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Biomedical subjects

K Miki

Publications and source records attributed to K Miki.

At least 127 records · Page 7Linked to original sources
PubMed1998

Dynorphin mRNA expression in dorsal horn neurons after traumatic spinal cord injury: temporal and spatial analysis using in situ hybridization.

Dynorphin, an endogenous opioid, may contribute to secondary nervous tissue damage following spinal cord injury. The temporal and spatial distribution of preprodynorphin (PPD) mRNA expression in the injured rat spinal cord was examined by in situ hybridization. Rats were subjected to traumatic spinal cord injury at the T13 spinal segment using the weight-drop method. Motor function of these rats was evaluated by their ability to maintain their position on an inclined plane. Two double-labeling experiments revealed that increased PPD mRNA and dynorphin peptide expression were found exclusively in dorsal horn neurons. Neurons exhibiting an increase in the level of PPD mRNA were concentrated in the superficial laminae and the neck of dorsal horn within several spinal segments from the epicenter of the injury at 24 and 48 h after injury. A number of neurons showing increased PPD mRNA were found in gray matter adjacent to the injury areas. Segments caudal to the injury site exhibited a long-lasting elevation of PPD mRNA in neurons, compared to the rostral segments. The number of neurons expressing PPD mRNA in each rat was significantly positively correlated with its motor dysfunction. These findings suggest that increased expression of dynorphin mRNA and peptide in dorsal horn neurons occurs after traumatic spinal cord injury. This also supports the hypothesis that the dynorphin has a pathological role in secondary tissue damage and neurological dysfunction after spinal cord injury.

Animals↗
PubMed1998

Crystal structure of human secretory phospholipase A2-IIA complex with the potent indolizine inhibitor 120-1032.

Phospholipase A2 is a key enzyme in a number of physiologically important cellular processes including inflammation and transmembrane signaling. Human secretory phospholipase A2-IIA is present at high concentrations in synovial fluid of patients with rheumatoid arthritis and in the plasma of patients with septic shock. Inhibitors of this enzyme have been suggested to be therapeutically useful non-steroidal anti-inflammatory drugs. The crystal structure of human secretory phospholipase A2-IIA bound to a novel potent indolizine inhibitor (120-1032) has been determined. The complex crystallizes in the space group P3121, with cell dimensions of a = b = 75.8 A and c = 51.3 A. The model was refined to an R-factor of 0. 183 for the intensity data collected to a resolution of 2.2 A. It was revealed that the inhibitor is located near the active site and bound to the calcium ion. Although the binding mode of the 120-1032 inhibitor to human secretory phospholipase A2-IIA is similar to that previously determined for an indole inhibitor LY311299, the specific interactions between the enzyme and the inhibitor in the present complex include the oxycarboxylate group which was introduced in this inhibitor. The oxycarboxylate group in 120-1032 is coordinated to the calcium ion and included in the water-mediated hydrogen bonding to the catalytic Asp49. In addition, the ethyl group in 120-1032 gains hydrophobic contacts with the cavity wall of the hydrophobic channel of the enzyme.

Binding Sites↗
PubMed1998

Role of tissue inhibitor of metalloproteinases-2 (TIMP-2) in regulation of pro-gelatinase A activation catalyzed by membrane-type matrix metalloproteinase-1 (MT1-MMP) in human cancer cells.

To clarify the regulatory mechanism of pro-gelatinase A (proGelA) activation at a cellular level, expression of gelatinase A (GelA), three MT-MMPs, and TIMP-2 was examined with 11 human cancer cell lines cultured in the presence and absence of stimulants. MT1-MMP mRNA was expressed in 8 cell lines, while MT2-MMP and MT3-MMP mRNAs were expressed in fewer cell lines. The cells with high proGelA activation strongly expressed MT1-MMP mRNA but not MT2-MMP and MT3-MMP mRNAs, suggesting that MT1-MMP was responsible for the proGelA activation in the cancer cells. Treatments with concanavalin A (Con A) and a phorbor ester (TPA) enhanced the MT1-MMP expression, but only Con A stimulated the proGelA activation in many cell lines. In HT1080 fibrosarcoma cells, however, TPA also stimulated the activation. The level of TIMP-2 secreted into culture medium inversely correlated with proGelA activation. For example, 2 squamous cell carcinoma lines (HSC-3 and HSC-4) and 3 HT1080 clones, which efficiently activated proGelA, secreted little TIMP-2 into medium, whereas other cell lines and other HT1080 clones, which hardly activated proGelA, secreted TIMP-2 at high levels. When HSC-3 cells were incubated with TIMP-2 protein or transfected with TIMP-2 cDNA, the proGelA activation was strongly inhibited. These results indicated that extracellular TIMP-2 was an important negative regulator of proGelA activation. However, the level of extracellular TIMP-2 was not consistent with that of TIMP-2 mRNA in some cell lines. Other experimental results suggested that TIMP-2 might be rapidly metabolized after binding to MT1-MMP, and Con A treatment might stabilize the complex of TIMP-2 and MT1-MMP on cell membranes.

