Trauma, degenerative disease, and other pathologies among the Gombe chimpanzees

The well-known and extremely well-documented chimpanzees from Gombe National Park were analyzed for presence of skeletal pathologies. Of the 15 animals available for study, 11 were old and complete enough to permit systematic analysis. Of these, 10 showed some evidence of skeletal pathological involvement. The most common type of lesion seen resulted from trauma. Those chimps with the most fractures (Old Female, 3; Flo, 4; Hugo, 8) are consistently the oldest individuals in the sample. In addition to accidental falls, the most common cause of trauma was from interpersonal violence, resulting in bite wounds (see in two individuals) and fractures (see in three individuals). Conversely to trauma, degenerative disease was exceedingly rare in this population, found in no large intervertebral joints (N = 344) and only two major synovial joints (N = 186). In fact, the complete lack of osteophytosis, even in older individuals, stands in stark contrast to the situation seen in modern humans, perhaps in our species reflecting a biomechanical cost of bipedality.     

Microgeographic distribution of immature Ixodes dammini ticks correlated with that of deer

In order to determine whether the small-scale distribution of immature Ixodes dammini Spielman et al. corresponds closely to the activity patterns of white-tailed deer, Odocoileus virginianus (Zimmerman), these relationships were examined in a site on Long Island, New York, U.S.A. We first determined the extent and temporal pattern of adult ticks feeding on deer by examining twenty-three resident deer tranquilized during September-December 1985. I. dammini adults infested deer throughout this fall period, most abundantly during October and November. With radio-telemetry collars attached to deer we determined the relative frequency that they occupied 0.25 ha quadrats of the study site. During the following summer, we examined white-footed mice, Peromyscus leucopus (Rafinesque), that inhabited these quadrats and removed immature ticks from each. 8975 larval and 163 nymphal I. dammini were removed from 208 mice trapped in forty-three such quadrats. The frequency of deer using these quadrats was positively correlated with both the number of larval and of nymphal ticks per mouse. These results suggest that risk of I. damminiborne zoonotic disease may be decreased by locally reducing deer density in sites that experience intense human activity.     

Accumulation of mansonones E and F in seedlings of Ulmus americana in response to inoculation with Ophiostoma ulmi

Summary The accumulation of mansonones E and F was investigated in Ulmus americana L. seedlings 5 weeks after inoculation with three aggressive and three non-aggressive isolates of Ophiostoma ulmi (Buism.) Nannf. The three non-aggressive isolates stimulated significantly more mansonone E and F accumulation than the three aggressive isolates of O. ulmi. Mansonone induction also varied within both the aggressive and the non-aggressive groups. Aggressive and non-aggressive isolates were recovered in equal frequencies from the inoculation wounds, whereas the aggressive isolates were recovered more frequently than the non-aggressive isolates 15 cm and 25 cm up the seedlings' stem. Vascular browning in the outer xylem of the seedlings correlated with mansonone E and F accumulation. Mansonone accumulation in U. americana seedlings is therefore associated with vascular browning and a reduction in fungal spread.     

Opioid receptors: Some perspectives from early studies of their role in normal physiology,stress responsivity,and in specific addictive diseases

The early history of research on the possible existence of specific opioid receptors and on developing a new form of pharmacotherapy for the treatment of heroin addiction in New York City, from 1960–1973, along with the special relationships between two leading scientists conducting these research efforts, Dr. Eric Simon and Dr. Vincent P. Dole Jr., are presented in a historical perspective. The linkage of these early efforts and the subsequent identification and the elucidation of the effects of exogenous opiates acting at specific opiate receptors in human physiology, including some findings from perspective studies of heroin addicts at time of entry to and during methadone maintenance treatment, are presented in the context of the important clues which thereby were provided concerning the possible roles of the endogenous opioids in normal mammalian physiology. From many of these early clinical research findings and studies in animal models, the hypothesis that the endogenous opioids system may play an important role in stress responsivity was formulated along with the related hypothesis, first presented in the early 1970s, that an atypical responsivity to stress and stressors might be involved in the acquisition and persistence of, and relapse to specific addictive diseases, including heroin addiction, cocaine dependency and alcoholism. More recent studies of the possible involvement of the specific opioid receptors in these three addictive diseases—heroin addiction, cocaine addiction and alcoholism—from our laboratory are discussed in a historical perspective of the development of these ideas from the early research findings of not only Dr. Eric Simon, but his numerous colleagues in opioid research in the United States and throughout the world. Special issue dedicated to Dr. Eric J. Simon.     

Alzheimer Aβ Amyloid Forms an Inhibitory Neuronal Substrate

Abstract: Alzheimer's disease (AD) is identified by the accumulation of amyloid plaques, neurofibrillary degeneration, and the accompanying neuronal loss. AD amyloid assembles into compact fibrous deposits from the amyloid β(Aβ) protein, which is a proteo-lytic fragment of the membrane-associated amyloid precursor protein. To examine the effects of amyloid on neuron growth, a hybrid mouse motoneuron cell line (NSC34) exhibiting spontaneous process formation was exposed to artificial "plaques" created from aggregated synthetic Aβ peptides. These correspond to full-length Aβ residues 1–40 (Aβ1–40), an internal β-sheet region comprising residues 11–28 (Aβ11–28), and a proposed toxic fragment comprising residues 25–35 (Aβ25–35). Fibers were immobilized onto culture dishes, and addition of cells to these in vitro plaques revealed that Aβ was not a permissive substrate for cell adhesion. Neurites in close contact with these deposits displayed abnormal swelling and a tendency to avoid contact with the Aβ fibers. In contrast, Aβ did not affect the adhesion or growth of rat astrocytes, implicating a specific Aβ-neuron relationship. The inhibitory effects were also unique to Aβ as no response was observed to deposits of pancreatic islet amyloid poly-peptide fibers. Considering the importance of cell adhesion in neurite elongation and axonal guidance, the antiadhesive properties of Aβ amyloid plaques found in vivo may contribute to the neuronal loss responsible for the clinical manifestations of AD.     

