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Biomedical subjects

S Suga

Publications and source records attributed to S Suga.

At least 199 records · Page 11Linked to original sources

A monoclonal antibody to C-type natriuretic peptide--preparation and application to radioimmunoassay and neutralization experiment.

C-type natriuretic peptide (CNP), the third member of natriuretic peptides, has recently been discovered from the porcine brain. Using a polyclonal antiserum to CNP, we demonstrated that CNP-like immunoreactivity (CNP-LI) is present mainly in the central nervous system. Recently, however, we have discovered the production and secretion of CNP in vascular endothelial cells. These observations suggested that CNP may act not only as a neuropeptide but also as a local regulator of vascular tone or growth. In order to further clarify the pathophysiological significance of CNP, we aimed at the preparation of a monoclonal antibody to CNP. A monoclonal antibody to CNP, KY-CNP-I, has been produced. This monoclonal antibody belongs to the immunoglobulin G1 subclass and has high affinity for CNP. Using this monoclonal antibody, we established a specific radioimmunoassay (RIA) for CNP. The RIA detected CNP-LI in rat brain extracts and culture media conditioned with bovine endothelial cells. In addition, the pretreatment of cultured aortic smooth muscle cells with KY-CNP-I attenuated cyclic GMP production induced by CNP in vitro. The preadministration of KY-CNP-I to rats also attenuated plasma cyclic GMP increase after intravenous injection of CNP in vivo. These results indicate that this monoclonal antibody is a useful tool to clarify the pathophysiological role of CNP as a neuropeptide and as a local vascular regulator.

Animals↗

Successful treatment of primary sclerosing cholangitis with cyclosporine and corticosteroid.

A case of primary sclerosing cholangitis (PSC) successfully treated with cyclosporine is described. A 65-year-old man who presented with jaundice and anemia was diagnosed as having PSC, accompanied by pancreatic duct abnormalities. Cholangiography and pancreatography showed marked improvements following combined therapy with cyclosporine and methylprednisolone. Cyclosporine seems to be a promising drug for the treatment of patients with PSC. This report reasons that the same disease process affects both the pancreatic ducts and the bile ducts, and that stagnation of pancreatic juice may have a role to play in the pancreatic duct abnormalities.

Aged↗

Clinical features of infants with primary human herpesvirus 6 infection (exanthem subitum, roseola infantum).

OBJECTIVE: To clarify clinical features of patients with primary human herpesvirus 6 (HHV-6) infection (roseola infantum, exanthem subitum) in a large-scale study. SUBJECTS AND METHODS: Clinical signs and symptoms were analyzed in 176 infants in whom exanthem subitum was initially suspected and primary HHV-6 infection was later confirmed. The infection was proved by isolation of the virus from blood, a significant increase in the neutralizing antibody titers to the virus, or both. RESULTS: The primary HHV-6 infection, which occurred throughout the year, was observed in 94 boys and 82 girls (mean age, 7.3 months). Fever developed in 98% (mean maximum fever, 39.4 degrees C) and lasted for 4.1 days. Macular or papular rashes appeared in 98%, on face, trunk, or both, mostly at the time of subsidence of the fever, and lasted for 3.8 days. Other clinical manifestations occurred as follows: mild diarrhea in 68%, edematous eyelids in 30%, erythematous papules in the pharynx in 65%, cough in 50%, and mild cervical lymph node swelling in 31%. Twenty-six percent had bulging of the anterior fontanelle and 8% had convulsions. CONCLUSIONS: Clinical features of patients with virologically confirmed exanthem subitum were comparable with those described before discovery of HHV-6.

Exanthema Subitum↗

Central action of C-type natriuretic peptide on vasopressin secretion in conscious rats.

The effect of intracerebroventricular injection of C-type natriuretic peptide (CNP) on arginine vasopressin (AVP) secretion was studied in conscious rats, and was compared to that of atrial natriuretic peptide (ANP). The AVP secretion induced by central injection of 0.1 nmol angiotensin II was significantly suppressed by the pretreatment with 1 nmol CNP. ANP at a dose of 0.1 nmol elicited almost equivalent suppressive action to 1 nmol CNP. Considering that CNP is a specific ligand for ANP-B receptor, while ANP is that for ANP-A receptor, the result demonstrates that CNP possesses the similar central action to ANP, and suggests that the distribution of ANP-A and ANP-B receptors and/or their affinity towards each natriuretic peptide are different in the central nervous system.

Angiotensin II↗

C-type natriuretic peptide (CNP) is the major natriuretic peptide in human cerebrospinal fluid.

