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Biomedical subjects

S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 289 records · Page 16Linked to original sources

Which type of underlying disease facilitates cytomegalovirus infection? Comparison of benign disease, hematopoietic malignancy, and post-bone-marrow or renal transplantation status by using the first standardized objective PCR test for cytomegalovirus detection.

All immunocompromised hosts, such as infants, the elderly, patients with advanced cancer, and patients being treated with immunosuppressants, etc., are said to be more susceptible to cytomegalovirus (CMV) infection or CMV disease. However, we questioned the validity of this conclusion and attempted to detect CMV viremia in the plasma of subjects by using the AMPLICOR CMV test (Roche Diagnostics Systems, Branchburg, NJ), the first standardized PCR kit for CMV infection. One hundred healthy volunteers whose CMV IgG titer was < 4 and 100 healthy volunteers whose IgG titer for CMV was > or = 4 were studied. None of the subjects in either healthy group was positive for CMV viremia. Patients who were suspected of CMV infection were divided into four groups and tested: [1] 104 patients with benign disease, only one of whom was positive for CMV [2] 99 patients with hematopoietic malignancy who had not undergone bone marrow transplantation and all of whom were negative for CMV infection [3] 120 post-bone-marrow transplantation, 28 of whom were CMV positive, [4] 37 post-renal transplantation patients, 19 of whom were CMV positive. A statistically significant difference in CMV positivity was found by the non-parametric Kruskal-Wallis test (p < 0.0001) among the four disease group. CMV infection has been said to occur in all types of immunocompromised patients, however, based on our findings, we conclude that CMV infection tends to occur in post-transplantation status and does not tend to occur in patients with hematopoietic malignancy if they have not undergone transplantation.

Adult↗

Effects of antibiotic therapy on Pseudomonas aeruginosa-induced lung injury in a rat model.

The effect of antibiotics on the acute lung injury induced by virulent Pseudomonas aeruginosa PA103 was quantitatively analyzed in a rat model. Lung injury was induced by the instillation of PA103 directly into the right lower lobes of the lungs of anesthetized rats. The alveolar epithelial injury, extravascular lung water, and total plasma equivalents were measured as separate, independent parameters of acute lung injury. Four hours after the instillation of PA103, all the parameters were increased linearly depending on the dose of P. aeruginosa. Next, we examined the effects of intravenously administered antibiotics on the parameters of acute lung injury in D-galactosamine-sensitized rats. One hour after the rats received 10(7) CFU of PA103, an intravenous bolus injection of aztreonam (60 mg/kg) or imipenem-cilastatin (30 mg/kg) was administered. Despite an MIC indicating resistance, imipenem-cilastatin improved all the measurements of lung injury; in contrast, aztreonam, which had an MIC indicating sensitivity, did not improve any of the lung injury parameters. The antibiotics did not generate different quantities of plasma endotoxin; therefore, endotoxin did not appear to explain the differences in lung injury. This in vivo model is useful to quantitatively compare the efficacies of parenteral antibiotic administration on Pseudomonas airspace infections.

Animals↗

Depletion of alveolar macrophages by treatment with 2-chloroadenosine aerosol.

Alveolar macrophages (AMs) are localized in the alveoli and alveolar ducts of the lung and are the only macrophages living in an aerobic environment. Recent studies have demonstrated that AMs play a central role in lung diseases, such as pneumonia and acute respiratory distress syndrome. It has become important to find a simple, effective way to eliminate AMs in order to investigate the function of AMs in vivo. 2-Chloroadenosine (2-CA), a purine analog, is reported to be selectively cytotoxic to cultured macrophages, and we hypothesized that it would deplete the number of AMs in the bronchoalveolar lavage fluid (BALF) of mice without any effect on neutrophil or lymphocyte counts. After mice had inhaled 1 mM aerosolized 2-CA for 2 h, AMs were found to be significantly depleted at 0 h [(4.42 +/- 0.16) x 10(4)/ml], 24 h [(4.17 +/- 0.89) x 10(4)/ml], 48 h [(3.17 +/- 0.21) x 10(4)/ml], and 72 h [(5.00 +/- 0.64) x 10(4)/ml] compared with concentrations in untreated controls [(12.1 +/- 0.21) x 10(4)/ml]. Neutrophil and lymphocyte counts in BALF did not change and histological changes in the lung were not observed after 2-CA treatment. The lung wet-to-dry weight ratio did not change at 0, 24, and 48 h after 2-CA aerosol application. The 2-CA aerosol had no effect on lung vascular permeability, as assessed by the intravenous administration of Evans blue, or on other phagocytes, as assessed by Kupffer cell counts. Our study demonstrates the efficacy of 2-CA in reducing AM numbers in vivo.