Catalysis↗
PubMed1998

Saliva level of free 3-methoxy-4-hydroxyphenylglycol in psychiatric outpatients with anxiety.

As a measurement of the level of anxiety in psychiatric outpatients with anxiety, we determined the saliva level of free 3-methoxy-4-hydroxyphenyleglycol (MHPG) using gas chromatography- mass spectrometry and scored the levels of anxiety with the Hamilton Anxiety Scale (HAS) in patients, before and after drug treatment with alprazolam for 1 week. The saliva level of free-MHPG at first visit to hospital was significantly higher than that of control individuals and disease control individuals and was reduced by alprazolam treatment for 1 week. There was no correlation between MHPG level and the HAS score at the first hospital visit. The MHPG levels after treatment correlated with the HAS scores. The reduction of the anxiety level as scored by the HAS correlated with the reduction of MHPG level. These results indicate that the free saliva MHPG level may be a useful indicator for assessing not only the level of anxiety, but also the response to drug treatment for anxiety in these patients.

Adult↗
PubMed1998

Three paediatric cases of primary sclerosing cholangitis treated with ursodeoxycholic acid and sulphasalazine.

We present here three paediatric patients with primary sclerosing cholangitis. In case 1, the serum gamma-glutamyl transpeptidase was decreased only temporarily by ursodeoxycholic acid (UDCA) treatment and 34 months later, sulphasalazine was added because of microscopic colitis. The enzyme level decreased with dual therapy. Similarly, in case 3, first diagnosed as autoimmune hepatitis, the transpeptidase levels remained elevated for 18 months during treatment with UDCA, prednisolone and mizoribin. The enzyme decreased only after a diagnosis of primary sclerosing cholangitis complicated with ulcerative colitis was established and sulphasalazine was introduced. Case 2 also had Crohn's colitis and was put on UDCA and sulphasalazine from the start. The enzyme level was normalized within 1 month and has remained normal for the following 5 years. Liver biopsies were analysed repeatedly in these three patients. In case 1, periductal fibrosis remained unchanged while being treated by UDCA. There appeared to be no progression in liver cirrhosis in case 3 while being treated by UDCA, prednisolone, and mizoribin. In case 2, who has been treated with both UDCA and sulphasalazine from the start, periductal fibrosis and portal fibrosis were remarkably improved 45 months later. We suggest that sulphasalazine in addition to UDCA might be a viable treatment for children with primary sclerosing cholangitis.

Adolescent↗
PubMed1998

Serous cystadenoma of the pancreas with invasive growth: benign or malignant?

We describe a case of serous cystadenoma, that invaded a lymph node and adipose tissue. Preoperatively, the cystic lesion of the pancreas was diagnosed as a serous cystadenoma and subsequently the patient, a 71-yr-old woman, underwent distal pancreatectomy with splenectomy. Macroscopically, a greyish white, externally lobulated and partly ovoid tumor, measuring 12 x 8.5 x 5 cm, occupied the pancreatic body and tail extensively. In cross-section, multiple nodules were observed, which measured from 0.5 to 3 cm in diameter, were separated by hyalinized fibrous septa and were filled with numerous microcysts. Light microscopic findings were consistent with those for serous cystadenoma. At the splenic hilus, the tumor was found to have invaded the lymph node and adipose tissue. Based on the clinicopathological features of the six reported cases, including the present case (which behaved in a malignant fashion in terms of pathological findings of invasion or metastasis), serous cystadenoma should be regarded as having the potential for malignant growth.

Adipose Tissue↗
PubMed1998

[Evaluation of pyuria by means of urinary sediment method--a comparison to the counting chamber method].

