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Biomedical subjects

H Kondo

Publications and source records attributed to H Kondo.

At least 397 records · Page 22Linked to original sources

Is the cannabinoid CB1 receptor a 2-arachidonoylglycerol receptor? Structural requirements for triggering a Ca2+ transient in NG108-15 cells.

The effects of delta9-tetrahydrocannabinol and 2-arachidonoylglycerol on the intracellular free Ca2+ concentration ([Ca2+]i) in NG108-15 cells were examined in detail. We found that delta9-tetrahydrocannabinol induces a rapid, modest increase in [Ca2+]i. The response was detectable with 3 nM delta9-tetrahydrocannabinol. We also found that very low concentrations of 2-arachidonoylglycerol elicit a rapid, more prominent increase in [Ca2+]i. Such a response was observed not only in NG108-15 cells but also in N18TG2 cells. The response induced by 2-arachidonoylglycerol in either NG108-15 cells or N18TG2 cells was abolished by pretreatment of the cells with a cannabinoid CB1 receptor specific antagonist, SR141716A, suggesting that 2-arachidonoylglycerol interacts with the CB1 receptor to induce the response. The results of an experiment involving a phospholipase C inhibitor suggested that phospholipase C is involved in the rapid increase in [Ca2+]i induced by 2-arachidonoylglycerol. We also found that 1(3)-arachidonoylglycerol exhibits similar activity to that of 2-arachidonoylglycerol, although its activity at low concentrations was somewhat weak compared with that of 2-arachidonoylglycerol. We further confirmed that several structural analogues of 2-arachidonoylglycerol were less active compared with 2-arachidonoylglycerol. These results suggest that the structure of 2-arachidonoylglycerol is strictly recognized by the CB1 receptor, which raises the possibility that the CB1 receptor is originally a 2-arachidonoylglycerol receptor.

Calcium↗

Six cases positive for anti-centromere antibodies with ulcer and gangrene in the extremities.

We report six cases that were positive for anti-centromere antibodies, with ulcer and gangrene in the extremities but mild or no skin thickening. The patients were five women and one man, and the mean age at onset of gangrene was 56 yr. Raynaud's phenomenon was found in five patients and calcinosis cutis in two patients. Three patients did not satisfy the criteria for systemic sclerosis and CREST syndrome in this study. Ulcer and gangrene occurred in the fingers in three patients, and in the fingers and toes in two patients. The gangrene was refractory to treatment, and amputation of fingers or toes was inevitable in five patients. Regardless of cutaneous lesion, the presence of anti-centromere antibodies may cause the same pathological presentation of vascular damage as seen in systemic sclerosis.

Adult↗

Effectiveness of mammographic screening for breast cancer in women aged over 50 years in Japan.

The optimal age for effective screening of subjects for breast cancer by mammography in Japan was studied based on the results of two mammographic screening systems (systems I and II) in Tokushima Prefecture. System I consisted of visit screening using a bus equipped with a mammographic apparatus. System II consisted of central screening performed at Tokushima Health Screening Center. The examinees numbered 2,500 and 3,707 in systems I and II, respectively. There was a significant difference between the two screening systems in the age distribution of the examinees. The detection rates of breast cancer were 0.6% and 0.24% in systems I and II, respectively, which are 2-5 times higher than that (0.12%) obtained by conventional screening using physical examination alone. The detection rate increased especially in the sixth and seventh decades of life. The sensitivity of mammography screening was 93.3% in system I and 81.1% in system II. Higher sensitivity (100%) than that (73%) of screening by physical examination was obtained in women aged over 50. The proportion of stage I was 60% in system I and 66.7% in system II, compared with 32-65% in the United States and Europe. The rates of no nodal involvement were high, being 77.8% and 83.3% in systems I and II, respectively, compared with 57-71% in other countries. Breast-conserving therapy was applied to 18 of the 24 patients with breast cancer detected by the two screening systems. In addition, in Wolfe's classification of mammograms, the proportion of DY (mammary dysplasia) pattern was remarkably low, being 3.2% in the sixth decade and 0.8% in the seventh decade, compared with 16.6% in women aged 49 years. These results indicate that mammographic screening is effective in women aged over 50 years in Japan, as has been found in other countries.

Aged↗

Activated microglial cells are colocalized with perivascular deposits of amyloid-beta protein in Alzheimer's disease brain.

