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Biomedical subjects

H Furuya

Publications and source records attributed to H Furuya.

At least 217 records · Page 12Linked to original sources
PubMed1990

[Response to CO2 and autoregulation of cortical cerebral blood flow during isoflurane anesthesia].

Response to CO2 and autoregulation of cortical cerebral blood flow (CBF) during isoflurane anesthesia were studied in 10 patients undergoing neurosurgery. The patients were anesthetized with 0.5 to 1.2% end-tidal isoflurane and 66% nitrous oxide in oxygen. The CBF was measured by thermal diffusion using a flow probe with a Peltier stack. PaCO2 was controlled to produce hypocarbia, normocarbia and hypercarbia by changing tidal volume and respiratory rate. Arterial blood pressure was altered. Hypotension was achieved by intravenous infusion of trimetaphan and hypertension was induced by intravenous administration of metaraminol. During isoflurane anesthesia the response to CO2 of CBF was kept at PaCO2 between 27.8 and 53.9 mmHg. The following relationship was obtained. CBF = 2.54 x PaCO2-53.0, r = 0.59, n = 131 The autoregulation of CBF was evaluated in 7 patients, and in 2 patients, the autoregulation of CBF was abolished.

Anesthesia, Inhalation↗
PubMed1989

Genetic analysis of familial amyloidotic polyneuropathy, an autosomal dominant disease.

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant genetic disease, and the major component of the amyloid fibrils from FAP patients was shown to be variants of transthyretin (TTR) with single amino acid substitutions. The nucleotide sequence analysis of the TTR cDNA and its corresponding gene enabled us to detect the base substitutions responsible for the variant TTR by conventional Southern blotting or polymerase chain reaction (PCR) method and allowed us to screen a number of FAP families in Japan. Among seven TTR variants related to FAP, all the FAP patients tested in Japan had the particular 30Val----Met mutation. Haplotype analysis revealed that the Val----Met mutation has recurred frequently in the population to generate the FAP families of independent origins. Although the primary cause of FAP has become clear, extensive screening of FAP families revealed that there existed late onset cases and also patients with atypical symptoms in FAP families with the Val----Met mutation, suggesting that the expression of FAP is a complex process and affected by some (unknown) factors other than TTR.

Adult↗
PubMed1989

Tetramer formation of a variant type human transthyretin (prealbumin) produced by Escherichia coli expression system.

A variant of human transthyretin(TTR, prealbumin) with methionine for valine substitution at position 30 is a major component of amyloid fibrils found in patients of familial amyloidotic polyneuropathy(FAP) type I, an autosomal dominant genetic disease. But the molecular nature of the variant TTR has been obscure, because most of plasma TTR from FAP patients is a mixture of variant and wild type TTR and no pure preparation of the variant has been available. For this reason, we constructed a system in which the variant type TTR was efficiently synthesized. In this system, the recombinant variant TTR was first synthesized as a fusion protein with E. coli outer membrane protein A (ompA) signal peptide, processed to eliminate the signal peptide and finally secreted to the culture medium. The final concentration of the recombinant variant TTR in the medium was about 5 mg/l. SDS polyacrylamide gel electrophoresis and gel filtration analysis suggested that the recombinant variant TTR can form tetramer as seen for native one. Purification of the protein was accomplished by only two steps of chromatography.

Blotting, Western↗
PubMed1989

Site-directed mutageneses of rat liver cytochrome P-450d: catalytic activities toward benzphetamine and 7-ethoxycoumarin.

Catalytic activities toward benzphetamine and 7-ethoxycoumarin of 11 distal mutants, 9 proximal mutants, and 3 aromatic mutants of rat liver cytochrome P-450d were studied. A distal mutant Thr319Ala was not catalytically active toward benzphetamine, while this mutant retained activity toward 7-ethoxycoumarin. Distal mutants Gly316Glu, Thr319Ala, and Thr322Ala displayed higher activities (kcat/Km) toward 7-ethoxycoumarin that were 2.4-4.7-fold higher than that of the wild-type enzyme. Although kcat/Km values of four multiple distal mutants toward benzphetamine were less than half that of the wild type, activities of these mutants toward 7-ethoxycoumarin were almost the same as or higher than the wild-type activity toward this substrate. The distal double mutant Glu318Asp, Phe325Tyr showed 6-fold higher activity than the wild-type P-450d toward 7-ethoxycoumarin. Activities of the proximal mutants Lys453Glu and Arg455Gly toward both substrates were much lower (less than one-seventh) than the corresponding wild-type activities. Catalytic activities of three aromatic mutants, Phe425Leu, Pro427Leu, and Phe430Leu, toward benzphetamine were less than 7% of that of the wild type, while the activities of these aromatic mutants toward 7-ethoxycoumarin were more than 2.5 times higher than the wild-type activity toward this substrate. From these findings, in conjunction with a molecular model for P-450d, we suggest that (1) the relative importance to catalysis of various distal helix amino acids differs depending on the substrate and that these differences are associated with the size, shape, and flexibility of the substrate and (2) the proximal residue Lys453 appears to play a critical role in the catalytic activity of P-450d, perhaps by participating in forming an intermolecular electron-transfer complex.

