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Biomedical subjects

K Honjo

Publications and source records attributed to K Honjo.

At least 19 recordsLinked to original sources

Perceived importance of being thin and smoking initiation among young girls.

BACKGROUND: Smoking among adolescents remains unacceptably high and the difference in potential risk factors for smoking initiation between male and female adolescents has been explored. Although the association between smoking initiation and dieting behaviour has been observed among girls, the mechanism of the association is unknown. OBJECTIVE: To examine prospectively the association between perceived importance of being thin at baseline and smoking initiation among girls. DESIGN: A four year prospective cohort survey including perceived importance of being thin at baseline and smoking behaviour, conducted in 1993 and 1996. SETTING AND PARTICIPANTS: 273 Massachusetts female adolescents aged 12-15 years at baseline who reported having smoked no more than one cigarette by the time of the baseline survey, drawn from households sampled by random digit dialing. MAIN OUTCOME MEASURE: Progression to established smoking, defined as having smoked 100 or more cigarettes in their lifetime. RESULTS: After adjusting for age, smoking status at baseline, and race/ethnicity, girls who valued thinness most strongly and somewhat strongly were both more likely to have become established smokers, compared to the girls who valued thinness least strongly. The odds ratios are 4.5 (95% confidence interval (CI), 1.4 to 16.7) and 3.4 (95% CI 1.04 to 10.9), respectively. CONCLUSIONS: The level of perceived importance of being thin among young female adolescents predicts future smoking initiation. Smoking prevention programmes designed for female adolescents may therefore benefit from the inclusion of content related to importance of being thin.

Adolescent↗

Four subunit a isoforms of Caenorhabditis elegans vacuolar H+-ATPase. Cell-specific expression during development.

We have identified four genes (vha-5, vha-6, vha-7, and unc-32) coding for vacuolar-type proton-translocating ATPase (V-ATPase) subunit a in Caenorhabditis elegans, the first example of four distinct isoforms in eukaryotes. Their products had nine putative transmembrane regions, exhibited 43-60% identity and 62-84% similarity with the bovine subunit a1 isoform, and retained 11 amino acid residues essential for yeast V-ATPase activity (Leng, X. H., Manolson, M. F., and Forgac, M. (1998) J. Biol. Chem. 273, 6717-6723). The similarities, together with the results of immunoprecipitation, suggest that these isoforms are components of V-ATPase. Transgenic and immunofluorescence analyses revealed that these genes were strongly expressed in distinct cells; vha-5 was strongly expressed in an H-shaped excretory cell, vha-6 was strongly expressed in intestine, vha-7 was strongly expressed in hypodermis, and unc-32 was strongly expressed in nerve cells. Furthermore, the vha-7 and unc-32 genes were also expressed in the uteri of hermaphrodites. RNA interference analysis showed that the double-stranded RNA for unc-32 caused embryonic lethality similar to that seen with other subunit genes (vha-1, vha-4, and vha-11) (Oka, T., and Futai, M. (2000) J. Biol. Chem. 275, 29556-29561). The progenies of worms injected with the vha-5 or vha-6 double-stranded RNA became died at a specific larval stage, whereas the vha-7 double-stranded RNA showed no effect on development. These results suggest that V-ATPases with these isoforms generate acidic compartments essential for worm development in a cell-specific manner.

Amino Acid Sequence↗

Inferior phrenic arteries: depiction with thin-section three-dimensional contrast-enhanced dynamic MR imaging with fat suppression.

