Biomedical subjects

H Furuya

Publications and source records attributed to H Furuya.

At least 199 records · Page 11Linked to original sources

PubMed1991

[Incidence of abnormal thyroid function in patients with low titers of thyroid microsomal antibodies].

The incidence of abnormal thyroid function related to autoimmune disorders was examined in a district of Shimane Prefecture in 1988. Thyroid microsomal antibodies (MCPA) in sera were measured in a general population of 1,646, including 678 males and 968 females, aged 57.8 +/- 14.8 (mean +/- SD) yr. MCPA titer was defined as high (less than 1:128), low (1:16, 1:32, 1:64) or negative (less than 1:16) according to the highest dilution of test serum capable of agglutinating gelatin particles coated with the appropriate antigen. Test of MCPA revealed high titers in 141 subjects (group A), low in 43 subjects (group B) and negative in 1,462 (group C). Twenty-four patients with overt thyroid disorders were found in groups A and B: five with Graves' disease, two with Hashimoto's thyroiditis and 15 with goiter in group A, and two with goiter in group B. In the remaining 119 subjects in group A and 41 subjects in group B, serum free T4 (FT4) and TSH levels were measured. According to abnormalities in the levels of serum FT4 and/or TSH, their thyroid function was divided into the following 3 subgroups: 1) hyperthyroid (FT4 greater than 2.0 ng/dl, TSH less than 0.4 mu U/ml), 2) latent hypothyroid (0.8 less than FT4 less than 2.0 ng/dl, TSH greater than 5.0 mu U/ml) and 3) hypothyroid (FT4 less than 0.8 ng/dl, TSH greater than 5.0 mu U/ml). The hyperthyroid group consisted of two patients in group A and one in group B. Ten latent hypothyroid patients were found in group A and two in group B. Hypothyroidism was found in four patients in group A. The incidence of abnormal thyroid function was not different between group A (16 out of 119, 13.4%) and group B (three out of 41, 7.3%). Graves' disease and primary myxedema were found in one patient each in group B; these patients had no subjective symptoms but showed low titers of MCPA. These findings suggest that not only high titers of MCPA but also low titers of MCPA are closely related to abnormal thyroid function.

Adult↗

PubMed1991

Production of recombinant human transthyretin with biological activities toward the understanding of the molecular basis of familial amyloidotic polyneuropathy (FAP).

Transthyretin (TTR) is a plasma protein interacting with thyroxine T4 and retinol binding protein (RBP). Several variants of TTR with single amino acid substitutions have been identified as the major components of the amyloid fibrils of familial amyloidotic polyneuropathy (FAP), a fetal, autosomal dominant genetic disease. The elucidation of the molecular nature of the variants distinct from that of the wild-type TTR is crucial for understanding the amyloidogenesis in FAP, but our understanding is very poor mainly because of the unavailability of pure variant TTRs. In the present study, we used an Escherichia coli OmpA secretion vector (Ghrayeb et al., 1984) and achieved an effective production of the variant TTRs related to FAP including Met-30, Ile-33, Ala-60, Tyr-77, Met-111, and Ile-122 types. The variant TTRs produced in this system were efficiently secreted to the culture media. The chemical analysis showed that the secreted TTR (Met-30 type) has the same N-terminus as the native one. IEF analyses also indicated that the secreted product is properly processed as assessed by its pI. Furthermore, the secreted TTR was shown to have biological activities, namely, the thyroxin binding activity and the ability to associate with retinol binding protein, indicating that the secreted TTR polypeptide is properly folded. The present work also demonstrated that the processing/secretion of the recombinant TTR molecules in E. coli was strongly affected by single amino acid substitutions.

Amino Acid Sequence↗

PubMed1991

[A case of adult T-cell leukemia (ATL) complicated with multiple nocardial abscesses].

A 45-year-old woman was admitted to our hospital with complaints of fever and lumbago. She was treated for adult T-cell leukemia and thrombocytopenia with 20 mg/day of prednisolone. CT scan showed multiple abscesses in right peri-kidney, right iliopsoas muscle, left subcutaneous region in the abdominal wall and the brain. Left subcutaneous abscess was drained. Gram-positive organisms consisting of filaments were found, and Nocardia farcinica was grown in cultures. After two months of chemotherapy (FMOX, MINO and AMK), all abscesses except one in the brain disappeared. Cerebral abscess was cured fifty days after the start of the treatment with oral administration of Sulfamethoxazole-trimethoprim (SMX/TMP). The mortality of Nocardial cerebral abscess is high. This patient is a very rare case in which multiple Nocardial abscesses including brain abscess was cured by chemotherapy.

