dementia ; Frontal Lobe ; Humans ; Occipital Lobe ; Parietal Lobe ; Perfusion* ; Prefrontal Cortex ; Rabeprazole ; Temporal Lobe ; Tomography, Emission-Computed ; Tomography, Emission-Computed, Single-Photon

BACKGROUND AND PURPOSE: Nicergoline is an ergoline derivative that is used to treat cognitive deficits in cerebrovascular disease and various forms of dementia. Although therapeutic effects of nicergoline have been established, little is known about its effects on cerebral perfusion in Alzheimer's disease (AD). The aim of this study was to examine the role of nicergoline in regional cerebral blood flow (rCBF) of AD patients using technetium-99m hexa-methyl-propylene-amine-oxime single photon emission computed tomography (SPECT). METHODS: Sixteen patients with early AD underwent a comprehensive clinical assessment including cognitive testing and SPECT scans before and after nicergoline treatment. Nicergoline (30 mg twice daily) was administered for an average duration of 1.5 years. Clinical and cognitive functioning was assessed using the Mini-Mental State Examination, Clinical Dementia Rating (CDR), CDR-Sum of Boxes, Global Deterioration Scale, Barthel Activities of Daily Living Index, Instrumental Activities of Daily Living, and Geriatric Depression Scale. RESULTS: Nicergoline treatment induced changes in the severity of dementia, cognitive function, activities of daily living, and depressive symptoms, which were not statistically significant. During the follow-up, the patients showed significant increases in their relative rCBF in the superior frontal gyrus, precentral gyrus, and postcentral gyrus. CONCLUSIONS: Nicergoline treatment improves perfusion of the frontal and parietal regions in early AD patients. It is possible that the increased perfusion in the superior frontal gyrus may be related to the mechanisms that delay or prevent progressive deterioration of cognitive functions in AD.
Activities of Daily Living ; Alzheimer Disease* ; Cerebrovascular Circulation ; Cerebrovascular Disorders ; Cognition ; Cognition Disorders ; Dementia ; Depression ; Ergolines ; Follow-Up Studies ; Frontal Lobe ; Humans ; Nicergoline* ; Parietal Lobe ; Perfusion* ; Pilot Projects* ; Prefrontal Cortex ; Somatosensory Cortex ; Therapeutic Uses ; Tomography, Emission-Computed, Single-Photon

BACKGROUND AND PURPOSE: Although acetyl-L-carnitine (ALC) treatment may have beneficial effects on Alzheimer's disease (AD), its underlying neural correlates remain unclear. The purpose of this study was to investigate cerebral perfusion changes after ALC treatment in AD patients using technetium-99m hexamethylpropylene amine oxime single photon emission computed tomography (SPECT). METHODS: A total of 18 patients with early AD were prospectively recruited and treated with ALC at 1.5 g/day for 1.4±0.3 years. At baseline and follow-up, brain SPECT, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), and Neuropsychiatric Inventory (NPI) were used to assess participants. After ALC administration, changes in brain perfusion, severity of dementia, cognitive performance, and neuropsychiatric disturbances were examined. RESULTS: After ALC administration, changes in scores of MMSE, CDR, GDS, and NPI were not statistically significant (p>0.05). Voxel-wise whole-brain image analysis revealed that perfusion was significantly (p<0.001) increased in the right precuneus whereas perfusion was reduced in the left inferior temporal gyrus (p<0.001), the right middle frontal gyrus (p<0.001), and the right insular cortex (p=0.001) at follow-up. CONCLUSIONS: Although previous studies have suggested that AD patients generally demonstrate progressive deterioration in brain perfusion and clinical symptoms, this study reveals that the perfusion of the precuneus is increased in AD patients after ALC administration and their cognitive and neuropsychiatric symptoms are not aggravated. Further studies are warranted to determine the potential association between perfusion increase in the precuneus and clinical symptoms after ALC treatment in AD patients.
Acetylcarnitine* ; Alzheimer Disease* ; Brain ; Cerebral Cortex ; Cognition ; Dementia ; Follow-Up Studies ; Humans ; Parietal Lobe ; Perfusion* ; Prospective Studies ; Temporal Lobe ; Tomography, Emission-Computed, Single-Photon*

BACKGROUND AND PURPOSE: Although the treatment efficacy of memantine in Parkinson's disease dementia (PDD) has been reported after several weeks of administration, the long-term effects on brain perfusion and clinical symptoms remain unclear. The current study aimed to follow-up PDD patients after 18 months of memantine treatment using (99m)Tc hexamethylpropylene amine oxime single photon emission computed tomography (SPECT). METHODS: A total of 15 patients with PDD and 11 healthy participants were recruited into this study and they were assessed with brain SPECT, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), and Neuropsychiatric Inventory (NPI). Differences in regional cerebral blood flow (rCBF) between the two groups were evaluated at baseline. After 18 months of memantine administration, changes in brain perfusion, severity of dementia, cognition, and neuropsychiatric disturbances were examined in the patients with PDD. RESULTS: The PDD group showed hypoperfusion in most of the cortical, subcortical, and cerebellar areas compared to healthy controls at baseline. At the follow-up, changes in rCBF, CDR (p=0.32), sum of box of CDR (p=0.49), MMSE (p=0.61), GDS (p=0.79), and NPI (p=0.23) were not significant in the PDD patients. CONCLUSIONS: Our findings implicate that memantine may delay the progression of brain perfusion deficits and clinical symptoms of PDD in the long term.
Brain ; Cerebrovascular Circulation ; Cognition ; Dementia* ; Follow-Up Studies ; Healthy Volunteers ; Humans ; Memantine* ; Parkinson Disease ; Perfusion* ; Prospective Studies* ; Tomography, Emission-Computed, Single-Photon* ; Treatment Outcome