BACKGROUND AND PURPOSE: Microglial cells are present in the center of senile plaques (SPs) in Alzheimer's disease (AD) brain. Such a localization of microglial cells suggests that they are involved in the deposition or the clearance of amyloid-beta protein (A beta) in the brain. We examined their association with another type of parenchymal A beta deposit, which is termed the perivascular deposits of A beta (PA beta). METHODS: Thick sections from AD brain were stained with a three-color immunofluorescence method that labeled A beta, activated microglial cells, and vascular endothelial cells simultaneously. RESULTS: Three-dimensional observation under a laser scanning microscope confirmed that perivascular aggregates of activated microglial cells were colocalized with PA beta. CONCLUSIONS: Microglia occur in association with both SPs and PA beta, suggesting that they play important roles in the metabolism of A beta in AD brain.

Aged↗

Phase I-II study of irinotecan hydrochloride combined with cisplatin in patients with advanced gastric cancer.

PURPOSE: A dose-escalation study of irinotecan hydrochloride (CPT-11) combined with fixed-dose cisplatin was conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and objective response rate in patients with advanced gastric cancer. PATIENTS AND METHODS: Twenty-four patients with or without prior chemotherapy were enrolled. All patients were assessable for toxicities and response. On day 1, CPT-11 was administered as a 90-minute intravenous (I.V.) infusion, which was followed 2 hours later by a 120-minute I.V. infusion of cisplatin 80 mg/m2. CPT-11 alone at the same dose was administered again on day 15. The treatment was repeated every 4 weeks until disease progression was observed. The initial dose of CPT-11 was 60 mg/m2, and was escalated in increments of 10 mg/m2 until severe or life-threatening toxicity was observed. RESULTS: The MTD of this combination was CPT-11 80 mg/m2. At this dose level, 16.7% of patients (two of 12) had leukopenia of less than 1,000/microL, 66.7% (eight of 12) had neutropenia of less than 500/microL, and 16.7% (two of 12) had severe diarrhea of grade 4 during the first course. The dose-limiting toxicity was neutropenia. Ten patients achieved a partial response (PR), and the overall response rate was 41.7% among 24 patients (95% confidence interval, 21.9% to 61.4%). CONCLUSION: The recommended dose and schedule is CPT-11 70 mg/m2 on days 1 and 15 and cisplatin 80 mg/m2 on day 1 every 4 weeks. This combination of CPT-11 and cisplatin, considered to be active against advanced gastric cancer with acceptable toxicity, should be further assessed in a phase II study.

Adult↗

[Study on the relationship between lifestyles and maximal oxygen uptake in healthy adults].

In this study, to determine the influence of different lifestyles on maximal oxygen uptake, we carried out a survey on the effects of age, smoking, physical exercise, clinical examination values and dietary habits of 899 male factory workers on their maximal oxygen uptake. The results of the study were as follows: Maximal oxygen uptake significantly decreased with age. In the male factory workers, there were significant correlations between maximal oxygen uptake and frequency of physical exercise, a greasy diet and seasoning of the diet. Multiple regression analysis showed that the variables which correlated best with the maximal oxygen uptake were serum total cholesterol and HDL cholesterol. These results indicated that good nutrition and physical activity are important for maintaining physical fitness.

Adult↗

Serological studies on porcine Pneumocystis carinii pneumonia: kinetics of the antibody titers in swine herds and the association of porcine reproductive and respiratory syndrome virus infection.

Serological titers to Pneumocystis carinii (Pc) and porcine reproductive and respiratory syndrome virus (PRRSV) were measured on a herd with epidemic Pc pneumonia (case herd) and two comparison herds, by an indirect fluorescent-antibody technique. In the case herd, the geometric mean titer (GMT) for Pc were 1:80 in pigs 1 week old, 1:10 in pigs 5 weeks old, and 1:80 to 1:190 in pigs over 6 weeks old. GMTs for PRRSV were > 1:145 in most of age groups over 7 weeks old. In comparison herds, Pc and PRRSV antibody titers were low in weanling pigs. The results clarified the kinetics of antibodies to Pc and concurrent infection of PRRSV in the case herd.

Aging↗

A novel developmental process of intestinal epithelial lesions in a calf infected with attaching and effacing Escherichia coli.

