Assessment of Molecular Cytogenetic Methods for the Detection of Chromosomal Abnormalities

Some marker chromosomes and chromosome rearrangements are difficult to identify using G-bands by Giemsa staining after trypsin treatment (G-banding) alone. Molecular cytogenetic techniques, such as spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH), can help to detect chromosomal aberrations precisely. We analyzed the karyotypes in 6 cases of multiple congenital abnormalities and 1 case of spontaneous abortion (case 2). Three cases (cases 1, 6, and 7) had marker chromosomes, and 4 cases (cases 2-5) had chromosomal rearrangements. The karyotypes in cases 1, 2, and 3 were determined using FISH with probes based on the clinical findings and family histories. Spectral karyotyping (SKY) analysis in cases 4-7 showed that this method is useful and saves time. The combination of SKY and FISH analyses defi ned the range of the ring chromosome in case 7. We demonstrated that a combination of G-banding, FISH, and SKY can be applied effectively to the investigation of chromosomal rearrangement and to the detection of marker chromosome origins. We suggest the use of these methods for prenatal diagnosis, in which the inherent time limitations are particularly important

Thrombocytopenia in Preterm Infants with Intrauterine Growth Restriction

Sick preterm infants often have thrombocytopenia at birth, and this is often associated with intrauterine growth restriction (IUGR), or birth weights less than the 10th percentile. The pathogenesis of the thrombocytopenia and its importance in IUGR are still unclear. We studied the characteristics of preterm IUGR infants with thrombocytopenia. Twenty-seven singleton Japanese preterm IUGR infants were born between January 2002 and June 2007 at Okayama University Hospital. Infants with malformation, chromosomal abnormalities, alloimmune thrombocytopenia, sepsis, and maternal aspirin ingestion were excluded. The infants were divided into group A (n&#65309;8), which had thrombocytopenia within 72h after birth, and group B (n&#65309;19), which did not. There were significant differences in birth weight, head circumference, umbilical artery (UA)-pulsatility index (PI), middle cerebral artery-PI, UA-pH, UA-pO2, and UA-pCO2. The infants in group A were smaller, had abnormal blood flow patterns, and were hypoxic at birth. We speculate that the infants with thrombocytopenia were more severely growth-restricted by chronic hypoxia. Thrombocytopenia is an important parameter for chronic hypoxia in the uterine.</p

Clinical Significance of Reverse Redistribution Phenomenon for 201Tl Scintigraphy in Nonischemic Disease

The reverse redistribution phenomenon (RR) on 201Tl SPECT has been focused mainly on ischemic improvement regions after reperfusion therapy or vasospastic angina pectoris. However, RR analysis has not been used in the context of non-ischemic disease. The aim of this study was to evaluate the clinical role of RR on 201Tl SPECT in patients without a history of myocardial ischemia. We retrospectively enrolled 86 patients showing RR by myocardial perfusion SPECT and studied 75 other patients as a control group. For quantitative analysis, each 201Tl SPECT polar map was divided into 13 segments. Differences between the RR and control group were assessed with respect to patient characteristics and cardiac event-free survival using the Kaplan-Meier method. RR was detected frequently in the inferoposterior wall, septal portion of the anterior wall, and septum. The two groups showed signi_cant differences in rates of heart failure (P ＜ 0.01), hypertrophic cardiomyopathy (P ＜ 0.05), and wall motion abnormality (P ＜ 0.05), but not in the rate of event occurrence. The study demonstrated that RR on 201Tl SPECT could indicate the existence of myocardial damage ; however, it would not be a factor that determines the prognosis

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

Use of the index of pulmonary vascular disease for predicting long-term outcome of pulmonary arterial hypertension associated with congenital heart disease

AimsLimited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH.MethodsThis retrospective study examined lung pathology images of 764 patients with CHD-PAH aged &lt;20 years whose lung specimens were submitted to the Japanese Research Institute of Pulmonary Vasculature for pulmonary pathological review between 2001 and 2020. Clinical information was collected retrospectively by each attending physician. The primary endpoint was cardiovascular death.ResultsThe 5-year, 10-year, 15-year, and 20-year cardiovascular death-free survival rates for all patients were 92.0%, 90.4%, 87.3%, and 86.1%, respectively. The group with an IPVD of ≥2.0 had significantly poorer survival than the group with an IPVD &lt;2.0 (P = .037). The Cox proportional hazards model adjusted for the presence of congenital anomaly syndromes associated with pulmonary hypertension, and age at lung biopsy showed similar results (hazard ratio 4.46; 95% confidence interval: 1.45–13.73; P = .009).ConclusionsThe IPVD scoring system is useful for predicting the long-term outcome of CHD-PAH. For patients with an IPVD of ≥2.0, treatment strategies, including choosing palliative procedures such as pulmonary artery banding to restrict pulmonary blood flow and postponement of intracardiac repair, should be more carefully considered