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Biomedical subjects

E Nakamura

Publications and source records attributed to E Nakamura.

At least 55 records · Page 3Linked to original sources
PubMed1999

Cyclopropenone-containing cysteine proteinase inhibitors. Synthesis and enzyme inhibitory activities.

By focusing on the amphiphilic properties of cyclopropenone (e.g. a good electrophile and a precursor for a stable 2pi-aromatic hydroxycyclopropenium cation), a new class of cysteine proteinase inhibitors containing a cyclopropenone moiety was designed. For the purpose of the present research, we needed to devise a new method to introduce a peptide-related moiety as a substituent on the cyclopropenone residue. We investigated the reaction of metalated cyclopropenone acetal derivatives (2, R2 = metal) with N-protected alpha-aminoaldehydes 4 to obtain the adduct 5, and succeeded in the preparation of highly potentiated cysteine proteinase inhibitors 8 after several steps transformations. They showed strong inhibitory activities only to cysteine proteinases such as calpain, papain, cathepsin B, and cathepsin L and not to serine (e.g. thrombin and cathepsin G) and aspartic proteinases (e.g. cathepsin D). Kinetic studies indicated that they are competitive inhibitors, and by the examinations of their inhibitory mechanism it became clear that they are reversible inhibitors.

Calpain↗
PubMed1999

A splicing mutation of the tyrosinase gene causes yellow oculocutaneous albinism in a Japanese patient with a pigmented phenotype.

BACKGROUND: Yellow oculocutaneous albinism (OCA) that is caused by tyrosinase gene mutations shows two characteristics: extreme hypopigmentation at birth and the eventual development of yellow or blond hair. OBJECTIVE: We studied a Japanese girl who had brown hair, a lighter skin color than her unaffected family and brown eyes at 9 months of age. METHODS: We performed direct sequencing analyses of the tyrosinase gene in her genomic DNA. RESULTS: The patient was a compound heterozygote for the +DeltaC310 mutation (known to result in absent melanogenic activity) and a second t-->a transition at the 3' end of intron 2. CONCLUSION: The t-->a transition has previously been reported as a splicing mutation in other Caucasian patients with a typical yellow OCA phenotype. However, this patient showed much more pigmentation than that reported in Caucasians. Therefore, we estimate that the mild phenotype results from her genetic pigment background.

Albinism, Oculocutaneous↗
PubMed1999

Rare cases of congenital bicuspid aortic valve with an abnormal fibrous band.

Pure aortic regurgitation is usually caused by a congenital bicuspid aortic valve (BAV). In this condition, there are a few cases accompanied by an abnormal fibrous band stretched from the center of the conjoined cusp to the aortic wall. This report describes two cases of congenital bicuspid aortic valve (BAV) with an abnormal fibrous band. The first case of BAV with an abnormal fibrous band developed aortic regurgitation and the second case exhibited aortic stenosis. These two abnormal fibrous bands were confirmed to be congenital by the microscopic findings. According to the literature, the majority of BAV with an abnormal fibrous band were found in the patients with aortic regurgitation. We report here a case study of an elderly female patient with aortic stenosis of BAV with an abnormal fibrous band. To our knowledge, no other case of BAV with an abnormal fibrous band in association with aortic stenosis has ever been reported.

Aortic Valve↗
PubMed1998

Biological ages of adult men and women with Down's syndrome and its changes with aging.

In order to examine to what extent a gene dysregulation such as Down's syndrome (DS) causes the advance of global biological aging as well as segmental progeroid syndrome, 8 years of longitudinal data were gathered on 14 hematology and blood chemistry characteristics of five adult men and six adult women with DS and four adult men with cerebral palsy (CP). Biological age (BA) was established through the application of principal component analysis based on the data for the same 14 variables of 436 healthy adult men. The BAs of five adult men and six adult women with DS, and four adult men with CP were estimated by using the equation calculated from healthy adult men data, and the BAs were compared. The result of this study indicated that: (1) a genetic condition such as Down's syndrome causes not only segmental progeroid syndrome but also premature aging accompanying global senescence in various organ levels; (2) premature aging exhibited by adult men and women with DS justifies the evidence of primary aging; and (3) the rate of aging for BA in DS patients is nearly a twofold increase as compared to healthy subjects.

Adult↗
PubMed1998

The tachykinin NK1 receptor antagonist GR205171 prevents vagal stimulation-induced retching but not neuronal transmission from emetic vagal afferents to solitary nucleus neurons in dogs.

