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Biomedical subjects

K Hamada

Publications and source records attributed to K Hamada.

At least 163 records · Page 9Linked to original sources

Increased substance P in subacromial bursa and shoulder pain in rotator cuff diseases.

The subacromial bursa is recognized as a site associated with the shoulder pain caused by rotator cuff disease in the middle-aged and elderly. Substance P is contained in primary afferent nerves, and its quantity increases during chronic pain. The amount of substance P in the subacromial bursa of patients with rotator cuff disease was examined. Radioimmunoassay and immunohistochemistry were employed to quantify and localize substance P. The preoperative pain level was measured with a visual analogue scale with 0 as no pain, 5 as moderate, and 10 as severe. Thirty-seven patients that had undergone operation were divided into two groups: one composed of 19 patients with subacromial bursitis and a partial-thickness tear of the rotator cuff (nonperforated cuff) and the other composed of 18 patients with a full-thickness tear (perforated cuff). Subacromial bursae obtained from seven fresh cadavers with no shoulder pain before death were used as controls. The visual analogue scale showed significantly greater pain in the group with the nonperforated rotator cuff than in the group with the perforated cuff. Consistent with these results, the amount of substance P in the subacromial bursa was significantly greater in the former group than in the latter. Nerve fibers immunoreactive to substance P were localized around the vessels, with a larger number of fibers in the group with the nonperforated rotator cuff. Therefore, an increased amount of substance P in the subacromial bursa appears to correlate with the pain caused by rotator cuff disease.

Adult↗

Shortening of action potential duration is not prerequisite for cardiac protection by ischemic preconditioning or a KATP channel opener.

Our purpose was to determine whether amelioration of myocardial contractile dysfunction by an ATP-sensitive potassium (KATP) channel opener or ischemic preconditioning is mediated by shortening of action potential duration during the early period of ischemia. Extracellular potassium concentration ([K+]e), monophasic action potential duration (MAPD) and thickening fraction were measured during ischemia and reperfusion of the left anterior descending coronary artery in anesthetized dogs. Control dogs were subjected to a 10-min occlusion (test occlusion) followed by a 120-min reperfusion. The five dogs which made up the pinacidil group, received 0.03 mg/kg as an i.v. bolus and then were infused at a rate of 0.04 mg/kg/h for 20 min prior to the test occlusion. In the preconditioning group, six dogs were subjected to a 5-min occlusion and a 10-min reperfusion prior to the test occlusion and reperfusion. Both pinacidil and preconditioning improved regional contraction during reperfusion after the test occlusion. In the control group, MAPD shortened and [K+]e increased during ischemia. Preconditioning abolished MAPD shortening and blunted the rise of [K+]e during ischemia. Pinacidil did not affect either the shortening of MAPD or [K+]e elevation during ischemia. These results suggest that the shortening of MAPD is not a prerequisite for amelioration of contractile dysfunction by a KATP channel opener or ischemic preconditioning.

Action Potentials↗

Estimation of regional lung function in interstitial pulmonary disease using 99mTc-technegas and 99mTc-macroaggregated albumin single-photon emission tomography.

For quantitative evaluation of the regional lung function in patients with interstitial pulmonary disease (IP) in the sitting position, 99mTc-Technegas and 99mTc-macroaggregated albumin (MAA) single-photon emission tomography (SPET) studies were performed in 12 healthy controls (HC) and 42 IP patients. Four transverse images were prepared from the data obtained and designated as slices no. 1-4 from the top downward. Regions of interest (ROIs) were determined in the anterior and posterior parts of the lung in each slice, and the ratio of the count per voxel in the ROIs to the count in the entire lung was calculated as the regional Technegas index (T). The regional perfusion index (Q) was calculated by a similar procedure using the data of 99mTc-MAA SPET. The ratios between T and Q (T/Q) in the anterior and posterior regions of the lung, and the ratios of T and Q between the anterior and posterior regions of the lung (Tp/Ta and Qp/Qa) were examined. In the HC group, T/Q decreased but Tp/Ta and Qp/Qa increased from the upper to the lower lung fields. When IP patients were classified into (I) those in whom T/Q decreased from the upper to the lower lung fields, (II) those in whom it was similar in all slices, (III) those in whom it increased from slice 3 to slice 4, and (IV) those in whom it increased from slice 2 to slices 3 and 4, this classification was more closely correlated with %VC than with %DLCO or PaO2. When the patients were classified according to Tp/Ta and Qp/Qa into (A) those in whom the values were greater in the lower than the upper lung field, (B) those in whom the values were similar in all slices, and (C) those in whom the values were smaller in lower than in upper lung fields, categories B and C were observed frequently even in patients whose %VC was in the normal range. This method is considered to be an effective means to evaluate the progression and pathology of IP and to detect early impairment of lung function.