2-Chloroadenosine↗

Identification of Vibrio parahaemolyticus strains at the species level by PCR targeted to the toxR gene.

The DNA colony hybridization test with the polynucleotide probe for Vibrio parahaemolyticus toxR gene was performed. All 373 strains of V. parahaemolyticus gave positive results, and the strains belonging to four other Vibrio species including Vibrio alginolyticus gave weakly positive results, suggesting that toxR sequence variation may reflect the phylogenetic relationships of Vibrio species. We then established a toxR-targeted PCR protocol for the specific detection of V. parahaemolyticus.

Bacterial Proteins↗

Purification and identification of p68 RNA helicase acting as a transcriptional coactivator specific for the activation function 1 of human estrogen receptor alpha.

The estrogen receptor (ER) regulates the expression of target genes in a ligand-dependent manner. The ligand-dependent activation function AF-2 of the ER is located in the ligand binding domain (LBD), while the N-terminal A/B domain (AF-1) functions in a ligand-independent manner when isolated from the LBD. AF-1 and AF-2 exhibit cell type and promoter context specificity. Furthermore, the AF-1 activity of the human ERalpha (hERalpha) is enhanced through phosphorylation of the Ser(118) residue by mitogen-activated protein kinase (MAPK). From MCF-7 cells, we purified and cloned a 68-kDa protein (p68) which interacted with the A/B domain but not with the LBD of hERalpha. Phosphorylation of hERalpha Ser(118) potentiated the interaction with p68. We demonstrate that p68 enhanced the activity of AF-1 but not AF-2 and the estrogen-induced as well as the anti-estrogen-induced transcriptional activity of the full-length ERalpha in a cell-type-specific manner. However, it did not potentiate AF-1 or AF-2 of ERbeta, androgen receptor, retinoic acid receptor alpha, or mineralocorticoid receptor. We also show that the RNA helicase activity previously ascribed to p68 is dispensable for the ERalpha AF-1 coactivator activity and that p68 binds to CBP in vitro. Furthermore, the interaction region for p68 in the ERalpha A/B domain was essential for the full activity of hERalpha AF-1. Taken together, these findings show that p68 acts as a coactivator specific for the ERalpha AF-1 and strongly suggest that the interaction between p68 and the hERalpha A/B domain is regulated by MAPK-induced phosphorylation of Ser(118).

Adenocarcinoma↗

Seasonal changes of human circadian rhythms in Antarctica.

The human circadian rhythms in sleep, activity, plasma melatonin, and rectal temperature were explored under two conflicting time cues in Antarctica: an extreme photoperiod and a strict work schedule. The nine healthy male subjects stayed at the Antarctic zone (latitude 66.5-90 degrees south) for 15 mo including a 13-mo wintering at the Dome station (latitude 77 degrees south). Neither the phases nor the amounts of sleep and daily activity underwent a seasonal change. On the other hand, the peak phase of melatonin rhythm was phase delayed by 4.1 h in winter compared with summer. When the analysis is limited to the Dome data, the seasonal difference was reduced to 1.3 h. Similarly the trough phase of rectal temperature rhythm in two of three subjects was phase delayed by approximately 2 h in winter. From these findings, the sleep or activity rhythm is concluded to be reset predominantly by the work schedule, whereas the circadian rhythm in plasma melatonin and rectal temperature is substantially influenced by the photoperiod.

