The effects of running stress on plasma vitamin A levels in rats.

The plasma concentrations of vitamin A, zinc and proteins and the hepatic level of vitamin A were determined in rats subjected to running as a model for stress and which were receiving standard or vitamin-A free diets. All rats showed a decrease in plasma vitamin A with running compared with non-running control animals. Hepatic levels of vitamin A were higher in these two test groups than in their weight- and age-matched non-running controls. The data support that running, like other forms of stress, decreases plasma vitamin A, consistent with the retention of vitamin A in the liver.

Prediction of students' USMLE step 2 performances based on premedical credentials related to verbal skills.

PURPOSE: To examine the relationship between the objective premedical credentials and performances on Step 2 on the United States Medical Licensing Examination (USMLE) of 480 students in three classes at the Virginia Commonwealth University Medical College of Virginia School of Medicine. The purpose of the study was to seek those selection criteria that might best predict performance on an examination designed to assess problem-solving skills, the essence of clinical medicine. METHOD: Premedical data from two classes (1193, 1994) were analyzed, and a regression equation was used to calculate theoretical USMLE Step 2 scores for the students in the class of 1995, who had not yet taken this examination. The premedical variables were scores on the verbal and math section on the Scholastic Aptitude Test (SAT), scores on the six sections of the pre-1991 Medical College Admission Test (MCAT), grade-point average (GPA) in science courses required of premedical students, and undergraduate major. Once the class of 1995 had taken the USMLE Step 2, the equation was cross validated, and the theoretical and actual scores of the class of 1995 were correlated. RESULTS: The correlation between theoretical and actual scores was r = .443. In the analysis for the classes of 1993 and 1994, the single variables most highly predictive of USMLE Step 2 performance were scores on the verbal section of the SAT (r = .317) and the Skills Analysis: Reading section of the MCAT (r = .331). However, the MCAT scores were excluded from the final regression analysis because of the pre-1991 MCAT cannot be useful in predicting the performances of present medical school applicants. The resulting regression equation (using the SAT verbal section and premedical GPA) was able to account for 21.2% of the variance for the class of 1995. CONCLUSION: The use of the verbal section of the SAT as a predictive factor is unique. It is significant that this variable was strongly related to premedical GPA, suggesting that high verbal aptitude serves one well, even when coping with complex scientific concepts.

Influence of a prolactin- and ACTH-secreting tumour on oestrous cyclicity, the pro-oestrous surges of LH and prolactin and ovarian hypertrophy in the rat.

These studies were designed to investigate the effects of a prolactin- and ACTH-secreting tumour (7315a) on reproductive cyclicity, pro-oestrous surges of LH and prolactin and ovarian hypertrophy in the rat. Normal adult Buffalo rats, which are syngeneic to the 7315a tumour, were found to have a significant pro-oestrous prolactin surge and a relatively low-level preovulatory LH surge. Within 14 days of s.c. injection of dispersed tumour cells, a small tumour was detectable by palpation in one rat, but measurable tumours were not observed until day 18. The pro-oestrous surge of LH, but not of prolactin, was effectively suppressed by day 17. Cessation of reproductive cyclicity (anoestrus) was apparent within 19.4 +/- 1.1 days of injection of tumour cells. Removal of a single ovary showed that there was no change in ovarian weight before anoestrus in the tumour-bearing animals. Subsequent hypertrophy of the second ovary was augmented during the early stages of tumour development (days 8 and 13), and this corresponded to the unexpected finding that the gonadotrophin surges on days 8 and 13 were significantly increased when compared with controls. Ovarian hypertrophy was not significantly different from that in controls after suppression of the gonadotrophin surge (day 17). The results suggest that inhibition of the preovulatory LH surge might be a critical event in the tumour-induced cessation of reproductive cyclicity. The fact that pre-surge concentrations of prolactin did not increase substantially until the conspicuous onset of tumour prolactin secretion on day 21 indicated that the preovulatory LH surge might be inhibited by relatively low levels of tonically secreted prolactin.