Tachykinin NK1 receptor antagonists injected into the medulla oblongata are known to abolish vomiting induced by vagal afferent stimulation. Emetic vagal afferents have been shown to synapse with neurons in the medial solitary nucleus (mNTS), which suggests that substance P is a transmitter in the synapse. To examine this possibility, the effects of GR205171, an NK1 receptor antagonist, on retching and mNTS neuronal responses to the stimulation of abdominal vagal afferents were investigated in decerebrate dogs. GR205171 (0.05-0.7 mg kg-1, i.v.) abolished retching induced by either vagal or mNTS stimulation within 5 min. Firing of mNTS neurons in response to pulse-train and sustained vagal stimulation did not change even after the abolition of retching. Similarly, GR205171 did not have any effects on mNTS evoked potentials induced by pulse-train vagal stimulation. In about 20% of mNTS neurons, the peak firing frequency was facilitated to about 150% with repetitive pulse-train vagal stimulation. This facilitation remained even after the abolition of retching. Administration of GR205171 (1 mg ml-1, 30 microliters) into the 4th ventricle abolished retching, with latencies in excess of 120 min These results suggest that substance P does not participate in synaptic transmission between emetic vagal afferents and mNTS neurons in dogs.

Animals↗
PubMed1998

Intrapulmonary cystic lymphangioma: report of a case.

We describe herein the case of a 52-year-old man found to have a solitary pulmonary lymphangioma. Computed tomography (CT) scan demonstrated a nodule with homogeneous density and a well-defined border in the lower lobe of the right lung. T2-Weighted magnetic resonance imaging (MRI) revealed a nodule with homogeneously high signal intensity. The tumor was removed by partial resection, and pathologic examination confirmed a diagnosis of primary lymphangioma of the lung.

Humans↗
PubMed1998

Further evaluation of physical fitness age versus physiological age in women.

The present study was conducted to examine further whether adult women who are in a state of high physical fitness possess high physiological functions, and also to investigate whether those who exercise regularly are able to maintain a high quality of various physiological functions. The subjects of this study were 249 healthy Japanese adult women (aged 20-70 years). Of these subjects 30 had jogged or walked regularly for more than 3 years. The physiological ages (PA) and physical fitness ages (FA) of the individuals were estimated from 17 physiological function tests and 5 physical fitness tests, respectively, by principal components analyses. The results indicated that there was a significant correlation between PA and FA (r = 0.76, P < 0.01). To examine this relationship in more detail, the subjects were classified into three physical fitness groups (high, normal and low) based on the deviation from the regression line of FA. Comparison of the mean PA among three physical fitness groups revealed that the high physical fitness groups demonstrated a much lower PA (physiologically younger), while the low physical fitness groups showed a relatively higher PA (physiologically older) in spite of their equivalent chronological ages. From this series of studies, a new concept is proposed where different individuals have different peak physiological capacities, but that these capacities change with age at similar rates. It is suggested that interventions such as exercise and a proper diet for promoting health could increase peak functional capacity but have little effect on the rate of decline.

Adult↗
PubMed1998

A strategy for identifying biomarkers of aging: further evaluation of hematology and blood chemistry data from a calorie restriction study in rhesus monkeys.

We examined a dataset derived from a battery of hematology and blood chemistry tests to identify candidate biomarkers of aging in a sample of 33 male rhesus monkeys (Macaca mulatta) ranging in age from 4-27 years. About half this sample comprised an experimental group subjected to 30% calorie restriction for six to seven years compared to the control group fed the same nutritionally fortified diet to approximate ad lib levels. Variables that met the following criteria were selected: (1) longitudinal change within the cohorts of control monkeys; (2) cross-sectional correlation with age across the adult lifespan in the control group; (3) stability of individual differences within all groups; and (4) no obvious redundancy with other selected variables. Five variables emerged from this step-wise selection, including the percentage lymphocytes, and serum levels of alkaline phosphatase, albumin, creatinine, and calcium. These variables were then submitted to a principal component analysis, which yielded a single component accounting for about 58% of the total variance. Based on this marked degree of covariance, these candidate biomarkers of aging could be combined into a biological age score (BAS) for the control and experimental groups. When chronological age was regressed onto BAS, the slopes of the control and experimental groups could be compared. Although a trend toward a slower aging rate in calorie-restricted monkeys was apparent, this analysis did not detect a statistically significant difference in the rate of aging between these groups estimated by this index. Despite this result, a logical strategy was confirmed for expanding the search for candidate biomarkers of aging to apply to this and to other studies assessing interventions that purport to affect the rate of aging in long-lived species.

Aging↗
PubMed1998

Interleukin-1beta inhibits growth factor-stimulated restoration of wounded rat gastric epithelial cell monolayers.

