The fidelity of phosphorylation of the adenovirus DNA-binding protein by an in vitro nuclear protein kinase from virus-infected cells.

The type 5 adenovirus single-strand-specific DNA-binding protein is phosphorylated and can be labeled by the addition of ³²PO₄ to the medium of infected cells. An infected cell nuclear protein kinase activity is capable of phosphorylatiog the single-strand-specific DNA-binding protein in vitro (A. D. Levinson, E. H. Postel, and A. J. Levine. The fidelity of phosphorylation by this in vitro protein kinase activity was tested by comparing the ³²P-labeled partial peptides generated by Staphylococcus aureus protease digestion of the ³²P-labeled DNA-binding protein which had been phosphorylated in vivo or in vitro. Identical ³²P-labeled partial peptides were obtained from the DNA-binding protein whether it was phosphorylated in vivo or in vitro. A second nuclear protein of 36,000 MW was also faithfully phosphorylated by the in vitro nuclear protein kinase activity.     

Dendritic reorganization of abdominal motoneurons during metamorphosis of the moth, Manduca sexta

During metamorphosis in the hawkmoth Manduca sexta, muscles of the abdominal body wall undergo a reorganization. Many die at the end of larval life and are replaced in the adult by newly generated muscles. We have identified several of the motoneurons innervating these muscles and followed them through metamorphosis. The morphology of larval motoneurons is correlated with their target location. Those with medial targets have bilateral dendritic fields, whereas those with lateral targets have dendrites restricted to one side of the segmental ganglion. Some motoneurons innervate the same muscle in all stages of life, but the majority lose their larval targets following entry into the pupal stage. Although some of the latter group also die at this time, most survive to innervate a new adult target. These "respecified" motoneurons undergo a period of dramatic dendritic growth during metamorphosis. The results demonstrate that these identified neurons are capable, under the appropriate conditions of existing in more than one stable morphology.     

"Crack" cocaine-associated stroke

We present three cases of "crack" cocaine-associated stroke, together with a review of cocaine-associated cerebrovascular complications. Unlike previously reported cases tentatively associating ischemic stroke with cocaine, our patients had no other potential causes for their strokes. Although the exact mechanism of cocaine-related stroke remains uncertain, both disordered neurogenic control of the cerebral circulation as well as systemic factors (ie, acute hypertension) may play a role.     

Characterization and cross-reactivity of rabbit antisera to plaque toxins

The effects of heat labile, high molecular weight water-soluble toxins from bacterial plaque on HL60 promyelocytic cells were examined. On gel filtration, four inhibitors of HL60 cell growth and two inhibitors of HeLa cell growth (PT1, PT2) were detected. The first and third HL60 cell inhibitors corresponded to the two HeLa cell inhibitors. The last eluted HL60 cell inhibitor (plaque leukotoxin, PL) did not inhibit HeLa cell growth. Anti-PT2 antibodies reduced the activity of enriched PT2 by 20-50%, but all other antisera tested exhibited no effect. Anti-PL antibodies detected antigens from Actinobacillus actinomycetemcomitans, although anti-A. actinomycetemcomitans and anti-Capnocytophaga sputigena antibodies did not react with plaque extract. These findings suggest that the plaque toxins examined in this study were probably not derived from these two bacteria.     

Malignancies in the acquired immunodeficiency syndrome

Aside from opportunistic infections, several neoplasms have been identified as part of the spectrum of acquired immunodeficiency syndrome (AIDS) as defined by the Centers for Disease Control. Kaposi's sarcoma (KS) was the first such neoplasm to be recognized within the spectrum of AIDS. Although the classic form of Kaposi's sarcoma had been well recognized prior to the epidemic of AIDS, it was quite distinct from the illness that was seen in its "epidemic" form in young homosexual males. In this setting, Kaposi's sarcoma is an aggressive disease, with extensive involvement of skin and mucous membranes, early dissemination to lymph nodes, impressive development of extreme lymphedema, even in the absence of bulky adenopathy, and rapid spread to visceral organs, including lungs and gastrointestinal tract, among others. Although rapid clinical progression and short median survival have been the rule, a spectrum of disease has been seen such that some patients have survived for many years with disease limited to the skin. Certain clinical and laboratory features, such as presence of unexplained fever, night sweats, weight loss ("B" symptoms), or significant T-4-lymphocytopenia, have been identified as indicators of poor prognosis. Various therapeutic interventions have been employed in epidemic KS, and although partial and complete remissions have occurred, no regimen yet reported has significantly improved the survival of treated patients. High-dose recombinant alpha interferon has produced response rates in approximately 30% of treated patients, although toxicity has been observed in approximately 30% as well. Likewise, vinblastine has produced similar response rates with no evidence of long-term efficacy or "cure." Aside from Kaposi's sarcoma, lymphoma primary to the central nervous system was recognized early in the AIDS epidemic as a criterion for inclusion within AIDS in patients less than sixty years of age. Several years after the initial reports of disease, it became apparent that specific types of systemic lymphoma were also quite extraordinary, and the definition of AIDS was amended in June 1985 to include high-grade B-cell lymphomas in individuals who had positive serology or virology for the human immunodeficiency virus (HIV). The AIDS-related lymphomas are characteristic, both pathologically and clinically. The vast majority of these cases have been high-grade B-lymphoid tumors of either immunoblastic or small-non-cleaved type (also known as "undifferentiated," Burkitt, or Burkitt-like).(ABSTRACT TRUNCATED AT 400 WORDS)     

