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Biomedical subjects

M Kashiwagi

Publications and source records attributed to M Kashiwagi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cholesterol sulfate, an activator of protein kinase C mediating squamous cell differentiation: a review.

Activity of protein kinase C (PKC) depends on the interaction with polar head-groups of two membrane lipids, i.e., phosphatidylserine and diacylglycerol. We demonstrated that cholesterol metabolism is directly involved in activation of the eta isoform of protein kinase C (PKCeta), which is predominantly expressed in epithelial tissues in close association with epithelial differentiation. We found that PKCeta was activated by cholesterol sulfate (CS), a metabolite of cholesterol formed during squamous cell differentiation. In the presence of CS, phorbol ester only weakly enhanced the activity of PKCeta. CS also activated PKCeta, PKCdelta and PKCepsilon in a dose-dependent manner, when assayed using purified recombinant materials. However, when partially purified materials were used from overexpressing normal human keratinocytes, only PKCeta was activated by CS among the isoforms examined. All the existing lines of evidence, mainly supplied from our laboratory, suggest that CS is involved in a signal transduction of squamous cell differentiation and thereby modifying squamous cell carcinogenesis.

Cell Differentiation↗
PubMed2000

Regulation of CDK7-carboxyl-terminal domain kinase activity by the tumor suppressor p16(INK4A) contributes to cell cycle regulation.

The eukaryotic cell cycle is regulated by cyclin-dependent kinases (CDKs). CDK4 and CDK6, which are activated by D-type cyclins during the G(1) phase of the cell cycle, are thought to be responsible for phosphorylation of the retinoblastoma gene product (pRb). The tumor suppressor p16(INK4A) inhibits phosphorylation of pRb by CDK4 and CDK6 and can thereby block cell cycle progression at the G(1)/S boundary. Phosphorylation of the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II by general transcription factor TFIIH is believed to be an important regulatory event in transcription. TFIIH contains a CDK7 kinase subunit and phosphorylates the CTD. We have previously shown that p16(INK4A) inhibits phosphorylation of the CTD by TFIIH. Here we report that the ability of p16(INK4A) to inhibit CDK7-CTD kinase contributes to the capacity to induce cell cycle arrest. These results suggest that p16(INK4A) may regulate cell cycle progression by inhibiting not only CDK4-pRb kinase activity but also by modulating CDK7-CTD kinase activity. Regulation of CDK7-CTD kinase activity by p16(INK4A) thus may represent an alternative pathway for controlling cell cycle progression.

Amino Acid Sequence↗
PubMed2000

An autopsy case of accidental asphyxiation in a storage room for apples.

A 12-year-old boy died in a storage room and his mother was rescued from the same storage room, where many apples were being stored. The atmosphere in the room was strictly controlled and the concentration of oxygen (O2) was recorded. The cause of death was suffocation. According to the records, the concentration of O2 was about 2.7% when the boy died. On the other hand, it was about 3.4% when his mother entered the room and she survived, although she remained unconscious for about four hours. These findings show that the absolute concentration of O2 causing acute death due to O2 deficiency is approximately 2.5-3.0%.

Accidents↗
PubMed2000

Chronic intestinal pseudo-obstruction due to dialysis-related amyloid deposition in the propria muscularis in a hemodialysis patient.

Dialysis-related amyloidosis (DRA) is one of the most serious complications interfering with rehabilitation in dialysis patients. Here, we report a case of beta2-microglobulin (beta2M)-related amyloidosis, in which the patient developed a severe intestinal pseudo-obstruction. The patient was a 42-year-old male who had been undergoing hemodialysis for 13 years, and who had no history of osteoarticular involvement of DRA. The first symptoms of the disease were severe abdominal fullness and nausea after meals. The whole intestinal wall biopsy revealed massive amyloid deposition in the propria muscularis. The patient became malnourished and died of acute subendocardial infarction 3 years after the onset. An autopsical examination revealed a massive deposition of amyloid, which was positively stained with anti-beta2M antibody but not AA amyloid, predominantly in the gastrointestinal muscular layer, including the tongue, esophagus, stomach, small intestines, colon, and rectum. These results suggest that the gastrointestinal involvement of beta2M-related amyloidosis might occur during the course of hemodialysis treatment, and that this possibility should be considered if patients suffer from intestinal pseudo-obstruction without osteoarticular symptoms.

Adult↗
PubMed1999

Regulation by 1alpha,25-dihydroxyvitamin D(3) of expression of stanniocalcin messages in the rat kidney and ovary.