Activity Cycles↗

Comparison of bone metabolic markers between maternal and cord blood.

We studied 41 normal pregnant women and their neonates in order to compare bone metabolism between them. We examined more specific bone formation markers (intact osteocalcin, bone-specific alkaline phosphatase) and a recently developed and more sensitive bone resorption marker (C-telopeptide of type I collagen; CTX) than previously available in maternal and umbilical cord venous blood taken at delivery. The concentrations of all markers of bone turnover, including CTX, in cord serum were significantly higher than those in maternal serum. There was no significant correlation between maternal and cord serum levels for any marker. These results indicate that fetal bone turnover is markedly enhanced compared with maternal bone turnover and is independent of maternal bone metabolism in late pregnancy.

Adolescent↗

Multilocular cystic adenomyoma of the pelvic cavity: A rare clinical and histological entity in a young man.

We report a large complex cystic pelvic mass encountered in a 16-year-old man complaining of perineal discomfort. A large and elastic hard mass was palpated on the right anterior wall of the rectum with no discernible prostate on digital rectal examination. Prostatic tumor markers were elevated. Excretory urography and urethrocystography showed a filling defect with a smooth edge on the right side of the bladder. Magnetic resonance imaging demonstrated a mass with a mosaic pattern between the right side of the bladder and the rectum. We performed ultrasound-guided transrectal needle core biopsy of the mass. The pathologist suspected hyperplastic glandular epithelium of prostatic origin with focal inflammatory cell infiltration, but there was no sign of malignancy. We thought that the tumor arose from the prostate. Surgery was successfully performed. The tumor was located on the right side of the pelvic cavity and adhered to the right lobe of the seminal vesicle. En bloc excision was performed. This lesion histologically proved to be a multilocular prostatic tissue with a seminal vesicle component, without communication to the surrounding tissue. Such a lesion has not previously been reported in the literature.

Adenomyoma↗

Characteristic cytokine products of Th1 and Th2 cells in hemodialysis patients.

Dysfunction of the host defense against infection in hemodialysis (HD) patients has major clinical and socioeconomic implications. T helper type 1 (Th1) and type 2 (Th2) cytokines are implicated in regulating the immune responses and, therefore, may be involved in impaired status. The present study was designed to examine Th1 and Th2 cytokine profiles in 22 stable HD patients (aged 63 +/- 11 years) and 22 healthy controls (aged 60 +/- 6 years). The T cell activity was significantly retarded in HD patients as compared with normal persons. The proportions of T cytotoxic/suppressor cells and natural killer cells were significantly higher in HD patients than in controls. In contrast, the proportions of T helper/inducer and B cells were significantly lower in HD patients than in controls. The production of interleukin (IL) 2, which is involved in cell-mediated immune responses, and the production of IL-4 and IL-10, which affect humoral immunity, were significantly lower in patients than in controls. The production of IL-12 by macrophages and of interferon gamma by Th1 cells was significantly higher in HD patients than in controls. The concentration of plasma sIL-2R was significantly higher in patients than in controls. These results suggest that both cellular immunity induced by Th1 and humoral immunity induced by Th2 decrease in HD patients, but that improved IL-12 secretion by macrophages activated natural killer cells to produce interferon gamma, which in turn induced macrophage activity.

Adult↗

Hyperosmolarity-induced interleukin-8 expression in human bronchial epithelial cells through p38 mitogen-activated protein kinase.