In order to investigate whether C-type natriuretic peptide (CNP) is present in human cerebrospinal fluid (CSF), we measured CNP-like immunoreactivity (-LI) in human CSF by specific radioimmunoassay (RIA) for CNP. We also measured atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations in human CSF. ANP-LI, BNP-LI, and CNP-LI concentrations of CSF collected from fifteen patients without neurological disorders were 0.20 +/- 0.13, 0.27 +/- 0.10, and 2.13 +/- 0.27 fmol/ml (mean +/- S.D.), respectively. In fifteen patients with neurological disorders, ANP-LI, BNP-LI, and CNP-LI concentrations in CSF were 0.21 +/- 0.18, 0.33 +/- 0.19, and 2.09 +/- 0.82 fmol/ml, respectively. Although ANP-LI and BNP-LI concentrations in plasma were much higher than those in CSF, CNP-LI was undetectable in plasma (less than 0.2 fmol/ml). These results demonstrate that three natriuretic peptides are present in CSF and that CNP is the major natriuretic peptide in human CSF. These results suggest that CNP in CSF is originated from and play important roles in the central nervous system.

Adult↗

Clinical and virological analyses of 21 infants with exanthem subitum (roseola infantum) and central nervous system complications.

Twenty-one infants who had virologically confirmed exanthem subitum and central nervous system (CNS) complications were studied to elucidate the clinical features, laboratory and virological findings, and outcome. The primary infection with human herpesvirus 6 was confirmed by isolation of the virus from blood, a significant rise in the antibody titers to the virus, or both. All convulsive seizures (15 generalized and 6 focal) occurred during the pre-eruptive stage of exanthem subitum. Four infants with encephalitis/encephalopathy had more severe clinical features with abnormalities demonstrated on electroencephalograms and cerebral computed tomograms. All infants except those with encephalitis/encephalopathy recovered without any sequelae. One infant with encephalitis/encephalopathy developed epilepsy and another one died. Human herpesvirus 6 DNA amplified by the nested polymerase chain reaction method was detected in the cerebrospinal fluid of 6 infants, including 3 with encephalitis/encephalopathy, of 11 patients examined by the fifth day of the illness. These findings suggest that CNS complications including encephalitis/encephalopathy occur at the pre-eruptive stage of exanthem subitum, that human herpesvirus 6 invades the CNS in some patients, and that the outcome is not always benign.

Base Sequence↗

Seroepidemiology of human herpesvirus 7 in healthy children and adults in Japan.

The isolation of human herpesvirus 7 (HHV-7) from saliva and blood, and the prevalence of antibodies to the virus in healthy individuals were investigated in Japan. By cocultivating samples with phytohemagglutinin-P-stimulated cord blood mononuclear cells, HHV-7 was isolated from the saliva of 1 of 20 children and from 4 of 38 adults but not from their blood. The isolates were confirmed as closely related to RK strain of HHV-7, but not to U1102 (human herpesvirus 6, HHV-6 type A) or Z29 (HHV-6 type B) strains by restriction cleavage patterns of the DNA. The virus antibody of 330 healthy children and adults was measured with an indirect immunofluorescence assay, using one of our isolates (FG7-6). The positivity rate of antibody was 40% in the first 2 months of life, declined during the first 6 months, then gradually increased and was 45% at 1-4 years of age. It reached the highest level (60%) at 11-13 years of age and was maintained until the end of the third decade, then decreased thereafter. Additionally, no simultaneous rise in the antibody titers was observed in 7 virologically confirmed exanthem subitum patients.

Adolescent↗

Stress protein and proto-oncogene expression as indicators of neuronal pathophysiology after ischemia.

Induction of hsp70 mRNA and protein appear to provide useful markers for delineating stages in the progression of neuronal pathophysiology after ischemia. Detection of hsp70 encoded by the induced mRNA is dependent on complex interactions between the time course of mRNA expression and recovery of protein synthesis in a given neuron population, and perhaps other factors relating to specific aspects of hsp70 physiology, during recirculation intervals of hours to days. Transient mRNA expression and subsequent detection of immunoreactive hsp70 protein appear to identify neurons more likely to survive ischemia and other insults, while prolonged expression of hsp70 mRNA is associated with more severe neuronal injury. Fos and Jun immunoreactivities are also increased after ischemia, and provide indexes of functional gene expression during earlier recirculation periods. The accumulation of Fos immunoreactivity in particular designates neurons in which rapid recovery of protein synthesis during 1-3 h recirculation has allowed translation of the very transiently expressed c-fos mRNA. Jun-like immunoreactivity allows an evaluation of events at later recirculation intervals, and provides a clear demonstration of synthesis and accumulation of induced protein in CA1 neurons at 6 h following 2 min ischemia. Detailed understanding of the significance of such interactions between transcriptional and translational events will continue to evolve as information accumulates regarding the expression of additional mRNAs and proteins after ischemia. The present demonstration that Jun-like immunoreactivity accumulates in CA1 neurons after brief ischemia indicates that widespread changes in gene expression, expected as a consequence of such primary effects on transcription factor activity, are likely to contribute to the phenomenon of induced ischemic tolerance and to other persistent changes in the brain following diverse insults.

