The distribution and chemical properties of compounds with tachykinin-like immunoreactivity (TK-LI) in the spinal cord and brain of lampreys (Lampetra fluviatilis and Ichthyomyzon unicuspis) were investigated by means of immunohistochemistry and various chromatographic methods combined with radioimmunoassay. The distribution of TK immunoreactive fibers in the lamprey spinal cord was investigated with 13 different TK antisera which gave positive staining in pilot experiments. The antisera were raised against substance P (SP) (n = 6), physalaemin (PHY) (n = 1), neurokinin A (NKA) (n = 2), kassinin (KAS) (n = 2) or eledoisin (ELE) (n = 2). Pre-incubation of these antisera with their corresponding TKs abolished or reduced the immunostaining. Four different patterns of distribution were found with the 13 antisera, and they did not seem to be related to the TKs against which the antisera were raised. The different patterns could be explained by assuming the presence of the three different TKs. Six different antisera, raised against SP (n = 2), KAS (n = 2) or ELE (n = 2), were used for radioimmunoassay. The TK-LI material eluted as several separate components in various chromatographic systems. The central nervous system (CNS) of the lamprey did not contain measurable amounts of SP, NKA, neurokinin B (NKB), KAS or ELE. The present data imply that the lamprey CNS contains at least three different TKs probably different from SP, PHY, NKA, NKB, KAS or ELE; these are possibly new, not earlier described TKs. The three hypothetical TKs differ in their distribution.

Animals↗

PubMedDate not supplied

The effect of increased longevity, produced by dietary restriction, on the neuronal population of area 17 in rat cerebral cortex.

Area 17 of the brains of Sprague-Dawley derived rats, maintained on a limited ration of food to maintain their weights at the levels attained by two months of age, was compared with area 17 in control groups of rats fed ad lib. The oldest rats in the diet restricted group were sacrificed at 46 and 48 months of age, by which time their life spans had been extended about 12 months beyond the oldest age that rats fed ad lib achieve, for only few of the latter live as long as 33 months. In this study, the rats which were compared consisted of two groups of ad lib fed rats, one 3 and 6 months of age, and the other 33 months old, and two groups of diet restricted rats, one 26 months old and the other 46 to 48 month old rats (designated as 47 month old rats). Two indices were used to assess whether age affects the volume of area 17. One, the number of clusters of apical dendrites of layer V pyramidal cells per unit area of tangential sections, was the same in all groups, indicating that the lateral spread of area 17 did not alter with age. However, the other index, the thickness of area 17, did change with age, for area 17 was significantly thinner in the 47 month old diet restricted rats than in the other three groups. It was also found that the number of neuronal profiles in strips of sections passing through the entire depth of area 17 is decreased in the 47 month old rats, indicating that neurons had been lost from their cortices. This decrease in the number of neuronal profiles in the 47 month old rats was not due to nuclear shrinkage since the sizes of neuronal nuclei were not significantly different in the older ad lib and diet restricted rats. Determinations of neuronal packing densities in layers II/III, IV, V and VIa suggest that neurons are most frequently lost from the deeper cortical layers of the 47 month old rats, and in these layers large vacuolated spaces, the sizes of neuronal cell bodies, have been encountered. It is suggested that these spaces represent places from which neurons have been lost. It is concluded, therefore, that neurons are lost from area 17 in rats whose longevity is increased by diet restriction.

Animals↗

PubMedDate not supplied

Neuronal population of area 4 during the life span of the rhesus monkey.

One right or left area 4 of each of 19 rhesus monkeys, ranging in age from 1 day to 35 years, was processed (frozen sectioned at 30 or 40 microns) for light microscopic analysis to assess age-related changes in the neuronal population. All neurons were examined regardless of their size. In addition, Betz cells were analyzed separately; to be regarded as Betz cells, pyramidal somata had to display a minimum height of 38 microns. A significant loss of approximately one-third was observed in the total number of neurons in maturing monkeys (less than 5.5 years). In contrast, in maturing rhesus monkeys significant increases with age were observed in the mean number of Betz cells, and in the means of Betz cell area, height, width, perimeter, and estimated volume. In adult monkeys (greater than 4.5 years), no age-associated loss of neurons was observed. Also, no loss of Betz cells occurred, although the perimeter, area, and estimated volume of Betz cells decreased slightly, but significantly, with increasing age in adult monkeys. Lipofuscin granules were discernable in Betz cells beginning at the age of 5 years and their number increased with increasing age. In the older rhesus monkeys, the lipofuscin granules were so large and numerous that in some Betz cell somata they displaced the nucleus from its usual location in the center of the cell. No age-related change in thickness of area 4 was found.

Aging↗

PubMedDate not supplied

The absence of significant neuronal loss from cerebral cortex with age.

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Aging↗

PubMedDate not supplied

Development of potent non-estrogenic estrone sulfatase inhibitors.

