DBA/2J Genetic Background Exacerbates Spontaneous Lethal Seizures but Lessens Amyloid Deposition in a Mouse Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is a leading cause of dementia in the elderly and is characterized by amyloid plaques, neurofibrillary tangles (NFTs) and neuronal dysfunction. Early onset AD (EOAD) is commonly caused by mutations in amyloid precursor protein (APP) or genes involved in the processing of APP including the presenilins (e.g. PSEN1 or PSEN2). In general, mouse models relevant to EOAD recapitulate amyloidosis, show only limited amounts of NFTs and neuronal cell dysfunction and low but significant levels of seizure susceptibility. To investigate the effect of genetic background on these phenotypes, we generated APP^swe and PSEN1^de9 transgenic mice on the seizure prone inbred strain background, DBA/2J. Previous studies show that the DBA/2J genetic background modifies plaque deposition in the presence of mutant APP but the impact of PSEN1^de9 has not been tested. Our study shows that DBA/2J.APP^swePSEN1^de9 mice are significantly more prone to premature lethality, likely to due to lethal seizures, compared to B6.APP^swePSEN1^de9 mice—70% of DBA/2J.APP^swePSEN1^de9 mice die between 2-3 months of age. Of the DBA/2J.APP^swePSEN1^de9 mice that survived to 6 months of age, plaque deposition was greatly reduced compared to age-matched B6.APP^swePSEN1^de9 mice. The reduction in plaque deposition appears to be independent of microglia numbers, reactive astrocytosis and complement C5 activity.     

Fleshing Out Vulnerability

In the literature on medical ethics, it is generally admitted that vulnerable persons or groups deserve special attention, care or protection. One can define vulnerable persons as those having a greater likelihood of being wronged – that is, of being denied adequate satisfaction of certain legitimate claims. The conjunction of these two points entails what we call the Special Protection Thesis. It asserts that persons with a greater likelihood of being denied adequate satisfaction of their legitimate claims deserve special attention, care or protection. Such a thesis remains vague, however, as long as we do not know what legitimate claims are. This article aims at dispelling this vagueness by exploring what claims we have in relation to health care – thus fleshing out a claim‐based conception of vulnerability. We argue that the Special Protection Thesis must be enriched as follows: If individual or group X has a greater likelihood of being denied adequate satisfaction of some of their legitimate claims to (i) physical integrity, (ii) autonomy, (iii) freedom, (iv) social provision, (v) impartial quality of government, (vi) social bases of self‐respect or (vii) communal belonging, then X deserves special attention, care or protection. With this improved understanding of vulnerability, vulnerability talk in healthcare ethics can escape vagueness and serve as an adequate basis for practice.     

Low-molecular-weight Ia antigens in normal mouse serum

Low-molecular-weight Ia antigens can be detected in mouse serum. A procedure for isolating these antigens from serum in high yield is described. The Ia antigen preparation was found to be rich in carbohydrate, low in protein, and strongly bound to Concanavalin A andLotus lectins. Furthermore, the Ia antigenicity was destroyed by periodate oxidation and neuraminidase treatment, but was unaffected by pronase. These observations strongly suggest that the Ia antigens in serum are oligosaccharide in nature. Such a conclusion implies that at least some of the genes in theI region of theH-2 gene complex code for glycosyl transferase enzymes.     

Neoaplectana glaseri: essential amino acids

Required for a nematode's reproduction in a chemically defined medium are the nine mammalian essential amino acids (sensu strictu). Needed in addition to lysine, tryptophane, histidine, phenylalanine, leucine, isoleucine, threonine, methionine, and valine is arginine which is marginally essential for mammals. Tyrosine, nonessential for mammals, is not absolutely required by the nematode but is beneficial in terms of onset time and quantity of reproduction. Aspartic acid, nonessential for the nematode and mammals, is toxic for adult nematodes at and above 4.8 mg/ml medium. The nematode, Neoaplectana glaseri, is parasitic in insect grubs but the strain used has been cultivated in species isolation on kidney slices continuously since (1944).     

THE RELATIONSHIP OF THE REFERRING PHYSICIAN TO THE PSYCHIATRIST

Tumors of the adrenal glands produce hormones which cause a variety of symptoms and signs including high blood pressure, excessive growth of hair on the body and precocious sexual development. By recently developed tests, it has been possible to differentiate high blood pressure due to these tumors from hypertension due to other causes. Removal of these tumors will often alleviate changes caused by them. Localization of the tumor and appraisal of the condition of the contralateral gland should be carried out preoperatively if possible. In this, several kinds of roentgen studies are helpful. Infusions of drugs during operation can be used to control the blood pressure which otherwise would vary widely. During a ten-year period (1942 to 1951) there were observed at the Los Angeles County General Hospital 100 proved cases of non-secreting and secreting primary neoplasms of the adrenal glands. In addition, there were three cases of Cushing's syndrome due to bilateral adrenal cortical hyperplasia, and ten probable cases (four, pheochromocytomas; five, Cushing's syndrome; one, adrenogenital syndrome) in which operation was not done.