Biomedical subjects

S Goto

Publications and source records attributed to S Goto.

At least 775 records · Page 43Linked to original sources

PubMed1989

Cloning of rabbit uricase cDNA reveals a conserved carboxy-terminal tripeptide in three species.

cDNA clones encoding uricase have been isolated from a rabbit liver cDNA library. The nucleotide sequences of the cDNAs have been determined and those of the rat uricase cDNA have been revised. In all three uricases, the carboxy-terminal tripeptides are Ser-Arg/Lys-Leu sequences, which have recently been suggested as an essential element of peroxisomal targetting signals for many but not all peroxisomal proteins.

Amino Acid Sequence↗

PubMed1989

An immunohistochemical investigation of the human neostriatum in Huntington's disease.

The neostriatum of 7 autopsied patients with Huntington's disease (HD) was examined immunohistochemically using purified antibody against calcineurin, which may be present only in the medium-size spinous neurons of the mammalian striatum. This study revealed a marked loss of calcineurin-positive cells in the caudate nucleus and the putamen in all HD patients, compared with control subjects, and there was some variation among the HD patients. Four HD patients showed significantly lower density of calcineurin-positive cells in the caudate nucleus than in the putamen. The remaining calcineurin-positive cells in the caudate nucleus and the putamen had a mosaic-like pattern, demonstrating a subregional difference in distribution. This finding suggests that there are subregional as well as compartmental differences in the vulnerability of the calcineurin-positive cells in the striatum of patients with HD.

Adult↗

PubMed1989

Subdivisional involvement of nigrostriatal loop in idiopathic Parkinson's disease and striatonigral degeneration.

A topographical immunocytochemical analysis was performed on the substantia nigra from patients with idiopathic Parkinson's disease and striatonigral degeneration. Antibodies to tyrosine hydroxylase, a marker for nigrostriatal dopaminergic neurons, and to calcineurin, a marker for striatonigral projection fibers, were used in this study. There was a marked depletion of dopaminergic neurons in the substantia nigra of parkinsonian patients compared with control subjects, the reduction being greater in the lateral portion than in the medial portion (p less than 0.001). Calcineurin immunoreactivity was densely distributed throughout the substantia nigra of patients with Parkinson's disease and control subjects. The numbers of dopaminergic neurons and of calcineurin-immunoreactive fibers were markedly reduced in the lateral portion of the substantia nigra in all patients with striatonigral degeneration. Our results suggest that many symptoms of these two diseases may be due to disruption of the functions of the putamen and the lateral portion of the substantia nigra, which have dense reciprocal connections as part of the dopamine-related nigrostriatal loop.

Aged↗

PubMed1989

Calcineurin in the postnatal striatum of the rat: an immunohistochemical study.

This report concerns the postnatal expression of calcineurin (CaN) in rat striatum. For this purpose an immunohistochemical procedure was used. In neonatal striatum CaN immunoreactivity was found in discrete patches composed of many immature cells. With development there was an increase in staining intensity and in the proportion of positively reacting cells. CaN expression and localization in the striatum of 22-25 day old rats were similar to those of adult animals.

Animals↗

PubMed1989

Calcineurin immunoreactivity in striatonigral degeneration.

The basal ganglia (including substantia nigra) of two patients with striatonigral degeneration, who had clinical histories of Parkinson's disease, were studied immunohistochemically using a purified antibody to calcineurin (CaN). Marked loss of CaN-immunoreactive neurons in the putamen and neuromelanin-pigmented neurons in the zona compacta of the substantia nigra was seen in both cases. A small number of CaN-immunoreactive neurons remained dispersed in "clusters" or "islands" in the medial portion of the putamen. In one case there was loss of CaN-immunoreactive neurons in the caudate nucleus to a lesser degree than that in the putamen. In addition, both cases showed marked depletion of CaN-immunoreactive afferent nerve fibers in the external and internal segments of the globus pallidus and the zona reticulata of the substantia nigra. This report emphasizes the usefulness of the CaN-immunostaining technique for assessing the striatal efferents in human basal ganglia, and shows the neuropathological changes in the basal ganglia with striatonigral degeneration which were not possible to ascertain with previous techniques.

Aged↗

PubMed1989

Immunohistochemical visualization of afferent nerve terminals in human globus pallidus and its alteration in neostriatal neurodegenerative disorders.

