Biomedical subjects

S S Tay

Publications and source records attributed to S S Tay.

At least 19 recordsLinked to original sources

PubMed2000

Changes in peptidergic nerves in the atrioventricular valves of streptozotocin-induced diabetic rats: a confocal microscopy study.

Several previous studies have described the distribution of neuropeptide Y (NPY)-like and calcitonin gene related peptide (CGRP)-like immunoreactive nerve fibres in the atrioventricular valves of humans and various animals. It has been suggested that peptide-containing nerve fibres might have motor or sensory roles in valvular function. Although there is evidence that diabetic changes occur in the sympathetic (preganglionic and postganglionic), parasympathetic (vagal) and peptidergic nerves of rats, the changes of peptide-containing nerve fibres in the atrioventricular valves of the diabetic rat have not been studied. The distribution, relative density and staining intensity of NPY-like and CGRP-like immunoreactive nerve fibres in the mitral and tricuspid valves were studied in whole mount preparations using confocal microscopy with a computer-assisted image analysis system. Streptozotocin-induced diabetic and control rats were sacrificed at 12 and 24 months. The nerve staining intensity within the tricuspid valve was greater than the mitral valve in both control (P < 0.01) and diabetic (P < 0.001) rats. Nerve density in the anterior leaflet was greater than the posterior leaflet of the mitral valve. However, the anterior leaflet of the mitral and tricuspid valves showed a decreased number of nerve fibres, followed by drastic reduction in the staining intensities for both the peptides studied (P < 0.001) in the long-term diabetic rat. The decrease in the number of nerve fibres that follow the mechanical interruption of nerves raises the possibility that cycles of degeneration may occur. It is suggested that these peptide-containing nerve fibres in the atrioventricular valves may be involved in valvular dysfunction in the diabetic state.

Animals↗

PubMed2000

An immunohistochemical study of neuronal and glial cell reactions in retinae of rats with experimental glaucoma.

Glaucoma is a common disease seen in the eye clinic, but its associated pathological processes, especially the role of glial cells in glaucomatous retinae, are still under debate. The aim of the present work was to study the responses of astrocytes, Müller cells and microglia in retinae of rats with experimental glaucoma. Glaucoma was induced in adult male Wistar rats by cauterizing limbal-derived veins and the changes in glial fibrillary acidic protein (GFAP), OX42, OX18, OX6 and EDI expression were studied by immunohistochemical staining. Neuronal cell viability was studied by immunostaining with the neuronal nuclei (NeuN) antibody. In the experimental glaucomatous eyes, a significant drop in the number of NeuN-positive neurons was observed from 7 days postoperation and beyond in both the ganglion cell layer and inner nuclear layer. The expression of GFAP and OX42 was increased during the first 2 months after operation and reduced in rats at 3 and 4 months. OX6 and OX18 immunoreactivity was induced in some microglia of both glaucomatous and sham-operated control eyes. Possible mechanisms of the reaction of astrocytes, Müller cells and microglia in neuronal degeneration following glaucoma are discussed.

Animals↗

PubMed2000

Nitrergic and peptidergic innervation in the developing rat heart.

The phenotypic expression and anatomic distribution of nitrergic and peptidergic innervation in the developing rat heart was localized by reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry and immunohistochemistry using antibodies against neuronal isoform of nitric oxide synthase (nNOS), neuropeptide Y (NPY) and calcitoningene-related peptide (CGRP). NPY-immunoreactive nerve fibers showed the earliest expression by 16 days of gestation, with preferential innervation of the nodal and perinodal areas, followed by the innervation of the valves and ventricles by postnatal day 7. NPY immunoreactivity was also localized to a large proportion of the intrinsic cardiac ganglia from 16 days of gestation onwards with a progressive increase in the number of neuronal cell bodies per ganglia with age. CGRP-positive nerve fibers appeared by 19 days of gestation and were less dense during the gestational and early postnatal periods, and showed a quantitative increase in density by 7 days, followed by a decrease by 3 weeks postnatal. None of the intrinsic ganglia were stained positive for CGRP, indicating the extrinsic sensory origin of these stained fibers. Nitrergic innervation paralleled the sensory innervation, with the cardiac ganglia and nerve fibers showing a positive labeling from 19 days of gestation onwards. NADPH-d and nNOS were partially co-localized. Double-label immunohistochemistry showed that a considerable proportion of sensory CGRP-immunopositive fibers were also immunoreactive for NOS. The results of the present study show that neuropeptides and nitric oxide are expressed by the late gestational period and that autonomic efferent innervation precedes sensory and nitrergic innervation in the developing heart.

