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Biomedical subjects

Y Haraguchi

Publications and source records attributed to Y Haraguchi.

At least 37 records · Page 2Linked to original sources
PubMed1998

Identification of the chemokine receptor TER1/CCR8 expressed in brain-derived cells and T cells as a new coreceptor for HIV-1 infection.

We have isolated HIV-1 variants that infect brain-derived CD4-positive cells, which are resistant to both macrophage (M)-tropic and T-cell line (T)-tropic HIV-1 strains. It is possible that this brain cell tropism of the HIV-1 variants is determined by the interaction of HIV-1 with a chemokine receptor (CKR) gene. We attempted to detect the expression of the CKR-like genes using degenerate PCR primers. The brain-derived cells expressed a CKR-like gene TER1/CCR8. Human CD4-expressing cells resistant to all HIV-1 strains became susceptible to brain-cell tropic HIV-1 variants after expression of TER1 in these cells, but these cells were still resistant to M-tropic strains or T-tropic IIIB strain. TER1 was expressed in brain-derived cells and human T-cells. These findings suggest that TER1/CCR8 functions as a co-receptor for HIV-1 infection for brain-derived cells as well as T cells.

Brain↗
PubMed1998

Features of early gastric cancer detected by modern diagnostic technique.

To ascertain how the clinicopathologic features of early gastric cancer detected by current diagnostic tools had changed clinical features, we compared 711 early gastric cancer patients with 933 advanced gastric cancer patients regarding age, sex, and tumor location. We found that the proportion of early gastric cancer cases did not change according to age. However, the proportion of early gastric cancer cases in the proximal part was significantly lower than that observed in the distal part (p < 0.01). We conclude that recent diagnostic improvements have rendered age no longer a major deterrent for early detection of gastric cancer. However, a careful examination of the proximal stomach is called for because it is so hard to detect small lesions in that area.

Adult↗
PubMed1997

Inhibition of plating of human T cell leukemia virus type I and syncytium-inducing types of human immunodeficiency virus type 1 by polycations.

We examined the effects of polycations, namely, diethylaminoethyl-dextran (DEAE-dextran) and hexadimethrine bromide (Polybrene), on infection with the retroviruses human T cell leukemia virus types I and II (HTLV-I and HTLV-II) and human immunodeficiency virus type 1 (HIV-1). The plating of vesicular stomatitis virus (VSV) pseudotype bearing envelope antigens of HTLV-I [VSV(HTLV-I)] was inhibited about 2- and 10-fold by treatment with DEAE-dextran and Polybrene, respectively. The formation of HTLV-I viral DNA detected 1 day after infection was also inhibited by these polycations. In contrast, polycations enhanced the plating of the VSV (HTLV-II) pseudotype two- to threefold. The polycations did not affect the plating efficiency of HTLV-I or HTLV-II when added after virus adsorption. Infection of human T cell lines, peripheral blood lymphocytes (PBLs), or brain-derived cells with syncytium-inducing (SI) types of HIV-1 strains (GUN1 and IIIB) was inhibited 3- to 20-fold by polycations. However, infection of PBLs or monocyte-derived macrophages with the macrophage-tropic Ba-L or SF162 strain was enhanced 1.5- to twofold by polycations. On the other hand, syncytium formation in coculture induced by HTLV-I, HTLV-II, or HIV-1 was enhanced two- to threefold unanimously by DEAE-dextran or Polybrene. Although polycations have been used to potentiate human retrovirus adsorption, they inhibited infection of cell-free HTLV-I or SI-type HIV-1 strains.

Animals↗
PubMed1997

Evolutionary pattern of intra-host pathogen antigenic drift: effect of cross-reactivity in immune response.

Several viruses are known to change their surface antigen types after infecting a host, thereby escaping the immune defence and ensuring persistent infection. In this paper, we theoretically study the pattern of intra-host micro-evolution of pathogen antigen variants under the antigen specific immune response. We assume that the antigen types of the pathogen can be indexed in one-dimensional space, and that a mutation can produce a new antigen variant that is one step distant from the parental type. We also assume that antibodies directed to a specific antigen can also neutralize similar antigen types with a decreased efficiency (cross-reactivity). The model reveals that the pattern of intra-host antigen evolution critically depends on the width of cross-reactivity. If the width of cross-reactivity is narrower than a certain threshold, antigen variants gradually evolve in antigen space as a travelling wave with a constant wave speed, and the total pathogen density approaches a constant. In contrast, if the width of cross-reactivity exceeds the threshold, the travelling wave loses stability and the distribution of antigen variants fluctuates both in time and in genotype space. In the latter case, the expected episodes after infection are a series of intermittent outbreaks of pathogen density, caused by distantly separated antigen types. The implication of the model to intra-host evolution of equine infectious anaemia virus and human immunodeficiency virus is discussed.