The afferent nerve terminal in the human globus pallidus, which receives the projection nerve fibers from both the striatum and the subthalamic nucleus, were clearly visualized immunohistochemically using antibodies to calcineurin, synaptophysin, Met-enkephalin (MEnk) and substance P (SP). In normal control case, MEnk and SP-like immunoreactivities were densely localized in the external and internal pallidal segments, respectively, whereas calcineurin and synaptophysin were distributed throughout the globus pallidus. Calcineurin, synaptophysin, MEnk and SP-like immunoreactive peroxidase products decorated most of the long radiating dendrites and the cell bodies of the pallidal neurons. In the cases with Huntington's disease (HD) and striatonigral degeneration (SND), marked loss of calcineurin, MEnk and SP-like immunoreactivities was seen in the globus pallidus corresponding to areas of striatal neurodegeneration, whereas synaptophysin immunoreactivity remained in areas which revealed almost complete loss of calcineurin, MEnk and SP-like immunoreactivities. Calcineurin, MEnk and SP, which show difference in their localization patterns, may provide reliable markers for the striatal efferent nerve terminals, and synaptophysin for the entire pallidal afferent nerve terminals. This report demonstrates the distribution patterns of these neurochemical molecules in the globus pallidus with HD and SND.

Afferent Pathways↗

PubMed1989

An immunohistochemical study of somatostatin-containing nerves in the aganglionic colon of human and rat.

The distribution of somatostatin-like immunoreactive (SOM-LI) nerves was elucidated immunohistochemically in the gut tissues from patients with Hirschsprung's disease and congenital aganglionosis rats. In the normoganglionic human colon, SOM-LI nerve cell bodies were found to a greater extent in the submucous plexus and to a lesser extent in the myenteric plexus. However, they were rarely observed in both the plexuses of the oligoganglionic segment. SOM-LI nerve fibres were widely distributed in the aganglionic bowel. The circular muscle layer of the distal aganglionic segment was densely innervated by SOM-LI nerve fibres which are probably derived from the extrinsic, hypertrophic nerve bundles. A decreased number of the intramuscular nerves fibres were seen in the proximal aganglionic segment. In the colon and rectum from adult and 21-day-old rats, SOM-LI cell bodies were numerous in both plexuses. On the other hand, enteric neurons were completely lacking from the colon and rectum of congenital aganglionosis rats of 21 days old. No neuronal elements staining for SOM were disclosed in these aganglionic segments of mutant rats. A possible origin and pathophysiological role of the extrinsic nerve fibres containing SOM in the diseased bowel are discussed. It is concluded that SOM-LI nerves in the human distal colon comprise both intrinsic and extrinsic elements, while SOM nerves in the rat colon and rectum are of only intrinsic origin.

Animals↗

PubMed1989

Alteration of tumour cell arrangement related to connective tissue stroma in metastatic brain tumours. Histological and immunohistochemical studies of 68 autopsy cases.

Tumour cell arrangements of a variety of 68 tumours metastatic to brain parenchyma and leptomeninges were compared histologically and immunohistochemically with those of the primary tumours in regard to their connective tissue stroma. In the brain parenchyma, more than 90% of 31 metastatic differentiated adenocarcinomas from various organs changed in cell arrangement from a tubular to a papillary pattern, in which tumour cells lined the increased perivascular connective tissue, rich in both type III collagen and fibronectin, the typical constituents of interstitial type extracellular matrices. Twelve (39%) and 3 of 31 cases were rearranged in a partially or completely tubular pattern respectively, within the metastatic nodules. Most of these neoplastic tubules were surrounded by diffusely proliferating connective tissue. Metastatic growth of carcinoma cells in the absence of supporting connective tissue in the nervous tissue was rare. A similar result was obtained for differentiated squamous cell carcinoma. In contrast, metastatic undifferentiated carcinoma and tumours with some neuro-ectodermal characteristics showed a sheet-like arrangement without pronounced connective tissue proliferation, similar to that of the primary tumours. In the leptomeninges, differentiated carcinoma cells were arranged in a tubular or a squamoid pattern and were frequently accompanied by marked stromal response. These results indicate that differentiated carcinomas require connective tissue stroma for metastatic growth, and that tumour cell arrangement in the brain varies depending upon the amount and distribution of proliferating connective tissue stroma. In undifferentiated carcinomas and tumours with neuro-ectodermal characteristics lacking stromal dependency, the tumor cell arrangement remains unchanged. The degree of stromal response to metastatic tumours in the brain parenchyma is related to the degree of epithelial differentiation.

Adenocarcinoma↗

PubMed1989

Clinical evaluation of sizofiran combined with irradiation in patients with cervical cancer. A randomized controlled study; a five-year survival rate.