The purpose of this study was to evaluate visibility of the inferior phrenic arteries in normal subjects at thin-section, multiphasic, three-dimensional (3D) contrast-enhanced dynamic magnetic resonance (MR) imaging with fat suppression, and to compare the appearances and frequencies of MR visualization of these vessels between normal and cirrhotic patients. This study included 95 patients (44 normal and 51 cirrhotic patients) who underwent 3D contrast-enhanced dynamic imaging on a high-performance gradient (25 mT/m) system as a part of abdominal MR examinations. The right and left inferior phrenic arteries were visible in 84% and 73% of the normal subjects, respectively. The averaged rating for visibility in the right inferior phrenic artery was significantly greater in the cirrhotic patients than in the normal subjects (2.1 +/- 0.1 vs. 1.7 +/- 0.2; P = 0.040). Mean diameters of the right inferior phrenic artery in the cirrhotic patients (1.7 +/- 0.1 mm) were significantly larger (P = 0.002) than those in the normal subjects (1.3 +/- 0.1 mm). No significant difference was noted in the mean diameters and the visibility of the left inferior phrenic artery between the two groups. The inferior phrenic arteries can frequently be identified on thin-section, 3D contrast-enhanced arterial-phase dynamic MR images with fat-suppression techniques. Dilatation of the right inferior phrenic artery depicted by this technique may be a nonspecific but an additional secondary finding suggestive of cirrhosis.

Adult↗

Sequence heterogeneity of the ten rRNA operons in Clostridium perfringens.

We have cloned and sequenced rRNA operons of Clostridium perfringens strain 13 and analyzed the sequence structure in view of the phylogenesis. The organism had ten copies of rRNA operons all of that comprised of 16S, 23S and 5S rDNAs except for one operon. The operons clustered around the origin of replication, ranging within one-third of the whole genome sequence as it is arranged in a circle. Seven operons were transcribed in clockwise direction, and the remaining three were transcribed in counter clockwise direction assuming that the gyrA was transcribed in clockwise direction. Two of the counter clockwise operons contained tRNA(Ile) genes between the 16S and 23S rDNAs, and the other had a tRNA(Ile) genes between the 16S and 23S rDNAs and a tRNA(Asn) gene in the place of the 5S rDNA. Microheterogeneity was found within the rRNA structural genes and spacer regions. The length of each 16S, 23S and 5S rDNA were almost identical among the ten operons, however, the intergenic spacer region of 16S-23S and 23S-5S were variable in the length depending on loci of the rRNA operons on the chromosome. Nucleotide sequences of the helix 19, helix 19a, helix 20 and helix 21 of 23S rDNA were divergent and the diversity appeared to be correlated with the loci of the rRNA operons on the chromosome.

Base Sequence↗

Heterogeneity of T cell clones specific for a single indirect alloantigenic epitope (I-Ab/H-2Kd54-68) that mediate transplant rejection.

BACKGROUND: One of the complexities of solid organ allograft rejection is the inherent diversity of the specific T cell antigenic epitopes that participate in this response, including the role of direct alloantigen recognition and indirect recognition of donor-derived peptides in recipient antigen-presenting cells. To probe the role of distinct T cell receptor (TCR) avidity differences and the role of cytokine expression patterns of different effector T cells that may participate in allograft rejections, we have identified a dominant allopeptide derived from the H-2Kd molecule, recognized by H-2b CD4 T cells in the context of syngeneic I-Ab. METHODS: To identify a stimulatory peptide derived from the H-2Kd molecule, a panel of synthetic overlapping peptides was screened for immunogenicity and a panel of T cell clones established. These clones were characterized for TCR Vbeta usage by mAb staining and/or reverse transcribed-polymerase chain reaction analysis, peptide dose sensitivity as a marker of TCR avidity, cytokine expression phenotype in vitro, and their ability to mediate rejection of a vascularized cardiac allograft after adoptive transfer to immunodeficient mice. RESULTS: The H-2Kd54-68 peptide was identified as a dominant stimulatory peptide by the ability of T cells from C57BL/6 (H-2b) mice primed by a combination of allogeneic spleen cell injection and mixed peptide immunization to mount an in vitro proliferative response and interferon-gamma production by peptide stimulation. Furthermore, direct immunization with synthetic H-2Kd54-68 peptide of normal C57BL/6 mice resulted in accelerated rejection of both skin and cardiac allografts from B10.D2 (H-2d) mice, but not 3rd party B10.BR (H-2k) grafts. A panel of 15 distinct CD4+ clones specific for H-2Kd54-68 peptide were established and shown to utilize a variety of TCR Vbeta and different apparent TCR avidities to H-2Kd54-68 peptide when stimulated in vitro. To characterize these clones further, two clones were chosen based on the difference of avidity to H-2Kd54-68 peptide. The cytokine expression pattern was determined and indirect alloantigen specificity confirmed by analysis of responses to purified peptide and B10.D2 spleen cells using normal H.2b and I-Abeta chain knockout mice as APC donors. Both of these T cell clones were able to mediate rejection of B10.D2, but not B10.BR hearts, in immunodeficient mice, but the morphological pattern of T cell infiltration was distinct. CONCLUSIONS: These results demonstrate the potential importance of fine dissection of the alloantigeneic response to solid organ transplants and provide unique insights into the role of TCR avidity and cytokine expression patterns in different morphological patterns of transplant rejection.