Distal tubule bicarbonate accumulation in vivo. Effect of flow and transtubular bicarbonate gradients.

We have performed microperfusion studies on distal tubules of normal and alkalotic rats in an attempt to demonstrate in vivo bicarbonate secretion. All perfusion solutions were free of phosphate and other nonbicarbonate buffers. In both normal and alkalotic rats, distal perfusions elicited significant tCO2 entry only at high flow (24 nl/min). Even when perfusate tCO2 concentration closely matched plasma tCO2 concentration (30 mM tCO2), significant tCO2 entry again occurred at high flow. This was associated with a rise of the perfusate tCO2 concentration, which indicated net entry of tCO2 against a concentration gradient. In this "symmetrical" perfusion situation, acetazolamide blockade prevented tCO2 entry. Accordingly: distal tubule tCO2 entry is demonstrable in both alkalotic and normal rats at high flow rates; increasing perfusate tCO2 concentration can suppress tCO2 entry; and entry can occur in the absence of a gradient and this effect can be blocked by acetazolamide.     

Application of ILO classification to a population without industrial exposure: findings to be differentiated from pneumoconiosis

The International Labour Office (ILO) classification of radiographs of pneumoconiosis is a standard means of assessing the presence or absence of pneumoconiosis in workers exposed to mineral dusts. Using this classification, 200 admission chest radiographs were reviewed on hospitalized patients in an urban university medical center to determine the prevalence and possible significance of "small opacities" in a population without known industrial exposure. Seventy-one men and 129 women were screened with the mean age of 44.2 years (range, 15-84). Thirty-six (18%) of the 200 patients had small opacities at profusion level 1/0 or greater, and this constituted the "positive radiographs" group. Twenty-two patients (11%) with positive radiographs had no documentable dust exposure or other specific medical etiology that would explain the presence of their lung opacities. The high prevalence of small opacities in "normal" older individuals has important implications in the assessment of patients with suspected pneumoconiosis.     

In Search of the Honest Executive: A View from The Top and the Middle

On 16 November 1983, a U.S. District Court judge granted the federal government's request that prison officials be allowed to force feed Ramon Sanchez, a hunger striking prisoner. Levine briefly describes the events leading to the court's involvement and summarizes the reasoning behind its decision. Declining to draw an analogy between the prisoner's refusing food and a patient's refusing life-prolonging treatment, the judge ruled that force feeding was permissible because Sanchez's hunger strike was motivated by his desire to escape prison and frustrate the authority of the courts, and not by religious or political convictions.     

The management of hypertension in Canada: a review of current guidelines, their shortcomings and implications for the future

CLINICIANS ARE EXPOSED to numerous hypertension guidelines. However, their enthusiasm for these guidelines, and the impact of the guidelines, appears modest at best. Barriers to the successful implementation of a guideline can be identified at the level of the clinician, the patient or the practice setting; however, the shortcomings of the guidelines themselves have received little attention. In this paper, we review the hypertension guidelines that are most commonly encountered by Canadian clinicians: the “1999 Canadian Recommendations for the Management of Hypertension,” “The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure” in the United States and the “1999 World Health Organization–International Society of Hypertension Guidelines for the Management of Hypertension.” The key points of these guidelines are compared and the shortcomings that may impede their ability to influence practice are discussed. The main implications for future guideline developers are outlined.