Animals↗

PubMed1999

Ultrastructural changes in the chick thymus following unilateral vagotomy.

The ultrastructure of the thymus in the chick (Gallus domesticus) was studied after unilateral vagotomy at survival times of 3, 7 and 10 days. Ultrastructural changes in the ipsilateral thymus were observed in axon boutons as well as in myoid and cystic cells in the medulla, especially those situated near the corticomedullary junction. Structural changes in axon boutons ranged from granular degeneration of the axonal cytoskeleton to vacuolation of the axoplasm. Myelin figures of different sizes and configurations and clumping of small agranular vesicles were commonly observed in the axon terminals. Degeneration of myoid cells appeared to peak at 7 days post-vagotomy. Changes ranged from oedematous appearance and intense vacuolation of the peripheral cytoplasm to disorganisation and clumping of myofibrils. In some myoid cells the sarcomeres showed granular degeneration at the I-bands and in others, the myofibrils were completely degenerated such that amorphous material and partially degenerated organelles filled the entire cell. The majority of cystic cells at 3 days post-vagotomy showed a uniform increase in electron density. Numerous electron dense bodies, some displaying concentric lamellation, were observed throughout the expanse of the cytoplasm. At 7 days post-vagotomy, the cytoplasm of some cells gave a "moth-eaten" appearance. Dying cystic cells were encountered at 10 days after vagotomy. Degeneration in the myoid and cystic cells suggests that these cellular components may be the putative targets of the vagal fibres in the chick thymus. The changes in these cells reflect a disturbance in the cell metabolism presumably brought about by the removal of vagal influence.

Animals↗

PubMed1999

Ultrastructural changes in the sinuatrial and atrioventricular nodes of the heart of the monkey (Macaca fascicularis) after bilateral vagotomy.

This study describes the ultrastructural changes in the sinu-atrial (SA) and atrio-ventricular (AV) nodes of the monkey (Macaca fascicularis) after bilateral mid-cervical vagotomy at 1, 3, 5, 7 and 14 days post-operations. The changes were similar in both types of nodal cells. The most obvious feature of the degenerating nodal cells was the swollen mitochondria with disrupted cristae. Other changes include increased granular sarcoplasmic reticulum, increased glycogen particles, vacuolation of mitochondria and increased lysosomal activity. Axonal profiles in the vicinity of the nodal cells showed swelling and vacuolation. Cardiac neurons also showed some changes such as distended granular endoplasmic reticulum, increased accumulation of glycogen particles and increased lipofuscin granules. Macrophages and Schwann cells were the main scavengers in removing the degenerated nodal cells and axonal profiles. In the case of affected cardiac neurons, satellite cells seemed to act as main scavenger cells. It is postulated that the nodal cells are dependent on the incoming fibres of the vagus nerve for their survival. By an understanding of the ultrastructural changes in the nodal cells after bilateral vagotomy, it may help in developing new strategies to explore in depth of the conducting system of the heart.

Animals↗

PubMed1999

Ultrastructural study of the effects of 6-hydroxydopamine on the sinuatrial and atrioventricular nodes of the heart of the monkey (Macaca fascicularis).