Opiate-serotonin synergism stimulating luteinizing hormone release in estrogen-progesterone-primed ovariectomized rats: mediation by serotonin2 receptors.

A tonic inhibition of LH release by endogenous opiate systems is apparent after administration of opiate antagonists to ovariectomized estrogen-progesterone-primed rats. In the presence of a serotonin agonist, morphine has been found to stimulate LH release in ovariectomized animals. Thus, in the present study the individual effects as well as interactions of the opiate and serotonin (5HT) systems have been examined using morphine and quipazine, respectively, as agonists and ketanserin (5HT2) and methysergide (5HT1 and 5HT2) as antagonists. Rats ovariectomized 2-4 weeks beforehand were primed with estradiol benzoate (15 micrograms; day 0) and progesterone (5 mg; day 2). Serial blood samples were collected from unrestrained rats via a jugular cannula inserted 3 days before, and plasma LH was measured by RIA. Neither morphine (4 mg sulfate) nor quipazine (2 mg/kg) administered iv at 1200 h significantly elevated plasma LH at 1210, 1220, or 1230 h compared to levels at 1200 h, although plasma LH concentrations at these times were significantly greater than those in animals receiving saline at 1200 h. However, injection of both morphine and quipazine at 1200 h greatly augmented LH release at 1210, 1220, and 1230 h compared to the response to either drug alone. The duration of the significant elevation of plasma LH was limited to 10 min by ketanserin (2.5 mg/kg, ip, at 0900 h) and to 20 min by methysergide (10 mg/kg, ip, at 0900 h), suggesting mediation of this response by 5HT2 receptors. These results suggest the possibility of an important interaction between opiate and serotonergic systems in controlling the release of LH and raise the intriguing question of its role, if any, in controlling events of the estrous cycle.

Evidence for multiple serotonergic influences on LH release in ovariectomized rats and for modulation of their relative effectiveness by estrogen.

Both opiates and serotonin (5HT) are known to inhibit LH release in ovariectomized rats, and estrogen has been shown to reverse certain serotonergic effects. Therefore studies were undertaken to compare the effects of morphine and the serotonin agonist 5-methoxy-N,N-dimethyltryptamine (5MEODMT) on LH release in ovariectomized rats with and without estrogen priming. Serial blood samples were collected via jugular cannulae before and 5, 15, 30 and 60 min after intravenous administration of morphine, 5MEODMT or both to rats receiving no pretreatment, or a serotonin receptor antagonist (methysergide, METH; or ketanserin, KET) 60 min earlier. In the absence of estrogen, morphine inhibited LH release, and the response was delayed by METH or abolished by KET, suggesting mediation by serotonin2 (5HT2) receptors. 5MEODMT alone failed to alter the release of LH significantly, but apparently activated both stimulatory and inhibitory serotonergic systems. Blockade of 5HT2 receptors with KET enabled an inhibitory system to prevail. No significant changes in LH concentrations were observed following combined administration of morphine and 5MEODMT. Similarly, in estrogen-primed rats morphine appeared to activate both inhibitory (5HT2) and stimulatory (5HT1) systems, resulting in no net change unless the inhibitory system had been antagonized by KET. Administration of 5MEODMT alone or in combination with morphine resulted in a strong stimulatory effect which appeared to be mediated by 5HT1 receptors. These results suggest the existence of a multiplicity of serotonergic influences on the release of LH in the rat, not only in terms of particular species of 5HT receptors, but also in neuronal connectivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of neovascularization. Vascular sprouting can occur without proliferation of endothelial cells.