A comparative study on the adhesion of attaching and effacing Escherichia coli (AEEC) to the enterocytes between the colon of a calf and the jejunum of a piglet showed differences in the developmental process of attaching and effacing (AE) lesions. In the calf, pedestals consisted of fused microvilli, while in the piglet they developed from the apical epithelial cell membranes after effacing microvilli. Microvilli adjacent to the AEEC attachment site were atrophic in the calf, whereas they were elongated in the piglet. The production of AE lesions in the calf may be indicative of a novel developmental process with AEEC infection.

Animals↗

Effects of central nervous stimulants on spino-bulbo-spinal reflex potentials in cats.

Effects of central nervous stimulants on the spino-bulbo-spinal reflex potential were evaluated in anesthetized intact cats, and compared with those on segmental spinal reflex potentials in anesthetized spinal cats. In spinal cats, strychnine augmented polysynaptic reflex potential, picrotoxin inhibited dorsal root reflex potential, aminopyrine potentiated mono- and poly-synaptic reflex potentials but inhibited dorsal root reflex potential, and 4-aminopyridine potentiated all the three types of segmental reflex potentials. A combination of fenbufen, a non-steroidal antiinflammatory agent, and enoxacin, a new quinolone antimicrobial, inhibited all the three types of segmental reflex potentials. In contrast, all these drugs consistently produced an augmentation of the spino-bulbo-spinal reflex potential in anesthetized intact cats. From these findings, we suggest that the spino-bulbo-spinal reflex potential may be used as an electrophysiological parameter for the evaluation of central nervous stimulants.

Action Potentials↗

Temporal changes of mRNA expression of matrix proteins and parathyroid hormone and parathyroid hormone-related protein (PTH/PTHrP) receptor in bone development.

Expression of parathyroid hormone and parathyroid hormone-related protein (PTH/PTHrP) receptor is one of the osteoblastic phenotypes; however, it has not been clear whether this phenotype expression is a marker of immature or mature osteoblasts. We examined the temporal expression pattern of PTH/PTHrP receptor in bone development in vivo and in vitro compared with the expression of other osteoblastic phenotypes: osteopontin (OPN), bone sialoprotein (BSP) and osteocalcin (OC), alkaline phosphatase (ALP), and mineralization. Total RNA was extracted from rat calvariae, and cell culture of rat bone marrow at different developmental stages and then Northern blot hybridization were performed. Mineralization was detected with contact microradiography (CMR) in calvaria or with Alizarin Red S staining in bone marrow cell culture. Both in calvaria and in marrow cell culture, extensive expression of OPN, BSP, type I collagen (COL I), and ALP coincided with the onset of mineralization, and OC expression was observed after mineralized tissue formation. Notably, PTH/PTHrP receptor was expressed at an early developmental stage (prenatal day 14 in calvaria, day 5 in culture) when mineralized tissue was not formed and other osteoblastic phenotypes were scarcely detected. Further study in cell culture revealed that the fold increase in cyclic adenosine monophosphate (cAMP) in response to PTH was elevated with the advance in the culture stage. These results indicate that mRNA expression of PTH/PTHrP receptor could be the early differentiation marker in osteoblastic lineage and that the levels of cAMP production in response to PTH represent the stage of osteoblastic differentiation.

Alkaline Phosphatase↗

Video-assisted lobectomy in the elderly.

STUDY OBJECTIVES: Video-assisted lobectomy for pulmonary malignancy seems to have potential merits, especially in compromised patients such as the elderly. This study was undertaken to assess the feasibility of this new approach in this special age group. PATIENTS: Video-assisted lobectomy was attempted in eight patients older than 78 years of age with preoperatively diagnosed T1N0 or T2N0 lung carcinomas of peripheral origin. In one patient with squamous cell carcinoma, the tumor was diagnosed after surgery as metastasis from tongue carcinoma. The patients ranged in age from 78 to 85 years (average, 81.3 years). RESULTS: The procedure was completed successfully in six patients (75%), while the other two patients underwent lobectomy after conversion to open thoracotomy because of bleeding from the pulmonary artery at the hilum in one and extensive pleural adhesions in another. Among the six patients who underwent video-assisted lobectomy, there were no operative deaths or serious complications attributable to this technique, although two patients had prolonged air leakage for 7 and 11 days, respectively. CONCLUSIONS: This approach, which is feasible even in patients older than 80 years, is likely to offer a benefit to such patients if they are selected properly. During this procedure, the possibility of wound extension in case of an intraoperative accident must always be borne in mind, especially in elderly patients. The advantage of this approach remains undetermined in this special age group.

Aged↗

Implications of staging in lung cancer.