Animals↗

Immunopathological study on the development of swine serum-induced bile duct lesions in BALB/c and DBA/2 mice.

To compare the difference in the development of swine serum (SS)-induced bile duct lesion (BDL) between high responder BALB/c and low responder DBA/2 mice, the mice of both strains injected with SS twice a week for up to 4 weeks were killed and examined immunopathologically after the 2nd, 4th, 6th and 8th SS-injection, respectively. In BALB/c mice, BDL developed rapidly following the SS-injections, and a slight enlargement of common bile ducts accompanied with infiltration of T helper cells and eosinophils was detected after the 2nd SS-injection. From the 4th injection on, BDL was characterized by proliferation of mucous glands, hyperplasia and hypertrophy of biliary and glandular epithelial cells, periductal fibrosis, infiltration of eosinophils, plasma cells and T helper cells, and increase of mast cells, resulting in more apparent enlargement of common bile ducts. Several hypertrophied biliary and glandular epithelial cells were positive for mouse immunoglobulins and SS. BDL subsided after cessation of the SS-treatment. On the other hand, in DBA/2 mice, immune response and inflammatory reaction were very weak, and only slight BDL were detected.

Animals↗

Effects of market liberalisation on smoking in Japan.

OBJECTIVE: To document the effect of the liberalisation of the Japanese tobacco market on Japanese smoking rates and on Japanese tobacco industry practices. DATA SOURCE: Asahi Shimbun (major daily newspaper) from 1980 to 1996. STUDY SELECTION: Review of media coverage on the effects of market liberalisation following the imposition of the USA's section 301 trade sanction. DATA SYNTHESIS: The opening of Japan's tobacco market to foreign cigarette companies stalled a decline in smoking prevalence. Smoking rates among young women increased significantly, and also appear to be on the rise among adolescents. Aggressive marketing and promotional activities by US and Japanese tobacco companies in response to trade liberalisation appear responsible for these adverse trends. Steep increases in sales through vending machines were also possible contributors to the rising smoking prevalence among adolescents. On the positive side, market liberalisation indirectly promoted smoking control efforts in Japan, by causing an anti-smoking movement to coalesce. CONCLUSION: Market liberalisation in Japan played a significant role in increasing smoking prevalence among young women and adolescents while helping to transform the issue of smoking in Japan from a matter of individual choice to a public health problem.

Adolescent↗

Foreign serum-induced bile duct lesion (BDL) in athymic BALB/c nude mice.

To investigate a role of cellular immunity in foreign serum-induced bile duct lesion (BDL) in mice, athymic BALB/c nude (nu/nu) mice were intraperitoneally injected with swine serum (SS) twice a week up to 8 weeks and were compared with euthymic BALB/c heterozygote (nu/+) and wild-type (+/+) mice treated with SS in the same way for 4 weeks. All immunized nu/+ and +/+ mice developed marked BDL, and their sera showed high anti-SS IgE and IgG1 antibody titers, whereas no immunized nu/nu mice developed lesions, and their sera showed no elevation of antibody titers. Next, nu/nu mice were reconstituted with splenocytes derived from nu/+ mice, and then were intraperitoneally injected with SS twice a week for 3 weeks. Most of the reconstituted nu/nu mice developed BDL, and their sera showed the elevation of anti-SS IgE and IgG antibody titers. These results suggest that cellular immunity may play a pivotal role in the pathogenesis of swine serum-induced BDL.

Adoptive Transfer↗

The evidence for tonic GABAergic regulation of basal L-DOPA release via activation of inhibitory GABA(A) receptors in the nucleus tractus solitarii of anesthetized rats.