The kinetics of endothelial cells during microvascular growth were studied using a model of inflammation-induced neovascularization of the rat cornea. Inflammation was produced by central silver nitrate cauterization, cellular proliferation was assessed by tritiated-thymidine autoradiography and nuclear counts on plastic sections, and formation of new vessels was studied on whole-mount preparations after vascular perfusion with colloidal carbon. The 3H-thymidine-labeling index of endothelial cells was significantly higher than normal at 1 day following cauterization, although neither mitotic figures nor vascular sprouts were present. The labeling index reached a peak at 2 days, when cell division was evidenced by mitotic figures and doubling of the number of nuclei per section. Actual vascular sprouting also began during the 1- to 2-day interval. To determine whether vascular sprouting was dependent upon endothelial cell division, proliferation was suppressed by X-irradiation (2000 or 8000 rads) prior to cauterization. In irradiated corneas displaying no cellular proliferation, vascular sprouting at 2 days was similar to that in contralateral shielded corneas. Vascular growth continued in irradiated corneas between 2 and 4 days, but at 4 days the length of the vascular ingrowth was reduced to 66.7 and 53.4% of control after 2000 and 8000 rads, respectively. Vascular ingrowth did not progress between 4 and 7 days. This study demonstrates that initial vascular sprouting does not require proliferation of endothelial cells, although under ordinary circumstances DNA synthesis has been stimulated and is in progress at the time of sprouting. After initial sprouting without proliferation, limited vascular growth can continue for about 2 more days but subsequently ceases. Ultrastructural evaluation suggested that migration and redistribution of existing endothelial cells from the limbal vessels enable vascular sprouting and elongation without cellular proliferation.

A light and electron microscopic study of the pineal body of the nutria (Myocastor coypus).

Light and electron microscopic studies of the nutria (Myocastor coypus) pineal gland revealed pinealocytes interspersed among glial, vascular, and neuronal elements. Each pinealocyte possessed a single process that terminated within the parenchyma near the perivascular region. The eccentrically located nucleus in these cells contained euchromatic chromatin, a prominent nucleolus, and a highly infolded nuclear envelope. The cytoplasm was rich in mitochondria, Golgi complexes, and glycogen particles. The smooth endoplasmic reticulum (SER) was better developed thant he rough endoplasmic reticulum (RER) and polyribosomes were not abundant. Long profiles of subsurface cisterns constituted prominent cytoplasmic features, and these were most conspicuous in the regions of soma-somatic apposition. The bulbous endings of the pinealocyte processes were filled with clear, round, secretory vesicles. Dense-cored vesicles were rarely observed. Glia reminiscent of protoplasmic astrocytes displayed cytoplasmic processes that enveloped blood vessels, invested the pineal periphery, and intervened among the pinealocytes. They thus seemed to form a barrier between the meningeal capsule and vascular space on the one hand and the parenchyma on the other.

Electron-microscopic study of the maturing rat red nucleus. I. The large-neuron population.

The maturing large neurons of the rat red nucleus in animals ranging in age from 1 to 21 days of postnatal life were studied ultrastructurally. Days 1--6 were characterized by rapid morphologic maturation occurring concomitantly with the onset of synaptogenesis. Morphogenesis was confined to the soma, while the first synaptic contacts were also formed in relationship to the soma. Days 6--9 demonstrated continued somal morphogenesis exemplified by cytoplasmic expansion and by the conspicuous presence of perisomatic and growth cone processes. Proximal dendritic morphogenesis was initiated, and synaptogenesis became complex with synaptic sites occurring in relation to the neuronal soma, the perisomatic processes and proximal dendrites. Days 9--15 were characterized by the completion of somal and proximal dendritic morphogenesis and by a massive degree of synaptogenic activity. During this interval, the soma lost perisomatic and growth cone processes, while somatic spines appeared. By the end of this period the neuronal soma and the proximal dendrites appeared mature in terms of both morphology and synaptic input. Complete neuronal maturation was ultimately attained by day 21 of postnatal life.

Electron-microscopic study of the rat masseter muscle following injection of lidocaine.