Adult↗

Molecular analysis of the androgen receptor gene in 4 patients with complete androgen insensitivity.

Androgen insensitivity syndromes are due to defects in the androgen receptor gene. In this study, we analyzed the androgen receptor gene in four cases with complete androgen insensitivity syndrome. In patient 1, one substitutional mutation [arginine (codon CGC) to cysteine (codon TGC) at position 774] of exon F was identified. This position was located in the hormone binding domain and appeared to be one hot spot of mutations because the mutations at the same position in several unrelated cases were reported before. In patient 2, one substitutional mutation [tyrosine (codon TAT) to cysteine (codon TGT) at position 571] of exon B was identified. This position was located in the DNA binding domain. In patients 3 and 4 (siblings), one substitutional mutation [arginine (codon CGA) to glutamine (codon CAA) at position 752] of exon E was identified. Taken together, these abnormalities might be related to the pathogenesis of complete androgen insensitivity.

Adolescent↗

Screening for glycosylphosphatidylinositol (GPI)-dependent cell wall proteins in Saccharomyces cerevisiae.

Open reading frames in the genome of Saccharomyces cerevisiae were screened for potential glycosylphosphatidylinositol (GPI)-attached proteins. The identification of putative GPI-attached proteins was based on three criteria: the presence of a GPI-attachment signal sequence, a signal sequence for secretion and a serine- or threonine-rich sequence. In all, 53 ORFs met these three criteria and 38 were further analyzed as follows. The sequence encoding the 40 C-terminal amino acids of each was fused with the structural gene for a reporter protein consisting of a secretion signal, alpha-galactosidase and a hemagglutinin (HA) epitope, and examined for the ability to become incorporated into the cell wall. On this basis, 14 of fusion proteins were classified as GPI-dependent cell wall proteins because cells expressing these fusion proteins: (i) had high levels of alpha-galactosidase activity on their surface; (ii) released significant amounts of the fusion proteins from the membrane on treatment with phosphatidylinositol-specific phospholipase C (PI-PLC); and (iii) released fusion proteins from the cell wall following treatment with laminarinase. Of the 14 identified putative GPI-dependent cell wall proteins, 12 had novel ORFs adjacent to their GPI-attachment signal sequence. Amino acid sequence alignment of the C-terminal sequences of the 12 ORFs, together with those of known cell wall proteins, reveals some sequence similarities among them.

Amino Acid Sequence↗

Effect of glucose on ureagenesis during exercise in amino acid-infused dogs.

The purpose of this study was to investigate the effect of glucose administered with amino acids before and during exercise on hepatic ureagenesis. Eight mongrel dogs subjected to treadmill running for 150 minutes at 10 km/h on a 12% incline were intravenously infused with either a mixture of amino acids and glucose (AAG) or amino acids alone (AA). The infusion was started 60 minutes before exercise and continued until the end of exercise. The rate of urinary urea excretion increased after infusion of both AAG and AA. However, the rate of urinary urea excretion was significantly lower in the AAG group versus the AA group during the first 1.5 hours of the recovery period ([R0 to R90] 514+/-24 v 637+/-24 mg/h, mean+/-SE, P < .05). Moreover, hepatic urea output was decreased during AAG versus AA infusion (229+/-62 v 367+/-55 microg/kg/min, P < .05). Hepatic glucose production during exercise was also significantly lower in AAG versus AA infusion (354+/-54 v 589+/-56 mg/kg, P < .05). On the other hand, no difference was observed in hepatic total amino acid uptake between the groups. Thus, these results indicate that AAG administered before and during exercise appears to reduce hepatic ureagenesis due to reduced hepatic gluconeogenesis as compared with administration of AA alone. These findings also suggest that nitrogen retention is enhanced by glucose administered during exercise.