The changes in airway osmolarity have been described to contribute to the production of exercise- induced bronchoconstriction (EIB) and the development of the late-phase response (LPR). The mechanism has been investigated; however, the responsiveness of bronchial epithelial cells (BEC) to hyperosmolarity and the intracellular signals leading to cell activation have not been determined. In this study, we examined the effect of hyperosmolar medium on interleukin-8 (IL-8) expression and the role of p38 mitogen-activated protein (MAP) kinase and c-Jun NH2 terminal kinase ( JNK) in human BEC in this response in order to clarify the intracellular signals regulating IL-8 expression in hyperosmolarity-stimulated BEC. The results showed that hyperosmolarity induced IL-8 expression in a concentration dependent manner, p38 MAP kinase phosphorylation and activation, and JNK activation whether NaCl or mannitol was used as the solute. SB 203580 as the specific p38 MAP kinase inhibitor inhibited hyperosmolarity-induced p38 MAP kinase activation and partially inhibited hyperosmolarity-induced IL-8 expression. These results indicate that p38 MAP kinase, at least in part, regulates hyperosmolarity-induced IL-8 expression in BEC. However, other signals such as JNK are possibly also involved. These results provide new evidence on the mechanism responsible for the development of the LPR induced by EIB, and a strategy for treatment with the specific p38 MAP kinase inhibitor.

Blotting, Northern↗

A patient with preclinical Cushing's syndrome and excessive DHEA-S secretion having unilateral adrenal carcinoma and contralateral adenoma.

We report a case of preclinical Cushing's syndrome in a 54-year-old male associated with bilateral adrenocortical tumours. Physical findings and general laboratory data were unremarkable except for mild hypertension (158/90 mmHg) and impaired glucose tolerance. Endocrinological evaluation revealed the presence of autonomous cortisol secretion including unsuppressible serum cortisol by 8 mg dexamethasone test (11 microg/dl), high serum DHEA-S (3580 ng/ml, normal: 400-3500) and increased urinary 17-KS excretion (31.0-35.8 mg/day, normal: 5.8-21.3). CT scan demonstrated the presence of tumours in both adrenals and bilateral adrenalectomy was subsequently performed. Histological examination of the resected specimens revealed an adrenocortical carcinoma on the right side and an adenoma on the left side with noticeable cortical atrophy in non-neoplastic adrenals. Immunohistochemical study of steroidogenic enzymes demonstrated that all the steroidogenic enzymes involved in cortisol biosynthesis were expressed in both right and left adrenal tumours. Enzymatic activities of 21, 17alpha, 18, 11beta-hydroxylases were detected in both right and left adrenals except for the absence of 11beta-hydroxylase activity in the left adrenal adenoma. Results of in vitro tissue steroidogenesis examined in short-term tissue culture of the specimens revealed no significant differences between carcinoma and adenoma in cortisol production, but the production of adrenal androgens in carcinoma was significantly higher than that in adenoma, which may indicate the importance of evaluating adrenal androgen levels in patients with adrenocortical neoplasms.

17-Ketosteroids↗

Atypical X-linked agammaglobulinemia diagnosed in three adults.

OBJECT: X-linked agammaglobulinemia (XLA) is one of the most common humoral immunodeficiencies characterized from childhood by the absence of peripheral B lymphocytes, reduced levels of serum immunoglobulins and recurrent and severe bacterial infections. These characteristics are the result of Bruton's tyrosine kinase (Btk) protein deficiency in peripheral B lymphocytes. In addition to typical XLA, several atypical cases have been recognized, who exhibited mild or even no clinical symptoms, although they were definitely deficient in Btk protein (atypical XLA). In these patients peripheral B lymphocytes and serum immunoglobulins (Igs) are detectable though at a lower level than in normal people. To clarify the discrepancies between the Btk gene mutations and the phenotypes more atypical patients should be examined. In this study we evaluated the cytoplasmic Btk protein in peripheral monocytes of some hypogammaglobulinemia adults by means of flowcytometric analysis. MATERIALS AND METHODS: Heparinized venous blood samples were collected from some hypogammaglobulinemia adults. Mononuclear cells were separated from their blood and first reacted with a phycoerythrin-labeled CD14 monoclonal antibody (MoAb) (staining of monocyte membrane). Next, the cells were fixed and permeabilized. And then these permeabilized cells were reacted with an anti-Btk MoAb (staining of cytoplasmic Btk protein) and incubated with a FITC-conjugated goat antimouse IgG1. The double-stained cells were analyzed on a flowcytometer. RESULTS AND CONCLUSION: By means of flowcytometric analysis we diagnosed three hypogammaglobulinemia adults as XLA, who did not show typical clinical progress of XLA. Advancements in diagnostic methods has facilitated a prompt and definite diagnosis of this disease.