Animals↗

The natriuretic peptide family.

The natriuretic peptide system is a complicated system comprising at least three endogenous peptides, atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide and three receptors, the atrial natriuretic peptide-A receptor (guanylyl cyclase A), the atrial natriuretic peptide-B receptor (guanylyl cyclase B), and the clearance receptor. The accumulated evidence indicates that this system is implicated in the control of blood pressure, body fluid homeostasis, and vascular remodeling as both cardiac hormone and local regulator.

Animals↗

Moyamoya disease associated with bilateral renal artery stenosis.

Recent research has suggested that an association exists between moyamoya disease and fibromuscular dysplasia which involves systemic vessels, including renal arteries. We report a 3 year old girl with moyamoya disease associated with bilateral renal artery stenosis. This case may support the common etiology of these two clinical conditions. To our knowledge this is the youngest case of moyamoya disease associated with bilateral renal artery stenosis.

Aortography↗

Effect of oral acyclovir against primary and secondary viraemia in incubation period of varicella.

The effect of oral acyclovir (approximately 40 mg/kg daily in four divided doses) against primary and secondary viraemia of varicella zoster virus (VZV) was examined in 27 children susceptible to VZV who were exposed to the virus in their families and their clinical features were compared with those of 19 non-treated subjects. The infection was confirmed by a fluorescent antibody to membrane antigen assay in 11 (85%) of 13 children who received acyclovir for the first seven days after exposure to VZV and in 11 (79%) of 14 who received acyclovir for the next seven days. The geometric mean antibody titre of the former group was significantly higher than that of the latter group. Varicella developed in 10 (91%) and was subclinical in one (9%) in the former group, whereas a very mild disease occurred in three (27%) and was subclinical in eight (73%) in the latter group. The severity of varicella was significantly greater in the former group than that in the latter group. On the other hand, all of the control group developed typical varicella and their clinical features were more severe than those of the acyclovir administered group. These data indicate that oral acyclovir more effectively inhibits replication of VZV in secondary viraemia than that of the primary viraemia.

Acyclovir↗

Downregulation of C-receptor by natriuretic peptides via ANP-B receptor in vascular smooth muscle cells.

The natriuretic peptide system comprises at least three ligands, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) and three receptors, the ANP-A receptor, the ANP-B receptor, and the clearance (C) receptor. In the present study, the regulation of natriuretic peptide receptors by their ligands was investigated in cultured rat vascular smooth muscle cells (SMC). The treatment of vascular SMC with ANP, BNP, or CNP decreased the C-receptor density significantly, and the rank order of potency for this downregulation was CNP > ANP > BNP. This rank order was the same as that for guanosine 3',5'-cyclic monophosphate (cGMP) production by ANP, BNP, or CNP in vascular SMC and also the same as that for the ligand selectivity of the ANP-B receptor rather than the C-receptor. The incubation of vascular SMC with 8-bromoguanosine 3',5'-cyclic monophosphate significantly decreased the C-receptor density and its mRNA expression. These results suggest that the down-regulation of the C-receptor by natriuretic peptides is induced not by the binding of natriuretic peptides to the C-receptor but by the activation of the ANP-B receptor-cGMP pathway.

Animals↗

Estrogen-sensitive neurons in the female rat ventral tegmental area: a dual route for the hormone action.

1. Electrical stimulation of the ventral part of the midbrain central gray (CG) elicited antidromic action potentials in 136 neurons in the ventral tegmental area (VTA) of 23 urethan-anesthetized ovariectomized female rats. 2. Antidromic action potentials were positive-negative biphasic and completed mostly within 2.4 ms. Many had a notch in their initial positive deflection, at which antidromic potentials often failed to propagate into the neuronal soma. 3. The latency for antidromic activation ranged 1.0-10.5 ms, and the threshold was 100-1,700 microA. The relative refractory period was 0.8-2.8 ms. In 23 neurons (17%) gradual changes in stimulus intensity caused latency jumps, suggesting that their axons terminate or spread into branches in stimulation sites. 4. The parameters for antidromic activation were compared among 12 animals with a subcutaneous Silastic capsule of estrogen and 11 others with a blank capsule. Estrogen raised the mean threshold from 675 +/- 40 (SE) microA (n = 69) to 908 +/- 40 microA (n = 67). At the same time, estrogen significantly decreased the probability of the antidromic propagation from 63 to 41%. No changes were detected in the latency or the refractory period. 5. The probability distribution of the threshold was different in ovariectomized animals from that in estrogen-treated animals. Estrogen increased the number of cells with thresholds in the 1,300- to 1,500-microA range. 6. The probability of antidromic propagation was stable in each neuron to stimuli repeated at 1.0 Hz. Electrical stimulation of the preoptic area (POA) with a 30-s train of 50-microA pulses at 100 Hz increased the probability of antidromic propagation into the soma.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Brain natriuretic peptide levels in the umbilical venous plasma are elevated in fetal distress.