Amino Acids↗

Amygdaloid kindling in brainstem bisected cats.

Results of previous studies suggested that the brainstem participates in amygdaloid (AM) kindled seizure generalization and the positive transfer effect at the secondary site AM. This study was undertaken to define the role of the brainstem in the patterning of AM kindling, the maintenance of AM kindled seizure and the formation of the positive transfer effect (PTE) at the secondary site AM in cats. Seven animals with midsagittal bisection of the brainstem were subjected to primary site and secondary site AM kindling and primary site retest. All the animals were kindled at the primary site. However, the following significant differences from the pattern seen in intact animals were observed: (1) reversed direction of stage 4 seizure, with circling from the contralateral to the ipsilateral, (2) a marked kindled seizure stage instability, and (3) frequent abortive termination of the kindled seizure. At the secondary site AM, all the animals showed a complete absence of the positive transfer effect, with two out of seven animals failing to progress beyond stage 2. A negative transfer or an interference after-effect remained preserved at the secondary site kindling and primary site retest. The findings indicate that the bisected midsagittal area in the brainstem plays an important role not only in the patterning and maintenance of the kindled seizure but also in the formation of the transhemispheric positive transfer effect in feline AM kindling.

Amygdala↗

Antiepileptic effects of topiramate on amygdaloid kindling in rats.

We examined the antiepileptic properties of topiramate (TPM) in amygdaloid (AM) kindling in rats. Electrodes were implanted into the left AM of adult male Wistar rats. The animals were kindled at the after-discharge (AD) threshold. After the completion of kindling, the generalized seizure triggering threshold was determined. The drugs were administered intraperitoneally in animals which showed stable generalized convulsions at near-threshold stimulation. Intraperitoneal administration of TPM at doses of 25 mg/kg or more produced an anticonvulsive effect, but did not readily suppress limbic seizures. Complete suppression of AD was observed in only 3/8 rats at the highest dose of 200 mg/kg, which was not statistically significant. On the other hand, TPM at 100 and 200 mg/kg significantly delayed AM kindling. Thus, TPM showed modest therapeutic properties of conventional antiepileptic drugs in kindling model, those of TPM more closely resemble those of phenobarbital and the benzodiazepines than those of phenytoin and carbamazepine.

Amygdala↗

Suppression of the immune response to an adenovirus vector and enhancement of intratumoral transgene expression by low-dose etoposide.

Adenoviral vectors are commonly used in gene therapy trials because of their efficiency in gene transfer. However, their use is limited by cellular and humoral immune responses that result in temporary transgene expression and reduced efficacy of repeated vector administration. We hypothesized that certain oncolytic agents commonly used to treat cancer patients could suppress the immune response to adenoviral vectors, and enable repeated adenovirus-mediated cancer gene therapy. Etoposide and cyclophosphamide were tested for their ability to suppress the humoral and cellular immune responses to an adenoviral vector in immunocompetent C3H mice. Intratumoral transgene expression was monitored in adenovirus-immunized animals treated with etoposide or cyclophosphamide. Neutralizing antibodies to adenovirus and cytotoxic T lymphocyte (CTL) lysis of virally transduced cells were significantly suppressed in mice treated with etoposide at 2 or 10 mg/kg/day or cyclophosphamide at 10 mg/kg/day compared with untreated mice (P < 0.05). Significantly larger areas of gene transduction were observed in treated animals compared with untreated mice or the mice treated with cyclophosphamide at 2 mg/kg/day (P < 0.05). Our results suggest that repeated adenovirally mediated gene therapy is achievable in cancer patients who are concurrently undergoing treatment with chemotherapy.

Adenoviridae↗

Evaluation of histological structure and its effect on the distribution of alpha1-adrenoceptors in human benign prostatic hyperplasia.

