Biomedical subjects
Publications and source records attributed to D J Fink.
Direct electron microscopic immunohistochemistry of the sural nerve of a patient with neuropathy and an IgMk paraprotein demonstrated that immunoglobulin was deposited throughout the compact myelin. These findings support the notion that immunoglobulin deposition plays a role in the pathogenesis of the neuropathy in vivo.
The American Cancer Society (ACS) conducted a nationally representative survey of ACS professional education committee volunteer chairpersons and ACS staff responsible for professional education programs in Divisions and Units of the Society. The survey questionnaire included a set of 25 items (15 in the chairperson questionnaires) representing potential obstacles to effective professional education programming. Subjects rated these obstacles on a four-point scale indicating the extent to which they were perceived as problems in professional education. The survey identified which potential obstacles to professional education programming by a voluntary health association were considered to be most problematic. These included competition from other providers of oncology professional education, outdated audiovisuals and publications, and the recruitment and retention of physician volunteers. The survey verified that there were differences within the organizational structure of the association. In particular, small Units of the Society faced more problems than did Divisions and large Units. The survey found differences in perceived problems between volunteers and staff, particularly in that staff found outdated audiovisuals and publications to be more of a problem than did chairpersons. In general, however, there was a commonality of opinion among all respondents as to which obstacles posed more of a problem than others in professional education.
To understand better the role of local factors in the response of peripheral nerve to crush injury, we studied the distribution of albumin-like immunoreactivity (A-LI) in the rat sciatic nerve from one day to eight weeks (wk) after a crushing injury; we used electron microscopic immunocytochemistry. In the nerve distal to the crush degenerating axons demonstrated intra-axonal A-LI, and by one wk most of the Schwann cells also showed A-LI. As regenerating sprouts entered the distal nerve, those Schwann cells in contact with sprouts lost their A-LI, while those cells not in contact with axons retained immunoreactivity up to eight wk after injury. Proximal to the nerve crush many axons showed intra-axonal A-LI from one to two wk after injury, despite appearing normal ultrastructurally. This immunoreactivity diminished as the distance from the crush site increased. Many Schwann cells proximal to the crush also showed A-LI from one to four wk after injury. These findings suggest that an albumin-like protein may play a role in the response of Schwann cells and axons to injury.
It is estimated that 480,000 types of cancer will occur in women during 1987, the most frequent being breast (27%), colon and rectum (16%), lung (11%), and uterus (10%). Of cancer deaths, lung (20%), breast (18%), and colorectal (14%) are most common. Uterine cancer is now the sixth cause of cancer death, after ovary and pancreas, due to the application of cancer detection. with an aging US population, cancer will become an even more significant health issue for women. Cancer in women aged 65 years and older occurs twice as frequently as in those aged 45 to 64 years. Melanoma is becoming an increasingly important public health problem because of its rising incidence during the last 20 years. Preventive strategies can be widely promoted to women in order to lower their cancer risk and to find cancer before symptoms appear. Smoking control, safe sun exposure, and simple recommendations for diet and nutrition can assist women in taking control of their lifestyles to reduce cancer risk. Early cancer detection, as outlined in the American Cancer Society's Cancer Related Checkup Guidelines, can be expected to find breast, colorectal, uterine, and other forms of cancer in asymptomatic women.
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Attenuated total reflectance Fourier transform infrared spectra of surface-adsorbed proteins are correlated with concentration measurements determined by 125I-labeled proteins. This paper demonstrates that linear correlations between the intensity of the major bands of proteins and the quantity of proteins can be obtained for human albumin and immunoglobulin G up to surface concentrations of approximately 0.25 microgram/cm2. A poorer correlation was observed for human fibrinogen. A linear correlation was also observed between the concentration in the bulk solution and the major bands of albumin up to a concentration of 60 mg/ml.
Without question, patients who have urologic cancers have had marked and significant improvements in the therapies available and, as well, there is an improved survival since the last symposium sponsored by the American Cancer Society. The authors are concerned that new results and advances frequently found in cancer centers and university hospitals may not always be promptly reflected in the community. To measure the technical transfer or scientific transfer, the American College of Surgeons successfully conducted national surveys of the 50 states, District of Columbia, and Puerto Rico. The analysis of such data has shown that between 1970 and 1983 the 2-year survival of nonseminomatous testicular cancer to have been improved from 74% to 92%. Similarly recorded improvements have been documented for both localized and regionalized prostatic cancer from 1974 through 1984 in some cases where the improvements have exceeded an improvement in 5-year survival rate exceeding a net 10%. Further details of the various urologic cancers, with respect to new treatments, techniques for dealing with recurrence, both local and distant, are enumerated at this issue and justify, without question, the basis for reasonable optimism and out anticipations for continued improvement.
