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Biomedical subjects

A Jayaraman

Publications and source records attributed to A Jayaraman.

At least 55 records · Page 3Linked to original sources

Is all cyclo(His-Pro) derived from thyrotropin-releasing hormone?

Cyclo(His-Pro), or histidyl-proline diketopiperazine, is an endogenous cyclic dipeptide that is ubiquitously distributed in tissues and body fluids of both man and animals. This cyclic dipeptide is not only structurally related to thyrotropin-releasing hormone (TRH, pGlu-His-ProNH2), but it can also arise from TRH by the action of the enzyme pyroglutamate amino-peptidase (pGlu-peptidase). The data on the distribution of TRH, cyclo(His-Pro), and pGlu-peptidase under normal and abnormal conditions are summarized and potential relationships analyzed. We conclude that all of the cyclo(His-Pro) cannot be derived from TRH. Two additional sources of cyclo(His-Pro) are suggested. It is proposed that 29,247 molecular weight TRH prohormone, prepro TRH, which contains 5 copies of TRH sequence, can be processed to yield cyclo(His-Pro). Thus, both TRH and cyclo(His-Pro) share a common precursor, prepro[TRH/Cyclo(His-Pro)].

Animals↗

Pyroglutamate aminopeptidase activity in human cerebrospinal fluid decreases with age.

The activity of pyroglutamate aminopeptidase, the major enzyme catalyzing thyrotropin-releasing hormone (TRH) metabolism in human CSF, decreased with age. This decrement is not due to age-dependent appearance of any enzyme inhibitor in CSF. The results of these studies underline the importance of using age-matched controls in assessing abnormalities of TRH metabolism in CSF during disease states.

Adult↗

The distribution pattern of adrenocorticotropin-like immunoreactivity in the cat central nervous system.

The distribution pattern of adrenocorticotropin-like immunoreactivity (ACTH-LI) in cats using the avidin-biotin modification of an immunocytochemical method shows cell bodies containing ACTH-LI in the medial basal hypothalamus, especially in the infundibular nucleus. The fibers from these neurons extended beyond the hypothalamus, into the paraventricular nucleus of the thalamus, rostral amygdala, periaqueductal gray, locus coeruleus, parabrachial nucleus and medial nucleus of the nucleus tractus solitarius. The distribution pattern of the cell bodies and fibers containing ACTH-LI bears several similarities to that seen in rats. The pattern differs from that of rats in the fact that the termination in the amygdala is more extensive and that ACTH-LI was not observed in cell bodies in any location other than the medial basal hypothalamus.

Adrenocorticotropic Hormone↗

Distribution and characterization of cyclo(His-Pro)-like immunoreactivity in human cerebrospinal fluid.

The distribution of cyclo(His-Pro), thyrotropin-releasing hormone and pyroglutamate aminopeptidase activity was examined in the CSF of human and a number of other mammalian species. Cyclo(His-Pro)-like immunoreactivity was present in the CSF of all species examined, and was immunologically and chromatographically identical with the authentic cyclo(His-Pro). Cyclo(His-Pro) concentration in CSF had no significant correlation with CSF TRH or pyroglutamate aminopeptidase.

Adult↗

Metabolism of thyrotropin-releasing hormone in human cerebrospinal fluid. Isolation and characterization of pyroglutamate aminopeptidase activity.

Pyroglutamate aminopeptidase, which catalyzes metabolism of thyrotropin-releasing hormone (TRH) to cyclo(His-Pro), is the major enzyme of TRH metabolism in human CSF. The partially purified CSF pyroglutamate aminopeptidase has a pH optimum between 6.0 and 7.4, and a Km of 15.9 +/- 3.1 microM. A number of potential competitive inhibitors of the enzymatic activity were examined, of which luteinizing hormone-releasing hormone and bombesin were the most effective. An examination of the structure of various peptides that inhibit pyroglutamate aminopeptidase activity indicated that the enzyme generally prefers a substrate having amino-terminal pyroglutamic acid (pGlu) and a COOH-terminal that is either blocked or distant from amino-terminal pGlu. Heavy metals, EDTA and reducing agents inactivated the enyzme, whereas benzamidine, phenylmethylsulfonylfluoride, trypsin inhibitor and alkylating agents had little or no effect on the enzymatic activity. Thiol-oxidizing agent 5,5'-dithiobis(2-nitrobenzoic acid), however, considerally inhibited the enzymatic activity. We hypothesize that CSF pyroglutamate aminopeptidase may play a role in the biologic actions of TRH.

Aminopeptidases↗

Organization of thalamic projections in the nucleus accumbens and the caudate nucleus in cats and its relation with hippocampal and other subcortical afferents.