Adult↗

After-effect of entrainment on the period of human circadian system.

The purpose of the present study is to examine changes of the circadian period in humans during temporal isolation, where the circadian rhythm is free-running. Twelve young males each spent 22 d alone in a temporal isolation room. Rectal temperature was continuously recorded and plasma melatonin was measured on day 3 (D3) and from days 10 to 13 (D10-D13). The light intensity in the room was less than 100 lx during the waking period. The free-run period of temperature rhythm from D3 to D10 (24.75 h) was not significantly different from those of the plasma melatonin rhythm (24.63 h) and sleep-wake cycle (24.69 h). The free-run period of temperature rhythm was 24.58 h in S-1 (D2-D6), which was gradually and significantly lengthened to 24.84 h in S-2 (D6-D10), 25.16 h in S-3 (D12-D16), and 25.18 h in S-4 (D18-D22). The free-run period of rectal temperature rhythm was steadily lengthened throughout the isolation period, which was probably due to the after-effect of previous entrainment to 24-h time cues.

Adult↗

Inhibitory effect of Cladosiphon fucoidan on the adhesion of Helicobacter pylori to human gastric cells.

We studied the inhibitory effect of Cladosiphon fucoidan on the attachment of Helicobacter pylori (H. pylori), a gastroduodenal pathogen, to human gastric cell lines. The bacterial binding in these cell lines was inhibited more by Cladosiphon fucoidan (IC50 = 16-30 mg/mL), than by the fucoidan from Fucus (IC50 > 30 mg/mL). Dextran sulfate, another sulfated polysaccharide, did not inhibit the binding at all. Pre-incubating the bacterial suspension with fucoidans reinforced the inhibitory ability of these components, and reduced the IC50 value of Cladosiphon fucoidan to approximately 1 mg/mL. However, the binding was not inhibited by pre-treatment of gastric cells with these components. It was also shown that this fucoidan blocks both Leb- and sulfatide-mediated attachment of H. pylori to gastric cells. Furthermore, fucoidan-binding proteins were found on the H. pylori cell surface by Western blot analysis. Thus, the inhibitory effect exerted by Cladosiphon fucoidan on binding between H. pylori and gastric cells might result from the coating with this component of the bacterial surface.

Antigens↗

[Multiple primary cancers of oral cavity and pharynx].

Multiple primary cancers were found in 23 of 68 patients (34%) with an index cancer in the oral cavity or pharyngeal area treated in our institute from June 1995 to July 1998. Four cases had triple primary cancers. All 68 cases underwent upper and lower gastrointestinal endoscopy as well as ultrasonography of the liver. Lung CT was performed in cases with abnormal findings on chest roentgenograms. Multiple cancers were found in 5 of 25 oral cavity cases (20%), 6 of 14 mesopharynx cases (43%) and 12 of 29 hypopharynx cases (41%). Nine of 23 cases (39%) were synchronous and 14 (61%) were metachronous. Eighteen of 27 (69%) secondary cancers occurred in the upper aerodigestive tract with an especially high incidence (22%) in the esophagus. Gastroendoscopy also revealed 7 neoplastic lesions, aside from cancers, with the total abnormal rate of 24% (24/68). Thus, gastroendoscopy is useful for the diagnosis of multiple primary cancers. The frequency of multiple primary cancers in males (33%) was not different from that in females (35%). The average age of multiple primary cancer patients (65.1 years) was a little higher than that of single cancer patient (62.7 years). Smoking or drinking was not related to the incidence of multiple cancers. The interval between the first and the second cancer in metachronous cancer cases was 25.5 months on average, and within 4 years in 71% (10/14) of the cases. This result suggests that close follow-up including endoscopy should be required for at least 4 years after treatment of oral or pharyngeal cancer. Radical treatment for each of the multiple cancer lesions was performed in 22 of 23 cases, and the mortality rate of multiple primary cancer cases was not significantly different from that of single cancer cases. Among 7 cases who died of disease, 5 cases died of distant metastasis, suggesting that control of distant metastasis is an important issue in the treatment of multiple primary cancers.