Modulation of adrenal cell functions by cadmium salts: 2. Sites affected by CdCl2 during unstimulated steroid synthesis

In previous studies cadmium chloride (CdCl₂) nonlethally inhibited Y-1 adrenal mouse adrenal tumour cell 20-dihydroxyprogesterone (20DHP) secretion, affecting unstimulated and stimulated steroidogenic pathway sites differently. We studied CdCl₂ effects on unstimulated steroidogenesis using Y-1 cells incubated 0.5 h in medium with or without cadmium (using the concentration that inhibited ACTH-stimulated steroid secretion by 50%). Exogenously added 20-hydroxycholesterol (20OHC), 22(R)-hydroxycholesterol (22OHC), 25-hydroxycholesterol (25OHC), pregnenolone (PREG), or progesterone (PROG) were used to bypass any rate-limited steroidogenic pathway sites that CdCl₂ might inhibit. 25OHC is a biologically active nonpathway steroid, while 20OHC, 22OHC, PREG, and PROG are pathway steroids; each increased unstimulated 20DHP secretion nearly 10-fold. Although CdCl₂ could not reduce dibutyryl cyclic AMP- (dbcAMP)-stimulated 20DHP secretion significantly, it did significantly reduce basal and 25OHC-induced 20DHP secretion 25% below untreated levels. When 20OHC, 22OHC, PREG, or PROG were incubated with unstimulated Y-1 cells, their synthesis into 20DHP was unaffected by cadmium. dbcAMP bypasses the plasma membrane enzyme complex that synthesizes intracellular cAMP during exogenous ACTH stimulation; dbcAMP was not inhibited by CdCl₂. The rate-limited step accelerated by cAMP involves plasma membrane and/or cytoplasmic cholesterol transport to and through outer and inner mitochondrial membranes before the cholesterol is synthesized into pregnenolone by side-chain cleavage enzymes on the inner membrane matrix face. Little is known regarding the mechanisms controlling unstimulated steroidogenesis. Under unstimulated conditions the 25-, 20- and 22(R)-monohydroxyls of cholesterol facilitate plasma membrane, cytoplasm and inner and outer mitochondrial solubility, diffusion and/or transport to bypass rate-limited steps and augment unstimulated steroid synthesis. Since conversion of endogenous mitochondrial cholesterol and 25OHC, but not dbcAMP-mobilized cytoplasmic cholesterol, 20OHC or 22OHC conversion, to 20DHP is inhibited by CdCl₂, this suggests that (a) control of mitochondrial cholesterol supplies is independent of the cAMP-regulated mitochondrial steps in the 20DHP steroid synthetic pathway, (b) CdCl₂ specifically inhibited endogenous mitochondrial cholesterol and 25OHC utilization, (c) CdCl₂ toxicity may affect adrenal, testicular, ovarian, and placental basal steroidogenic functions, and (d) 25OHC may be a useful compound to examine unstimulated steroid synthesisAbbreviations ACTH adrenocorticotropin - ANOVA analysis of variance - CdCl₂ cadmium chloride - cAMP cyclic 3,5-adenosine monophosphate - DMSO dimethylsulfoxide - DNA deoxyribonucleic acid - FMEM serum-free Eagle's Minimum Essential Medium - Hepes N-2-hydroxyethyl-piperazine-N-1,2-ethanesulfonic acid - 20OHC 20-hydroxycholesterol - 22OHC 22(R)-hydroxycholesterol - 25OHC 25-hydroxycholesterol - IC_50' concentration inhibiting stimulated steroid secretion by 50% - IU international unit - MEM Eagle's Minimum Essential Medium - P450scc cytochrome P450 side-chain cleavage enzyme - PREG pregnenolone - PROG progesterone - RNA ribonucleic acid - SEM standard error of the mean - SMEM serum-containing Eagle's Minimum Essential Medium - 20DHP 20-hydroxy-4-pregnen-3-one     

Trace elements in hair of blackfoot disease

Blackfoot disease is a peripheral vascular disease resulting in gangrene of the lower extremities. Though extensive epidemiological study has implicated that high arsenic content in artesian well water of the endemic area, bears some important connection with the disease, the etiology of the disease is still unknown. In this study, attention is paid to multielement determination in order to find out whether the trace elements in hair of Blackfoot disease patients are different from those of the controls. Experimental results indicate that the concentrations of As and Se in hair of patients are significantly higher than those of the controls, but Ca and Zn are significantly lower than those of the controls. The possible connection of these elements with the etiology of the disease is discussed.     

Neurotrophic factor therapy for nervous system degenerative diseases

The ability of neurotrophic factors to regulate developmental neuronal survival and adult nervous system planticity suggests the use of these molecuales to treat neurodegeneration associated with human diseases. Solid rationales exist for the use of NGF and neurotrophin-3 in the treatment of neuropathies of the peripheral sensory system, insulin-like growth factor and ciliary neurotrophic factor in motor neuron atrophy, and NGF in Alzheimer's disease. Growth factors have been identified for neurons affected in Parkinson's disease, Huntington's disease, and acute brain and spinal cord injury. Various strategies are actively pursued to deliver neurotrophic factors to the brain, and develop therapeutically useful molecules that mimic neurotrophic factor actions or stimulate their production or receptor mechanisms. 1994 John Wiley & Sons, Inc.