We compared the urinary sediment method to counting chamber method in evaluating pyuria, in order to elucidate an issue of urinary sediment method. The KOVA system was used for counting chamber method. Three hundred and ten urine specimens from the patients who visited Fuji City Central Hospital in March, 1995, were employed. The numbers of leukocytes of each specimen was counted by means of urinary sediment method and counting chamber method, and compared. The urinary leukocyte count evaluating by means of these two methods were correlated well. However, the discrepancy of urinary leukocyte counts by means of these two methods were recognized in two specimens. In these two specimens, the leukocyte count was 1 to 4/5HPF by means of urinary sediment method, but more than 50/microliter by means of counting chamber methods. Significant bacteria (10(4) cfu/ml or more), positive esterse reaction, and high pH (8.5) were recognized in both specimens. In addition, one of two these specimens was hypotonic (specific gravity was 1.008). Therefore, it was suggested that leukocytes were sometimes disrupted with centrifugation. These results indicate that counting chamber method is more useful urinary sediment method to detect pyuria.

Adolescent↗
PubMed1998

[Correlation in Staphylococcus aureus infections between toxic shock syndrome toxin-1 production and clinical feature].

Toxic shock syndrome (TSS) is caussed by toxic shock syndrome toxin-1 (TSST-1) of Staphylococcus aureus. We studied the incidence of TSST-1 production by the clinical isolates of S. aureus, in order to clarify the possibility of TSS caused by S. aureus. One hundred and seventeen clinical isolates of S. aureus were tested. Of 117 strains, 74 were methicillin-cephem resistant S. aureus (MRSA), and 43 were methicillin-cephem sensitive S. aureus (MSSA). TSST-1 production and penicillinase (PCase) activity were measured by means of reversed passive Latex aggulutination method and acidmetric assay, respectively. The incidences of TSST-1 production by PCase positive MRSA, PCase negative MRSA, PCase positive MSSA and PCase negative MSSA were 92% (55/60), 78% (11/14), 21% (7/33) and 0% (0/10), respectively. TSS occurred in a patient with chronic complicated pyelonephritis after endopyelotomy for hydronephrosis. In this patient, PCase positive MRSA which produced TSST-1 was isolated from urinary tract, and he was cured after administration of arbekacin. These results indicsate that methicillin-cephem resistance and PCase production are the risk factors for TSST-1 production in S. aureus.

Bacterial Toxins↗
PubMed1998

Recurrent T354P mutation of the Na+/I- symporter in patients with iodide transport defect.

Iodide transport defect (ITD) is a rare disorder causing congenital hypothyroidism. We previously reported that homozygous T354P mutation in the sodium/iodide symporter (NIS) gene caused ITD. To clarify the prevalence of this mutation, artificial substitution introducing PCR followed by restriction enzyme analysis was developed as a rapid screening method to detect the T354P mutation. Three apparently unrelated families with ITD, one patient with low thyroidal 99mTc pertechnetate (99mTcO4-) uptake and 52 healthy controls (104 alleles) were analyzed for this mutation. All families with ITD harbored the mutation, suggesting that T354P is a recurrent mutation and a major cause of ITD. This was not a widespread mutation, because it was not detected in the 52 unrelated normal controls. Because two cases with homozygous T354P mutation developed multinodular goiters within their second decade of life though they had been maintained in euthyroid state, homozygous T354P mutation alone and/or low intrathyroidal iodide and high serum TSH level in early life might account for tumorigenesis. The patient with low thyroidal 99mTcO4- uptake did not harbor the T354P mutation. Because familial hypocalciuric hypercalcemia was also present in this family, a possibility of the combined abnormality of TSH receptor and calcium functions, which includes an abnormality around the G protein, may be examined further.

Carrier Proteins↗
PubMed1998

Hypophosphatemic rickets accompanying congenital microvillous atrophy.

This report concerns an 11-year-old boy who manifested hypophosphatemic rickets associated with congenital microvillous atrophy (CMA). He had been suffering from vomiting and severe diarrhea from the first day of life and had been treated with total parenteral nutrition (TPN) since he was 67 days old. At 4 years of age, intestinal biopsy resulted in a diagnosis of CMA. He was admitted to our hospital complaining of leg pain at the age of 11. Laboratory data revealed hypophosphatemia, elevated serum 1, 25-dihydroxyvitamin D (1,25(OH)2D) levels, and hypercalciuria. A roentgenogram showed rickets in the extremities. A balance study of phosphate in urine and stool indicated that the amount of phosphate leaking into the stool was greater than that into the urine. Moreover, the total amount of phosphate leaking from both the intestine and kidney exceeded the amount of phosphate intake from TPN. The rickets was healed by increasing the phosphate concentration in TPN. This case is different from X-linked hypophosphatemic rickets but similar to hereditary hypophosphatemic rickets with hypercalciuria (HHRH) in terms of hypercalciuria and elevated serum 1,25(OH)2D levels. The effectiveness of phosphate treatments used here is also similar to that used for HHRH. However, this type of hypophosphatemic rickets is unique in that phosphate leaking into the intestine plays an important role in its pathogenesis.