Animals↗
PubMed1997

Endoscopic submucosal tumorectomy for gastrointestinal submucosal tumors restricted to the submucosa: a new form of endoscopic minimal surgery.

BACKGROUND: Endoscopic minimally invasive therapy for submucosal tumors of the gastrointestinal tract by use of endoscopic ultrasound has not yet come into widespread use, and this technique has not been fully evaluated. We therefore investigated this method of treatment in patients with gastrointestinal submucosal tumors. METHODS: Forty-five patients with suspected gastrointestinal submucosal tumors (esophagus [5], stomach [1], duodenum [16], colon [23]) based on barium enema studies and endoscopy underwent endoscopic ultrasound by the water-filled or balloon method. The layer of origin and the internal echogenicity of the lesions were evaluated. After confirming that the tumors were submucosal, the lesions were resected using injection of physiological saline solution and electrocautery. RESULTS: Using a one-channel or two channel method, all tumors were completely resected without serious complications and the diagnosis was histologically confirmed. Ulceration at the site of resection healed within 2 to 4 weeks (mean 23 days) and there has been no local recurrence. CONCLUSIONS: Our technique of endoscopic submucosal tumorectomy appears to be a safe and useful diagnostic-cum-therapeutic procedure for gastrointestinal submucosal tumors.

Adult↗
PubMed1996

Host-parasite arms race in mutation modifications: indefinite escalation despite a heavy load?

If constantly changing genotypes are favorable in host and parasite coevolution, an indefinite escalation of mutation rates would result despite heavy mutational loads. We theoretically study this possibility by examining the mutation modifier dynamics of host and parasite that engage in genotype-specific epidemiological interaction. In the first model, we study the evolutionarily stable (ESS) mutation rate or switching rate if two alleles in a single locus are subjected to frequency-dependent selection favoring the rarer of the two. Mutation modifier locus is either tightly linked or unlinked to the selected locus. Sufficiently strong frequency-dependent selection may cause cycles in allele frequencies and a modifier with higher mutation rate enjoys the long-term advantage by randomizing the genotype of their offspring. Through the repeated events of invasion and replacement of mutation modifiers, the mutation rate continues to increase until the allele frequencies are stabilized. If some fraction of mutations are deleterious, there is no longer a pure ESS mutation rate: the evolutionarily stable population then consists of multiple strains concerning mutation modifier, typically one with a very high mutation rate and the other with a very low rate, stably coexisting and fighting off invasion by any other modifiers. These results are almost independent of the linkage between the selected and the modifier loci. In the second model, we consider the joint evolution of host and parasite mutation modifiers, assuming that a specific pair of host and parasite genotype densities change following the Nicholson-Bailey type model. If there is no cost of deleterious mutations, mutation rates of both species are escalated indefinitely by modifier evolution until they completely suppress the fluctuation of genotype densities. However, a small cost of deleterious mutation is enough to collapse this coevolutionary equilibrium of inflated mutations. Typical coevolutionary outcome is that the parasite mutation rate is accelerated to a high level; whereas the host mutation rate is driven to zero. Extension of our results to host-parasite coevolution of recombination modifier evolution is discussed.

Animals↗
PubMed1996

Immunohistochemical expression of sialyl Tn, sialyl Lewis a, sialyl Lewis a-b-, and sialyl Lewis x in primary tumor and metastatic lymph nodes in human gastric cancer.

Sialyl Lewis Tn(STN), sialyl Lewis a(CA-9-9), sialyl Lewis a-b-(DU-PAN-2), and sialyl Lewis x(SLX) antigens were immunohistochemically examined in the primary tumor and metastatic lymph nodes in 35 patients with advanced gastric cancer. STN, CA-19-9, DU-PAN-2, and SLX were expressed in 91%, 60%, 31%, and 60% in the primary lesion, and 77%, 54%, 22%, and 51% in the metastatic lesion, respectively. In only four cases, (11%) were all four antigens expressed in both the primary and metastatic lesions. Three antigens were expressed in 49% of primary lesions and in 20% of metastatic lesions. Compared with expression in primary lesions, increased, unchanged and decreased expressions in metastatic lesions were noted in 23%, 37%, and 40% for STN, 20%, 40%, and 40% for CA-19-9, 17%, 57%, and 26% for DU-PAN-2, and 26%, 31%, and 43% for SLX, respectively. These results indicate that the tumor in the primary and metastatic lesions has a heterogeneous expression of sialyl-related antigens. However, metastases cannot be predicted based upon the expression of these antigens.