The present study examined the ultrastructural changes in the sinuatrial and atrioventricular nodes of the heart of the monkey (Macaca fascicularis) after 6-hydroxydopamine (6-OHDA) at survival times of 1, 3, 5, 7 and 14 days. Changes ranged from dissolution of the cytoplasm to amorphous appearance and darkening of the nodal cells. Initially, the ultrastructural changes were quite similar in both sinuatrial (SA) and atrioventricular (AV) nodal cells but in the later stage, especially at fourteen days, affected SA nodal cells showed empty-looking appearance while affected AV nodal cells displayed a darkened appearance. The cardiac neurons also showed ultrastructural changes such as diffuse accumulation of glycogen particles, distended cisternae of the rough endoplasmic reticulum and increased lipofuscin granules. Some of the vacuolated axonal profiles containing large dense-cored vesicles were in close association with the somata of the cardiac neurons. There were also changes in the non-neuronal cells such as darkening and vacuolation of the cells capping the neurons. Macrophages and Schwann cells were activated to engulf the degenerating nodal cells and axonal profiles. The ultrastructural changes in the nodal cells and the cardiac neurons reflect a disturbance in the cell metabolism presumably brought about by the impairment of the sympathetic nervous system.

Adrenergic Agents↗

PubMed1999

Ultrastructural changes in the atrioventricular valves of streptozotocin-induced diabetic rats.

The present study describes ultrastructural changes in the atrioventricular (AV) valves of diabetic rats at 3, 6, 9 and 12 months. At 3 and 6 months of diabetes, the interstitial cells were characterized by an accumulation of vacuoles, lysosomes, electron-dense vesicles, mitochondria and cisternae of rough endoplasmic reticulum in the cytoplasm. There were numerous collagen fibres in the interstitial space. Unmyelinated axons were ensheathed by Schwann cells. Infiltration of macrophages was observed near the interstitial cells. Each macrophage showed a large round or oval nucleus containing heterochromatin masses at the periphery of the cell nucleus. At 9 and 12 months of diabetes, the interstitial cells contained numerous vacuoles, dilated mitochondria, agranular vesicles and a prominent multivesicular body in the cytoplasm. Degenerating unmyelinated nerve fibres were encountered near the interstitial cells. Phagocytic macrophages contained numerous vacuoles of various sizes, which occupied most of the cytoplasmic area. Several vacuoles and degenerated electron-dense granules (some of them appeared to be fragmented) were present in the cytoplasm of interstitial cells and macrophages. It is concluded that interstitial cells in the AV valves contribute to valvular dysfunction in the streptozotocin-induced diabetic rats.

Animals↗

PubMed1998

Sensory nerve endings in monkey hip joint capsule: a morphological investigation.

This study was undertaken to identify the sensory nerve endings in the monkey hip joint capsule. The capsules from six monkeys were stained in bulk by using a modified gold chloride method. Three morphologically distinct nerve endings: Type I, II and IV receptors resembling Ruffini end organs. Pacinian corpuscles and free nerve endings, respectively, were identified. The results showed that the hip joint capsules were densely innervated. Based on the present findings it is suggested that the monkey hip joint capsule is endowed with several types of afferent nerve endings, thus providing the anatomical basis for discriminating afferent outflow to the central nervous system.

Animals↗

PubMed1998

Colocalization of ChAT, DbetaH and NADPH-d in the pancreatic neurons of the newborn guinea pig.

Choline acetyltransferase (ChAT) as a rate-limiting enzyme in the biosynthetic pathway of acetylcholine is thought to be present in all cholinergic neurons. However, its immunoreactivity has not been successfully applied to the study of cholinergic neurons in the pancreas. In a previous study in the pancreas of newborn guinea pig we reported the colocalization of nicotinamide adenine dinucleotide hydrogen phosphate-diaphorase (NADPH-d), a marker for nitric oxide synthase (NOS) with various neuropeptides as well as dopamine-beta-hydroxylase (DbetaH), the enzyme responsible for converting dopamine to noradrenaline. Whether NADPH-d is colocalized with ChAT in the pancreatic neurons is not known. Also it would be interesting to find out whether noradrenaline and acetylcholine could be colocalized in the same pancreatic neurons. In the present study, a method for triple labelling of ChAT, DbetaH and NADPH-d was used to answer the above questions. Colocalization of ChAT, DbetaH and NADPH-d was constantly demonstrated in the same neurons in the same sections. It is concluded that some of the pancreatic neurons may utilize more than one neurotransmitter such as nitric oxide (NO), acetylcholine and noradrenaline to achieve their function. The possible cotransmission of acetylcholine and noradrenaline was extremely intriguing, and its mechanism and significance needs to be further investigated.