We have proposed that DOPA is a neurotransmitter of the primary baroreceptor afferents terminating in the rat nucleus tractus solitarii (NTS). GABA is a putative inhibitory neuromodulator for baroreflex inputs in the NTS. Thus, GABA may inhibit DOPAergic transmission in the NTS. We tried to clarify whether basal DOPA release is inhibited by muscimol, a GABA(A) agonist, and facilitated by bicuculline, a GABA(A) antagonist, during microdialysis of the NTS in anesthetized rats. DOPA release was consistently detectable. Muscimol 10-100 microM perfused via probes gradually inhibited concentration-dependently DOPA release. Peak 30% inhibition occurred 2 h after perfusion. Muscimol (30 microM)-induced inhibition was antagonized by non-effective 10 microM bicuculline. Bicuculline (30 microM) elicited peak 30% facilitation of DOPA release 2 h after perfusion. Endogenous GABA seems to regulate tonically basal DOPA release via activation of inhibitory GABA(A) receptors in the rat NTS. These findings further support the above proposal.

Anesthesia↗

GABA may function tonically via GABA(A) receptors to inhibit hypotension and bradycardia by L-DOPA microinjected into depressor sites of the nucleus tractus solitarii in anesthetized rats.

We have proposed that DOPA is a transmitter of the primary baroreceptor afferents terminating in the rat nucleus tractus solitarii (NTS). GABA is a putative inhibitory neuromodulator for baroreflex inputs in the NTS. GABA may inhibit DOPAergic transmission. Drugs were microinjected into depressor sites of the NTS in anesthetized rats. DOPA (10-60 ng) elicited dose-dependent depressor responses. GABA (3-300 ng) elicited dose-dependent pressor responses. Nipecotic acid (100 ng) elicited pressor responses. Bicuculline (10 ng) elicited depressor responses. Responses to DOPA (30 ng) were inhibited by pretreatment with GABA and nipecotic acid, but potentiated by bicuculline, when vascular responses to pretreated drugs returned to basal levels. DOPA ME, a competitive DOPA antagonist, did not displace specific [3H]GABA binding. Prior DOPA ME (1 microg) inhibited by one-half pressor responses to 300 ng GABA. GABA seems to inhibit tonically via GABA(A) receptors depressor responses to DOPA and to elicit pressor responses partially by inhibition of tonic function of endogenous DOPA to activate depressor sites in the NTS. These findings further support the above proposal.

Anesthesia↗

Detection of hepatocellular carcinoma: comparison of T2-weighted breath-hold fast spin-echo sequences and high-resolution dynamic MR imaging with a phased-array body coil.

The purpose of our study was to compare T2-weighted breath-hold fast spin-echo sequence (BHFSE) and high-resolution dynamic MR imaging (HR-DMRI) in the detection of hepatocellular carcinoma (HCC). Short and long T2-weighted BHFSE sequences and biphasic HR-DMRI including arterial-dominant and delayed phase images with a phased-array body coil were performed in 30 consecutive patients with 37 HCCs. The lesion-to-liver contrast-to-noise ratio (CNR) was quantitatively measured. The lesion conspicuity and delineation was qualitatively rated according to a four-point scale. The lesion-to-liver CNR was highest with the arterial-dominant phase HR-DMRI and was significantly higher than those obtained with both short and long T2-weighted BHFSE and those obtained with unenhanced and delayed HR-DMRI. The CNR obtained with short T2-weighted BHFSE was significantly higher than those obtained with long T2-weighted BHFSE and with unenhanced and delayed HR-DMRI. The sensitivity for the sequences was 78.4% (29/37) for short T2-weighted BHFSE, 67.6% (25/37) for long T2-weighted BHFSE, 37.8% (14/37) for unenhanced HR-DMRI, 97.3% (36/37) for arterial-dominant phase HR-DMRI, and 43.2% (16/37) for delayed HR-DMRI. The sensitivity of serial dynamic MR imaging combined with unenhanced, arterial-dominant phase imaging and delayed phase imaging was 100% (37/37). The score in the qualitative analysis of the lesion conspicuity and delineation was highest for the arterial-dominant phase HR-DMRI and was significantly higher than that for the short T2-weighted BHFSE. The score for the short T2-weighted BHFSE was significantly higher than that for the long T2-weighted BHFSE and that for the unenhanced HR-DMRI. Arterial-dominant phase HR-DMRI is superior to the T2-weighted BHFSE technique, and also HR-DMRI combined with unenhanced, arterial-dominant and delayed phases is the most sensitive technique in the detection of HCC.