Following a previous report we ascertained the effectiveness of sizofiran (Schizophyllan:SPG) to prolong the survival and time to recurrence of the patients with Stage II or III cervical cancer, as evaluated in a 5-year randomized controlled study conducted in 19 institutions in Japan. Of the overall patients with Stage II or III cancer, time to recurrence and survival rate in the group on SPG were significantly longer than in the control group. In the Stage II patients, there was significant difference in time to recurrence, and survival of SPG group tended to be longer than that of the control group. However, in the Stage III patients, there was no significant difference in either time to recurrence or survival rate.

Antineoplastic Agents↗

PubMed1989

Effect of dietary n-3 polyunsaturated fatty acids on cholesterol synthesis and degradation in rats of different ages.

Male Sprague-Dawley rats four weeks or eight months of age were fed purified diets containing 10% fat, either as a blend of safflower oil and palm olein (polyunsaturated fatty acids, PUFA, 34%), a blend of linseed oil and palm olein (PUFA, 33%) or sardine oil (PUFA, 33%) for four weeks. In other trials, sterol contents were made equivalent by supplementing cholesterol to a blend of corn oil and palm olein (PUFA, 30%) or phytosterol to sardine oil (PUFA, 30%). Fish oil was hypolipidemic in rats of different ages, but it tended to increase liver cholesterol in adult animals and this was not improved by the addition of phytosterol. The age-dependent increase in liver cholesterol was not duplicated in rats fed a vegetable fat blend supplemented with cholesterol. At both ages, liver 3-hydroxy-3-methylglutaryl coenzyme A reductase activity was lower in the sardine oil than in the other groups. There were no significant age- or diet-related differences in the activity of liver cholesterol 7 alpha-hydroxylase. Fecal steroid excretion was comparable in age-matched rats fed diets supplemented either with cholesterol or phytosterol. Sardine oil reduced the delta 6-desaturase activity markedly as compared with linseed oil, and age-dependent reduction of the desaturase activity was observed in all dietary groups examined. Thus, the results showed a specific effect of fish oil on lipid metabolism.

Age Factors↗

PubMed1989

Isolation and characterization of two monoclonal antibodies that recognize remote epitopes on the cell-binding domain of human fibronectin.

Two monoclonal anti-fibronectin antibodies that inhibit fibronectin-mediated cell adhesion have been established and characterized. One antibody, FN12-8, inhibited attachment of rat kidney fibroblasts on the fibronectin-coated substrate in a concentration-dependent manner, attaining a maximal inhibition of greater than 85% at 850 micrograms/ml. Another antibody, FN30-8, caused about 70% inhibition at a concentration as low as 0.85 microgram/ml, although further increase of the antibody concentration did not significantly augment the inhibitory effect. Immunoblot analysis with defined proteolytic fragments revealed that both antibodies are directed to the cell-binding domain of fibronectin. The epitopes for these antibodies were further narrowed down using recombinant cell-binding fragments expressed in Escherichia coli. FN12-8 recognized the 11.5-kDa cell-binding fragment previously characterized by Pierschbacher et al. (1981, Cell 26, 259-267), suggesting that FN12-8 blocks the Arg-Gly-Asp (RGD) cell adhesion signal. FN30-8 could not bind this fragment but did recognize a longer cell-binding fragment containing additional greater than 111 amino acid residues upstream of the 11.5-kDa fragment. Since the RGD-dependent cell adhesion seems to require another signal located at a region 50-160 residues upstream of the 11.5-kDa fragment for full activity, FN30-8 may exert its inhibitory effect by blocking the latter signal.

Amino Acids↗

PubMed1989

The effect of a neurotoxin (benzalkonium chloride) on the lower esophagus.

Achalasia of the esophagus may be associated with abnormalities of the myenteric plexus (hypo- and anganglionosis). This report evaluates this relationship by studying the effect of benzalkonium chloride (BK, a topical neurotoxin) on the lower esophagus. Following midline laparotomy, topical BK (0.5%) was applied to the muscularis of the lower 1.0 cm of the esophagus for 30 min in 38 Sprague-Dawley rats (200 g). Thirty-eight additional rats acted as controls (unoperated, n = 19; sham laparotomy, n = 19). At 1 and 3 months animals were evaluated for weight gain, daily food intake (g/100 gm body wt), lower esophageal sphincter (LES) manometry, and contrast esophagram. At 3 months, the esophagus was evaluated for histologic study and acetylcholinesterase staining. Esophagram showed distal narrowing with proximal dilatation in BK rats (inner diameter 4.71 +/- 0.61 vs 6.17 +/- 0.58 in controls, P less than 0.001). Daily food intake was significantly less in BK rats (5.57 +/- 0.41 g vs controls 7.69 +/- 0.33 g P less than 0.001). Daily weight gain was also less in BK rats (1.13 +/- 0.34 vs controls 1.83 +/- 0.25, P less than 0.001). An increased LES pressure was noted in BK rats (5.45 +/- 0.89 mmHg vs controls 4.04 +/- 1.04 mmHg; P less than 0.1). A histologic study showed aganglionosis in BK rats with positive cholinesterase staining fibers compared to controls. Topical BK results in distal esophageal aganglionosis characterized by distal narrowing, proximal dilatation, decreased food intake, and limited weight gain when compared to controls. These findings are similar to those observed in achalasia and support a primary neurogenic cause for its etiology.