Animals↗

PubMed1998

Prehension in man revisited: lesson from the monkey (Macaca fascicularis).

The manus in human is capable of performing intricate movements. To determine whether human dexterity is the result of neuromuscular co-ordination arising from a rich cortical network or due to biomechanical adaptation, the multitendoned extrinsic flexor muscles and intrinsic flexor musculature of the hand were examined in nine human cadavers and compared to those in three macaque monkeys. The flexor pollicis longus was present in all the upper limbs of the human cadavers and absent in all the upper limbs of the monkeys. An accesory origin of the flexor pollicis longus was seen in the upper limb of an Indian cadaver. The opponens pollicis which is possibly the most important intrinsic muscle of the hand was observed to be present in the manus of both human and monkey. Although the macaque monkey lacks a flexor pollicis longus, its digital dexterity has been reported to be equal to man. In this context, it would appear that neural output is the more important factor in prehensile activities.

Aged↗

PubMed1997

Microglia responses in the CNS following sciatic nerve transection in C57BL/Wld(s) and BALB/c mice.

The present study employed C57BL/Wld(s) mice to investigate whether a delay in microglia reaction would occur similar to the delay that occurs in macrophage response after sciatic neurectomy. The results were compared with control BALB/c mice. The observations showed that in both strains of mice there was no delayed microglia response around lesioned motoneurons and around the central processes of the dorsal root ganglion cells after sciatic neurectomy in the adult. The increased Mac-1 staining appeared as early as 1 day postoperation (dpo). This indicates that microglial cells and macrophages respond to different signals generated by neurectomy. In both strains of mice, the number of microglia in the neonate was much less than that in the adult and the increase in Mac-1 staining was detectable only at 3 dpo in both strains of mice. A significant loss of motoneurons was detected after sciatic neurectomy in the neonate. However, there were no significant differences in the mean percentages of motoneuron loss between the two strains of mice at 5, 10, and 15 dpo. It is surmised that the lack of an adequate number of mature microglia in the neonates and their tardy expression of CR3 antigenicity may contribute to the motoneuron loss.

Aging↗

PubMed1997

Expression of NADPH-diaphorase and nitric oxide synthase in lumbosacral motoneurons after knee joint immobilisation in the guinea pig.

The expression of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) and nitric oxide synthase (NOS) in spinal ventral horn neurons was studied in the guinea pig after right knee joint immobilisation (RKJI). At 1 wk after RKJI, neurons in the ipsilateral ventral horn from L4 to S1 segments showed a moderate reactivity for NADPH-d staining. At 2 wk, NADPH-d labelled neurons were also observed in the contralateral ventral horn. Ipsilateral NOS immunoreactive cells were not detectable until wk 2. The intensity of NADPH-d and NOS labelled neurons in the bilateral ventral horns was sustained, peaking at the 4th wk after RKJI. In guinea pigs subjected to 4 wk of RKJI and subsequently released from the immobilisation for 2 and 4 wk, NADPH-d and NOS reactivity in ventral horn neurons diminished. The expression of NADPH-d positive neurons differed from that of NOS labelled neurons in terms of time interval, cell number and staining intensity, the latter being later, fewer and weaker. It is suggested that the induction and upregulation of NADPH-d and NOS are attributable to reduced activity of muscles acting on the knee joint after RKJI; the changes are reversible. It is speculated that increased levels of NO production are involved in protective mechanisms against possible neuronal degeneration as a consequence of target dysfunction.

Animals↗

PubMed1997

Localization of glutamate receptor subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) type in the pancreas of newborn guinea pigs.