We examined the effect of interleukin-1beta (IL-1beta) on spontaneous and enhanced restoration (cell migration and proliferation) using an in vitro wound model comprising a confluent monolayer of rat gastric epithelial RGM1 cells. Repair of an artificial wound in a cell monolayer was found to be time- and concentration-dependent when the cells were incubated with epidermal growth factor (EGF) or transforming growth factor (TGF) -alpha alone for up to 24 hr. The growth factors also stimulated DNA synthesis significantly for 24 hr in a concentration-related manner. IL-1beta had no effect on wound restoration in the absence of the growth factors. However, it markedly inhibited the restoration enhanced by EGF and TGF-alpha, the inhibition being about 60% and 70%, respectively. In addition, IL-1beta significantly reduced the DNA synthesis stimulated by the growth factors. The EGF- and TGF-alpha-enhanced restoration was reduced by about 30% by mitomycin C, which potently inhibited the stimulated DNA synthesis. Mitomycin C had no effect on the spontaneous restoration. Even when treated with mitomycin C, the inhibitory effect of IL-1beta on the enhanced wound repair was still observed; however, the extent of the inhibition was decreased. These results indicate that IL-1beta inhibits the migration as well as the proliferation of gastric epithelial cells enhanced by EGF and TGF-alpha, resulting in a failure of wound healing.

Animals↗
PubMed1998

Effects of cytokines, without and with Helicobacter pylori components, on mucus secretion by cultured gastric epithelial cells.

Cytokines are suspected to play a crucial role in the pathogenesis of Helicobacter pylori-associated gastric diseases. Hence, considerable attention has been paid to the actions of cytokines on gastric cells. We examined the effects of cytokines on mucus secretion by gastric epithelial cells, without or with H. pylori components. Mucus secretion by cultured gastric epithelial cells was assessed as secretion of [3H]glucosamine-prelabeled high-molecular-weight glycoproteins. Interleukin (IL)-1beta and IL-6 significantly stimulated mucus secretion, but other cytokines such as IL-7, IL-8, IL-10, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha had no effect. H. pylori lysate caused a decrease in both basal and stimulated secretion of mucus. In addition, IFN-gamma significantly potentiated the lysate-induced reduction of basal and stimulated secretion. Cell viability was not affected by any of treatments. These results indicate that IL-1beta and IL-6 stimulate mucus secretion, while IFN-gamma potentiates H. pylori-decreased secretion by gastric epithelial cells.

Animals↗
PubMed1998

Disruption of the midkine gene (Mdk) resulted in altered expression of a calcium binding protein in the hippocampus of infant mice and their abnormal behaviour.

BACKGROUND: Midkine (MK) is a growth factor implicated in the development and repair of various tissues, especially neural tissues. However, its in vivo function has not been clarified. RESULTS: Knockout mice lacking the MK gene (Mdk) showed no gross abnormalities. We closely analysed postnatal brain development in Mdk(-/-) mice using calcium binding proteins as markers to distinguish neuronal subpopulations. Intense and prolonged calretinin expression was found in the dentate gyrus granule cell layer of the hippocampus of infant Mdk(-/-) mice. In infant Mdk(+/+) mice, calretinin expression in the granule cell layer was weaker, and had disappeared by 4 weeks after birth, when calretinin expression still persisted in Mdk(-/-) mice. Furthermore, 4 weeks after birth, Mdk(-/-) mice showed a deficit in their working memory, as revealed by a Y-maze test, and had an increased anxiety, as demonstrated by the elevated plus-maze test. CONCLUSION: Midkine plays an important role in the regulation of postnatal development of the hippocampus.

Animals↗
PubMed1998

Case report: Metachronous early gastric carcinoma in a reconstructed gastric tube after radical operation for oesophageal carcinoma.

The incidence of double cancer has increased as a result of the significant advances in both diagnostic procedures and anti-cancer therapy, and as the outcome of oesophageal squamous cell carcinoma (ESCC) has improved, the number of cases of double cancer of the oesophagus and stomach has also increased. Two patients with metachronous early gastric carcinoma in a reconstructed gastric tube were successfully treated after subtotal oesophagectomy for ESCC. These cases have shown that early diagnosis of second cancer is very important for curative therapy.

Adenocarcinoma↗
PubMed1998

Ovarian mucinous cystadenocarcinoma with malignant mural nodules.