Lung cancer staging, based on anatomic extent of disease and described by the TNM staging system (T, primary tumor; N, regional lymph nodes; M, distant metastasis), is an important parameter for determining the clinical course of this disease. To evaluate the prognostic importance of TNM staging for lung cancer, we conducted a retrospective study analyzing survival rates according to TNM staging in 2,382 patients who had pulmonary resection for non-small cell lung cancer. Postoperatively, 3 patients were classified in stage 0, 796 in stage I, 304 in stage II, 719 in stage IIIA, 233 in stage IIIB, and 327 in stage IV. The 5-year survival rates for these patients were as follows: stage I, 68.5%; stage II, 46.9%; stage IIIA, 26.1%; stage IIIB, 9.0%; and stage IV, 11.2% (including ipsilateral, intrapulmonary metastases); 5-year survival rates for 140 patients with stage IV disease with intrapulmonary metastases in either the same lobe or another ipsilateral lobe were 17.8% and 8.3%, respectively. There was prognostic significance between stage I and stage II disease, stage II and stage IIIA disease, and stage IIIA and stage IIIB disease, but not between stage IIIB and stage IV disease. Only a few modifications will be required for the TNM staging system, which at present accurately reflects the prognosis of patients with lung cancer and is helpful in determining treatment.

Adult↗

An adult case of Cockayne syndrome without sclerotic angiopathy.

We report an autopsy case of Cockayne syndrome (CS). A 40-year-old Japanese woman was admitted to our hospital for cachexia. She had displayed the striking features of CS, including dwarfism, mental retardation, neural deafness, ataxia, intracranial calcifications, and progeria since her childhood. Endocrinological examinations suggested normal pituitary function and a disorder of the hypothalamus or the cerebrum. She died of acute pneumonia at the age of 42. Autopsy findings showed typical abnormalities in the central nervous system compatible with CS; however, no atherosclerotic change was observed in the systemic arteries.

Adult↗

BE-32030 A, B, C, D and E, new antitumor substances produced by Nocardia sp. A32030.

New antitumor substances, designated BE-32030A, B, C, D and E, were isolated from the culture broth of Nocardia sp. A32030. The active principles were extracted from the mycelium by methanol and purified by Sephadex LH-20 and reversed-phase column chromatographies and finally by reversed-phase HPLC. BE-32030A, B, C, D and E inhibited the growth of P388 murine leukemia, DLD-1 human colon cancer, PC-13 human lung cancer and MKN-45 human stomach cancer cell lines.

Animals↗

Prosthodontic treatment for patients with large mandibular defects; porous hydroxyapatite grafts.

It is difficult for both prosthodontists and their patients with large marginal defects to achieve a satisfactory prosthodontic result, because retention, support, and stability of the prosthesis are limited and recovery of esthetics is unsatisfactory owing to large mandibular defects. Alveolar ridge augmentation therapy is performed to compensate for such problems. We have experienced a good prognosis of prosthodontic treatment for over 10 years in two patients with large marginal defects of the partially edentulous mandible, who had undergone grafting of porous hydroxyapatite blocks to their bone defects. It has been reported that porous hydroxyapatite blocks are unsuitable for edentulous patients, because the mucosa covering the hydroxyapatite block is too thin and delicate to support dentures. We, therefore, designed the denture to prevent concentration of occlusal stress on the mucosa. In both of these two cases, we achieved recovery of occlusal function and esthetics by affixing denture to the large marginally resected defect augmented with a graft of porous hydroxyapatite block.

Adult↗

[A case of lung adenocarcinoma associated with remarkably high levels of CA 19-9 and lymphangitis carcinomatosa].

A 69-year-old male was admitted to our hospital because of dry cough. Chest X-P and CT scans showed a mass shadow in the right lung, thickening of pulmonary vessels and pleural effusion. Cytological examination of transbronchial brushing specimen revealed lung adenocarcinoma. Cancer cells were also detected in pleural effusion. High levels of CA 19.9 were noticed: 48,400 U/ml in serum and 395,000 U/ml in pleural effusion, respectively. Two courses of combined chemotherapy (CDDP + VDS) were done. Concurrent chest radiation therapy (40 Gy) to primary tumor was also performed. After treatment the primary tumor decreased in size on CT scan analysis, but the patient suffered from respiratory failure due to the increase of sputa and pleural effusion and died 104 days after admission.

Adenocarcinoma↗