Evidence for involvement of clonally expanded CD8+ T cells in anticancer immune responses in CLL patients following nonmyeloablative conditioning and hematopoietic cell transplantation.

We have analyzed the clonotype composition of CD8+ T cells following nonmyeloablative (NMA) conditioning and hematopoietic cell transplantation (HCT), of patients with chronic lymphocytic leukemia (CLL). Consecutive analyses of blood samples taken up to 2 years following HCT, demonstrated that CD8+ T-cell clonality was highly dynamic in the early phases after HCT, but became more stable after 4-5 months. Moreover, donor lymphocyte infusion (DLI) given for disease progression in one of the patients led to establishment of recurrent as well as new T-cell clonotypes. This coincided with disease remission, strongly suggesting that these T cells were engaged with anti-CLL cytotoxicity. To examine the functional capacity of stable clonally expanded T cells after HCT, CD8+ T cells isolated post-transplant from the recipients were stimulated ex vivo with CLL cells and subsequently analyzed by FACS for surface expression of the marker for cytotoxic activity, CD107a. Stimulation with CLL cells indeed led to surface expression of CD107a, and clonotype analyses of sorted cells demonstrated that CD107a positive T cells were stably expanded following HCT. Our data suggest that clonally expanded CD8+ T-cell clones participate in the ongoing T-cell response against CLL cells following HCT with NMA conditioning.     

Night life: nocturnal behavior patterns among hospitalized elderly

1. In contrast to previous studies where elderly living in an institution were found to demonstrate a consistent, predictable pattern of nocturnal activity, hospitalized elderly were found to be asleep less and awake more over a period of 3 consecutive nights. 2. Medication, treatments, and assessment were scheduled with little regard for the hospitalized elderly's need for restorative sleep. 3. Each time an elderly patient was awakened, it took him or her at least 30 minutes to return to sleep. 4. Nurses are advised to determine and maintain as much as possible the patient's usual bedtime routine, keep interruptions during the night to a minimum, schedule medications and treatments efficiently, decrease noise, and medicate for pain as appropriate.     

Pharmacologically evoked fictive motor patterns in the acutely spinalized marmoset monkey (Callithrix jacchus)

The existence of a spinal network capable of generating rhythmic alternating activity resembling locomotion still has not been firmly established in primates, including man, although evidence for one is accumulating. The present study investigated whether it is possible to activate such a network by administration of a variety of pharmacological agents to acutely spinalized marmoset monkeys (Callithrix jacchus) in the absence of phasic afferent input to the spinal cord. Fourteen marmoset monkeys were decerebrated, spinalized, and paralyzed. The nerves supplying both hindlimbs were cut and recorded from. In 5 monkeys the effect of electrical stimulation of the brainstem was investigated before spinalization. In 3 of these monkeys, rhythmic activity alternating between extensors and flexor nerves was seen. In the 2 other monkeys only synchronized activity was elicited. In acutely spinalized monkeys, administration of l-3,4-dihydroxyphenylalanine (l-dopa; 3–4 h after treatment with nialamide) failed to evoke any rhythmic alternating activity. In contrast, administration of clonidine elicited alternating activity in all of 8 monkeys tested. In 4 of these monkeys, the activity was restricted to alternation between ipsilateral and contralateral flexor nerves, whereas alternating activity between ipsilateral flexors and extensors was also seen in the other 4 monkeys. Administration of excitatory amino acids (NMDA or NMA) also elicited rhythmic alternating activity in 7 of 10 spinalized monkeys. In 4, rhythmic alternating activity was seen between extensors and flexors on one limb as well as between ipsilateral and contralateral flexors. In 3 monkeys NMDA/NMA produced alternation between extensors and flexors of one limb without alternation between the ipsilateral and contralateral sides. Administration of noradrenaline failed to elicit any rhythmic activity, but rather completely depressed already existing activity. Administration of serotonin (5-HT) was ineffective in facilitating alternating activity in 6 of 8 monkeys and was facilitatory to rhythmic activity in the other 2. We suggest that these data provide further evidence of a network capable of eliciting rhythmic alternating activity resembling locomotion in the primate spinal cord. The network, however, seems to be more difficult to activate pharmacologically in those conditions than in other mammals. This may especially be the case in higher primates, including man. Received: 6 November 1997 / Accepted: 21 April 1998     

Assessment of mortality in the construction industry in the United States, 1984–1986

Construction, one of the larger industries in the United States, employs 7.6 million workers, many in skilled trades occupations. Previously published data about potential worksite exposures and mortality of construction site workers are limited. We analyzed occupation and industry codes on death certificates from 19 U.S. states to evaluate mortality risks among men and women usually employed in construction occupations. Proportionate mortality ratios (PMRs) for cancer and several other chronic diseases were significantly elevated among 61,682 white male construction workers who died between 1984 and 1986. Men younger than age 65, who were probably still employed immediately prior to death, had significantly elevated PMRs for cancer, asbestos-related diseases, mental disorders, alcohol-related disease, digestive diseases, falls, poisonings, traumatic fatalities that are usually work-related, and homicides. Elevated PMRs for many of the same causes were observed to a lesser degree for black men and white women whose usual industry was construction. In addition, women experienced excess cancer of the connective tissue and suicide mortality. Various skilled construction trades had elevated PMRs for specific sites, such as bone cancer and melanoma in brickma-sons, stomach cancer in roofers and brickmasons, kidney and bone cancer in concrete/terrazzo finishers, nasal cancer in plumbers, pulmonary tuberculosis in laborers, scrotal cancer and aplastic anemia in electricians, acute myeloid leukemia in boilermakers, rectal cancer and multiple sclerosis in electrical power installers, and lung cancer in structural metal workers. Using a standard population of blue collar workers did not result in fewer elevated PMRs for construction workers. Despite lifestyle differences and other limitations of the study, the large numbers of excess deaths observed in this study indicate the need for preventive action for construction workers. © 1995 Wiley-Liss, Inc.     

Cryptosporidiosis in patients infected with the human immunodeficiency virus.

Infection caused by Cryptosporidium species has proved to be one of the most taxing and frustrating conditions faced by clinicians caring for patients with AIDS. Unfortunately, this unique organism, which was identified as a human pathogen only shortly before the AIDS epidemic began to manifest itself, has received only minimal attention during the past decade. Dr. Carolyn Petersen, an assistant professor of medicine at the University of California, San Francisco, and a member of the Division of Infectious Diseases at San Francisco General Hospital, is a molecular parasitologist whose investigative career is focused on elucidating the biology of Cryptosporidium species. In this AIDS Commentary Dr. Petersen provides an update on recent developments in this field.