OBJECTIVE: To evaluate the histological structure of benign prostatic hyperplasia (BPH) and its relationship with the density of alpha1-adrenoceptors in smooth muscle. MATERIALS AND METHODS: Specimens from hyperplastic tissues obtained from 14 patients with BPH were evaluated for the density of alpha1-adrenoceptors in smooth muscle using autoradiography, Mallory-Azan staining and computer-assisted image analyses. The binding of [3H] tamsulosin (a selective alpha1-blocker) and the ratio of smooth muscle area was calculated, and the density of alpha1-adrenoceptors per area of smooth muscle determined by dividing the degree of binding by the ratio of smooth muscle to total area. RESULTS: There was a significant difference between the ratio of smooth muscle area in the hyperplastic acinar nodule and the surrounding stroma (P < 0.01). The density of alpha1-adrenoceptor per smooth muscle area was significantly higher in the hyperplastic acinar nodule than in the surrounding stroma (P < 0.05). There was no correlation between prostatic weight and the ratio of smooth muscle area or the density of alpha1-adrenoceptors in each region. CONCLUSION: The distribution of alpha1-adrenoceptors on smooth muscle differed with histological structure; both the histological conformation and the difference in the distribution of alpha1-adrenoceptors could affect urethral obstruction in BPH.

Autoradiography↗

Androgen-dependent beard dermal papilla cells secrete autocrine growth factor(s) in response to testosterone unlike scalp cells.

Androgens stimulate many hair follicles, e.g., beard, but may cause regression on the scalp; occipital areas are considered androgen independent. The mesenchyme-derived dermal papilla that regulates the hair follicle is considered the site of androgen action. Because hair size has been clearly related to dermal papilla size, one of the key functions androgens must regulate is the size of the dermal papilla. This implies that androgens stimulate dermal papilla cells to divide or to secrete autocrine mitogenic factors. As physiologic levels of androgens do not stimulate mitogenesis in cultured dermal papilla cells, this study was designed to determine whether dermal papilla cells cultured from human hair follicles with different responses to androgens in vivo, i.e., androgen-dependent beard and androgen-independent nonbalding scalp, produce soluble autocrine mitogenic factors and, if so, whether either cell type altered their secretion in response to testosterone in vitro. Conditioned medium was prepared by incubating individual primary lines of cells for 24 h with, and without, testosterone (10(-10)-10(-5) M). All conditioned media significantly increased [3H] thymidine incorporation by other dermal papilla cells; trypsin treatment significantly reduced the effect. Although both beard and scalp cell conditioned media had a similar stimulatory potential, beard cells incorporated approximately double the [3H]thymidine of scalp cells, in both types of media. Physiologic levels of testosterone increased mitogenic factor production by beard, but not scalp cells; only beard cells responded to these factor(s). Testosterone added after conditioning had no effect, indicating stimulation was not a synergistic effect of testosterone and conditioned medium. Thus, both beard and scalp cells release similar autocrine growth factor(s), but their response to these factor(s) is determined by their in vivo origin. Testosterone in vitro stimulates secretion of an autocrine growth factor(s) by beard, but not scalp cells, to which only beard cells are able to respond, reflecting the responses to androgens in vivo. These factors may be involved in the key increase of dermal papilla size necessary for androgen-induced changes in hair size.

Adult↗

Production of immunoreactive 2',5'-oligoadenylate synthetase in p48-deficient mice.

2',5'-Oligoadenylate synthetase (2'5'OAS), an enzyme induced by interferon (IFN), is physiologically produced in IFN-untreated normal healthy mice. The enzyme is localized mainly in the epithelium of the digestive tract, reproductive organs, and the choroid plexus in the brain. 2'5'OAS is also detected in oocytes in the ovary and in neurons and glial cells of both the telencephalon and cerebellum. Here, we examined the role of p48 (ISGF3gamma), a component of IFN-stimulated gene factor 3 (ISGF3), in the physiologic production of 2'5'OAS using p48-deficient mice generated by gene targeting. In the p48-deficient mice, the physiologic production of 2'5'OAS localized in the following cells was severely impaired: hepatocytes, Kupffer cells, splenocytes, epithelium of the large intestine, oviduct, and uterus, and neurons and glial cells in both the telencephalon and cerebellum. The results show that 2'5'OAS in these cells is induced physiologically through a pathway including p48. However, the production of 2'5'OAS in oocytes was not affected in the p48-deficient mice, indicating that oocyte 2'5'OAS is produced through a p48-independent pathway. A possible function of the GAS sequence found in the promoter region of the 2'5'OAS gene to which Stat6 may bind also is discussed.