Absorptiometry, Photon↗
PubMed1998

Urinary and salivary stress hormone levels while performing arithmetic calculation in a noisy environment.

The effects of environmental conditions on stress responses to mental work, were examined by measuring urinary catecholamine and cortisol excretion and salivary cortisol concentrations before, during and after an arithmetic calculation task under 90 dB(A) white noise and quiet conditions. Adrenaline excretion increased similarly during the task under both environmental conditions. The salivary cortisol level was significantly higher than the pre-task level during the task with noise, but not under quiet, conditions. The subjects reported that they felt more irritable when performing the task with noise, than under quiet conditions. The results suggest that environmental conditions may affect on the pattern of hormonal response to mental work, which may be related to psychological states of the subjects.

Adult↗
PubMed1998

[Magnetic resonance images of hematospermia].

BACKGROUND: We performed MRI (magnetic resonance imaging) in the pelvic region of 70 cases with hematospermia and conducted a study on the abnormal MRI findings to which hematospermia could be attributed. METHODS: We conducted a study on the morphological anomaly and change in the signal intensity in the prostate gland and of the seminal vesicle as well as on the presence or absence of dilation in the plexus venous surrounding the deferent duct or the prostate gland out of the abnormal MRI findings. As for the seminal vesicle, the patients whose seminal vesicle was seen in higher intensity than the prostate gland in T1 weighted images were diagnosed as having hemorrhagic focus and the patients whose seminal vesicle was seen in low intensity both in T1 and T2 weighted images were diagnosed as having fibrosis caused by chronic inflammation. RESULTS: Abnormal MRI findings were seen in 40 out of the 70 cases (57%). Anomaly in the prostate gland was indicated in 6 (9%) cases. Abnormality in the seminal vesicle was indicated in 30 cases (43%) including hemorrhage of seminal vesicle in 25 cases, chronic inflammation in five cases and cyst of seminal vesicle in one case. CONCLUSION: In conducting an examination of the patients with hematospermia, MRI is the noninvasive and reproducible method and it is possible to identify the hemorrhagic region. Therefore, MRI is thought to be useful to identify the causal organs of hematospermia.

Adult↗
PubMed1998

[Bilateral simultaneous epididymal leiomyoma: a case report].

Primary epididymal leiomyoma is relatively rare. We experienced a case of bilateral simultaneous primary epididymal leiomyoma. A 61-year-old man visited our clinic, with the chief complaint of bilateral painless nodules in the scrotum. Each nodule was palpated at the tail of each epididymis (the diameters of these nodules were 12 mm on left and 5 mm on right). We followed the patient for 18 months. Since the nodules were increasing in size, the nodules were surgically removed. Histological examination revealed primary leiomyomas of the epididymis.

Epididymis↗
PubMed1998

A novel mutation of the down-regulated in adenoma gene in a Japanese case with congential chloride diarrhea. Mutations in brief no. 198. Online.

Congenital chloride diarrhea (CLD) is an autosomal recessive disease characterized by excretion of watery stool with a high chloride content. Pathogenesis of CLD is a deficient absorption of chloride in exchange for bicarbonate in the ileum and the colon. In 1996, it was reported that 36 patients with CLD had mutations in the down-regulated in adenoma (DRA) gene; 32 Finnish patients had a three base deletion (951delGGT), 2 Polish patients had a one base mutation (371AtoT) and 2 Polish patients had a one base deletion (344delT). In this study we analyzed the DRA gene in a Japanese boy patient with CLD and in members of his family. The patient was found to have a two base deletion (TT) at nucleotide 1526-1527 within codon 509 which results in a frameshift leading to a permature stopping at codon 517. The patient was homozygous for the deletion, his parents and brother were heterozygous, and his sister was normal. This is the first case of CLD identified to carry a mutation of the DRA gene in Asia.

Adenoma↗
PubMed1998

Elevated expression of membrane-type 1 and 3 matrix metalloproteinases in rat vascular smooth muscle cells activated by arterial injury.