Carcinoma, Hepatocellular↗

Process of carboxylation of glutamic acid residues in the gla domain of human des-gamma-carboxyprothrombin.

In the absence of vitamin K (VK) or in the presence of VK antagonists, hepatic VK-dependent carboxylase activity is inhibited and des-gamma-carboxyprothrombin (DCP) is released into the blood. We analyzed the number of glutamic acid (Glu) residues and their positions in the Gla domain (GD) of DCP to investigate the gamma-carboxylation mechanism of VK-dependent carboxylase. Several DCPs were found in each subject studied. The 10 Gla residues of human prothrombin were carboxylated in order from the N-terminal (residues 26, 25, 16, 29, 20, 19, 14, 32, 7 and 6). The process of Glu carboxylation seemed to proceed three-dimensionally from inside to outside the molecule.

Adult↗

Hepatocellular carcinoma: association with increased iron deposition in the cirrhotic liver at MR imaging.

PURPOSE: To determine whether the frequency of hepatocellular carcinoma (HCC) in patients with cirrhosis is affected by hepatic iron deposition as detected with magnetic resonance (MR) imaging. MATERIALS AND METHODS: In a retrospective search of MR imaging and histopathology records, 196 patients with histopathologically proved cirrhosis and with (n = 80) or without (n = 116) HCC who underwent T2-weighted conventional or fast spin-echo and gradient-echo (GRE) (echo time > or = 6.0 msec) imaging were identified. MR images were qualitatively and quantitatively evaluated for diffuse hepatic iron deposition and siderotic regenerative nodules to assess their correlation with the presence of HCC. RESULTS: Hepatic parenchymal iron deposition was seen in 79 (40%) patients, and iron deposition in regenerative nodules was seen in 71 (36%) at MR imaging. The mean signal intensity ratio of GRE images in patients with hepatic iron deposition was significantly lower than that in patients without it (P < .001). The frequency of HCC in patients with iron deposition in regenerative nodules (52% [37 of 71 patients]) was significantly higher (P = .015) than that in patients without iron in regenerative nodules (34% [43 of 125 patients]). CONCLUSION: The occurrence of HCC may be associated causally with iron deposition in regenerative nodules in patients with cirrhosis. MR imaging can enable detection of iron deposition in regenerative nodules as a possible risk factor for the development of HCC.

Adult↗

Viral-induced cirrhosis: grading of severity using MR imaging.

OBJECTIVE: The purpose of this study was to determine whether MR imaging can be used to grade the severity of cirrhosis. MATERIALS AND METHODS: The MR examinations of 46 patients with cirrhosis were retrospectively reviewed independently by two radiologists and correlated with clinical severity assessed by Child-Pugh classification. MR imaging analysis by reviewers who were unaware of clinical status included comparison of volume indexes (computed as the product of three axis measurements) of the spleen and each segment of the liver, and changes in hepatic contour, iron or fat deposition, and presence of varices and collaterals. RESULTS: Volume index of the spleen and the presence of ascites and varices were significantly and positively correlated (p = .008, .002, .0001, respectively) with the clinical severity of cirrhosis (Child-Pugh classifications), and volume indexes of the posterior, medial, and lateral segments of the liver were significantly and inversely correlated (p = .001, .049, .041, respectively). On an MR scoring system based on four items (volume index of the spleen; volume index of posterior + medial + lateral segments; presence of ascites; and presence of varices and collaterals), averaged total MR scores were 2.5 +/- 0.3, 4.9 +/- 0.6, and 7.9 +/- 0.8 for Child-Pugh grades A, B, and C, respectively (p < .0001). The accuracy of MR scoring in distinguishing between clinical Child-Pugh grade A cirrhosis and further grades was 89%, the sensitivity was 93%, and the specificity was 82%. CONCLUSION: An MR scoring system can be used to grade the severity of cirrhosis.