Adult↗
PubMed1996

Laparoscopic approach to incarcerated inguinal hernia.

The safety and effectiveness of laparoscopic treatment for incarcerated inguinal hernia have not been clarified. Six patients who underwent laparoscopic reduction and repair of incarcerated inguinal hernias were reviewed retrospectively. All operations were initiated within 1 h after establishment of the diagnosis. Laparoscopically, the incarcerated small-bowel segments could be easily returned to the abdominal cavity by a combination of pulling them with Babcock forceps while pushing back the bowels from outside the abdominal wall. The hernial portals were not cut in three patients, while they were dissected in the other three. All incarcerated bowels were congested and red immediately after reduction; however, their color returned to normal during hernia repair and unnecessary bowel resection was therefore avoided. The mean operation time was 88 min. Although one patient underwent laparotomy because of the suspicion of necrosis of the incarcerated inguinal hernia, which was finally found to be due to postoperative paralytic ileus, the postoperative courses of the remaining five were uneventful. Laparoscopic reduction and repair of incarcerated inguinal hernia was useful, and unnecessary bowel resection could be avoided.

Adult↗
PubMed1996

Inhibition of human immunodeficiency virus type 1 infectivity by a new amine bellenamine.

Bellenamine, (R)-3,6-diamino-N-(aminomethyl)hexanamide (molecular weight 174), produced by Streptomyces nashvillensis, which has been reported to have weak antibacterial activity and to slightly enhance the immune response, showed potent activity against human immunodeficiency virus type 1 (HIV-1). Its mode of action was investigated. Bellenamine inhibited de novo infection of human T cells with HIV-1, at a 50% effective concentration (EC50) of 0.62 micrograms/ml (3.6 microM). Its 50% cytotoxic concentration (CC50) was over 2000 micrograms/ml (11.5 mM) and thus its cytotoxicity was quite low. When HIV-1-infected cells were treated with bellenamine or glycosylation inhibitors, they produced virus with reduced infectivity, and thus bellenamine inhibited the secondary spread of HIV-1 in vitro similarly to glycosylation inhibitors. However, bellenamine did not change the apparent molecular weights of env or gag proteins, unlike glycosylation inhibitors. Bellenamine showed no significant activity against virus adsorption, reverse transcriptase, viral protease or the glycosylation process. The antiviral mechanism of bellenamine remains to be examined further.

Antiviral Agents↗
PubMed1996

Sulfated colominic acid: an antiviral agent that inhibits the human immunodeficiency virus type 1 in vitro.

Colominic acid is a homopolymer of N-acetylneuraminic acid (NANA), which has an alpha-2,8 ketosidic linkage between its polymer units. In this study, colominic acids were sulfated under different conditions and their antiviral activities against human immunodeficiency virus type 1 (HIV-1) were examined. Sulfated colominic acids, containing 6-12% sulfur, blocked the expression of HIV-1 antigen in MT-4 cells or C8166 cells following exposure to MOLT-4/HTLV-IIIB or HIV-1[GUN-1]. The compounds inhibited syncytium formation upon co-cultivation of MOLT-4 cells (clone 8) with MOLT-4/HTLV-IIIB cells and abolished the production of HIV-1 p24 antigen in culture medium of peripheral blood lymphocytes (PBLs). HIV-1 reverse transcriptase (RT) activity was not directly affected by the drugs. The compounds did not prolong activated partial thromboplastin time (APTT) at 10 and 1.0 microgram/ml, suggesting that they may not have appreciable side effects in vivo. These agents were still able to block the expression of HIV-1 antigen even when the cells were infected with HIV-1 in RPMI-1640 medium containing high percentages of fetal calf serum (FCS). These properties may be therapeutically advantageous if these compounds were considered for possible clinical use.

Anti-HIV Agents↗
PubMed1996

Extramedullary plasmacytoma of the jejunum.

A case of extramedullary plasmacytoma (EMP) of the jejunum, an uncommon neoplasia, is reported. A 56-year-old Japanese woman who experienced intermittent upper abdominal pain and weight loss had a large movable mass in the upper abdomen. The mass was hypervascular in an angiographic study and positive for gallium-67 citrate scintigraphy. Immunoelectrophoresis showed the presence of an M-component of immunoglobulin (Ig) A-lambda in the serum. It was identified as an EMP immunohistochemically positive for IgA-lambda. This M-component disappeared after resection and chemotherapy. The clinical features of this rare neoplastic disorder are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Flow cytometric analysis of DNA heterogeneity in superficial carcinoma of the esophagus.

