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Biomedical subjects

K Sakuma

Publications and source records attributed to K Sakuma.

At least 55 records · Page 3Linked to original sources
PubMed1998

Pathological changes in levels of three small stress proteins, alphaB crystallin, HSP 27 and p20, in the hindlimb muscles of dy mouse.

Using three different analyses, we investigated the levels of the three small stress proteins alphaB crystallin, HSP 27 and p20 in the slow-twitch soleus muscle and fast-twitch tibialis anterior muscle of normal and dy mice. All of these analyses (immunoassay, Western blot and immunohistochemistry) showed markedly increased levels of these stress proteins in fast-twitch type muscle (tibialis anterior muscle) of dy mouse. In contrast, the levels of alphaB crystallin, HSP 27 and p20 of dy mouse were reduced in slow-twitch type muscle (soleus muscle). Manipulation of this protective response may reduce injury and may have potential therapeutic application in congenital muscular dystrophy (CMD), which possesses a deficiency of laminin-alpha2 chain in muscle fiber basement similar to dy mouse.

Animals↗
PubMed1998

Replacements of single basic amino acids in the pleckstrin homology domain of phospholipase C-delta1 alter the ligand binding, phospholipase activity, and interaction with the plasma membrane.

The pleckstrin homology (PH) domain of phosphatidylinositol-specific phospholipase C-delta1 (PLC-delta1) binds to both D-myo-inositol 1,4, 5-trisphosphate (Ins(1,4,5)P3) and phosphatidylinositol 4, 5-bisphosphate (PtdIns(4,5)P2) with high affinities. We have previously identified a region rich in basic amino acids within the PH domain critical for ligand binding (Yagisawa, H., Hirata, M., Kanematsu, T., Watanabe, Y., Ozaki, S., Sakuma, K., Tanaka, H., Yabuta, N., Kamata, H., Hirata, H., and Nojima, H. (1994) J. Biol. Chem. 269, 20179-20188; Hirata, M., Kanematsu, T., Sakuma, K., Koga, T., Watanabe, Y., Ozaki, S., and Yagisawa, H. (1994) Biochem. Biophys. Res. Commun. 205, 1563-1571). To investigate the role of these basic residues, we have performed site-directed mutagenesis replacing each of the basic amino acid in the N-terminal 60 residues of PLC-delta1 (Lys24, Lys30, Lys32, Arg37, Arg38, Arg40, Lys43, Lys49, Arg56, Lys57, and Arg60) with a neutral or an acidic amino acid. The effects of these mutations on the PH domain ligand binding properties and their consequence for substrate hydrolysis and membrane interactions of PLC-delta1 were analyzed using several assay systems. Analysis of [3H]-Ins(1,4,5)P3 binding, measurement of the binding affinities, and measurements of phospholipase activity using PtdIns(4,5)P2-containing phospholipid vesicles, demonstrated that residues Lys30, Lys32, Arg37, Arg38, Arg40, and Lys57 were required for these PLC-delta1 functions; in comparison, other mutations resulted in a moderate reduction. A subset of selected mutations was further analyzed for the enzyme activity toward substrate present in cellular membranes of permeabilized cells and for interaction with the plasma membrane after microinjection. These experiments demonstrated that mutations affecting ligand binding and PtdIns(4,5)P2 hydrolysis in phospholipid vesicles also resulted in reduction in the hydrolysis of cellular polyphosphoinositides and loss of membrane attachment. All residues (with the exception of the K43E substitution) found to be critical for the analyzed PLC-delta1 functions are present at the surface of the PH domain shown to contain the Ins(1,4,5)P3 binding pocket.

Amino Acid Sequence↗
PubMed1998

Muscular dystrophy: centronucleation may reflect a compensatory activation of defective myonuclei.

Muscular dystrophy has long been believed to be characterized by degeneration and abortive regeneration of muscle fibers (the muscle degeneration theory), but unfortunately its pathogenesis is still unclear and an effective treatment has yet to be developed. As a challenge to the theory, we have proposed an alternative muscle-defective-growth theory and a further bone muscle growth imbalance hypothesis supposing possible defects in bone-growth-dependent muscle growth based on our findings in hereditary dystrophic dy mice (C57BL/6J dy/dy). This review presents some new insights into the pathogenesis of the disease along with our hypothesis, focusing on the physiological meaning of centronucleation, one of the major pathological changes commonly observed in dystrophic muscles of man and experimental animals.