Glutamate and related molecules are the major excitatory neurotransmitters in the central nervous system, and their receptors have been localized therein. Little is, however, known about them in the peripheral nervous system. The present study investigated the localization of glutamate receptor subunits of the alpha-amino-3-hydroxy- 5-methyl-4-isoxazolepropionate (AMPA) type (GluR1, GluR2-3, and GluR4) in the pancreas of newborn guinea pigs. With a double-labeling method of immunofluorescence and immuno-tetrahydrochloride reaction, GluR1 and GluR4 immunoreactivities were localized mostly in the insulin-secreting cells in the central mass of the islet, and GluR2-3 immunoreactivity in the peripheral rim of the islet, which consists mainly of non-insulin-secreting islet cells. With a double-labeling method employing immunofluorescence and NADPH-diaphorase (NADPH-d) histochemistry, GluR2-3 and GluR4 immunoreactivities were localized in most of the NADPH-d positive pancreatic ganglion cells. None of the NADPH-d-positive ganglion cells showed GluR1 immunoreactivity. In fact, GluR1 immunoreactivity was not detected in any of the pancreatic ganglion cells. The results indicate that glutamate is likely to exert its effects on the pancreas by activating different AMPA receptor subunits located in endocrine cells and intrapancreatic ganglia.

Animals↗

PubMed1997

An ultrastructural study of the innervation of the guinea pig pancreas.

The present ultrastructural study investigated the innervation of the guinea pig pancreas, with special emphasis on the pancreatic ganglia and the sympathetic and parasympathetic boutons/terminals. The pancreatic ganglion cells, ensheathed in a thin layer of connective tissue, showed typical features of autonomic neurons. Each contained a prominent eccentric round nucleus with 1 to 5 nucleoli and a copious cytoplasm with many organelles. Synapses were scattered in the ganglion and were of the axodendritic type. Axosomatic synapses were not encountered even after examination of semiserial sections in one of the tissue blocks. Desmosome-like junctions (puncta adhaerentia) were found between somata of the ganglion cells, and between their dendrites, and also between somata of the ganglion cells and satellite cells. The sympathetic nerves supplying the pancreas were demonstrated by the 5-hydroxydopamine loading method. Axon terminals loaded with the false transmitter were filled with intensely stained small dense-cored vesicles. These were present in close contact with acinar cells, islet cells as well as smooth muscle cells of arterioles. No 5-hydroxydopamine loaded axon terminals or ganglion cells were observed within the ganglia. The preganglionic parasympathetic nerve fibres supplying the pancreas traveling with the vagus nerve were studied by sectioning the left vagus nerve at mid-cervical level. Three to 7 days after left cervical vagotomy, degenerating axon terminals containing small spherical agranular vesicles, together with degenerating dendrites and neuronal somata showing electron dense cytoplasm were encountered within the pancreatic ganglion. The satellite cells were hypertrophied, showing a pale cytoplasm in which were embedded degenerating axon terminals and dendrites. In conclusion, the present study described the normal structure of pancreatic ganglia, provided ultrastructural evidence of the presence of sympathetic and parasympathetic fibres in the pancreas of the guinea pig, and reported postsynaptic changes in the dendrites after mid-cervical sectioning of the left vagus nerve.

Animals↗

PubMed1997

The effects of bilateral vagotomy on substance P-like immunoreactive nerves in the cardiac ganglia of the monkey (Macaca fascicularis).

The present study showed that neural degeneration occurred in the cardiac ganglia after bilateral vagotomy. At 1 week after operation, a majority of the substance P-like immunoreactive (SP-IR) nerve fibres were affected and they showed signs of degeneration. SP-IR nerve endings forming the pericellular baskets around seemingly normal neuronal cell bodies were also degenerated. By 2 weeks after operation, numerous macrophage-like cells infiltrated the cardiac ganglia and they engulfed the degenerating SP-IR cellular debris. At 3 months after operation, a few fine SP-IR nerve fibres were detected in the cardiac ganglia, together with a few small solitary SP-IR neurons. At 6-12 months after operation, numerous SP-IR nerve fibres were observed in the cardiac ganglia. Some of the SP-IR nerve endings started to form pericellular baskets around the seemingly normal neuronal cell bodies. It is concluded that there is reinnervation of the heart by SP-IR nerve fibres after surgical interruption to both vagi. However, the origin of these SP-IR nerve fibres and terminals remains unknown.

Animals↗

PubMed1997

Do microglial cells have a neuroprotective function?

