Tropomyosin paracrystals formed by divalent cations.

Rabbit tropomyosin exhibits a polymorphism dependent on divalent cations and pH. Above a critical divalent cation concentration fibers with a period of about 400 angstroms are formed. Below this concentration, and near the isoelectric point, lattices are formed. Implications for the morphology and function of striated and smooth muscle are discussed.

Paramyosin: molecular length and assembly.

Paratnyosin paracrystails formned with divalent cations have a 725-angstrom axial period and show simple negative staining patterns in the electron microscope. The structure of the aggregates is interpreted in terms of an array of polar molecules about 1275 angstroms long, with "gaps" and "overlaps" in the molecular assembly. Antiparallel relatiotns between molecules lead to the assembly of paracrystals with opposite polarity at either end. Implications of the in vitro structure for filaments containing paramyosin in muscle are discussed.

Efficacy and safety of an oral device to reduce food intake and promote weight loss.

Objective: Minimal risk weight loss tools are needed. This study's objective was to confirm Food and Drug Administration submissions of the SmartByte™ System's safety and efficacy. Methods: This 16-week, prospective, single-arm, four-centre, observational study assessed the oral device in combination with a video-delivered lifestyle programme in adults aged 18-49 years with body mass index 27 to <35 kg m-2. Results: Seventy-six subjects received the device and video lifestyle instruction. The prespecified per protocol (PP) population (N = 40) required sensor-verified use of the device ≥7 times per week for 14 of 16 weeks, overall device usage rate of ≥33% and study completion. At week 16, 12 (30%) achieved ≥5% weight loss, 16 (40%) achieved ≥4% and 21 (52.5%) achieved ≥3%. Week 16 mean loss for the PP population was 2.93%, and among 36 participants who did not meet PP criteria, it was 1.45%. Among 76 intent-to-treat subjects, two subjects reported three mild to moderate device-related adverse events, resolving spontaneously (one hard palate abrasion and two tongue lacerations). Conclusion: The System, a minimal risk tool, can help individuals achieve meaningful weight loss, when used with a lifestyle video. More frequent device use was associated with more weight loss, on average, and greater chance of achieving ≥4% or ≥5% weight loss.

Age at onset and pattern of neuropsychological impairment in mild early-stage Alzheimer disease. A study of a community-based population.

OBJECTIVES: To examine the effects of age at onset on neuropsychological functioning in a group of patients with probable Alzheimer disease (AD) and, within this group, to scrutinize further those patients with mild early-onset disease as it was hypothesized that within this group specific patterns of cognitive impairment could be identified that correlated with neuropathological staging of the disease. DESIGN: Each patient underwent an extensive neuropsychological test battery to examine a wide range of cognitive processes to provide information to identify subtypes of dementia. SETTING: The Memory Clinic in the Department of Geriatric Medicine, Concord Hospital, Concord, New South Wales, Australia. PATIENTS: One hundred forty-five community-residing case patients with probable AD were studied; within this group, 51 case patients with mild AD and a Mini-Mental State Examination score greater than 19 were further examined; 36 similarly aged control patients who were part of a larger case-control study of AD in an urban population were also examined. A diagnosis of probable and possible AD was made if the case patient had evidence of memory impairment and met criteria according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. OUTCOME MEASURES: Individual neuropsychological test scores were compared. The tests were then grouped into 7 cognitive domains. Patterns of early cognitive impairment were derived from these comparisons. RESULTS: With an earlier age at onset, significantly more impairment on tests of digit span and praxis was seen, while the duration of disease had no independent effect once the age at onset was fixed. Patients with mild early-onset dementia and a Mini-Mental State Examination score greater than 19 showed significant impairment in tests of attention, memory, frontal/executive functions, visuospatial ability, praxis, and visual agnosia compared with that shown by control patients. In this group, further analyses revealed that impairment in memory and frontal/ executive functions were the earliest signs of cognitive impairment. CONCLUSIONS: These data showed that when the duration of disease was adjusted for, case patients with an earlier age at onset of AD demonstrated significantly more impairment on tests of attention span and working memory (digit span), graphomotor function (copy loops), and apraxia than those with an older age at onset. Our findings support the view that the hippocampus and its connections are affected in the early stages of AD. The deficits in the frontal/executive functions also suggest that a disruption of cortical pathways to the frontal lobes and the pathological changes in this region occur early in the disease.

Monozygotic twins discordant for Alzheimer's disease.

We identified 3 pairs of monozygotic twins discordant for probable Alzheimer's disease from a twin register and found no systematic differences in potential risk factor exposures between affected and unaffected twins. Such cases predict a role for environmental factors in the etiology or clinical onset of Alzheimer's disease.

A case-control study of Alzheimer's disease in Australia.