Animals↗
PubMed1998

Differential adaptations of insulin-like growth factor-I, basic fibroblast growth factor, and leukemia inhibitory factor in the plantaris muscle of rats by mechanical overloading: an immunohistochemical study.

We investigated changes in several growth factors in the rat plantaris muscle produced by mechanical overloading by ablation of synergists using immunohistochemistry. At 1 and 3 days post surgery, the insulin-like growth factor-I (IGF-I) level was slightly increased in the cytosol and markedly increased in the invading cells of the extracellular space. Thereafter, the IGF-I immunoreactivity evoked by overloading rapidly decreased to the normal level. The level of leukemia inhibitory factor (LIF), which was not shown to change at 1 day post surgery, was increased in the cytosol at 3, 5, 7 and 10 days and at 2 weeks. Basic fibroblast growth factor (bFGF) immunoreactivity did not change during the entire period of overloading (1 day-3 weeks post surgery). These results indicate that the elevations of the levels of IGF-I and LIF show differential time course in the plantaris muscle subjected to functional overload. Furthermore, bFGF appears not to be related to the compensatory hypertrophy produced by overloading.

Adaptation, Physiological↗
PubMed1998

Dietary fructooligosaccharides increase calcium absorption and levels of mucosal calbindin-D9k in the large intestine of gastrectomized rats.

BACKGROUND: In gastrectomized rats intestinal calcium absorption and bone calcium levels markedly decrease and the levels recover as a result of feeding fructooligosaccharides (FOS). In the present study we examined the effects of gastrectomy and dietary FOS on intestinal calbindin-D9k (CaBP) levels. METHODS: One group of rats was subjected to a sham operation and fed a control diet. Two other groups of rats were gastrectomized, and those in one group were fed the control diet, whereas those in the other group were fed a diet containing 10% FOS. Intestinal calcium, magnesium, and phosphorus absorption levels and intestinal CaBP levels were measured. RESULTS: Gastrectomy increased CaBP levels in the distal small intestine, cecum, and colorectum but markedly decreased calcium absorption. Dietary FOS increased CaBP levels in the cecum and colorectum in the case of gastrectomized rats and improved calcium absorption. CONCLUSIONS: The results suggest that dietary FOS not only improve intestinal calcium absorption but also serve to maintain local calcium homeostasis in the intestine by increasing mucosal CaBP levels in the large intestine of gastrectomized rats.

Animals↗
PubMed1998

Dietary fructooligosaccharides change the concentration of calbindin-D9k differently in the mucosa of the small and large intestine of rats.

Previously, we confirmed that dietary fructooligosaccharides (FOS) increase calcium absorption in rats. In this study, we examined the influence of FOS feeding on the concentration of calbindin-D9k of several intestinal segments in rats. Rats in the control group were fed a diet without FOS. Rats in the other two groups were fed the diet containing FOS at either 50 or 100 g/kg for 10 d and subjected to a calcium absorption study. On the final day of feeding, the rats were killed and the entire intestine was removed. The intestinal mucosa was collected from four segments, i.e., the proximal and distal segments of the small intestine, the cecum and the colorectum, respectively. The apparent absorption of calcium increased dose dependently (r = 0.9256, P < 0.0001). Significant positive correlations between apparent calcium absorption and the relative amounts of calbindin in both large intestinal segments were observed (cecum, r = 0.8956, P = 0.0011; colorectum, r = 0.8828, P = 0.0016). Also, significant negative correlations between apparent calcium absorption and the relative amounts of calbindin-D9k in both small intestinal segments were observed (proximal, r = -0.7149, P = 0. 0304; distal, r = -0.8740, P = 0.0021). In conclusion, FOS feeding increases levels of calbindin-D9k in the large intestine, but decreases those in the small intestine. Moreover, these results suggest that part of the stimulatory effect of fructooligosaccharides relates to the transcellular route of calcium absorption in the large intestine of rats.

Absorption↗
PubMed1998

Cryoglobulinaemia among maintenance haemodialysis patients and its relation to hepatitis C infection.