Abscess↗

PubMed1991

Site and mechanism of action of epidermal growth factor in rabbit cortical collecting duct.

To examine the exact target cell and mechanism of action of epidermal growth factor (EGF) in the isolated cortical collecting duct from rabbit kidney, we compared electrical properties of collecting duct (CD) cells (principal cells) and intercalated (IC) cells in absence and presence of EGF at 10(-8) M. Differentiation of CD and IC cells was based on values of basolateral membrane voltage (Vb) and fractional apical membrane resistance (fRa). In CD cells, upon addition of EGF to bath, lumen-negative transepithelial voltage (VT) was decreased from -8.0 +/- 1.9 to -2.4 +/- 1.3 mV (n = 22, P less than 0.001), but Vb was little changed (from -85.1 +/- 2.8 to -83.1 +/- 2.7 mV, n = 19), indicating that EGF in bath mainly caused changes in apical membrane voltage. In addition, peritubular EGF increased transepithelial resistance (RT) from 132.9 +/- 15.8 to 153.8 +/- 18.4 omega.cm2 (n = 16, P less than 0.001) as well as fRa from 0.31 +/- 0.06 to 0.39 +/- 0.07 (n = 12, P less than 0.01). These actions of EGF were prevented by pretreatment with 50 microM luminal amiloride. Luminal EGF had no effects on VT, Vb, RT, or fRa of CD cells. In IC cells, upon addition of EGF to bath, neither Vb nor fRa was affected. From these results, we conclude that EGF acts on the CD cell at the basolateral border and inhibits mainly the amiloride-sensitive Na+ conductance in the apical membrane.

Amiloride↗

PubMed1991

Functional characterization of alpha- and beta-intercalated cell types in rabbit cortical collecting duct.

Single-cell electrical measurements and spectrophotometric determinations of intracellular pH were used to determine unique features of alpha- and beta-intercalated cells (alpha-IC, beta-IC) in in vitro perfused rabbit cortical collecting ducts (CCD). pHi rose in alpha-IC and fell in beta-IC after bath Cl- removal. Luminal Cl- removal did not change pHi of alpha-IC, but pHi of beta-IC rose by 0.36 +/- 0.01 pH units. Cl- concentration-dependent recovery of beta-IC pHi revealed a Cl- Km of 18.7 mM for the luminal Cl(-) -HCO3- exchanger. Measurements of basolateral membrane voltage (Vbl) also showed two IC cell types. Removal of luminal Cl- did not change Vbl in alpha-IC, whereas Vbl hyperpolarized by a mean of 73.2 +/- 3.5 mV in beta-IC. Reducing bath Cl- depolarized both alpha- and beta-IC Vbl. In alpha-IC a large repolarization of 39.8 +/- 5.2 mV followed acute depolarization after bath Cl- removal. Reducing bath HCO3- (constant CO2) had little effect on beta-IC Vbl, whereas alpha-IC Vbl depolarized by 5.2 +/- 0.7 mV. Reducing luminal HCO3- in the absence of luminal Cl- produced a 17.6 +/- 1.8 mV depolarization in beta-IC. This change was independent of luminal Na+ and was not blocked by luminal 10(-4) M 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). In beta-IC, Vbl was not altered by either bath or lumen DIDS in the presence of luminal Cl-. However, when luminal Cl- was removed, luminal DIDS reversibly depolarized Vbl by 9.6 +/- 2.9 mV.(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1991

Effects of nicardipine on cerebral vascular responses to hypocapnia and blood flow velocity in the middle cerebral artery.