Regulation by vitamin D(3) of expression of the genes for stanniocalcins 1 and 2 (STC-1 and STC-2) was studied and their levels were shown to be oppositely regulated in the kidney and to remain unaffected in the ovary. Female rats were treated with calcitriol, the active form of vitamin D(3), and alterations in the levels of STC-1 and STC-2 mRNA were determined by Northern blot analysis in the kidney and ovary where the STC-1-expressing cells have previously been identified by in situ hybridization histochemistry. In the kidney, calcitriol treatment increased the STC-1 mRNA levels more than 3-fold, but decreased the STC-2 message to trace levels. In the ovary, however, both STC-1 and STC-2 mRNA levels were not significantly affected by the calcitriol treatment. These results support the hypotheses that (1) STC-1 and STC-2 have opposite effects on calcium and phosphate homeostasis, namely anti-hypercalcemic and anti-hypocalcemic actions, respectively, and (2) the mammalian stanniocalcin system acquired, in addition to the role in the systemic mineral metabolism, a role in the reproduction system that operates independently of the systemic condition.

Animals↗
PubMed1999

Identification by differential display of a hypertonicity-inducible inward rectifier potassium channel highly expressed in chloride cells.

By using differential mRNA display to monitor the molecular alterations associated with adaptation of euryhaline eels to different salinities, we identified a cDNA fragment strongly induced in seawater eel gills. Cloning of a full-length cDNA and its expression in COS-7 cells indicated that the clone codes for an inward rectifier K+ channel (eKir) of 372 amino acid residues, which has two transmembrane segments and a typical pore-forming region (H5). Only low sequence similarities are present, except the H5 region, compared with other members of the inward rectifier K+ channel family (Kir). Consistent with this divergence in the amino acid sequence, a phylogenetic analysis indicated early divergence and independent evolution of eKir from other members; it is only distantly related to the Kir5.0 subfamily members. RNase protection analysis showed that eKir is highly expressed in the seawater eel gill, kidney, and posterior intestine but very weakly in freshwater eels. Immunohistochemistry of gill sections revealed dense localization of eKir in the chloride cells. Immunoelectron microscopy indicated that eKir is mainly present in the microtubular system in the chloride cell. This location and its salt-inducible nature suggest that the eKir channel cloned here is a novel member of the Kir5.0 subfamily of the Kir family and is implicated in osmoregulation.

Adaptation, Physiological↗
PubMed1999

Diagnosis and staging of pancreatic cancer by positron emission tomography.

The detection of pancreatic cancer or the discrimination between pancreatic cancer and chronic pancreatitis remains an important diagnostic problem. Several imaging modalities are now used to diagnose pancreatic cancer, including transabdominal ultrasonography (US), contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI), endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasonography, and selective angiography. None of these six methods is perfect: Each has advantages and disadvantages, and their sensitivity and specificity are in a high range. In 1990 positron emission tomography (PET) was first applied to diagnose pancreatic cancer. This new diagnostic modality is based on functional changes in the pancreatic cancer cells caused by enhanced glucose metabolism. Increased glucose utilization is one of the characteristics of malignantly transformed cells, independent of their origin. The technical development of PET has allowed this new procedure to be used for clinical evaluation. Using 2-((18)F)-fluoro-2-deoxy-d-glucose, PET can identify pancreatic cancer and differentiate pancreatic cancer from chronic pancreatitis with a sensitivity of 85% to 98% and a specificity of 53% to 93%. However, high sensitivity and high specificity are strongly dependent on the tumor stage. At present PET is still experimental and is available only in specialized centers. It may represent a new and noninvasive diagnostic procedure for the detection and the staging of pancreatic cancer. Further clinical studies, especially including patients with early tumor stages (small tumor size), are needed. This review discusses the possibilities and limits of PET and evaluates its importance in the future.

Adenocarcinoma↗
PubMed1999

Sudden unexpected death following stellate ganglion block.

A 29-year-old woman, who had been suffering from left facial palsy, died 3.5 hours after undergoing stellate ganglion block (SGB). Autopsy revealed subcutaneous emphysema of the body, bilateral pneumothorax and a huge post-tracheal hematoma. The lower half of the trachea was markedly flattened by pressure from this hematoma. The cause of death was certified as airway obstruction due to a post-tracheal hematoma following SGB. The doctor cut both the anterior and the posterior wall of the trachea, because the trachea was flattened by the hematoma. He then intubated and sent air into the post-tracheal space. We consider that the patient could have recovered if she had received the correct tracheotomy. We therefore conclude that there was professional error on the part of the doctor in the form of medical malpractice.

