令和５年度
琉球大学医学部医学科第２年次特別編入学（学士入学）
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次のアルツハイマー型認知症に関する文章を読んで設問１，２および３について簡潔・明瞭に答えなさい。

Genome-wide association studies in typical late-onset Alzheimer's disease (AD) (i.e.,after age 65) have converged on risk alleles in diverse genes mediating cholesterol andlipid regulation, synaptic network functions, and especially microgliosis (alteredmicroglia) and neuroinflammation. The most potent genetic risk factor is theapolipoprotein E (APOE) 4 variant: Heterozygosity raises AD risk 2- to 5-fold, andhomozygosity increases it >5- to 10-fold. Its pathogenic mechanism appears to involve
decreased glial-mediated clearance of Aβ from the brain's extracellular space, leading tomore amyloid in cerebral plaques and microvessels. In mice, the APOE4 protein canalso promote tau-mediated neurodegeneration and glial activation, both in the presence
and absence of amyloid. Some other AD genetic risk factors have likewise been linked
to enhanced Aβ deposition and/or the macrophage and microglial reaction to it.
Two decades ago, theories about AD pathogenesis seemed divided over the primacyof amyloid versus tau deposition. This false dichotomy has been supplanted by a
growing consensus that Aβ aggregation in the brain [indicated by declines in soluble Aβ※非公開

monomers in cerebrospinal fluid (CSF) and accrual of insoluble plaques seen on
amyloid-PET (positron emission tomography) scans] begins early in people destined todevelop AD and is followed by glia-mediated inflammation and the accumulation andspread of tau tangles in brain regions that serve cognition. Rising amounts ofextracellular Aβ lead to aggregates, including soluble oligomers, that appear to enhance
the accrual of tau tangles and altered neurites beyond the medial temporal lobe, wherethese lesions are often present in older people without AD. Such tau accumulation andspread in the brain, perhaps via neuron-to-neuron connections, seems necessary for thedevelopment of cognitive symptoms in AD. In the Aβ precursor protein transgenic
mice, deletion of the gene that encodes tau does not alter amyloid plaques but
significantly lessens their behavioral consequences. Thus, Aβ oligomerization appears
to initiate AD neuropathology, leading to altered tau in neurites and cell bodies as well
as microgliosis and blood monocyte infiltration into the brain.
alleles 対立遺伝子, heterozygosity ヘテロ接合性, accrual 発生, aggregates 凝集,oligomerization オリゴマー化, Aβ precursor protein アミロイド β 蛋白前駆物質
出典:2021 年 Scienece 8 月 6 日号に掲載された DENNIS J. SELKOE による「Treatments forAlzheimer's disease emerge」から抜粋

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次の英文は、COVID-19 感染に関わる学術論文(出典：Obstet Gynecol. 2020 ; 136 : 1109-13)の一部です。この英文を読んで解答用紙の問いに答えなさい。

Introduction：Nitric oxide is a therapeutic gas that typically is delivered at 10–80 ppm
to produce selective pulmonary vasodilation and improve arterial oxygenation. Morerecently, nitric oxide at a high dose (160–200 ppm) has demonstrated broad
antimicrobial activity on bacteria and viruses such as severe acute respiratory syndrome
coronavirus (SARS-CoV-1), the virus that caused severe acute respiratory syndrome in2003. Owing to the efficacy of inhaled nitric oxide in adults with other causes of acuterespiratory distress syndrome and pulmonary hypertension with a relatively safe
therapeutic profile, we formed an interdisciplinary team to provide nitric oxide therapy
to patients admitted to our hospital with severe or critical COVID-19 respiratory
symptoms who were rapidly deteriorating. Rescue therapies to treat or prevent
progression of coronavirus disease 2019 (COVID-19) hypoxic respiratory failure inpregnant patients are lacking.
Method：To treat pregnant patients meeting criteria for severe or critical COVID-19
with high-dose (160–200 ppm) nitric oxide by mask twice daily and report on theirclinical response.

※非公開

Experience：Six pregnant patients were admitted with severe or critical COVID-19 at
Massachusetts General Hospital from April to June 2020 and received inhalational nitricoxide therapy. All patients tested positive for severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) infection. A total of 39 treatments was administered. An
improvement in cardiopulmonary function was observed after commencing nitric oxidegas, as evidenced by an increase in systemic oxygenation in each administration session
among those with evidence of baseline hypoxemia and reduction of tachypnea in all
patients in each session. Three patients delivered a total of four neonates duringhospitalization. At 28-day follow-up, all three patients were home and their newborns
were in good condition. Three of the six patients remain pregnant after hospitaldischarge. Five patients had two negative test results on nasopharyngeal swab for
SARS-CoV-2 within 28 days from admission.
Conclusion：Nitric oxide at 160–200 ppm is easy to use, appears to be well tolerated,and might be of benefit in pregnant patients with COVID-19 with hypoxic respiratory
failure.

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