We noninvasively evaluated the effects of nicardipine on cerebral vascular responses to hypocapnia and blood flow velocity in the middle cerebral artery of 10 patients aged 17-60 (mean +/- SD 46.1 +/- 11.8) years. During fentanyl/diazepam/nitrous oxide anesthesia, mean blood flow velocity in the middle cerebral artery was measured and cerebral vascular reactivity to hypocapnia induced by hyperventilation was assessed before and during the administration of nicardipine. Mean blood flow velocity was measured using transcranial Doppler ultrasonography, and the cerebral vascular reactivity was expressed as the percentage change in mean blood flow velocity per unit change in end-tidal PCO2. During the administration of 5.1 +/- 1.3 micrograms/kg/min nicardipine, which caused a 26% reduction in mean arterial blood pressure, mean blood flow velocity increased significantly from 57.2 +/- 19.2 to 64.2 +/- 21.6 cm/sec (p less than 0.01, paired t test), whereas cerebral vascular reactivity showed no significant change (4.0 +/- 1.2% and 4.9 +/- 2.5%, respectively). In conclusion, during fentanyl/diazepam/nitrous oxide anesthesia in patients, cerebral vascular reactivity to hypocapnia was maintained and nicardipine-induced hypotension resulted in increased middle cerebral artery blood flow velocity with maintenance of carbon dioxide reactivity to hypocapnia.

Adolescent↗

PubMed1991

Plasma free triiodothyronine response to thyrotropin-releasing hormone to predict the remission of Graves' disease treated with antithyroid drugs.

The responses of both plasma TSH and free T3 (FT3) to TRH were examined in 31 patients with Graves' disease who were euthyroid after treatment with antithyroid drugs, 6 patients with primary hypothyroidism, and 14 control subjects. TSH was measured 0, 15, 30, 60, 90, and 120 min and FT3 was measured 0, 30, 60, 90, 120, 150, and 180 min after TRH injection (500 microgram, iv). The increment in FT3 above the basal level (delta FT3) in normal controls ranged from 1.2-3.7 pmol/L, with a mean +/- SD of 2.2 +/- 0.8 pmol/L. The mean (+/- SD) delta FT3 in patients with primary hypothyroidism was 0.3 +/- 0.2 pmol/L. After the TRH test, antithyroid drugs were stopped in patients with Graves' disease. Nine of 31 Graves' patients relapsed within 6 months after the TRH test. The other 22 patients with Graves' disease were followed while in remission during the observation period of up to 48 months. The mean (+/- SD) delta FT3 were significantly lower in 9 Graves' patients who relapsed than in those who achieved remission (0.5 +/- 0.3 vs. 2.6 +/- 1.1 pmol/L; P less than 0.01). Eight of 9 Graves' patients who relapsed showed lower delta FT3 values than the lowest value (1.1 pmol/L) in 22 Graves' patients in remission. Although the mean increment of TSH above the basal level (delta TSH) was also significantly different between the Graves' patients who relapsed and those in remission (1.4 vs. 12.3 mU/L; P less than 0.01), there was considerable overlap between the 2 groups. These findings suggest that delta FT3 reflects the endocrinological recovery of the pituitary-thyroid axis and is a beneficial indicator for the termination of antithyroid drugs in Graves' disease.

Antithyroid Agents↗

PubMed1991

Histamine-induced mucociliary dysfunction and otitis media with effusion.

Histamine, which has been found in middle ear effusions, is a potent pharmacological mediator released at an early stage of allergic reactions or general inflammatory process, increasing permeability of small blood vessels. Histamine might be involved in the origin and chronicity of middle ear effusions. In this study we studied the effect of histamine on the mucociliary function. First we examined the effect of histamine and its H1 and H2 blockers on the ciliary activity in the middle ear. 10(-2) M of histamine deteriorated ciliary activity; however, at lower concentrations ciliostimulatory effects were demonstrated for histamine (between 10(-8) M and 10(-4) M). Such ciliostimulatory effects were not affected by diphenhydramine (H1-blocker) but were reduced by cimetidine (H2-blocker). Thus histamine stimulates ciliary activity by combining with H2-receptor. Intratympanic injection of 10(-4) M of histamine induced accumulation of middle ear effusions (MEEs). The volume of MEEs was largest at 1 day postinjection when its mucociliary clearance time was longest. Then the mucociliary clearance time became shorter, but it was still significantly longer than that of the control animal. Ciliary activity in the tubotympanum showed no recovery through the observation period. On the other hand, intratympanic injection of 10(-6) M of histamine produced MEEs at 1 and 3 days postinjection when the mucociliary clearance time was longer than that of the control group. At 8 days, when most ears did not demonstrate MEEs, the mucociliary clearance time and ciliary activity in the Eustachian tube and tympanic orifice reached the level of the control group. Our present study demonstrates that histamine can induce mucociliary dysfunction of the tubotympanum resulting in middle ear effusions, and that cilia, especially those present in the tube and the tympanic orifice, have a significant role in eliminating middle ear effusions.