Amino Acid Sequence↗
PubMed1989

Mutations at the distal and proximal sites of cytochrome P-450d changed regio-specificity of acetanilide hydroxylations.

Regio-specificities of acetanilide hydroxylations were studied for 11 distal, 9 proximal and 3 aromatic mutants of cytochrome P-450d. Ratios of turnover numbers among these products were remarkably changed depending on the mutants. For example, the ratio of turnover number, para:ortho:meta = 7:0.1:0.3 for the wild type changed to 11:4:3 for a distal mutant, Thr322Ala, or to 13:13:1 for a proximal mutant, Arg455Gly. It was suggested that regio-specificities of microsomal P-450 enzymes are controlled cooperatively by the whole structure of the protein molecules which influences the tertiary structure of the distal environment.

Acetanilides↗
PubMed1989

Autosomal recessive motor and sensory neuropathy with excessive myelin outfolding.

Two Japanese persons with consanguinous parents had a motor and sensory neuropathy of the hypertrophic type with excessive myelin outfolding in the myelinated fibers. A morphometric analysis of the biopsied sural nerve was made. Excessive myelin outfolding, segmental demyelination, and remyelination and decrease in the density of both large and small myelinated fibers were evident. Using linear regression, myelin spiral length was shorter relative to axonal area. These patients may have a new variant of hereditary motor sensory neuropathy.

Adolescent↗
PubMed1989

Haplotype analysis of familial amyloidotic polyneuropathy. Evidence for multiple origins of the Val----Met mutation most common to the disease.

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant genetic disease characterized by systemic accumulation of amyloid fibrils. A major component of FAP amyloid has been identified as variant transthyretin (TTR, also called prealbumin). In particular, a variant with the substitution 30Val----Met has been commonly found in FAP of various ethnic groups. To understand the origin and spread of the Val----Met mutation, we analyzed DNA polymorphisms associated with the TTR gene in six Japanese FAP families and several Portuguese FAP patients. Three distinct haplotypes associated with the Val----Met mutation were identified in Japanese FAP families, one of which was also found in Portuguese patients. On the other hand, it was found that the Val----Met mutation can be explained by a C-T transition at the CpG dinucleotide sequence of a mutation hot spot. Thus, our findings indicate that the Val----Met mutation has probably recurred in the human population, to generate FAP families of independent origin.

Haplotypes↗
PubMed1989

Effect of carteolol on renal function in healthy subjects and patients with hypertension.

The effect of short- and long-term administration of carteolol on renal function has been examined in healthy subjects and in hypertensive patients with or without renal failure. In healthy subjects neither a single dose of 10 mg carteolol nor continuous administration of 20 mg/day for 7 days had any effect on creatinine clearance and renal blood flow. In all subjects the clearance rate of carteolol was about 400 ml/min and its fractional excretion of carteolol exceeded 300%, suggesting that the drug is secreted actively from renal tubules. Twenty-three hypertensive patients with or without renal dysfunction were given carteolol 10 to 20 mg/day for more than 50 weeks in addition to their standard antihypertensive regimens, which were left changed. Laboratory results were compared with the mean values of 50 weeks before and after the addition of carteolol, and none, including plasma creatinine, blood urea nitrogen and electrolytes, were significantly changed. Neither the estimated glomerular filtration rate nor the effect of the drug on blood pressure changed significantly during this prolonged treatment. It is concluded that carteolol had no effect on renal function in healthy subjects and in hypertensive patients with or without renal failure.

Adult↗
PubMed1989

Inverted eyelashes in patients with type 1a glycogen storage disease.

We examined three adult Japanese patients who had a history of decreased hepatic glucose-6-phosphatase activity. All three patients had increased bilateral subcutaneous (SC) fat in the lower eyelids and inverted eyelashes. One patient additionally showed retinal hemorrhages and microaneurysms in both fundi. The inverted eyelashes may have been related to type 1a glycogen storage disease.

Adipose Tissue↗
PubMed1989

Glucagon stimulates chloride transport independently of cyclic AMP in the rat medullary TAL.