Journal Article↗
PubMed1999

Antigenicity of the carbohydrate moiety of ganglioside GM3 having 3-O-acetyl ceramide.

To elucidate the effect of a modification of ceramide on antigenicity of the carbohydrate of ganglioside, the reactivity of O-acetyl GM3 having 3-O-acetyl ceramide, which has been characterized as a glioma-related ganglioside, with monoclonal antibody M2590 was examined in comparison to that of non-acetylated GM3, by means of quantitative enzyme-linked immunosorbent assay, TLC-immunostaining and liposome immune lysis assay. In all these assay systems, O-acetyl GM3 showed less activity than GM3 as follows: GM3 was detected till 0.1 nmol in TLC-immunostaining, whereas O-acetyl GM3 could not be detected even at 0.25 nmol; the GM3 reaction was approximately twofold that of O-acetyl GM3 at each diluted point in the enzyme-linked immunosorbent assay; and 20% of the liposomes containing GM3 were lysed at 6 mol%, while liposomes containing O-acetyl GM3 did not lyse at that concentration. The lesser antigenicity of the sugar moiety of O-acetyl GM3 could be ascribed to the presence of an acetyl group in the ceramide at the 3-position of sphingosine.

Ceramides↗
PubMed1999

Adenovirus-mediated gene transfer to keratinocytes--a review.

The introduction and expression of a foreign gene provide a powerful tool for investigating functions and regulation of a gene of interest; however, keratinocytes have a major drawback in that foreign genes are hardly transfected by conventional methods and stable transformants are most difficult to establish in normal keratinocytes with a limited short life span. To overcome these problems, we used an adenovirus vector, Ax, developed by Saito et al, which yields desired recombinant viruses at an efficiency about 100-fold that of conventional methods, and by which genes are expressed at a high level under the control of a composite CAG promoter. We established Ax vectors carrying various isoforms of protein kinase C (PKC). Using these vectors, we found that the eta and delta isoforms of PKC, but not the alpha and zeta isoforms, mediate terminal differentiation in normal human keratinocytes. These Ax-vectors are also applicable to organ culture of mouse embryos. Advantages and disadvantages of adenovirus vectors and their use for keratinocyte biology are reviewed.

Adenoviridae↗
PubMed1999

Cloning, properties and tissue distribution of natriuretic peptide receptor-A of euryhaline eel, Anguilla japonica.

During the course of cloning and characterization of natriuretic peptide receptor-A (NPR-A) from the euryhaline fish eel, Anguilla japonica, we identified a splice variant with unique structural properties that affect ligand-inducible intrinsic guanylate cyclase activity. The variant, generated from a splice between a cryptic donor site and the normal acceptor site, lacked nine amino acid residues (VFTKTGYYK) in the kinase-like regulatory domain. This deletion of a very short segment resulted in the complete loss of the ligand inducibility of the cyclase activity. The nine-amino acid segment may therefore be useful as a target for studies aimed at clarifying the mechanism of activation of the guanylate cyclase domain. Characterization of the normal form of eel NPR-A also led to the following interesting findings. Although eel NPR-A had a domain structure very similar to that of mammalian counterparts, it lacked the third cysteine residue in the extracellular domain which is conserved among mammalian NPR-A molecules. The eel receptor bound both amidated and nonamidated eel atrial natriuretic peptide (eANP) with high affinity but, when assayed for ligand-inducible cGMP generation, it responded efficiently only to physiological concentrations of the amidated ligand, suggesting that the biologically active form is the amidated eANP, and the nonamidated form acts as a partial antagonist; similarly, nonhomologous rat ligands behaved like antagonists toward the eel receptor in the concentration range 0.1-10 nm. The receptor message was found to be relatively abundant in the osmoregulatory organs such as the gill, kidney, intestine and urinary bladder.

Adaptation, Physiological↗
PubMed1999

Group II and IV phospholipase A(2) are produced in human pancreatic cancer cells and influence prognosis.