Matrix metalloproteinases (MMPs) play critical roles in tissue remodeling under various physiologic and pathologic conditions. We recently reported the expression of three membrane-type MMPs (MT-MMPs) by cultured vascular smooth muscle cells (SMCs) of rats (Shofuda et al, 1997). To investigate the roles of the MT-MMPs in the matrix remodeling of blood vessels, expression of MT1-MMP and MT3-MMP was examined in normal and balloon-injured rat carotid arteries by in situ hybridization and immunohistochemistry. Both MT-MMP mRNAs were detected in the intimal-dedifferentiated SMCs, but were negligible in the medial SMCs or in any of normal vascular cells. To elucidate the regulatory mechanism for the MT-MMPs expression, effects of various factors on cultured rat SMCs were also examined. MT1-MMP mRNA was constantly expressed at a high level, and its expression was weakly increased by treatment with interleukin-1beta or tumor necrosis factor-alpha. When the cells were incubated with type IV collagen, the MT1 -MMP expression was markedly decreased. On the other hand, expression of MT3-MMP mRNA was strongly increased by platelet-derived growth factor and fibronectin. These results suggest that type IV collagen may act as a negative regulator for the expression of MT1-MMP in the medial SMCs, whereas platelet-derived growth factor and fibronectin may up-regulate MT3-MMP expression under pathologic conditions. Furthermore, the elevated expression of MT1-MMP and MT3-MMP in SMCs was well associated with their dedifferentiated phenotype.

Animals↗
PubMed1998

[Assessment of local staging of prostate cancer by endorectal surface coil].

We assessed the usefulness of endorectal surface coil MRI (ERSC-MRI) for staging diagnosis of prostate cancer to compare preoperative ERSC-MRI findings with pathological staging in patients performed radical prostatectomy. MR imaging was performed on a 1.5 T MR system with an endorectal surface coil designed for imaging the prostate. At the time the coil was inserted, 1.0 mg of glucagon was injected in tramuscularly. T1-weighted MR images were obtained in the axial plane, and T2-weighted, spin echo MR images were obtained in the sagittal, coronal, and axial planes for each patient. The capsular penetration of prostatic cancer was defined according to the six diagnostic criteria by Outwater et al.: (1) a bulge formation of the low-signal-intensity area beyond the prostatic capsule, (2) low-signal-intensity stranding in the periprostatic tissue, (3) retraction of the prostatic capsule besides the low-signal-intensity area, (4) elongation of the low-signal-intensity area in the prostatic capsule, (5) thickening of prostatic capsule. (6) extracapsular tumor. The sensitivity, specificity and accuracy of ERSC-MRI for capsular penetration of the prostatic cancer were 95.5%, 40.0%, and 85.2%, respectively. These results indicate that ERSC-MRI is useful for staging diagnosis of prostatic cancer.

Humans↗
PubMed1997

Expression of beta-calcitonin gene-related peptide in axotomized rubrospinal neurons and the effect of brain derived neurotrophic factor.

The mRNA levels for alpha- and beta-calcitonin gene-related peptide (CGRP) in rat rubrospinal neurons were studied by in situ hybridization 3, 7, 14, 28 and 56 days following cervical spinal hemisection. CGRP-like immunoreactivity (LI) in the rubrospinal neurons and the rubrospinal tract in cervical spinal cords were examined using immunohistochemistry. There was almost no signal for alpha- and beta-CGRP mRNAs and undetectable level of CGRP-LI in the rubrospinal neurons ipsilateral to cervical spinal hemisection (control side). Fourteen days after spinal hemisection, the rubrospinal neurons contralateral to cervical hemisection (axotomized side) showed CGRP-LI in their cell bodies, and CGRP containing fibers were observed in the lateral funiculi just proximal, but not distal, to the injury sites. In situ hybridization showed upregulation of beta-CGRP mRNA in a subpopulation of the rubrospinal neurons on the axotomized side. The proportion of beta-CGRP mRNA-expressing neurons reached its maximum (approximately 19%) 4 days following axotomy and slowly decreased to about 5% 56 days after axotomy. The percentage of alpha-CGRP mRNA-expressing neurons was much lower than that of beta-CGRP mRNA (maximum about 2.6% 4 days after axotomy) and not significantly different from the control side throughout the time period studied. These data indicate that axotomy induces de novo synthesis of the CGRP beta-subtype in rubrospinal neurons and that the beta-CGRP is transported to the injury site through the rubrospinal tract. In addition, we studied the effect of the intracerebral injections of brain derived neurotrophic factor (BDNF). BDNF treatment fully reversed the severe cell atrophy that followed axotomy and increased the number of neurons labeled for beta-CGRP mRNA, but did not increase the percentage of rubrospinal neurons expressing beta-CGRP mRNA. Thus, topical application of BDNF does not have direct modulatory effect on CGRP induction in axotomized neurons in the red nucleus.

Animals↗