It has been shown that hepatitis C virus (HCV) infection is closely associated with mixed type cryoglobulinaemia. It is also known that HCV infection is rampant among chronic haemodialysis patients. We studied 531 renal failure patients on maintenance dialysis including 170 with positive HCV antibodies for cryoglobulinaemia, and its incidence was compared with controls which consisted of 242 chronic hepatitis C patients without renal failure and 183 healthy adults. Cryoglobulinaemia was present in 30.6% of dialysis patients with HCV infection, 10.8% of dialysis patients without HCV infection, 29.8% of patients with chronic hepatitis C without renal failure, and 0% of healthy adults. Among the 30 new renal failure patients who were started on dialysis within 6 months, four were positive for HCV antibodies, and one of them had cryoglobulinaemia; of the 26 HCV-negative patients, four (15%) were cryoglobulinaemic. The cryocrit values among dialysis patients were much lower than those of the control cases and other reports on non-dialysis cases. Patients with cryoglobulinaemia were generally younger compared with patients negative for this condition. There was no correlation between cryoglobulinaemia and past blood transfusion, underlying disease or length of dialysis. Cryoglobulinaemic patients seem to develop renal failure at relatively young ages and a considerable proportion of cryoglobulinaemic dialysis patients may have already had cryoglobulinaemia at the time of the start of haemodialysis. There was no indication that the presence of cryoglobulin in serum adversely affects the liver disease nor increases serum virus load in HCV-infected dialysis patients. Thus, it was concluded that although HCV infection has a certain role in the development of cryoglobulinaemia in dialysis patients, they develop cryoglobulinaemia less frequently and produce cryoglobulin to a lesser degree in the presence of HCV infection as compared with non-dialysis patients.

Adult↗
PubMed1998

Arthroscopic management of temporomandibular closed lock.

Sixty-three consecutive patients with painful closed lock involving 83 temporomandibular joints were treated by surgery and followed up for at least 24 months. Prior to surgical treatment all had imaging to demonstrate that the cause of their painful jaw locking was an anterior displaced disc without reduction. All patients had received at least three months non-surgical treatment without response. The arthroscopic surgery consisted of release of adhesions, manipulation and placement of 25 mg hyaluronic acid into the joint space. No significant surgical complications occurred. Postoperative treatment involved physical therapy and stabilization splints. At 24 months after surgery 57 patients (90.5 per cent) had no pain and month opening had improved from preoperative 27.2 +/- 5.4 mm to 44.4 +/- 4.1 mm (p < 0.001). This study shows that arthroscopic surgery with continuing non-surgical therapy is a highly effective treatment for painful closed lock.

Adolescent↗
PubMed1998

[Inhibitory effects of shimotsu-to, a traditional Chinese herbal prescription, on ultraviolet radiation-induced cell damage and prostaglandin E2 release in cultured Swiss 3T3 cells].

We have investigated the effects of Shimotsu-to, a traditional Chinese herbal prescription (Kampo medicine), on ultraviolet (UV) radiation-induced cell damage and prostaglandin E2 (PGE2) release in cultured Swiss 3T3 cells to examine the anti-inflammatory mechanism of Shimotsu-to. Short-term UV irradiation significantly induced cell damage and stimulated PGE2 release in Swiss 3T3 cells cultured for 4 h. The UV-radiation-induced cell damage and the stimulation of PGE2 release were significantly suppressed by the treatment with Shimotsu-to. Among the single crude drug components of Shimotsu-to, Rehmanniae Radix showed significant protective effects against UV-radiation-induced cell damage and PGE2 release. Other synthetic anti-inflammatory agents, such as dexamethasone, dipotassium glycyrrhizinate and allantoin also protected against UV-induced cell damage and inhibited PGE2 release in cultured Swiss 3T3 cells. These results suggest that the anti-inflammatory mechanism of Shimotsu-to against UV-irradiated erythema (acute skin inflammation) in guinea pigs in vivo may be mediated by the inhibition of PGE2 release from cutaneous target cells.

3T3 Cells↗
PubMed1998

Transcriptional regulation of rat calbindin expression during development determined by bacterially expressed protein.

Calbindin-D9k expression in intestinal mucosal cells reveals a specific pattern during development in rats. It shows a low basal level in suckling and adult rats, but after weaning at 21 d of age, increases to three times that of the basal level for several days only, around 24 d. We attempted to clarify whether the regulation of developmental change was at the transcriptional or post-transcriptional level. The calbindin-D9k protein and mRNA concentrations during pre- and postweaned development were determined by Western blot and Northern blot analysis, respectively, and compared with calcium binding activity by 45Ca. For Western blot analysis, a corresponding antibody was raised in rabbit using a bacterially expressed fusion protein, glutathione S-transferase (GST, EC 2.5.1.18), and calbindin-D9k. Calbindin-D9k cDNA was linked to a GST gene within a molecule of vector plasmid and a fusion protein was expressed in Escherichia coli. There were significant (p < 0.001) correlations between calbindin-D9k protein, mRNA concentrations and calcium-binding activity: r = 0.90 for protein vs. mRNA, r = 0.93 for protein vs. binding activity and r = 0.95 for mRNA vs. binding activity. These results indicate that calbindin-D9k expression during postnatal development is regulated at the transcriptional level.