We used the oxalate-pyroantimonate technique to determine the ultrastructural distribution of Ca++ in neurons of the rat sciatic nerve. The content of the precipitate was confirmed by X-ray microanalysis and appropriate controls. In the cell bodies of the dorsal root ganglia, Ca++ precipitate was found in the Golgi, mitochondria, multivesicular bodies and large vesicles of the cytoplasm but not in lysosomes, and was prominently absent from regions of rough endoplasmic reticulum and ribosomes. It was seen in the nucleus but not in the nuclear bodies or nucleolus. Within the axon itself, Ca++ precipitate was also found sequestered in mitochondria and smooth endoplasmic reticulum. In addition Ca++ precipitate found diffusely throughout the axoplasm exhibited a discrete and heterogeneous distribution. In myelinated fibers the amount of precipitate decreased predictably in the axoplasm beneath the Schmidt-Lanterman cleft and in the paranodal regions at the nodes of Ranvier. This correlated with the presence of dense precipitate in the Schmidt-Lanterman cleft themselves and in the paranodal loops of myelin. Intracytoplasmic ionic Ca++ is maintained at 10(-7) M by balanced processes of influx, sequestration and extrusion. The irregular distribution of Ca++ precipitate in the axoplasm of myelinated fibers suggests that there may be specific regions of preferential efflux across the axolemma.
We investigated the quantitative alterations in retrograde transport of proteins following a nerve crush injury using the 3H N-succinimidyl propionate (3H NSP) method in rat sciatic nerve. After subepineurial injection of 3H NSP into the nerve the amount of radioactively labeled proteins accumulating in the cell bodies of the motor and sensory neurons was determined 1 day or 7 days later in nerves which had been crushed distal to the injection site 1, 3, 5, 7, or 33 days prior to 3H NSP labeling. One day accumulation in the DRG and spinal cord was not altered by nerve crush. Seven day accumulation in the DRG was initially slightly increased, then fell to 73% of control by 7 days, remaining reduced 33 days after crush. Seven day accumulation in the spinal cord was reduced to 25% of control 1 day after crush and remained at that low level except for 5 days post-crush when a normal amount of labeled protein was transported to the spinal cord. The time course of these changes suggests that quantitative alterations in retrograde transport may be involved in the long-term trophic interactions between the cell body and periphery, but are too slow to account for the earliest perikaryal responses to injury. In addition, the difference between the alterations of retrograde transport in motor and sensory neurons may reflect fundamental differences in the composition of retrograde transport in those different systems.
To clarify the nature of the blood-nerve barrier (BNB) in excluding serum proteins from peripheral nerve endoneurium, we studied the ultrastructural distribution of albumin in peripheral nerve using light and electron microscopic immunocytochemistry. We found that serum albumin is commonly found within the endoneurium, but that it is not normally found intraaxonally. After subperineurial injection of labeled albumin, the albumin redistributed within intrafascicular clefts towards the perivascular spaces and the perineurium. These results suggest that, contrary to previous evidence, axons are exposed to serum proteins in normal nerves, and implies that they may be subject to interaction with abnormal proteins or altered serum proteins without any disruption of the BNB.
The pattern of antimicrobial resistance of common bacterial isolates obtained from various groups of patients at a large tertiary-care center was compared with the pattern of resistance seen at a primary-care community hospital. At the tertiary-care center, significant differences in susceptibility were seen between pediatric and adult groups. In the tertiary-care center, the inpatients were more likely than the outpatients to have resistant staphylococcal and enterobacterial strains. Comparison of the overall resistance at the tertiary-care center and the primary-care hospital showed that resistance to cephalosporins, piperacillin, and aminoglycosides was significantly higher at the tertiary-care hospital than at the community hospital. Striking differences were noted in the resistance of nosocomial Enterobacter and Citrobacter isolates. Hospitals should be cautious in extrapolating nationwide data to their particular institutions.
Retrograde axonal transport in the sciatic nerve of rats with streptozocin-induced diabetes was studied by the [3H]N-succinimidyl propionate [( 3H]NSP) method. The accumulation of retrogradely transported labeled proteins in the dorsal root ganglia and the ventral horn of spinal cord 1 day after [3H]NSP injection was not statistically significantly different from controls in rats diabetic for 1 or 14 days at the time of [3H]NSP injection. However, accumulation of labeled proteins in the dorsal root ganglia 7 days after [3H]NSP injection was reduced by 35% and transport to the ventral horn of spinal cord 7 days after [3H]NSP injection was reduced by 70% at the same time points. Partial control of the diabetes with insulin resulted in a partial reversal of these deficits. The early occurrence of defects in retrograde transport suggests that such defects may play a role in the pathogenesis of the neuropathy.