Adult↗

[Simultaneous reconstruction of pharyngoesophagus and phonetic shunt following laryngopharyngoesophagectomy].

Because of its many advantages, free jejunal transfer has gained wide acceptance for pharyngoesophageal reconstruction after ablative surgery. Because the jejunum is well vascularized, it facilitates good wound healing, and has a low incidence of anastomotic insufficiency, fistula formation and stricture. However, voice rehabilitation in this group of patients can be difficult. Therefore, we performed primary tracheojejunal shunt operations for voice restoration with jejunum siphons using Nozaki's method (type 3). In this procedure, after dividing a section of the jejunum into two segments, the reconstructed neopharyngoesophagus is anastomosed in a side-to-end fashion to the fabricated shunt using the other segment of the jejunum, as an "elephant nose shunt" so called because of its appearance. Voice restoration can be achieved in patients who undergo laryngopharyngoesophagectomy through these reconstructive procedures. We performed this surgery for nine hypopharyngeal cancer patients after total pharyngo-laryngo-esophagectomy. Following placement of the shunt, no special care was required. Only one patient developed a severe aspiration. No leakage was seen and the swallowing function was preserved in all patients. Four of nine patients could speak well following these procedures. A vibratory source is created in the neoesophagus, above the elephant shunt. During speech production, narrowing of the inside and vibration of the jejunal mucosa can be observed using a laryngeal fiber scope. In order to study the acoustical characteristics of shunt speech, voice analysis was performed in patients with restored phonatory function using Computerized Speech Lab Model 4300 (KAY). Irregularities of pitch periods in the voice sample were measured using Jita (the pitch period) and Jitt (relative evaluation of the pitch) for the very short term (cycle-to-cycle), and PPQ (pitch period pertubation quotient) for the short term (cycle-to-cycle with a smoothing factor of 5 periods). Irregularities of the peak-to-peak amplitude were measured using ShdB (evaluation in dB of the peak-to-peak amplitude) and Shim (relative evaluation of the peak-to-peak amplitude) for the very short term (cycle-to-cycle), and APQ (amplitude perturbation quotient) for the short term (cycle-to-cycle with a smoothing factor of 11 periods). The pertubation parameters of shunt speech are larger than normal ones not only in terms of the period but also in terms of the amplitude. These results are similar to those of laryngeal polyps, recurrent nerve palsy and esophageal speech. Recovery of phonation using Nozaki's type 3 method with the elephant nose shunt appears promising for pharyngo-laryngo-esophagectomized patients.

Aged↗

[Indication of tracheostomy for advanced oral or mesopharyngeal cancer resection].

In advanced oral or mesopharyngeal cancer requiring reconstruction, preventive tracheostomy have been performed to insure an airway postoperatively. However, tracheostomy often causes difficulty in swallowing and stress in the postoperative period for the patients. We have devised a strategy to avoid tracheostomy as much as possible in the cases requiring reconstruction except for the cases with over 2/3 resection of the base of the tongue or with prospective difficulty of re-intubation. Eleven cases were treated without tracheostomy out of 20 cases operated on with reconstruction in our hospital from 1995 through 1997. These patients were managed under nasal intubation for less than 2 days on average with careful observation postoperatively. In 11 non-tracheostomized cases, 1 case experienced venous thrombosis of a free flap and tracheostomy was performed at the salvage operation. Other 10 non-tracheostomized case were compared with 10 tracheostomized cases who were treated from 1991 though 1995. It was revealed that non-tracheostomized cases tended to have shorter periods until they could speak or eat, and also have a shorter postoperative admission term. In these cases, we have not experienced serious complications such as aspiration pneumonia or dyspnea, instead, special care in the postoperative period was needed. Thus, certain advanced cases who undergo curative resection followed by reconstruction can be managed without tracheostomy. The indication of tracheostomy in surgery for oral or mesopharyngeal cancer should be decided carefully.

Adult↗