Estrogen levels in breast tumors of post-menopausal women are as much as 10 times higher than estrogen levels in plasma, presumably due to in situ formation of estrogen. The major source of estrogen in breast cancer cells may be conversion of estrone sulfate to estrone by the enzyme estrone sulfatase. Thus, inhibitors of estrone sulfatase have potential for the treatment of estrogen-dependent breast cancers. Several steroidal agents have been developed that are potent estrone sulfatase inhibitors, most notably estrone-3-O-sulfamate. These compounds may have undesired actions, especially estrogenicity. Recently, non-steroidal estrone sulfatase inhibitors have been designed that avoid the problems associated with an active steroid nucleus; however, these have not achieved the potency of estrone-3-O sulfamate. We have designed and synthesized a series of compounds, 17 beta-(N-alkylcarbamoyl)-estra-1,3,5(10)-trien-3-O-sulfamates (6a-d) and 17 beta-(N-alkanoyl)-estra-1,3,5(10)-trien-3-O-sulfamates (11a-d) that combine the structural features of the steroidal estrone sulfatase inhibitors with a membrane insertion region that should increase the affinity for the sulfatase enzyme and decrease the estrogenicity of the steroid. We tested the compounds for estrone sulfatase inhibition by measuring estrone sulfatase activity in intact cultures of human breast cancer cells (MDA-MB-231). We tested for estrogenicity by measuring growth of estrogen-dependent MCF-7 human breast cancer cells. All of the test compounds (10 nM) substantially inhibited estrogen sulfatase activity of intact MDA-MB-231 cells. Dose-response analysis indicated an IC50 of approximately 0.5 nM for two of the compounds (6a and 11a). In the test for estrogenicity, estrone and estrone-3-O-sulfamate significantly stimulated MCF-7 cell growth. In contrast, neither the 17 beta-(N-alkylcarbamoyl)-estra-1,3,5,(10)-trien-3-O-sulfamates++ + nor the 17 beta-(N)-alkanoyl)-estra-1,3,5,(10)-trien-3-O-sulfamates stimulated growth of MCF-7 cells at a concentration of 1 microM, indicating that they are not estrogenic at levels 2000 times greater than their IC50 for estrone sulfatase. Our data indicate the utility of the new compounds for inhibition of breast cancer cell estrone sulfatase activity. Further, our data support the concept that estrone sulfatase inhibitors may be useful as therapeutic agents for estrogen-dependent breast cancers.

Breast Neoplasms↗

PubMedDate not supplied

The effects of aging on the frequency of nerve fibers in rhesus monkey striate cortex.

In the rhesus monkey primary visual cortex, there are bundles of vertically oriented myelinated axons, which mainly contain efferent fibers originating from pyramidal cells. At the level of layer 4Cbeta, the bundles are regularly arranged and the nerve fibers in them are closely packed. In order to determine if a significant loss of intracortical nerve fibers occurs as the primate cerebral cortex ages, the frequency of vertically oriented myelinated fibers was examined at the level of layer 4Cbeta in 1 microm-thick, tangential sections. The results show no statistically significant differences in the numbers of vertically oriented fibers beneath 1 mm(2) of cortical surface between young, middle-aged, and old monkeys, and electron microscopic examination reveals few signs of degenerating axons. There is, however, an age-related breakdown of the myelin in sheaths that surround some axons. Thus, the data indicate that there is not a loss of vertically oriented myelinated fibers from the cortical gray matter during aging, although their sheaths may be altered.

Aging↗

PubMedDate not supplied

Effects of aging on visual recognition memory in the rhesus monkey.

As part of an effort to develop a primate model of human age-related memory dysfunction, performance by six rhesus monkeys 26 to 27 years of age was compared to that of six young adult monkeys (four to five years of age) on a trial unique delayed nonmatching to sample (DNMS) task. This task assesses the monkey's ability to identify a novel from a familiar stimulus over a delay and resembles closely clinical tests that are used to assess memory function in geriatric patients. The task was presented in three stages: acquisition, delays and lists. As a group, aged monkeys were impaired relative to the young adult group on all three conditions. However, within the aged group, individual cases of efficient performance were observed. Error analyses of item positions of the lists condition revealed the absence of enhanced performance for items presented at the end of a list by aged animals, suggesting an abnormal sensitivity to proactive interference. The finding of a recognition impairment with age is in parallel with studies of normal human aging and lends support to the notion that the rhesus monkey is a suitable animal model of human aging.

Aging↗

PubMedDate not supplied

A further evaluation of the effect of age on striate cortex of the rhesus monkey.