Animals↗
PubMed1997

Denervation-induced region-specific changes in fibre types in the soleus and plantaris muscles of rats.

Muscle fibre composition was compared among the proximal (25%), middle (50%) and distal (75%) regions of muscle to investigate whether denervation induces region-specific changes of fibre types in the soleus and plantaris muscles of rats. Decreases in mass were observed in both muscles after denervation. In the soleus muscle, denervation increased the percentage of type I fibres with a concomitant increase in the proportion of type IIC and IIA fibres. The extent of such transformations was greater in the proximal region than the middle and distal regions. In normal plantaris muscle, the middle region showed a higher proportion of type IIA fibres with a lower percentage of type IIB fibres reciprocally than other regions. These regional differences in fibre types were not detected in the 4-week denervated plantaris muscle. These findings suggest that denervation-induced transformations from type I to type II fibres begin in the proximal region in the soleus muscle of rats. In addition, regional differences in fibre types along the muscle length could be regulated by neuromuscular activity through normal innervation in the plantaris muscle.

Animals↗
PubMed1997

Odorant evoked magnetic fields in humans.

We investigated the olfactory evoked magnetic fields (OEFs) in 14 normal subjects. Pulses of odorant air containing amyl acetate or phenethyl alcohol, and odorless air were administered to the subject through a nasal tube. A clear and consistent OEF component, 1M, was identified in all subjects, and a second component, 2M, was detected in seven subjects, but no consistent component was identified in response to the odorless air. The peak latencies of the 1M and 2M components were approximately 320 and 630 ms, respectively. The waveforms produced by the odorless air were subtracted from the waveforms produced by the odorant air to obtain the 'subtraction' waveform, which indicated the 1M and 2M component more clearly. Their equivalent current dipoles (ECDs) were estimated in the regions around the Sylvian fissure symmetrically in both hemispheres. Therefore, these areas are proposed to be involved in olfactory perception in humans.

Adult↗
PubMed1997

Lactase decline in weaning rats is regulated at the transcriptional level and not caused by termination of milk ingestion.

Lactase activity declines during postnatal development in rats, but little is known about the underlying molecular mechanism of this phenomenon. We attempted to clarify whether the regulation was at the transcriptional or post-transcriptional level and to examine the effects of dietary factors on that regulation. Newborn rats were divided into two groups, prolonged nursing and weaning, at d 21. The prolonged nursing rats were nursed for a further 6 d, whereas weaning rats were separated from their dams and fed nonpurified diet for the same period. The patterns of declining lactase protein and mRNA concentrations during weaning were determined by Western blot and Northern blot analyses, respectively, and compared with lactase activity. There were significant (P < 0.001) correlations between them: r = 0.97 for specific activity vs. protein, r = 0.99 for specific activity vs. mRNA and r = 0.96 for protein vs. mRNA. The lactase activity per milligram DNA showed a pattern similar to that of the specific activity. This result argues against the decline in lactase activity being due to the dilution caused by newly synthesized materials during the weaning period and suggests transcriptional regulation. Furthermore, the prolonged nursing rats showed the same results as weanlings for lactase protein, mRNA, specific activity and activity per milligram DNA. These observations indicate that the regulation of lactase expression is at the transcriptional level and that it is not affected by the termination of milk ingestion.

Actins↗
PubMed1997

[Oro-pharyngeal burn during electrodissection of the adenoid and tonsil].