Acetylcholinesterase↗

PubMed1989

Distribution and localization of glial fibrillary acidic protein in colons affected by Hirschsprung's disease.

The distribution and localization of glial fibrillary acidic (GFA) protein were examined by means of immunohistochemistry in normoganglionic, oligoganglionic, and aganglionic segments of colons from 25 patients with Hirschsprung's disease, including four cases of long segment aganglionosis. In normoganglionic segments, GFA protein-positive glial cells were densely distributed within the myenteric plexus, but sparse in the submucous plexus. Aganglionic segments were completely devoid of glial cells with GFA protein immunoreactivity, coinciding with the lack of enteric ganglia. Instead, GFA protein was found specifically in association with the hypertrophic nerve fasciculi and their branches, which were mainly located in the intermuscular zone and submucosal connective tissue in the distal aganglionic segment of diseased bowels. However, two types of short and long segment aganglionosis differed in the distribution pattern of GFA protein; the extrinsic nerve fasciculi in short segment disease extended toward the normoganglionic segment, but in long segment disease they did not reach this area. A moderate number of GFA protein-positive fasciculi were observed within the circular muscle layer of proximal aganglionic and oligoganglionic parts in short segment aganglionosis, while no immunoreactive fasciculi were encountered within the circular muscle layer of the corresponding parts in long segment aganglionosis. Immunohistochemistry for GFA protein can be of excellent diagnostic value for the aganglionic colon with Hirschsprung's disease, since GFA protein immunohistochemistry discloses exclusively extrinsic, hypertrophic nerve fasciculi, characteristic of the bowel in cases of Hirschsprung's disease.

Child↗

PubMed1989

Autonomic innervation of the intestine from a baby with megacystis microcolon intestinal hypoperistalsis syndrome: I. Immunohistochemical study.

A typical case of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is reported. The patient, an infant girl, was fed only by total intravenous nutrition and is now 3 years old. The distribution of several gut peptides was examined in the resected small intestine using an immunohistochemical method. Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM)-containing nerve fibers were decreased; however, substance P- and leucine enkephalin (Leu-ENK)-containing fibers were increased. The imbalance between several kinds of gut peptides might be one the causes of aperistalsis in MMIHS. This is the first report about the gut peptides of MMIHS.

Autonomic Nervous System↗

PubMed1989

A new polyvinylchloride blood bag plasticized with less-leachable phthalate ester analogue, di-n-decyl phthalate, for storage of platelets.

To compare changes in platelets stored in the new di-n-decyl phthalate (DnDP)-plasticized polyvinyl chloride (PVC) bag with those in a di-(2-ethylhexyl) phthalate (DEHP)-plasticized PVC bag, single-donor apheresis platelet concentrates (PCs), 133 +/- 11 x 10(7) platelets per ml (n = 7), were stored with 94 +/- 3 ml of plasma in a new 1-liter bag with a surface area of 44 +/- 7.1 cm2 per 10(10) platelets. Oxygen and carbon dioxide gas diffusion properties of PVC-DnDP films were respectively, 1.6 and 2 times those of standard PVC-DEHP films. The amounts of DnDP leaked into the plasma of PCs were low at 0.58 +/- 0.06 mg per bag after 5-day storage, which is about one-eightieth the amount of DEHP leaked. The pH of PCs in PVC-DnDP bags amounted to 6.99 +/- 0.03 after 5-day storage, with glycolysis accelerated somewhat in the new bags. However, the platelet oxygen consumption was no different from that in the PVC-DEHP bags. Platelet aggregation and responses to hypotonic shock were significantly better in the new bags at the end of storage. Shape changes of platelets into spherical forms with dendrites were more frequently observed in PVC-DnDP bags than in PVC-DEHP bags. The study indicated that platelets stored in the new DnDP-plasticized PVC bags have retained aggregation and responses to hypotonic shock more than platelets in the PVC-DEHP bags, but spherical forms and anaerobic metabolism increased in the new bags.