2',5'-Oligoadenylate Synthetase↗

The target cells of injected type I interferons in mouse liver.

Type I interferons (IFNs) have been used for the treatment of viral hepatitis, but it is unclear which cells in the liver are affected by injected IFN. The effects of IFN have been studied by the production of 2',5'-oligoadenylate synthetase (2'5'OAS), an IFN-inducible enzyme. Here, we studied the distribution of 2'5'OAS in mouse liver after injection of natural mouse IFN-alpha/beta by Western blotting and immunohistochemistry using a monoclonal antibody specific to mouse 42-kDa 2'5'OAS. Injection of IFN-alpha/beta increased the levels of liver 2'5'OAS and enhanced the intensities of immunohistochemical staining for this enzyme in both hepatocytes and Kupffer cells. In IFN-untreated normal mice, hepatocytes were lightly stained, but some of the Kupffer cells showed rather strong staining. The 2'5'OAS-positive Kupffer cells comprised approximately 60% of those in normal liver, whereas this increased to approximately 90% following IFN-alpha/beta injection. Thus, hepatocytes and Kupffer cells were the targets of injected IFN.

2',5'-Oligoadenylate Synthetase↗

Posteroinferior acromioclavicular dislocation with supraspinatus tear. A case report.

A 20-year-old man was treated for posteroinferior acromioclavicular dislocation. The diagnosis was based on standard radiographs and intraoperative findings. The distal end of the clavicle had impaled the supraspinatus muscle. Open reduction was performed 2 weeks after injury, followed by wire fixation of the acromioclavicular joint and repair of the torn superior acromioclavicular ligament and coracoclavicular ligaments. Two years after the procedure, standard radiographs revealed normal anatomic alignment of the acromioclavicular joint, with pain free range of motion. Active elevation in the scapular plane was 180 degrees, active external rotation was 80 degrees in the anatomic position, and passive internal rotation was to the T5 vertebra. The patient returned to playing baseball and tennis and was satisfied with the postoperative result.

Acromioclavicular Joint↗

Association of replication error positive phenotype with lymphocyte infiltration in endometrial cancers.

Microsatellite instability (MI) has been detected in certain sporadic cancers as well as in hereditary non-polyposis colorectal cancer (HNPCC). In order to determine the precise clinicopathological characteristics of MI in endometrial cancer, we examined 90 sporadic endometrial cancers (83 endometrioid adenocarcinomas, 3 adenosquamous carcinomas, 3 papillary serous carcinomas, and 1 clear cell carcinoma) and eight lesions of endometrial hyperplasia for replication error (RER) using polymerase chain reaction amplification of CA repeated microsatellite sequences at 15 loci. RER was observed in 23 (28%) of the 83 endometrioid adenocarcinomas at at least one locus and in 19 (23%) at two or more loci (RER+ phenotype) in the seven most commonly observed loci, but not in carcinomas of other histological types or in endometrial hyperplasia. Lymphocyte infiltration around carcinoma cells, which is one of the histological features seen in tumors from HNPCC, was severer in RER+ phenotype tumors (79%, 11/14) than in the RER- tumors (25%, 11/44) (marked/moderate infiltration versus slight, P < 0.001, chi 2 test), when 58 tumors with muscular invasion were examined. The RER+ phenotype was associated with a higher parity and gravidity (P < 0.05, Wilcoxon test). However, RER+ phenotype was not associated with tumor stage, histological grade, muscular invasion, lymph node metastasis or patient survival. In conclusion, MI occurs in a subset of endometrial cancers, which often show marked infiltration of lymphocytes around the tumor.