To explore the possible neuroprotective role of microglia after a peripheral nerve lesion, the present study used athymic mice shown to have a lower number of microglia to highlight some functions of microglia not normally obvious in animals with a normal number of such cells. Observation of semithin sections showed that unoperated 5-day-old athymic mice had a significant lower number of microglial cells around sciatic motoneurons, compared to their BALB/c littermates. After right sciatic nerve cut at mid-thigh level, motoneuron loss occurred faster at 5 and 10 days after operation in neonatal athymic mice than BALB/c mice. The motoneuron loss by 15 days after nerve cut was, however, the same in both strains of mice. Microglial reaction after sciatic neurectomy, as revealed by Mac-1 immunohistochemistry, was obviously less in intensity and number in athymic mice than in BALB/c mice. The results indicated a neuroprotective function of microglia, which, when not present in adequate numbers, could result in a faster motoneuron death. The study also showed that while microglia were reduced in number in athymic mice, there was no significant difference in the number of astrocytes and oligodendrocytes in the spinal cord of the athymic mice, compared to that in BALB/c mice. This indicates that the development of astrocytes and oligodendrocytes in the spinal cord may not be affected by a reduced number of microglia.

Animals↗

PubMed1997

Nitrergic, peptidergic and substance P innervation of the chick thymus.

Nitrergic and peptidergic innervation of the chick thymus was studied using histochemical and immunohistochemical methods. Nicotinamide adenine dinucleotide hydrogen phosphate-diaphorase (NADPH-d) histochemistry and anti-nitric oxide synthase (NOS) antibodies stained both nerve fibres and 'neuron-like' cells located in the septal connective tissue. NADPH-d and NOS were partially colocalised. Staining of NADPH-d positive neuron-like cells with the neuronal marker, neuron specific enolase, confirmed the neuronal nature of these cells. Antibodies against vasoactive intestinal peptide (VIP), neuropeptide tyrosine (NPY), substance P (SP) and calcitonin gene related peptide (CGRP) were used to map the peptidergic innervation of the chick thymus. The distribution of nerve fibres staining for the various neuroactive chemicals in specific thymic compartments was non-uniform. Out of all the peptides, VIP-containing nerves appeared to be the most abundant. In addition, double-labeling of the thymic sections revealed that VIP and NADPH-d were colocalised in the neuronal structures. Immunostaining of the chick embryos demonstrated that VIP, NPY, SP and CGRP were first expressed in the chick thymus during late ontogeny. The significance of these novel findings was discussed.

Animals↗

PubMed1996

Nitrergic neurons in the pancreas of newborn guinea pig: their distribution and colocalization with various neuropeptides and dopamine-beta-hydroxylase.

The distribution of nitrergic neurons in the pancreas of the newborn guinea pig was first investigated, using nitric oxide synthase (NOS) immunofluorescence and nicotinamide adenine dinucleotide hydrogen phosphate-diaphorase (NADPH-d) histochemistry. There was total colocalization of NOS and NADPH-d in the pancreatic ganglion cells. NADPH-d was then used as a marker for NOS. In the whole mount preparation of the pancreas, most of the nitrergic neurons were located in the head and the body region, along the branches of pancreatic blood vessels. Some were also associated with the main pancreatic duct, islets of Langerhans and pancreatic acini. To investigate whether NADPH-d stained cells were neurons and whether NADPH-d was colocalized with various neuropeptides and dopamine-beta-hydroxylase (D beta H), an enzyme involved in the synthesis of noradrenaline, antibodies against neuron specific enolase (NSE), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY). D beta H, substance P (SP), calcitonin gene-related peptide (CGRP) and bombesin (BOM) were used. Of all NSE positive ganglion cells, 76.8% were NADPH-d positive. NOS, VIP, NPY and D beta H immunoreactivities were found in both the neuronal cell bodies and nerve fibres in the pancreas while SP, CGRP and BOM immunoreactivities were detected only in the nerve fibres. SP-, CGRP- and BOM-containing nerves were in close contact with both NADPH-d positive as well as NADPH-d negative neurons. The percentages of NADPH-d/VIP, NADPH-d/NPY, NADPH-d/D beta H neurons in the total number of pancreatic neurons were 67.4%, 53.5%, 21.5% respectively. With double labelling in adjacent sections three subpopulations of pancreatic ganglion cells were demonstrated: NADPH-d/VIP/NPY, NADPH-d/VIP/D beta H and NADPH-d/NPY/D beta H.

Animals↗