We measured, by a specific radioimmunoassay, brain-natriuretic-peptide-like immunoreactive (BNP-LI) levels in the umbilical venous and arterial plasma of normal and distressed newborns. The indicated BNP-LI level in umbilical arterial plasma of normal newborns (3.5 +/- 0.9 fmol/ml, mean +/- SEM, n = 10) was significantly higher than that in umbilical venous plasma of the same newborns (2.2 +/- 0.5 fmol/ml). In the distressed newborns at term, the indicated BNP-LI level in umbilical venous plasma was 62.2 +/- 25.7 fmol/ml (n = 4), which was 19-fold higher than that of elective cesarean section cases (3.2 +/- 0.3 fmol/ml, n = 6; p < 0.05). The findings demonstrated that BNP was present in the human fetal circulation and that the plasma BNP level was elevated under fetal distress conditions.

Atrial Natriuretic Factor↗

Ventricular expression of brain natriuretic peptide in hypertrophic cardiomyopathy.

BACKGROUND: Brain natriuretic peptide (BNP), as a cardiac hormone, is expressed together with atrial natriuretic peptide (ANP) in the ventricles in congestive heart failure. However, the ventricular expression of BNP in hypertrophic cardiomyopathy (HCM) with normal systolic function is still unclear. METHODS AND RESULTS: The study population consisted of 39 HCM patients with asymmetric septal hypertrophy and 10 control subjects without any specific cardiac disease. Eleven cases of HCM were obstructive (HOCM), and the other 28 cases were nonobstructive (HNCM). All of these patients had a normal ejection fraction. Immunohistochemical analysis of endomyocardial biopsy specimens with specific monoclonal antibodies showed BNP immunoreactivity in the HOCM group (5/10, 50%) but not in the HNCM group (0/22) or in control subjects (0/5). In HOCM, left ventricular end-diastolic pressure was significantly higher in the BNP-positive patients than the BNP-negative patients. Histological changes such as myocardial fiber disarray, hypertrophy of myocytes, and fibrosis were greater in BNP-positive patients than BNP-negative patients in HCM. However, the expression had no significant relation with other clinical parameters. The elevation of the BNP plasma level versus control subjects was marked in both HOCM (85-fold) and HNCM (23-fold). By contrast, the elevation of the ANP plasma level versus control subjects was mild in HOCM (5.7-fold) and HNCM (4.2-fold). The ratio of BNP level to ANP level was higher in HOCM (4.16) than in HNCM (1.46) and control subjects (0.28), and it was higher than the ratio previously reported for severe congestive heart failure (1.72). CONCLUSIONS: These findings suggest that BNP is expressed in the ventricular myocytes of HCM with normal systolic function. In HOCM, ventricular expression of BNP may be augmented in response to both obstruction and diastolic dysfunction.

Adult↗

Fluoride and iron concentrations in the enameloid of lower teleostean fish.

Our quantitative elemental analyses with the electron microprobe indicated that the fluoride and iron concentrations in the enameloid of bony fish are related to the phylogeny of fish. The enameloid of some bony fish with high F also contained high Fe. In order to clarify the phylogenetic significance of such a peculiar dual deposition of F and Fe into developing enameloid, quantitative electron microprobe analyses of these elements were made on the teeth of taxonomically lower teleosts. There were significantly different trends of F and Fe concentrations in the enameloid among various forms of lower teleosts. In the Osteoglossiformes, the enameloid of the osteoglossid species contained very low levels of F and Fe, whereas in the single representative of the Mormyroidei, the F was very low but Fe was very high. In the Elopomorpha, the enameloid of the elopiform species contained a medium level of F and high Fe, and that of the anguilliform high levels of F and Fe. In the Salmoiformes, the salmonid species had medium F and high Fe, and in a species of the Esocidae, high F and high Fe levels were found. The stomiiform fish exhibited levels of medium and high F and high Fe. The results of the present study and our previous investigations made on archaic non-teleostean and various teleostean fish indicate that the mechanisms of F and Fe concentrations into developing enameloid are independent of each other, and that the mechanisms of Fe concentration appeared earlier and disappeared later than, or concurrently with, that of the F concentration, in the course of fish evolution.

Amelogenesis↗