A case of ovarian mucinous cystadenocarcinoma with malignant mural nodules is reported. The patient was a 28-year-old Japanese female (gravida 0, para 0) with a 2 year history of increasing abdominal fullness and edema of the lower extremity. Physical examination showed a large mass in the abdomen. An abdominal ultrasound and computed tomography demonstrated a multilocular cyst with a solid component. Lymph node and distant metastases were not found. These tests were followed by surgery. The resected right ovarian tumor measured 25 x 22 x 18 cm. On cut sectioning, it was multilocular with multiple mural nodules. Microscopically, the cyst wall was lined with papillary infoldings of atypical mucinous epithelium (intestinal type). Nuclear stratification, cribriform and back-to-back glandular patterns and stromal invasion were observed. In addition, the solid area of the mural nodules showed spindle or polygonal cells with increased mitotic activity including atypical mitoses. Nuclear pleomorphism was marked. Necrosis and hemorrhage were also present. Reticulin stain showed these pleomorphic cell clusters circumscribed by reticulin fibers and these cells were immunoreactive for vimentin and p53.

Adult↗
PubMed1998

Papillary squamous cell carcinoma of the uterine cervix: diagnostic pitfalls.

A case of papillary squamous cell carcinoma (PSCC) of the uterine cervix is reported. The patient was a 73-year-old Japanese woman with acute renal failure and bilateral hydronephrosis. A cauliflower-like mass was found in the uterine cervix. A uterine cervical biopsy specimen revealed PSCC in situ, while clinically it was an invasive carcinoma. Uterine cervical biopsy was performed a second time to confirm its stromal invasion. However, only small fragments were obtained because of heavy bleeding from the tumor and they showed PSCC in situ again. Following this, computed tomography of the pelvis revealed a 5 cm mass in the uterine cervix, invading the vagina and urinary bladder. Though deep-wedge biopsy, loop electrosurgical excision, or cone biopsy is recommended to evaluate PSCC, it may be impossible to perform any of these procedures because of bleeding such as that seen in our case. In these circumstances, good communication between pathologists and clinicians is important since lack of communication may cause PSCC to be microscopically misinterpreted as in situ carcinoma rather than invasive carcinoma.

Aged↗
PubMed1998

Mutational analysis of superantigen activity responsible for the induction of skin erythema by streptococcal pyrogenic exotoxin C.

Streptococcal pyrogenic exotoxin C (SPEC), when injected intradermally, induces erythema in unsensitized rabbits. In the present study, we examined whether this erythema induction is due to the T-cell stimulatory activity of SPEC as a superantigen. Analysis by using single-residue mutant SPECs indicated that mutant SPECs Y15I, A16E, and Y17I, in which tyrosine 15, alanine 16, and tyrosine 17 were replaced with isoleucine, glutamic acid, and isoleucine, respectively, exhibited significantly reduced mitogenic activity for Vbeta2(+) human T cells in vitro, and Y15I showed as much as a 1, 000-fold reduction. Y15I mutant SPEC, however, retained the ability to bind to major histocompatibility complex class II antigen and to form a homodimer, implying that residue 15 is critically important for the interaction of SPEC with T-cell antigen receptor beta chains. When injected intradermally into normal rabbits, wild-type SPEC induced a characteristic erythema after 3 h in a dose-dependent fashion, which was associated with polymorphonuclear and mononuclear cell infiltration. This erythema formation was found to be severely suppressed by systemic pretreatment with cyclosporin A, suggesting the involvement of host T cells. Y15I mutant SPEC exhibited nearly 1, 000-fold less erythema induction in vivo than wild-type SPEC. Altogether, the present results strongly suggest that erythema induction in rabbits by SPEC is attributable mostly to its T-cell stimulatory activity as a superantigen.

Amino Acid Sequence↗
PubMed1998

Sequence-based diagnosis of tyrosinase-related oculocutaneous albinism: successful sequence analysis of the tyrosinase gene from blood spots dried on filter paper.

BACKGROUND: A large number of mutations of the tyrosinase gene result in oculocutaneous albinism (OCA). Therefore, at present, sequence analysis of the tyrosinase gene has become necessary to diagnose OCA patients and their relatives. OBJECTIVE: The aim of this study was to facilitate the sequence-based diagnosis of tyrosinase-related OCA by using small amounts of the patient's blood. METHODS: Blood spots dried on filter papers were used as sources of genomic DNA. The exons and flanking regions of the tyrosinase gene were amplified by polymerase chain reaction (PCR) and were directly sequenced in both directions. RESULTS: We successfully amplified all exons of the tyrosinase gene by PCR and were able to characterize compound heterozygous mutations of R278X and + delta C310 in the patient's gene. CONCLUSION: Recent advances of PCR-related technology allowed us to use fairly limited samples of blood for sequence analysis of the tyrosinase gene.

Albinism, Oculocutaneous↗