We present a case of oro-pharyngeal burn which occurred during electrodissection of the adenoid and tonsil in a 5-year-old boy. We intubated the patient with an uncuffed spiral tube of appropriate size and noticed a slight gas leak during positive-pressure ventilation. Anesthesia was maintained with a mixture of 60% nitrous oxide, 40% oxygen and 2.5% sevoflurane. During manipulations of the right tonsil, orange-colored flame blew out about 5 cm from the mouth. Fortunately, the patient underwent the operative procedures without any further troubles, recovered fully from the grade 1 burn in the oral mucosa, and was discharged 23 days after surgery. The surgeons speculated that sevoflurane had been ignited. Although it is well known that sevoflurane is nonflammable in the concentration of clinical use, several reports show that sevoflurane is flammable in concentration of 10% under pure oxygen or nitrous oxide. We concluded that this accident was caused by electrocautery-induced ignition of the gauze packed into the larynx under a high concentration of oxygen which leaked through an uncuffed endotracheal tube. We have to bear in mind that any flammable substance may ignite when using electrocautery in a small space such as the mouth under oxygen-rich environment.

Adenoidectomy↗
PubMed1997

Helicobacter pylori infection in early gastric adenocarcinoma: relationship between histologic subtypes and ulcer-formation.

Early stage of gastric cancers were divided into two subtypes; differentiated and undifferentiated adenocarcinomas, histologically. We examined the involvement of Helicobacter pylori (Hp) infection in the development and progression of cancer, and presence or absence of peptic ulcer (UL+/UL-). From the results, these findings obtained as follows; 1) Hp positive rate of UL+ group was significantly higher than that of UL-group. 2) Neither of gross features nor depth of the tumor did not correlate with Hp positive rates. 3) Hp positive rate of undifferentiated type carcinoma was significantly higher than that of differentiated type, contrarily to our expectation. These findings suggested that Hp infection might relate with ulcer formation in the cancerous lesion. The hypothesis which is "gastritis-intestinal metaplasia-differentiated type carcinoma sequence" was not supported by present study. Hence, Hp infection was suggested as an important factor of the gastric cancer development and progression, not only in differentiated type but also in undifferentiated type.

Adenocarcinoma↗
PubMed1996

Changes in fibre types in rat soleus and plantaris muscles following hypophysectomy and compensatory overload.

We investigated whether hypophysectomy could modify the change in muscle fibre types caused by compensatory overload. Male Wistar strain rats were assigned to groups of either normal control (NC), hypophysectomized control (HC), normal compensatory overloaded (NO), or hypophysectomized compensatory overloaded (HO). Compensatory overload was induced by the bilateral removal of the gastrocnemius muscle. Five weeks later, there were losses in the soleus and plantaris muscle weights as a result of hypophysectomy. Compensatory overload increased muscle weights independently of the hypophysectomy. Growth hormone and 3,5,3'-triiodothyronine levels were significantly decreased following hypophysectomy. In the soleus, hypophysectomy increased the percentage of type I fibres at the expense of type IIA fibres. Compensatory overload decreased type IIA fibres under the hypophysectomized condition. In the plantaris, the percentage of type IIC fibres was increased at the expense of both type IIA and IIB fibres following hypophysectomy. The decrease in type IIB fibres cause by compensatory overload was induced irrespective of hypophysectomy. The changes in muscle fibre types in the HO group were equal to the sum of the changes in the HC and NO groups. These results suggest that after a period of 5 weeks hypophysectomy may induced decrease in type IIA and IIB fibres in association with the lack of pituitary and thyroid hormones, and that the hypophysectomy could not modify the change in muscle fibre types caused by compensatory overload.

Aging↗
PubMed1996

Olfactory evoked potentials in Parkinson's disease, Alzheimer's disease and anosmic patients.

Olfactory evoked potential (OEP) recordings were undertaken using amyl acetate stimulation in 20 patients with Parkinson's disease, nine patients with Alzheimer's disease, seven patients with olfactory dysfunction with no other neurological disorder, and 17 control subjects. In order to eliminate the somatosensory factor from the combined somatosensory and olfactory components produced by amyl acetate stimulation, we substracted the potentials using odorless air from those using amyl acetate. In normal subjects, three components were observed, the mean latencies of which were 309 +/- 46, 484 +/- 61 and 710 +/- 55 ms. In all subjects with anosmia (n = 7), no responses were observed. In the patients with Alzheimer's disease, the components were fewer despite having no olfactory dysfunction. In the 20 patients with Parkinson's disease, eight [corrected] patients showed no components, seven patients showed one component and four [corrected] patients showed two components. The components rarely were detected in spite of whether the patients had olfactory dysfunction or not. Olfactory evoked potentials are useful in detecting olfactory dysfunction and the early stages of Alzheimer's disease and Parkinson's disease.

Aged↗