BACKGROUND AND PURPOSE: Although subjective cognitive impairment (SCI) is often accompanied by Parkinson's disease (PD) and may predict the development of mild cognitive impairment or dementia, longitudinal brain perfusion changes in PD patients with SCI remain to be elucidated. The current prospective study examined cerebral perfusion changes in PD patients with SCI using technetium-99m hexamethylpropylene amine oxime single photon emission computed tomography (SPECT). METHODS: Among 53 PD patients at baseline, 30 patients were classified into the PD with SCI group and 23 patients were assigned to the PD without SCI group. The mean follow-up interval was 2.3±0.9 years. The Mini-Mental State Examination, Clinical Dementia Rating, and Global Deterioration Scale were used to assess impairments in cognitive function. Brain SPECT images were acquired at baseline and follow-up. RESULTS: Significant differences between the two groups were not found for demographic variables, PD severity, or cognitive function at either baseline or follow-up. At baseline, the PD with SCI group showed decreased perfusion in the left angular gyrus compared to the PD without SCI group. Longitudinal analysis revealed widespread perfusion reductions primarily in the bilateral temporo-parieto-occipital areas and cerebellum in the PD with SCI group. Relative to the PD without SCI group, an excessive decrease of perfusion was found in the left middle frontal gyrus of the PD with SCI patients. CONCLUSIONS: Our findings suggest that perfusion deficits in the middle frontal area may play an important role in the pathophysiology of SCI in PD.
Brain ; Cerebellum ; Cognition ; Cognition Disorders* ; Dementia ; Follow-Up Studies ; Humans ; Mild Cognitive Impairment ; Parietal Lobe ; Parkinson Disease* ; Perfusion* ; Prospective Studies ; Tomography, Emission-Computed, Single-Photon

The C-terminal domain of RNA polymerase II is an unusual series of repeated residues appended to the C-terminus of the largest subunit and serves as a flexible binding scaffold for numerous nuclear factors. The binding of these factors is determined by the phosphorylation patterns on the repeats in the domain. In this study, we generated a synthetic antibody library by replacing the third heavy chain complementarity-determining region of an anti-HER2 (human epidermal growth factor receptor 2) antibody (trastuzumab) with artificial sequences of 7–18 amino-acid residues. From this library, antibodies were selected that were specific to serine phosphopeptides that represent typical phosphorylation patterns on the functional unit (YSPTSPS)₂ of the RNA polymerase II C-terminal domain (CTD). Antibody clones pCTD-1stS2 and pCTD-2ndS2 showed specificity for peptides with phosphoserine at the second residues of the first or second heptamer repeat, respectively. Additional clones specifically reacted to peptides with phosphoserine at the fifth serine of the first repeat (pCTD-1stS5), the seventh residue of the first repeat and fifth residue of the second repeat (pCTD-S7S5) or the seventh residue of either the first or second repeat (pCTD-S7). All of these antibody clones successfully reacted to RNA polymerase II in immunoblot analysis. Interestingly, pCTD-2ndS2 precipitated predominately RNA polymerase II from the exonic regions of genes in genome-wide chromatin immunoprecipitation sequencing analysis, which suggests that the phosphoserine at the second residue of the second repeat of the functional unit (YSPTSPS)2 is a mediator of exon definition.
Antibodies ; Chromatin Immunoprecipitation ; Clone Cells ; Complementarity Determining Regions ; DNA-Directed RNA Polymerases* ; Exons* ; Peptides ; Phosphopeptides ; Phosphorylation* ; Phosphoserine ; Receptor, Epidermal Growth Factor ; RNA Polymerase II* ; RNA* ; Sensitivity and Specificity ; Serine

The aim of the study was to investigate the inhibitory effects of calcium against intestinal cancer in vitro and in vivo. We first investigated the effects of calcium treatment in HCT116 and HT29 human colon cancer cells. At the concentration range of 0.8-2.4 mM, calcium significantly inhibited cell growth (by 9-29%), attachment (by 12-26%), invasion (by 15-31%), and migration (by 19-61%). An immunofluorescence microscope analysis showed that the treatment with calcium (1.6 mM) for 24 h increased plasma membrane beta-catenin but decreased nuclear beta-catenin levels in HT29 cells. We then investigated the effect of dietary calcium on intestinal tumorigenesis in ApcMin/+ mice. Mice received dietary treatment starting at 6 weeks of age for the consecutive 8 weeks. The basal control diet contained high-fat (20% mixed lipids by weight) and low-calcium (1.4 mg/g diet) to mimic the average Western diet, while the treatment diet contained an enriched level of calcium (5.2 mg calcium/g diet). The dietary calcium treatment decreased the total number of small intestinal tumors (by 31.4%; P < 0.05). The largest decrease was in tumors which were > or = 2 mm in diameter, showing a 75.6% inhibition in the small intestinal tumor multiplicity (P < 0.001). Immunohistochemical analysis showed significantly reduced nuclear staining of beta-catenin (expressed as nuclear positivity), but increased plasma membrane staining of beta-catenin, in the adenomas from the calcium-treated groups in comparison to those from the control group (P < 0.001). These results demonstrate intestinal cancer inhibitory effects of calcium both in human colon cancer cells and Apc Min/+ mice. The decreased beta-catenin nuclear localization caused by the calcium treatment may contribute to the inhibitory action.
Adenoma ; Animals ; beta Catenin ; Calcium ; Calcium, Dietary ; Cell Membrane ; Cell Transformation, Neoplastic ; Colon ; Colonic Neoplasms ; Diet ; Fluorescent Antibody Technique ; HT29 Cells ; Humans ; Hydrazines ; Intestinal Neoplasms ; Mice