The ultrastructure of rat masseter muscle was examined at 15 min, 1 and 6 h, and 1 and 2 days following a single injection of 2% lidocaine. Lesions developed within 15 min. The plasma membrane was disrupted and invaginated. The nuclei were pyknotic and the mitochondria appeared swollen. The myofibrils separated and became disoriented. By 1 and 6 h, these changes were severe. By 1 day, the macrophages appeared in damaged myofibers. The presence of a few presumptive myoblasts signaled the onset of regeneration. By 2 days, presumptive myoblasts formed within the basement membrane. The basal lamina proved most resistant to injury. Regeneration of masseter muscle following the damage produced by lidocaine appeared discontinuous in nature. The singly nucleated presumptive myoblasts seemed to arise within the lesions.

Degenerative changes in masseter muscle following injection of lidocaine: a histochemical study.

Changes in succinic dehydrogenase, adenosine triphosphatase, and phosphorylase activities occurred in masseter muscle by 15 minutes following injection of 2% lidocaine. Abolishment of phosphorylase activity suggested an effect on the sarcoplasmic reticulum. Increased staining for succinic dehydrogenase and adenosine triphosphatase activities suggested damage to mitochondria and myofibrils, respectively. Leucine aminopeptidase and glucose-6-phosphate dehydrogenase activities appeared in macrophages.

Canine renal glomerular ultrastructural changes after preservation and autotransplantation.

Glomeruli of canine kidneys were studied by light and electron microscopy to determine whether significant structural alterations occur during 24 hr of hypothermic perfusion. The kidneys of eight dogs were preserved by continuous pulsatile perfusion with cold cryoprecipitated plasma; they were subsequently reimplanted as autographs and contralateral nephrectomy was performed at that time. Biopsies of the experimental kidneys were taken before nephrectomy, after 24 hr of perfusion, and at 1 hr postanastomosis. Tissue samples from two animals were studied at autopsy. Structural changes observed in the glomeruli after preservation were: margination of nuclear chromatin, nuclear pyknosis, and dilation of smooth and rough endoplasmic reticulum membranes. These changes were observed in all cell types, but were more severe in the endothelial cells. The basement membrane in four cases was edematous and thickened. At 1 hr postanastomosis the glomerular ultrastructural appearance was greatly improved. Blood urea nitrogen, serum creatinine, and the ability of the kidney to sustain the life of the recipient were used as criteria for determining the viability of the preserved kidneys. Blood urea nitrogen and serum creatinine returned to a normal range in five dogs. The physiologic tests and the length of survival attest to the functional capability of the preserved kidneys. Study of tissue samples at autopsy indicated that, although a number of the structural alterations observed after preservation were reversible, some changes persisted.

Blinding and pinealectomy in male hamsters: Effects of pineal indoles and P-chlorophenylalanine on testes, seminal vesicles, pituitary and adrenal glands.

No antigonadotrophic (AGT) activity was found after injecting 5 methoxytryptophol (5 MTPH) or both serotonin and melatonin simultaneously in normal male hamsters or hamsters subjected to blinding, pinealectomy, or both surgical procedures. Treatment with these indoles did not induce changes in weights of testes, seminal vesicles, pituitary or adrenal glands. Reproductive organs in hamsters blinded by enucleation atrophied in spite of daily consumption of the vasodilator, Apresoline. Feeding of p-Chlorophenylalanine (PCPA) revealed this antagonist to be mildly toxic. PCPA seemed to interfere in the hypophyseal-adrenal axis: these hamsters lowt the most weight, pituitary glands were enlarged and some hyperactivity occurred in the hamsters.

The pineal complex and its relationship to other epithalamic structures.

The pineal complex of rodents is made up of a pineal gland which developmentally always originates from the area between the habenular and posterior commissure and a pineal sac which is continuous with the choroid plexus of the third ventricle. At the light-microscopic level, this sac appears to be identical to the choroid plexus. The pineal sac abuts the deep and superficial pineal glands of the golden hamster. In the PET mouse, gerbil, kangaroo rat, and Chinese hamster, the sac is contiguous with only small areas of the pineal gland. This sac never abuts true pineal parenchyma in the albino rat. The variability of the relationship between this sac and pineal parenchyma indicates that the sac may not be the main physiological route of pineal secretion. Venous drainage of the pineal gland consistently seemed to be into the superior sagittal sinus by means of the vena cerebri magna.