BACKGROUND: There are few studies of flow cytometric analysis for DNA heterogeneity of patients with superficial carcinoma of the esophagus limited to the epithelium or superficially invading the lamina propria or submucosa. METHODS: Flow cytometric analysis of cellular DNA content was performed on superficial carcinomas of the esophagus using paraffin embedded blocks of the surgically resected specimens from 56 patients. To evaluate the intratumoral DNA heterogeneity, a total of 141 samples of the 56 tumors were analyzed, depending upon the tumor size. RESULTS: One or two of the samples was available from 18 of 19 patients with tumors 2 cm or less in greatest dimension, whereas more than three of the samples were available from 22 of 37 patients with tumors 2.1 cm or greater in dimension (P < 0.003). Of 56 tumors, 40 (71.4%) exhibited DNA aneuploidy; DNA heterogeneity was found in 26 tumors (46.4%). The remaining 16 tumors exhibited DNA diploidy. Two of the five tumors that were limited to the epithelium had DNA heterogeneity. The mean dimension of the tumors with DNA heterogeneity was significantly greater (5.8 +/- 2.8 cm) than those exhibiting DNA diploidy (2.3 +/- 1.1 cm) and DNA aneuploidy without heterogeneity (2.9 +/- 2.4 cm). Recurrences after esophagectomy were detected in 6 of the 56 patients; the DNA ploidy pattern of these six patients exhibited DNA heterogeneity. CONCLUSION: The incidence of DNA heterogeneity increases as tumor size increases and is associated with an increased risk of tumor recurrence after esophagectomy in patients with superficial carcinoma of the esophagus.

Adult↗
PubMed1995

Correlation between tumor volume doubling time and histologic findings in gastric smooth muscle tumors: clinical implications of tumor volume doubling time.

To assess the clinical implications of the tumor volume doubling time of gastric smooth muscle tumors based on a comparison with the histologic findings, seven tumors (four leiomyomas and three leiomyosarcomas) were followed up by consecutive upper gastrointestinal studies between March 1985 and December 1993. The patients were four men and three women with an average age of 58 years (range: 50-71 years). The observation period ranged from 6 to 51 months, with an average of 35 months. All tumors were surgically resected and the histologic diagnosis was confirmed. The following microscopic features were evaluated: 1) mitotic rate, 2) nuclear atypia, and 3) cellularity. Each tumor was also evaluated for the presence or absence of necrosis, hemorrhage, and degeneration. The doubling time ranged from 5 to 27 months with a mean of 16 months. There was a strong negative correlation between the mitotic rate and the doubling time (r = -0.935, P = 0.0019). The doubling time was also significantly related to nuclear atypia, but the number of tumors studied was so small that its reliability was questionable. The doubling time was not related to any other histologic findings. This study shows that the doubling time is useful for estimating the malignant potential of gastric smooth muscle tumors, and that tumors with a doubling time of 16 months or less should be considered as malignant.

Aged↗
PubMed1995

Natural history of minute sessile colonic adenomas based on radiographic findings. Is endoscopic removal of every colonic adenoma necessary?

PURPOSE: With the development of colonoscopy and double-contrast barium enema, detection of minute sessile colonic adenomas has increased. We evaluated progression of these lesions radiologically and attempted to clarify the natural history. METHODS: A total of 125 minute sessile adenomas (< or = 5 mm in size) with histologic confirmation were examined by double-contrast barium enema at an interval of more than one year. The average follow-up period was 24 (range, 12-36; standard deviation, 9.4) months. To allow for differences in magnification, adenomas increasing in size by 2 mm or more were defined as growing, and the other lesions were defined as unchanged. RESULTS: Eighty-six adenomas showed no interval change in size. Four adenomas decreased 1 mm in size, and 27 adenomas increased 1 mm in size. The remaining eight adenomas (6 percent) increased by 2 or 3 mm in size. None of the adenomas showed any morphologic changes. There was also no difference in degree of histologic atypia between growing and unchanged adenomas. None of the adenomas developed into carcinomas during the follow-up period. CONCLUSIONS: These data show that most minute sessile adenomas remain unchanged in size and morphology over the long term. Accordingly, these adenomas probably should be followed up radiologically or endoscopically to avoid excessive polypectomy.

Adenoma↗