Adenosine Triphosphate↗

PubMed1989

Experimental free muscle transplantation to the anus using microsurgical technique--a new treatment for anal incontinence.

Experimental free muscle transplantations to the anus with microneurovascular anastomoses were performed in twenty-one dogs as a model of new treatment for anal incontinence. After undergoing subtotal external sphincterectomy, gracilis muscles were transferred to the anus with microneurovascular anastomoses in Group I (n = 9), without microneurovascular anastomoses in Group II (n = 6), and the muscle transfers were not performed in Group III (n = 6). The mean anal canal pressures decreased to 24.4% of preoperative pressure at one month after subtotal external sphincterectomy. But at six months after muscle transplantation they restored up to 80.7% of preoperative pressure in Group I, 54.7% in Group II and the pressure did not restore in Group III (p less than 0.001 Group I vs Group II and III). Electromyographic study of the graft showed the electrical activity in six of seven dogs (85.7%) in Group I and electrical activity of the graft were not recognized in Group II at six months after transplantation. Histologic study of the graft showed the normal pattern of the muscle fibers in 75-80% of the graft in Group I, and fibrotic degeneration in most areas of the graft in Group II at six months after gracilis muscle transplantation.

Anal Canal↗

PubMed1989

Interaction of dietary protein, cholesterol and age on lipid metabolism of the rat.

1. Male rats at 1 (young) and 9 months (adult) of age were fed on purified diets, supplemented with or without cholesterol, containing 200 g protein/kg (casein (CAS), whey protein (WHY) or soya-bean protein (SOY] for 4 weeks. 2. SOY exerted a hypocholesterolaemic effect in young rats regardless of dietary cholesterol, whereas in adult rats it was observed only when a cholesterol-enriched diet was given. WHY was also hypocholesterolaemic in rats of both ages given cholesterol. SOY tended to reduce the liver cholesterol both in young and adult rats. 3. The liver hydroxymethylglutaryl-CoA reductase (NADPH) (EC 1.1.1.34) activity tended to be lower in the vegetable-protein groups than in the animal-protein groups in young rats, but the age-related reduction was observed only in the latter groups. 4. There was no significant age-related difference in the activity of liver cholesterol 7 alpha-monooxygenase (EC 1.14.13.17) in response to diets. However, when cholesterol was given, activity tended to decrease with age. Rats given SOY excreted more faecal steroids than those given casein, particularly adult rats. 5. The fatty acid profile of phosphatidylcholine and the delta 6-desaturase activity of liver microsomes indicated the reduced desaturation of linoleate in the SOY and WHY groups compared with the CAS groups. 6. The results thus showed a complex interaction of protein type, cholesterol and age on cholesterol homeostasis.

Aging↗

PubMed1989

Prolongation of heterotopic heart allograft survival by local delivery of continuous low-dose cyclosporine therapy.

The effectiveness of local versus systemic low-dose CsA (2 mg/kg/day) therapy delivered by osmotic pump for a 14-day continuous infusion was examined in the rat model. Systemic subtherapeutic CsA treatment of WFu recipients either by oral gavage or intravenously using an osmotic pump resulted in quick rejection of BUF heart allografts within a median survival time (MST) of 8 days in comparison with untreated controls (MST = 7 days). In contrast, direct local subtherapeutic CsA delivery to BUF heart allografts produced significantly (P less than 0.01) prolonged heart allograft survivals up to MST of 40 days. Splenic T cells, isolated on days 10 to 12 from locally immunosuppressed WFu recipients, revealed a nonspecifically reduced proliferative response toward alloantigens. Coculture experiments demonstrate that these T cells have the capacity to inhibit normal T cell proliferative responses in a nonspecific fashion either by their suppressor function or more likely by carrying CsA to the culture plate. In contrast, T cells isolated from WFu recipients three weeks after transplantation and tested in vitro demonstrated the presence in alloantigen specific T suppressor cells that coincided with a decreased frequency of alloantigen-specific T cytotoxic cells and may explain the extended heart allograft survival beyond the time of CsA delivery. CsA therapy delivered directly to the graft resulted in high CsA levels within the heart graft (1108 ng/0.1 g) but subtherapeutic levels in other tissues. These results demonstrate that local drug delivery is effective in inhibiting the rejection process within the graft itself, as manifested by prolonged heart allograft survival. Further, subtherapeutic CsA therapy facilitates development of Ts cells that may be responsible for the survival of heart allografts beyond the CsA delivery time.

Animals↗