A series of recent studies has shown an association between low serum cholesterol level and cancer, particularly of the large bowel. To explore this issue, serum cholesterol measurements were collected from 244 patients with adenomatous polyps of the colon, 182 patients with Dukes' A or B colon cancer, and 688 hospital controls who were diagnosed between 1979 and 1981 at a New York City hospital. The mean serum cholesterol levels were lower for patients with cancer (207.2 mg/dL) than for controls (219.5 mg/dL), with patients with Dukes' B cancer accounting for most of the difference. Patients with adenomatous polyps (219.8 mg/dL) were similar to controls. After adjustments for nutritional status using the serum albumin level, there were no statistically significant differences among any of the groups. We conclude that the low serum cholesterol level previously associated with malignancies, and colon cancer in particular, is a consequence rather than a cause of the cancer.
We used the oxalate-pyroantimonate method to demonstrate the ultrastructural distribution of calcium within rat sciatic nerve 4 h after a crush injury. In normal nerve there are discrete gradients of axoplasmic calcium precipitate with the amount of precipitate decreasing in the axoplasm beneath the Schmidt Lantermann clefts and in the paranodal regions at the node of Ranvier. Near the crush site a marked increase in endoneurial and intra-axonal calcium precipitate correlated with morphologic evidence of axonal degeneration. More distant from the crush site, both in the distal segment destined to degenerate and in the proximal segment destined to regenerate, the most prominent finding was a loss of the normal gradient of precipitate beneath the Schmidt Lantermann clefts. The calcium influx at the crush site corresponds to the known role of calcium in triggering degeneration. The alterations in the distal axon may be an early stage leading to degeneration. Alteration in calcium distribution in the proximal nerve stump may play a role in the regulation of the response to injury.
We used 3H N-succinimidyl propionate to covalently label in vivo proteins of the rat sciatic nerve, and studied the accumulation of radioactively labeled proteins in the cell bodies of the ipsilateral dorsal root ganglion and ventral horn of spinal cord to assess retrograde axonal transport in sensory and motor neurons respectively. In each case the early accumulation of a small amount of radioactively labeled protein is followed by the later accumulation of a larger amount, which subsequently declines to lower levels. The differences between accumulation in the motor neuron and sensory neuron are discussed. Quantitative assessment of retrograde axonal transport will allow future determination of alterations in that transport after nerve injury and in toxic states, which will help elucidate the role of retrogradely transported proteins in neuronal cell biology.
The American Cancer Society is the major organization that provides cancer education to health professionals in the United States. This is implemented not only by the National Office but through 58 Divisions and over 3000 local Units. Objectives for professional education emphasize informing physicians and the multiple disciplines of health professionals engaged in primary care about cancer detection and prevention, particularly for breast, lung, colon, rectal, and cervical cancers. A plan is now being developed for a professional education program to the year 2000. Cancer control programs sponsored or planned by the Society include the Colorectal Health CHECK program, Smoke Free Young America, Breast Cancer Detection Awareness, and Cancer Risk Reduction. These programs demonstrate an effective partnership between professionals and lay volunteers. The Society also offers Clinical Fellowships, Medical and Nursing Professorships, and Nursing Scholarships to further professional education. National conferences are sponsored by the Society, as are special graduate courses for physicians from foreign countries. In addition, numerous publications and audiovisuals are available through Units to supplement professional, as well as lay, education.
beta,beta'-Iminodipropionitrile (IDPN), a neurotoxin, causes redistribution of neurofilaments in axons followed by the development of proximal axonal swellings and, in chronic intoxication, a distal decrease in axonal caliber. The latter changes are caused by a selective impairment in the slow anterograde axonal transport of neurofilament proteins. To assess the role of retrograde axonal transport in IDPN toxicity, we used [3H]N-succinimidyl propionate ([3H]NSP) to label covalently endogenous axonal proteins in sciatic nerve of the rat and measured the accumulation of radioactively labeled proteins in the cell bodies of motor and sensory neurons over time. IDPN was injected intraneurally 6 h or intraperitoneally 1 day before subepineurial injection of [3H]NSP into the sciatic nerve, and the animals were killed 1, 2, and 7 days after [3H]NSP injection. Neurotoxicity was assessed by electron microscopic observation of the nerves of similarly treated animals. Both intraneural and intraperitoneal injection of IDPN caused an acute reduction in the amount of labeled proteins transported back to the cell bodies. The early appearance of these changes suggests that alterations in retrograde transport may play a role in the production of the neuropathic changes.
Twenty-four hours following the injection of N-succinimidyl[2,3-3H]propionate into rat sciatic nerve, labeled protein appeared in the ipsilateral dorsal root ganglia. Autoradiography showed that the labeled proteins were found only in neuronal cell bodies. Gel electrophoresis showed a distinct pattern of rapidly retrogradely transported proteins were accumulating in the DRG cells. This is the first demonstration of the rapid retrograde transport of endogenous axonal proteins in mammalian peripheral nerve.