Adenocarcinoma↗

[A clinical study of respiratory infection isolating non-pathogenic Neisseria by transtracheal aspiration].

Neisseria species other than N. meningitidis and N. gonorrhoeae are generally regarded as commensal bacterial flora of the oropharynx, and little is known regarding cases of these non-pathogenic Neisseria species in the lower respiratory tract. We clinically examined respiratory tract infections from which non-pathogenic Neisseria species were isolated by transtracheal aspiration (TTA). The incidence of non-pathogenic Neisseria isolated was 54 (15.7%) out of 344 episodes of respiratory tract infections with isolated microorganisms from TTA, and was 17.6%, 15.8%, 14.3% for pneumonia, acute bronchitis, and chronic lower respiratory tract infection, respectively. All 54 episodes were isolated with other microorganisms such as alpha-Streptococcus spp. (75.9%), Haemophilus influenzae (25.9%) and anaerobics (22.2%). The isolation ratio according to the age group increased at 45 years of age or more, but did not increase with the advance of age. Predisposing factors were identified such as overt aspiration, iatrogenic procedure and heavy smoking. Cases without overt aspiration that had fevers of 38 degrees C or more or hypoxemia of less than PaO2 70 torr when detecting non-pathogenic Neisseria were observed more frequently in the aged than the non-aged. The findings suggest the detection of non-pathogenic Neisseria by TTA is influenced by the host state that the fall of microorganisms from the upper to lower respiratory tract cannot be defended or excluded by mucociliary transportation disorder due to underlying disease and smoking, or deterioration of physical status other than overt or silent aspiration.

Age Factors↗

[Bacillus cereus septicemia in a patient with severe aplastic anemia].

A 78-year-old female was admitted with complaints of malaise and fatigue in the legs. The patient was diagnosed as severe aplastic anemia and treatment was started with metenolone and steroid pulse therapy. Administration of antibiotics and granulocyte-colony stimulating factor which led to a resolution of the high fever. About four months after admission, the patient developed vomiting and abdominal pain with a spiking fever. The next day after suddenly losing consciousness, she died. B. cereus was isolated from blood cultures. Autopsy specimens of the liver, cardiac muscle and lung showed changes due to B. cereus. This pathogen is widely distributed in nature. We should not overlook B. cereus as a contamination, but rather should consider it a potential pathogen in immunocompromised hosts, when it is isolated from blood cultures.

Aged↗

Ionized calcium and 1,25-dihydroxyvitamin D concentration in serum of patients with sarcoidosis.

The aim of this study was to evaluate alterations in calcium metabolism in sarcoidosis. The serum concentrations of calcium (sCa), ionized calcium (sCa2+), 1,25-dihydroxyvitamin D (s1,25(OH)2D3) and parathyroid hormone (sPTH), serum angiotensin-converting enzyme activity (sACE) and urinary excretion of calcium (uCa) were studied in 36 Japanese patients with pulmonary sarcoidosis, aged 48.1+/-15.3 yrs (mean+/-SD), 15 males and 21 females. During the study the patients were on a daily diet with 500 mg calcium and 1000 mg phosphorus for a total of 6 days. sCa2+ was above the normal range (>1.26 mmol x L(-1)) in 10 patients (27.8%), 12 patients (33.3%) were hypercalciuric, and 16 patients (44.4%) showed alteration in calcium metabolism, with an increase in values of sCa, sCa2+ or uCa. There was a significant correlation between sCa2+ and s1,25(OH)2D3 (p<0.001), as well as between sCa2+ and sACE (p<0.001). s1,25(OH)2D3 in patients with extrathoracic involvement (ETI) tended to be higher than in patients without ETI. sCa2+ was less than 1.23 mmol x L(-1) (p<0.05) in the majority of patients without ETI, and sCa2+ was less than 1.24 mmol x L(-1) in the majority of normocalciuric patients. In conclusion, a disease-related alteration in calcium metabolism was seen in about 40% of patients with sarcoidosis, and 1,25-dihydroxyvitamin D probably plays a crucial role in this abnormality. The serum concentration of ionized calcium was considered to be a useful index for the disease activity of sarcoidosis.

Adult↗