Contrast Media↗

[Outpatient chemotherapy with infusional 5-fluorouracil in advanced gastrointestinal cancer].

These studies were designed to evaluate the efficacy, toxicity, and resulting quality of life (QOL) of outpatient chemotherapy with infusional 5-FU for advanced gastrointestinal cancer. Schedule, sch. A: Treatment consisted of CI 5-FU 200 mg/m2/day, days 1-28, IVB Leucovorin 20 mg/m2 q week. Fifteen patients with advanced gastrointestinal cancer were treated to maintain the efficacy of prior inpatient chemotherapy. Twenty-one patients treated with adjuvant chemotherapy were added to evaluate toxicity and QOL. The mean time to progression (TTP) was 2.6 months. Grade 2 toxicities were seen, including mucositis (23%) and diarrhea (7%). Hand-foot syndrome was seen 60% of patients. The mean QOL score was 89.5 +/- 7.8. Sch.B: Treatment consisted of weekly 24 h infusion of 5-FU 2,600 mg/m2. 5-FU was administered using a Groshong catheter and Baxter infusor LV5 (5 ml/hr). Nine patients with advanced gastrointestinal cancer were treated. Twenty-one patients were treated with adjuvant chemotherapy. The mean TTP was 3.6 month. Grade 2 toxicities were seen, including leucocytopenia (7%), mucositis (3%), diarrhea (10%), and nausea and vomiting (10%). The mean QOL score was 82.6 +/- 10.7. In conclusion, both 5-FU schedules are feasible for outpatient chemotherapy for advanced gastrointestinal cancer.

Ambulatory Care↗

Splenic hamartoma presenting as a "hot spot" on Tc-99m phytate SPECT imaging.

The cases of two patients with surgically proven splenic hamartomas with "hot spots" on Tc-99m phytate SPECT imaging are presented. There was intense radiocolloid accumulation in the peripheral portion of a large single tumor in one patient, and in each of three isolated tumors in the other patient. The intense uptake might be related to the function of proliferated reticuloendothelial cells in the tumors. These unique findings were not clearly identified on the planar images.

Adult↗

Progressive viral-induced cirrhosis: serial MR imaging findings and clinical correlation.

PURPOSE: To determine which magnetic resonance (MR) imaging findings of cirrhosis change as disease severity progresses. MATERIALS AND METHODS: Seventy-six abdominal MR imaging studies in 38 patients (two per patient) with Child-Pugh grade A cirrhosis were retrospectively reviewed. All patients were followed up clinically and with MR imaging for 12 months or longer. MR images were used to determine volume indexes of the spleen and of each liver segment, as well as changes in hepatic contour, iron or fat deposition, and presence of varices and collateral vessels. RESULTS: During follow-up in patients with progressive cirrhosis (n = 13), the volume indexes of the anterior, posterior, and medial segments of the liver decreased significantly (P = .011, .013, .002, respectively), and the number of varices and collateral vessels increased significantly (P = .018). In patients with stable cirrhosis (n = 25), the volume indexes of the spleen, caudate lobe, and lateral segment increased significantly (P = .032, .018, .003, respectively). The atrophic index was significantly greater in progressive cirrhosis than in stable cirrhosis (P = .009). CONCLUSION: Progressive atrophy of the right hepatic lobe and the medial segment correlated with progression of clinical severity of cirrhosis, whereas increasing size of the caudate lobe and the lateral segment correlated with stability.

Adult↗

[Efficacy of multidirection MRCP].

Pancreatobiliary system has complex and thin structure except for gallbladder, thereby MRCP having lower spatial resolution gives sufficient information compared with the direct cholangiopancreatography. Multidirection MRCP using HASTE sequence obtains the data in plane to compensate the lower spatial resolution, thus high detectability of all over pancreatobiliary system is performed in a few minutes. This technique overcomes the demerits pointed by former investigators and gives sufficient information to diagnose the pancreatobiliary diseases.

Biliary Tract↗