Regeneration of masseter muscle following lidocaine-induced degeneration. A histochemical study.

The histoenzymatic characteristics of regenerating myofibers of rat masseter muscle following injection of 1% lidocaine, as well as morphometric and histochemical characteristics of the typical myofibers, were investigated. Myoblasts appeared initially by day 1 among numerous macrophages within the confines of degenerating myofibers. Myotubes predominated by the 3rd day. Complete regeneration of the muscle occurred by at least 45 days. Phosphorylase activity was absent at day 1 and reappeared by the 5th day when the regenerating myofibers showed slight activity. By the 15th day the myofiber types had partly differentiated; red myofibers were smaller and stained less intensely than the white myofibers. Myotubes stained uniformly for succinic dehydrogenase activity from 3 until 5 days. After 5 days this staining increased gradually. Myofiber types began differentiation by 15 days and were fully differentiated by 45 days. ATPase activity was barely evident by 1-3 days. This activity appeared uniformly low up to 5 days and increased to an intensity comparable with that of the typical myofiber by 15 days. Slight leucine aminopeptidase activity occurred in macrophages 1 day following injection. By 3 days this activity appeared in the remaining myoblasts and in the myotubes. Some activity was found in the fibroblasts. This staining intensity at 5 days was equal to that of earlier lesions. A trace of this activity was found at 7 days, and none at 15 days. Glucose-6-phosphate dehydrogenase activity was present in the macrophages by day 1. It increased by 3 days and occurred mainly in myoblasts and myotubes. This activity decreased by 5 days, and none was found by 7 days.

Recurrent glomerulonephritis in human renal homografts.

Recurrent glomerulonephritis in kidneys transplanted to glomerulonephritic recipients is becoming more obvious. It has been suggested that the disease process which caused the original disease in the recipient is also operative in the transplanted tissue. This study compared the ultrastructure and immunofluorescence of the native kidneys of four patients with their respective sequential, transplant biopsies. In each case, subepithelial humps and IgG, characteristic of a complex type of nephritis, were observed in both the original diseased kdineys and in the transplants. This would indicate that the immunopathologic process which caused the original glomerulonephritis and led to transplantation is also operative in the transplanted tissue.

Anatomy, biochemistry, and physiology laboratory programs in the education of physicians.

The amount of laboratory time devoted to anatomy, biochemistry, and physiology has decreased substantially while lecture time has remained essentially unchanged. Most laboratories consist of student conduction of assigned exercises with a sprinkling of demonstrations, conferences, and seminars. Various objectives for laboratory programs are discussed. A great percentage of the student's final anatomy grade (approximately 40%) still depends on his laboratory performance, while in biochemistry and physiology, lab work contributes only 12% and 10%, respectively, toward his final grade. There is great reluctance to abandon the laboratory program, however, because of the significant role it is thought to play in medical education.

A light and electron microscopic study of the pineal gland of the ground squirrel, Citellus tridecemlineatus.

The pineal gland of the 13-lined ground squirrel (Citellus tridecemlineatus) has been examined at the light and electron microscopic level. This gland is composed of low-density parenchymal cells interspersed among which are occasional glial, vascular and neural elements. Punctuating the glandular parenchymal mass are prominent perivascular and intercellular spaces. The parenchymal cells possess numerous mitochondria and less prominent profiles of rough and smooth-surfaced endoplasmic reticulum. Golgi apparatus, microtubules and lipid droplets of varying size and electron density constitute regular cytoplasmic features, with dense-core vesicles being present occasionally. The parenchymal cells have numberous processes. One among these in each cell extends for several micra to terminate in a bulbous expansion containing both clear and dense-core vesicles and occasional electron-dense inclusions. These bulbous terminals are found within the perivascular and intercellular spaces where they course in close proximity to both other parenchymal elements and axon terminals. Glial cells and their processes invest the pineal periphery and incompletely separate the parenchymal cells.