We conducted a case-control study of clinically diagnosed Alzheimer's disease (AD) on 170 cases aged 52 to 96 years, and 170 controls matched for age, sex and, where possible, the general practice of origin. Trained lay interviewers naive to the hypotheses and to the clinical status of the elderly person carried out risk-factor interviews with informants. Significant odds ratios were found for 4 variables: a history of either dementia, probable AD, or Down's syndrome in a 1st-degree relative, and underactivity as a behavioral trait in both the recent and more distant past. Previously reported or suggested associations not confirmed by this study include head injury, starvation, thyroid disease, analgesic abuse, antacid use (aluminum exposure), alcohol abuse, smoking, and being left-handed.

Does pulsatile flow influence the incidence of postoperative hypertension?

Twenty patients undergoing primary elective aorta--coronary artery bypass were divided into two equal groups, both receiving identical premedication, anesthetic, and pump primes. The control patients received hypothermic nonpulsatile flow and the study patients received hypothermic pulsatile flow. Hypertension, defined as a pressure of 160/100 mm Hg or higher, was observed in 80% of the control patients and 20% of the patients receiving pulsatile flow (p less than 0.05). Serial renin measurements demonstrated maximum values in the intensive care unit and coincided with the onset of postoperative hypertension in the control patients. Those patients who had received pulsatile flow did not demonstrate notable renin stimulation. Catecholamines were markedly elevated during bypass and in the intensive care unit, but there was no significant difference between the two groups. Peripheral vascular resistance was not significantly lower with pulsatile flow, except in the first study performed in the intensive care unit. We conclude that catecholamines and the renin-angiotensin system contribute to the production of postoperative hypertension and that pulsatile flow diminishes renin stimulation. Pulsatile flow results in a decreased incidence of postoperative hypertension.

Development of the area centralis and visual streak in the grey kangaroo Macropus fuliginosus.

To further our understanding of area centralis and visual streak formation we have investigated the distribution and number of the total cell population in the retinal ganglion cell layer of the western grey kangaroo Macropus fuliginosus using adults and young from 7-200 days postnatal. This species was chosen since, as we describe, the adult possesses a particularly prominent area centralis and visual streak. By studying the total cell population we were able to compare cell distributions in immature retinae, in which cell types could not be distinguished, with topography in the adult. By 57 days postnatal a weak visual streak was apparent; a pronounced area centralis and visual streak were seen by 84 days although densities across the retina, particularly in the far periphery, were still considerably higher than in the adult. Dying cells were also observed up to 160 days, but not at 188 days or in the adult. The fall of approximately one third in the total cell number as the area centralis and visual streak developed is presumably related to cell death. Furthermore, at 57 days, dying cells were seen preferentially in retinal regions outside the immature visual streak and may therefore play a part in refining density gradients to their mature form. As the area centralis and visual streak developed, the relative lengths of the dorso-ventral and naso-temporal axes remained similar, suggesting that differential radial growth cannot underlie the changing live cell density gradients.

Medial hypothalamic and medial accumbens lesions which induce mouse killing enhance biting and attacks on inanimate objects.

The response to a series of objects by rats with lesions of the medial hypothalamus or medial accumbens was compared to that of spontaneous killing rats and sham-lesioned nonkillers. When exposed sequentially to a piece of wood, a wad of cotton, or a freshly killed mouse, there were no differences in the intensity of the initial response toward the stimulus object by spontaneous mouse killing rats and lesioned animals that were later shown to kill mice. However, lesioned animals did spend more time biting these objects and were more likely than spontaneous killers to attack the objects if they were moved about by the experimenter. When allowed to kill mice, there were no differences in the intensity of the attack by spontaneous and lesion-induced killers but again the lesioned animals bit the prey more following the kill and were more likely to attack the dead prey when it was moved by the experimenter. Sham-lesioned nonkillers spent less time biting the stimulus objects than spontaneous killers and never attacked the objects when they were moved by the experimenter. It is argued that the killing of lesioned animals is homologous to that of spontaneous killers but that the lesioned animals exhibit most components of the predatory behavior to an exaggerated degree.

A comparison of prey eating by spontaneous mouse killing rats and rats with lateral septal, medial accumbens, or medial hypothalamic lesions.

Rats with lesions of the medial hypothalamus and spontaneous mouse killing rats were tested for mouse and rat pup killing in their living cages 1 and 3 days postoperatively. The lesioned and spontaneous killers did not differ significantly in amount of prey eaten within 10 min following a mouse kill on either Day 1 or 3 postoperatively. Both groups ate significantly more of the prey than did sham-lesioned rats that were presented with a freshly killed mouse. When 4 hr was allowed for eating following a kill, rats with lesions of the lateral septum, medial accumbens, and medial hypothalamus each ate significantly more than spontaneous mouse killing rats. The greater prey eating by the lesioned animals is probably not the result of the prey being a highly palatable food since rats with medial hypothalamic lesions but not those with medial accumbens or septal lesions showed enhanced consumption of a sweetened lab chow over a 4 hr period. The quantitative similarity in the prey eating by spontaneous and lesion-induced mouse killers in the period immediately following the kill serves to further establish a relationship between these two kinds of killing. The greater eating that occurs in lesioned animals when a longer time is allowed for eating is consistent with other observations of excesses in the killing behavior of lesioned animals relative to spontaneous killers.