BACKGROUND: Phospholipase A(2) (PLA(2)) is involved in regulating biosynthesis of arachidonic acid and its metabolites. There are three major structurally different forms of PLA(2): group I, also called pancreatic PLA(2) (PLA(2)-I); group II, referred to as secretory non-pancreatic or synovial or platelet PLA(2) (PLA(2)-II); group IV, referred to as cytosolic PLA(2) (PLA(2)-IV). AIMS: To examine PLA(2)-I, PLA(2)-II, and PLA(2)-IV in normal and pancreatic cancer tissues. Patients-PLA(2) was studied in 58 pancreatic adenocarcinomas, obtained from 25 women and 33 men undergoing pancreatic resection. Normal organ donor pancreas served as control. METHODS: The enzymes were analysed by northern blot, in situ hybridisation, and immunohistochemistry. The molecular findings were correlated with clinical variables of the patients. RESULTS: Northern blot analysis of total RNA showed enhanced PLA(2) group II and IV mRNA expression in 52% and 55% of the pancreatic cancer samples respectively compared with the normal controls (p = 0.0013 and p = 0.0025). On immunohistochemical analysis, intense PLA(2)-I immunoreactivity was seen in acinar cells, but not in ductal cells, in the normal pancreas. In pancreatic cancer cells, PLA(2)-I immunostaining was absent. PLA(2)-II immunostaining was visible only in some acinar and ductal cells in the normal pancreas, whereas in pancreatic cancer increased PLA(2)-II immunoreactivity was present in 65% of the cancer samples. On in situ hybridisation, weak PLA(2)-IV mRNA signals were detected in acinar and ductal cells of normal samples; these signals were present to a much greater extent in pancreatic cancer cells. The presence of PLA(2)-II in pancreatic cancer was associated with a higher degree of fibrosis (p<0.01). Furthermore, there was a significant correlation between the enhanced expression of PLA(2)-II and longer survival after surgery (p<0.03), but not of PLA(2)-IV and longer postoperative survival. CONCLUSION: These data suggest that PLA(2)-II and PLA(2)-IV are upregulated in human pancreatic cancer, and that upregulation of PLA(2)-II in pancreatic cancer covariates negatively with cancer cell growth.

Adenocarcinoma↗
PubMed1999

Autosomal dominant muscle cramp syndrome in a Japanese family.

OBJECTIVES: To identify the clinical, electrophysiological, histological, and genetic characteristics of a Japanese family with a muscle cramp syndrome. METHODS: Fourteen patients (eight men, six women) were studied in four generations of a single family. Electrophysiological examinations were performed in four cases and muscle and nerve biopsies were performed on the propositus. RESULTS: The mode of inheritance seemed to be autosomal dominant. The cramps occurred during both exertion and at rest, and during sleep. Electromyographic examination indicated a neurogenic aetiology. There was a decreased number of large myelinated fibres in the sural nerve, and fibre type grouping in the quadriceps femoris muscle biopsy. CONCLUSIONS: The autosomal dominant muscle cramp syndrome in this family is probably caused by a polyneuropathy.

Aged↗
PubMed1999

Successful treatment of cerebral aspergillosis with a high oral dose of itraconazole after excisional surgery.

We report a case of cerebral aspergillosis which originated from the sphenoid sinus, and involved a progressive decrease of visual acuity. The neurological signs indicated a cavernous sinus invasion. After extensive intracranial surgery we treated the residual aspergillosis with a high oral dose of itraconazole (800 mg/d for 4 months, followed by 400 mg/d for 5 months). The neurological impairments of the patient gradually subsided with the resolution of the fungal lesion shown on MRI. The successful therapy indicated that itraconazole has a significant role in the treatment of advanced cerebral aspergillosis if it is used in high doses (16 mg/kg/d for adults).

Administration, Oral↗
PubMed1999

Reciprocal facilitation of motor evoked potentials immediately before voluntary movements in Parkinson's disease.

Changes of motor evoked potentials (MEPs) from the agonist and antagonist forearm muscles were investigated in 13 patients with Parkinson's disease and age-matched controls, in whom transcranial magnetic stimulation (TCMS) was delivered to the cortical hand motor area immediately before voluntary wrist flexion. MEPs recorded from the agonist muscles, namely the wrist flexors, were gradually facilitated in accordance with a shortening of the interval between TCMS and wrist flexion in both groups. In contrast, MEPs recorded from the antagonist muscles, namely the wrist extensors, were gradually facilitated as the intervals were shortened only in parkinsonian patients. The reciprocal facilitation of the antagonist MEPs was statistically significant when TCMS was delivered within 80 msec before the voluntary movements, suggesting the presence of the same underlying mechanism of symptomatic cocontraction observed in patients with Parkinson's disease.

Adult↗