The effect of glucagon on chloride transport was studied in the rat medullary thick ascending limb (MTAL) perfused in vitro. In the bath, 10(-6) M glucagon increased the efflux coefficient of Cl (KeCl) from 6.88 +/- 0.21 x 10(5) to 9.65 +/- 0.38 x 10(-5) cm.sec -1 (P less than 0.01) without changing the influx coefficient (KiCl; 2.87 +/- 0.54 x 10(-5) in control vs. 2.83 +/- 0.57 x 10(-5) cm.sec-1 with glucagon) or transepithelial potential difference (4.8 +/- 0.76 in control vs. 5.0 +/- 0.71 mV with glucagon). A physiological concentration of glucagon (10(-8), (10(-10) M) also increased chloride efflux significantly. Pretreatment of tubules with luminal furosemide (10(-5) M) and/or basolateral ouabain (10(-4) M) completely abolished the effect of glucagon. In isolated MTALs incubated in the same medium as that used in the microperfusion study, 10(-6) M glucagon stimulated cAMP production by 255.2 +/- 33.7% (P less than 0.01). However, neither dibutyryl cAMP (10(-3), 10(-4) M) nor forskolin (10(-4), 10(-6) M) increased the chloride efflux. It is concluded that: 1) Glucagon stimulates net Cl reabsorption by increasing Cl efflux in the rat MTAL; and 2) cyclic AMP is not responsible for this effect of glucagon.

Animals↗
PubMed1989

Genetic and clinical studies of Japanese patients with familial amyloid polyneuropathy.

We examined the DNA analysis of familial amyloid polyneuropathy (FAP) patients and their families from Nagano and Hiroshima prefectures in Japan using recombinant DNA techniques and compared the results with the clinical features. This study indicated that the valine-methionine change prealbumin gene was closely related to the clinical features of type 1 FAP. The DNA analysis was valuable for the definite diagnosis of type 1 FAP even in sporadic and asymptomatic cases. FAP patients from Iiyama city and Ogawa village area in the Nagano prefecture had the same mutation despite differences in clinical features. The onset of the sporadic FAP cases was later than that of the FAP patients who had family histories.

Adult↗
PubMed1989

Increased ciliary beating frequency of nasal mucosa following immunotherapy for allergy.

The present study was designed to elucidate the effect of immunotherapy on the beating frequency of nasal cilia in patients with nasal allergy. Of 40 patients with nasal allergy due to Dermatophagoides farinae, 20 were treated with immunotherapy by the use of D farinae extracts, and 20 control patients were treated with antihistamine tablets. Mucosal pieces were taken from the right inferior turbinate before and 1 year after the initiation of treatment, and the ciliary beating frequency (CBF) was examined by a photoelectric method. The use of antihistamine tablets did not increase CBF even when it relieved the nasal symptoms. Immunotherapy, on the other hand, increased CBF in 66.7% of patients when it alleviated their nasal symptoms. The CBF before immunotherapy of patients who showed an increase CBF after treatment was statistically higher than that of patients who did not.

Adolescent↗
PubMed1989

Mucociliary disease of the middle ear during experimental otitis media with effusion induced by bacterial endotoxin.

Lipopolysaccharide (10 micrograms/mL) derived from Klebsiella pneumoniae was injected into the middle ear of guinea pigs. The animals were killed painlessly on days 1, 3, and 7 after inoculation, and the mucosal samples from two sites within the tympanic cavity, close to the tympanic orifice and distal to the orifice, were examined for ciliary activity and epithelial morphology. At day 1 and day 3 serous effusion was observed and deterioration of ciliary activity and morphologic changes were observed. No effusion was recognized at day 7, when the ciliary activity in the distal mucosa was still diminished and that in the proximal mucosa had recovered to a normal level. Our data have shown that lipopolysaccharide extracted from K pneumoniae can produce otitis media with effusion in laboratory animals, and dysfunction of cilia due to lipopolysaccharide probably is responsible for the accumulation of middle ear effusion. The mucociliary system is indeed an important defense system and failure of such a system, especially in the mucosa close to the tympanic orifice, can cause the buildup of effusions.

Animals↗
PubMed1989

Biomedical engineering for the conservation of teeth--the use of a Nd-YAG laser for a treatment of apical focus.

When the apical focus (root cyst) is treated, if the tooth concerned can be preserved, the root canal should first be enlarged and cleaned sufficiently, and then sealed with filling materials. However, if an expensive prothesis is placed on the crown of the tooth concerned, or if the root canal is blocked with a post core of calcification, root canal treatment becomes difficult from a practical point of view. We therefore tried irradiation using the Nd-YAG laser, which is known for its high transmissibility into teeth, to the root canal, and the apical area. In its histological images it is considered to the action on bacteria and bacteria-infected substances inside the root canal through calcification of the dentinal surface layer facing the dental pulp, closure of the dentinal canal opening, and there was substantial change in the dentine in the outer layer. We have achieved good clinical results using this method; we eventually extracted only two teeth in 200 cases; it is thus very significant that most of the teeth of the patients still maintain their function, although they were diagnosed as non-preservable using conventional methods.

Adult↗