The organization of thalamic projections in the nucleus accumbens (NA) and the caudate nucleus of cats and its relation to other subcortical striatal afferents were studied with a retrograde tracing technique by use of lectin-conjugated horseradish peroxidase. The study showed that the paraventricular and medial parafascicular nuclei (PF) of the thalamus project to the medial NA and the parataenial and medial PF project to the lateral NA. The ventral tegmental area and substantia nigra pars dorsalis (SNpd) project to medial and lateral NA. The midline thalamic nuclei, rostral intralaminar nuclei, ventroanterior nucleus, medial and lateral PF, lateral posterior complex, and nucleus limitans project to medial caudate nucleus. The most medial substantia nigra pars compacta (SNpc) and rostral SNpd project to medial caudate nucleus. The center median, ventrolateral, and the central lateral nuclei of thalamus, SNpc, and SNpd project to lateral caudate nucleus. These results suggest that the thalamic and subcortical nuclei known to connect with the limbic and frontal cortices project to NA and medial caudate nucleus. Those thalamic nuclei connected with the motor system project to lateral caudate nucleus. The hippocampus projects selectively to medial NA. The amygdala, raphe, and other mesencephalic nuclei project only to NA and medial caudate nucleus. The organization of hippocampal, amygdala, and other subcortical afferents suggests that NA and caudate nucleus can be separated into medial "limbic" and lateral nonlimbic "sensory-motor" compartments. A brief review of the distribution pattern of some neurotransmitters, neuropeptides, and their receptors and behavior studies provides additional support to the concept that the striatum can be divided into several subcompartments.

Amygdala↗

Spatio-temporal processing in multiple sclerosis.

The processing of spatial and temporal detail was investigated in patients with multiple sclerosis. Normal observers and 13 patients with optic neuritis secondary to multiple sclerosis performed a battery of visual tests that included contrast sensitivity, temporal integration, evoked potentials, and visual masking. The multiple sclerosis patients exhibited losses of pattern processing, and these deficits became more noticeable when the patterns were presented briefly. Moreover, these patients exhibited diverse response patterns for the different visual tests. For some, temporal integration functions appeared severely attenuated, while evoked potential latency was within normal limits. Others displayed poor performance in the visual masking test, yet contrast sensitivity functions were comparable to those of the control group. We suggest that a battery of tests that incorporates spatial as well as temporal stimuli is necessary for the detection of visual dysfunction in multiple sclerosis.

Adult↗

Topographic organization and morphology of peripallidal and pallidal cells projecting to the striatum in cats.

Injections of small amounts of horseradish peroxidase (HRP) or HRP coupled with wheat germ agglutinin within the caudate nucleus in adult cats resulted in retrograde labeling of neurons within the globus pallidus and within the fibers of internal capsule near the globus pallidus. These triangular and fusiform neurons, measuring 27-30 micron, project topographically to the striatum. The morphology and the location of some of the labeled neurons in these cases resemble the acetylcholinesterase-positive neurons of the nucleus basalis magnocellularis described by other authors. The findings from this study support the existence of a projection from the globus pallidus and peripallidal region to the striatum in cats.

Afferent Pathways↗

Anatomical evidence for cortical projections from the striatum in the cat.

Several anatomical and physiological studies have thus far failed to confirm the existence of striatocortical projections proposed in 1895 by Cajal. Evidence for such striatocortical projections was obtained in the present study using the horseradish peroxidase (HRP) tracing method. When 0.1-0.8 microliter of 30-50% HRP in saline was injected into different cortical regions in cats, HRP was transported to cells in different thalamic nuclei, striatum and the globus pallidus. Only large striatal cells, 30--60 micrometers in their long axes, contained HRP reaction product. After injection in area AI, the striatocortical cells were located in the dorsal parts of the middle third of putamen, where auditory cortical afferents are known to project, thereby suggesting reciprocal connections between the cerebral cortex and the striatum.

Afferent Pathways↗

Organization of visual cortical projections to the claustrum in the cat.

The projection patterns from different visual areas of the parieto-occipital cortex to the claustrum were studied autoradiographically in cats. When [3H]proline was injected into 17, 18, 19 or Clare-Bishop areas, the label was transported to an area restricted to the dorsal and caudal parts of the claustrum without any suggestion of retinotopic organization. Injection in each of these visual areas resulted in individual patterns of projection but with overlapping fields of termination, a pattern similar to corticocaudate projection. When injected into area 7, a region shown to have neurons involved in visuomotor mechanisms, the label was transported to the same area as that of the visual projection. These and other findings suggest that claustrum may be reciprocally and topographically connected with the cerebral cortex.

Animals↗