Animals↗

PubMed1991

Regeneration of nasal mucosa following mechanical injury.

Nasal mucosa is a subject of surgical operation for patients with nasal disorders. However, our knowledge about the regeneration of nasal mucosa after such a mechanical injury is still limited. In this study we investigated the recovery or regenerative process of nasal mucosa in rabbits after mechanical injury on the basis of ultrastructural as well as functional observations. Complete recovery of nasal mucosa was obtained in 5 days if the basal cells and basement membrane were intact. When the total layer of nasal mucosa was injured mechanically, regenerative stratified epithelium covered the defect in 1 week, new ciliated cells appeared in 3 weeks, and complete regeneration was observed at 6 weeks. At 3 weeks when the first appearance of cilia was observed, the beating activity of the cilia was in the normal range. In conclusion, we observed a great regeneration ability following mechanical injury in the nasal mucosa. The process of regeneration in the nasal mucosa after mechanical injury appears to depend on whether the basal cells and basement membrane are intact or not.

Animals↗

PubMed1991

[Influenza A virus-induced mucociliary dysfunction of tubotympanum].

There is amount of epidemiologic, clinical and laboratory evidence to document that viral infection is involved in otitis media with effusion (OME). However, few studies have demonstrated the direct influence of viruses on the tubotympanum. The purpose of this study is to establish the effect of influenza A virus invaded in the tubotympanum, in an attempt to elucidate the possible mechanism by which the virus contributes to the pathogenesis of OME. 80 guinea pigs with normal otoscopic findings were inoculated with 0.2ml suspension of influenza A (3.3 x 10(8)PFU/ml) into their tympanic cavities through their tympanic membranes. To serve as controls, the same number of guinea pigs were injected with 0.2ml of physiologic saline solution into their tympanic cavities. At 3, 7, 14, and 28 days postinoculation, they were used for examination of the mucociliary function. Middle ear effusions were observed only in the animals inoculated with the virus. Mucociliary dysfunction was observed only in the animals inoculated with the virus. The ciliary activity in the bulla was declined at any time examined. On the other hand, the ciliary activity in the eustachian tube and the tympanic orifice was slightly lowered between 7 and 14 days, but the level was not different from that of the control. However, the number of active ciliated cells (showing more than 500 beats/min) was significantly smaller than that of the control. The mucociliary clearance time of the tubotympanum was more prolonged than that of the control at 3, 7, and 14 days, and returned to the control level at 28 days. A variety of morphologic changes were observed in the tubotympanum treated with the virus. Major pathologies observed included a general inflammatory cell infiltration, vacuolation and other degeneration of ciliated cells, and vascular damage and increased vascular permeability. Regeneration of cilia or ciliated cells followed the degeneration, which included an increased number of basal cells and new formed centrioles. However, the viral infection had an influence on the epithelial cells with new centrioles. Our study has demonstrated that viral infection could evoke mucociliary dysfunction of the tubotympanum and create an increased susceptibility to bacteria. Therefore, viral infection could enhance bacterial infectious process in the tubotympanum. Through the failure viruses could contribute to the occurrence of OME.

Animals↗

PubMed1991

Mechanism and regulation of proton transport in the outer medullary collecting duct.

Our understanding of transport and its regulation in the OMCDi has expanded significantly over the past 5 years. The OMCDi cells of the rabbit appear to be ideal for studying the mechanism and regulation of proton transport in a cell which is functionally similar to the alpha intercalated cell of the cortical collecting tubule. Characterization of the specific transporters at the apical and basolateral membrane allows us to explore further the mechanism whereby hormones and their second messengers regulate net transport in these cells. Simultaneous electrophysiologic measurements and determination of intracellular ion activities with fluorescent dyes, a technique we are currently employing in studies of single alpha and beta intercalated cells of the cortical collecting tubule, will be required to make progress in our study of regulation. Finally, characterization of the transporters has demonstrated that these cells are more complex than initially thought. Especially exciting is the possibility that the apical membrane proton extrusion step may be accomplished by more than one mechanism, i.e., a proton ATPase or an H(+)-K(+)-ATPase.