The brains of 14 rhesus monkeys (Macaca mulatta) between 4 and 35 years old were examined to determine the effects of aging on the thickness, neuronal frequency, fine structure, surface area, and volume of striate cortex. The effects of aging were ascertained by comparing the striate cortex in the six monkeys between 4 and 12 years of age with that of the eight monkeys over 25 years of age. The brains of the monkeys were all fixed by vascular perfusion and except for one of the old monkeys, whose age was estimated, the exact ages of all of the monkeys are known. One micron thick sections of plastic embedded cortex from one hemisphere of each monkey were examined by light microscopy to determine the thickness of the striate cortex, and neuronal frequency was determined by counting the numbers of neurons displaying nuclei in 250 microns-wide strips passing through the thickness of the cortex. When young monkeys were compared with the old ones, no differences were found in either the thickness of the cortex or in the numbers of neuronal profiles beneath unit areas of cortical surface. This suggests that neurons are not lost with age, and when the cortices were examined by electron microscopy there was no indication that the cell bodies of neurons are degenerating, except possibly in layer 1. Serial, 30 microns-thick, Nissl stained frozen sections from the other hemisphere of each monkey were used to determine both the surface area and the volume of the striate cortex. Overall, the surface area varied between 702 and 1480 mm2, with a mean value of 956 mm2, but there was no indication that the surface area decreased with age, and the same is true for the volume of striate cortex. The conclusion is that while there is a large variation in the amount of cortex occupied by area 17, there is no indication that its thickness, volume, or number of neurons is altered by age.

Aging↗

PubMedDate not supplied

Human platelets frozen with glycerol in liquid nitrogen: biological and clinical aspects.

Platelets were frozen using glycerol (3% in plasma) as a cryoprotective agent, a rapid cooling rate, and liquid nitrogen for storage. The cryopreserved platelets were thawed at 42 C and infused without washing. The results indicate that the quality of the thawed platelets is equivalent to platelets stored for 24 to 48 hours at room temperature. The availability of HLA phenotyped leukocyte poor platelets can reduce the frequency of sensitization to strong antigens and provide clinically effective platelets for alloimmunized patients.

Blood Platelets↗

PubMedDate not supplied

[Evaluation of the North American Spine Society Instrument for assessment of health status in patients with chronic backache].

PURPOSE OF THE STUDY: The translation/back and translation and validation of the North American Spine Society (NASS) Instrument in German was published recently. This contribution aims at describing the scoring of this questionnaire. METHOD: The scoring is oriented on the recommendations of the developing scientists of the US-American original, with whom we cooperated during the German validation. RESULTS: The scoring algorithm is described, a program for computerized scoring in SPSS was written. Program syntax and the questionnaire are reproduced. CONCLUSION: The contribution enables interested researchers to apply and score the NASS questionnaire in German-speaking countries.

Back Pain↗

PubMedDate not supplied

[Outcome sensitivity of the North American Spine Society Instrument with special consideration for the neurogenic symptoms of chronic back pain].

BACKGROUND: Back pain is one of the most common chronic diseases in developed countries. The related enormous direct and indirect costs demand evidence-based decisions on rehabilitative care. Our study is intended to evaluate the two NASS outcome dimensions pain and neurological symptoms regarding their sensitivity to change within an inpatient rehabilitation scheme for chronic back pain. METHODS: The study observed a cohort of consecutive patients for one year (n = 70). By applying two outcomes instruments which are in common use internationally (SF-36 and NASS) it enhances comparability with other studies. Moreover the FFbH-R was applied for cross validation. RESULTS: On discharge from hospital an improvement of physical and emotional health as well as pain reduction were found. The results of the various instruments are consistent and support each other and suggest sensitivity to change of the NASS instrument regarding its pain and neurology subdimensions. CONCLUSION: The NASS outcome instrument monitors well the established therapeutic effects of chronic back pain inpatient rehabilitation schemes in the short run and in the long run over a twelve-month period following hospital discharge.

Adult↗

PubMedDate not supplied

[A posterior mini-incision for total hip arthroplasty -- results of 76 consecutive cases].

AIM: A refinement of the classic surgical approaches to the hip for total hip arthroplasty (THA) is presently being developed with a drastic shortening of the skin incision. The aim of this study was to explore if a minimal-invasive posterior approach (1) is technically feasible regardless of varying patient anatomy and (2) is associated with such results that do not suggest increased patient risk. We sought to find out how surgical time, blood loss, requirement for pain medication, pain perception and implant position were affected by a posterior mini-incision approach for THA. METHODS: Prospectively, the results of 76 consecutive THAs operated by the same surgeon via a posterior mini-incision approach were recorded. RESULTS: The length of skin incision ranged from 6.0 to 11.0 cm. On average, surgical time was 83 minutes, intraoperative blood loss was 343 ml, and the amount of PCA-administered Piritramid i. v. in the first 24 hours was 21.4 mg. Pain-free (defined as a 0-10 self rating on a VAS) were 8 % of the patients on day one following mini-incision THA, 41 % on day three, 54 % on day five and 71 % of patients on day seven. The average cup inclination and anteversion were 46 and 13 degrees, stem position was regarded as neutral in 76 %. Complications occurred in 7 patients (9 %). CONCLUSION: Our posterior mini-incision approach allowed for the placement of 76 consecutive THAs through a skin incision of equal to or less than 11.0 cm in a non-selected population without jeopardising patient safety.

Adult↗