Animals↗

PubMed1991

[Hyperperfusion syndrome following bilateral aorto-carotid bypass--a study of transcranial Doppler].

A 22-year old female with Takayasu disease, who underwent bilateral aorto-carotid bypass surgery developed hyperperfusion syndrome postoperatively. Following the operation, convulsion and headache developed and mean velocity in the middle cerebral artery, measured by transcranial doppler, elevated. Mean velocity gradually decreased on the 10th postoperatively day and became a plateau at 200% of preoperative value. Pulsatility index as a index of cerebral vascular resistance was low just after the operation, became normal the following day and gradually increased 10 days after the operation. These changes seem to be recovery of cerebral autoregulation. On the 20th postoperative day, computed tomography scan was examined and multiple low density areas were found in the basal ganglia regions, but these changes disappeared 2 months after the operation. These reversible changes of CT scan might show ischemic changes or cerebral edema induced by cerebral vasospasm.

Adult↗

PubMed1991

[Perioperative monitoring of cerebral circulation in a patient with Takayasu disease].

Transcranial Doppler (TCD) and fiberoptic oximetry for continuous measurement of jugular venous oxygen saturation (SjO2) were used as perioperative monitoring of cerebral circulation in a patient with Takayasu disease who received bilateral aorto-carotid bypass. Following revascularization of the left carotid artery, mean velocity in the middle cerebral artery (MV) increased (lt 300%, rt 200% of control values) and SjO2 also increased. Following revascularization of right carotid artery, MV increased (lt 500%, rt 400% of control values) but SjO2 was unchanged. After bilateral revascularization, high velocity continued for about 10 days, and convulsion with headache occurred. Therefore hyperperfusion syndrome was suspected. By perioperative monitoring of MV and SjO2, it might be possible to evaluate intracranial hemodynamics, necessity of shunt operation as well as bilateral bypass, and postoperative hyperperfusion syndrome.

Adult↗

PubMed1991

[Adult type of idiopathic paroxysmal cold hemoglobinuria].

A 78-year-old female suffered from idiopathic paroxysmal cold hemoglobinuria (PCH). Her symptom occurred immediately after she worked outside in the cold early morning. This case is characterized by the eldest case with non-syphilitic PCH reported in Japan and by the most advanced anemia (Hb 4.2 g/dl) possibly due to prolonged hemolysis after cold exposure. Analysis of the serum revealed positive Donath-Landsteiner antibody of IgG type, which could react to hemolysis not only below 15 degrees C but also at 15-20 degrees C in vitro.

Aged↗

PubMed1991

Polymerase chain reaction-directed identification, cloning, and quantification of human CYP2C18 mRNA.

Sequencing of genomic polymerase chain reaction (PCR) products synthesized using primers generated from the CYP2C8 and CYP2C9 cDNAs revealed the presence of a new CYP2C gene in the human genome. Primers specific to exons of this new gene were used to perform PCR on human liver cDNA libraries and cDNA synthesized from human liver mRNA to generate a cDNA containing a complete cytochrome P450 amino acid reading frame. This cytochrome P450 cDNA, designated CYP2C18, displayed 85% and 87% nucleotide and 77% and 81% amino acid sequence similarities, respectively, with cDNAs and proteins corresponding to CYP2C8 and CYP2C9. cDNA-directed synthesis of CYP2C18 revealed a protein with relative Mr 49,000 on sodium dodecyl sulfate-polyacrylamide gels, which is considerably less than that calculated from the deduced amino acid composition, Mr 55,747. A preferred substrate for this enzyme has not been uncovered. Levels of CYP2C8, CYP2C9, and CYP2C18 mRNAs were examined in 17 human liver specimens using a PCR-based assay. CYP2C18 mRNA was found in all livers examined, albeit at mean levels 7-8-fold lower than those of mRNAs encoding CYP2C8 and CYP2C9. Marked interindividual differences in levels of expression of all three CYP2C mRNAs were also found.

Amino Acid Sequence↗

PubMed1991

[Effect of halothane, fentanyl and ketamine on the threshold for the passage of venous air embolism through lungs in dogs].

Effect of halothane, fentanyl and ketamine on the passage of air injected bolus across the pulmonary circulation was studied in dogs using transesophageal M-mode echocardiography. Dogs in Group 1 (N = 5) were anesthetized with halothane and then halothane with fentanyl. At least 3 weeks later the dogs were anesthetized with fentanyl and then fentanyl with halothane. The same procedure was utilized in group 2 (N = 4) using halothane and ketamine. The doses of halothane, fentanyl and ketamine were 1% inspired concentration, 100 micrograms.kg-1 followed by 1 microgram.kg-1.min-1 iv, and 10 mg.kg-1 followed by 0.1 mg.kg-1.min-1 iv, respectively. The threshold for bolus air detection during halothane, fentanyl and ketamine alone were 0.05, 0.5 and 0.2 ml.kg-1, respectively. The threshold during fentanyl administration, but not during ketamine administration, was significantly higher than that during halothane. The addition of halothane to fentanyl or ketamine lowered the threshold to the same level as with halothane alone, and the addition of either fentanyl or ketamine to halothane made no difference. Although there was no difference in baseline shunt fraction resistance index [PVRI/(Qs/Qt)] during administration of each anesthetic, every air injection decreased shunt fraction resistance index during halothane without fentanyl or during halothane with or without ketamine, and increased it during fentanyl administration.

Animals↗

PubMed1990

Genomic organization of the human amyloid beta-protein precursor gene.

Amyloid beta-protein (BP) deposited in Alzheimer brains is a cleavage product of a larger precursor (BPP). The BPP gene encodes three types of mRNA generated by alternative splicing, two of which contain the sequence encoding Kunitz-type serine-protease inhibitor (serpin). To investigate the regulatory mechanisms of BPP synthesis at the gene level, we isolated 36 genomic DNA clones covering all the exons of the human BPP gene. This gene consists of 18 exons and spans more than 170 kb. BP is encoded by the 16th and the 17th exons and the serpin domain by the 7th exon. Sequence analysis showed that the 7th and 8th introns lack a typical branchpoint for splicing. This might relate to the alternative splicing. The promoter of the BPP gene has some characteristics of those of housekeeping genes and contains a number of possible methylation sites. The methylation status of the promoter was analyzed by Southern blotting but no alteration was observed among tissues and between control and Alzheimer brains. We also tested the roles of two possible activator protein-1-binding sites and a possible heat-shock element found within the promoter. Northern blotting showed that the transcription of the BPP gene was apparently induced by 12-O-tetradecanoylphorbol-13-acetate (phorbol derivative) in HeLa cells.

Alzheimer Disease↗

PubMed1990

Electron spin resonance studies of wild-type and mutant cytochromes P-450d: effects of mutations at proximal, aromatic and distal sites on g values.

Low-temperature (6-40 K) electron spin resonance (ESR) spectra of cytochrome P-450d (P-450d) and its 17 mutants have been measured. The spectra of the wild-type and all mutant P-450ds showed signals at around g = 8, 3.7 and 1.7, while they didn't show any signal at around g = 2 up to 40 K. It was thus suggested that all of these P-450ds essentially take the ferric high-spin form. The g values of the proximal mutants were closer to those of the wild-type than those of the distal and aromatic mutants, suggesting that mutations at the distal and aromatic sites influence the electronic state of the heme more profoundly than those of the proximal site. The distal multiple mutants whose distal sequences are the same as those of the low-spin type P-450s such as rat P-450c, mouse P1-450 and P3-450 showed only high-spin ESR signals. Thus the spin state of P-450ds (the wild-type and all mutants) may not be solely due to specific characteristics of the distal site, but to the unique nature of the whole heme environment of P-450d. It is also suggested that the amino acids at the distal region of P-450d may be located close to the heme, so that the water molecule cannot bind to the heme, thus taking the high-spin state. Both the aromatic mutants showed rather large deviations of the g values from those of wild-type P-450d, suggesting that the aromatic region somehow interacts with the heme.

Animals↗