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Biomedical subjects

I Nakamura

Publications and source records attributed to I Nakamura.

At least 163 records · Page 9Linked to original sources
PubMed1995

A possible mechanism of the specific action of bisphosphonates on osteoclasts: tiludronate preferentially affects polarized osteoclasts having ruffled borders.

The mechanism of action of tiludronate [(4-chlorophenyl)-thiomethylene bisphosphonate] on osteoclastic bone resorption was examined in mouse culture systems. Tiludronate did not inhibit the formation of osteoclast-like multinucleated cells (OCLs) induced by 1 alpha,25-dihydroxyvitamin D3 in cocultures of mouse osteoblastic cells and bone marrow cells. OCLs obtained from cocultures on collagen gel-coated dishes, treated with tiludronate, formed as many resorption pits on dentine slices as those obtained from the control cocultures. However, pit formation by OCLs was dose-dependently inhibited when tiludronate was added directly to the pit formation assay. Other bisphosphonates such as alendronate and etidronate dose-dependently inhibited pit formation according to the in vivo potencies of the respective bisphosphonates to inhibit bone resorption. However, they had no inhibitory effect on the recruitment of OCLs induced by 1 alpha,25-dihydroxyvitamin D3 in the cocultures. When OCLs were placed on dentine slices, they formed the ringed structure of F-actin-containing podosomes and ruffled borders (polarized OCLs) even in the presence of tiludronate. However, the actin rings in OCLs were disrupted by the addition of tiludronate soon after they began to resorb dentine. In contrast, OCLs placed on collagen gel formed neither actin rings nor ruffled borders (nonpolarized OCLs), and showed no response to tiludronate. OCLs formed from the spleen cells of osteosclerotic (oc/oc) mice developed the ringed structure of podosomes, but not ruffled borders, on dentine slices. The actin ring in the oc/oc spleen cell-derived OCLs placed on dentine slices was not disrupted by the addition of tiludronate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Spinal tract degeneration confined to the bilateral posterior columns in malnutrition: report of an autopsy.

An autopsy case of malnutrition with spinal tract degeneration confined to the bilateral posterior columns is reported. The patient had schizophrenia in adolescence, and suffered from aplastic anemia in late middle age. Subsequently, he took little food due to delusions for 18 months until his death. He had malnutrition resulting in severe hypoproteinemia. He developed gait disturbance, loss of deep tendon reflexes and paresthesia of limbs. Neuropathological examination disclosed tract degeneration confined to the bilateral spinal posterior columns, in addition to the findings of aplastic anemia and hypoxic encephalopathy in the cerebrum. The myelin and axons were severely affected throughout the spinal cord; status spongiosus with many fatty-laden macrophages was seen in these lesions. Neurons in the posterior column nuclei were intact, while the dorsal roots and their ganglia were moderately affected. The unusual distribution and extension of the degeneration of the bilateral posterior columns in the poor nutritional state is discussed.

Anemia, Aplastic↗
PubMed1995

Twenty-four hour monitoring of blood pressure and heart rate in patients with chronic renal failure or renal transplant recipients: analysis by the cosinor method.

Hypertension is a major problem of patients with chronic renal failure or renal transplant recipients. To clarify the characteristics of blood pressure, heart rate, and circadian rhythms of these patients we used an ambulatory blood pressure monitor (ABPM) for 24 h monitoring and analyzed the data by the cosinor method. In eight chronic renal failure patients without dialysis the midline estimating statistic of rhythm (MESOR) of diastolic blood pressure was higher than in controls, but the MESOR of systolic blood pressure was not. Of 11 patients on dialysis some had hypertension and some had hypotension. In 14 renal transplant recipients, especially those with chronic graft rejection, the MESOR of systolic and diastolic pressures were higher than controls, and the increase of blood pressure MESOR had a significant correlation with the elevation of serum creatinine levels. Circadian rhythms of blood pressure were frequently absent in the patients on dialysis, but circadian rhythms of heart rate were not. The use of an ABPM is a non-invasive method to monitor patients and allowed us to know changes of blood pressure and heart rate in the daytime as well as during the night. For the control of hypertension in chronic renal failure, monitoring with an ABPM seems to provide invaluable information.

Adolescent↗
PubMed1995

Numerical chromosome aberrations in bladder cancer detected by in situ hybridization.

OBJECTIVE: To investigate the relationship between interphase cytogenetics and the grade and stage of bladder cancer in patients with transitional cell carcinomas of the urinary bladder. PATIENTS AND METHODS: By use of in situ hybridization with chromosome-specific DNA probes, the copy number of pericentromeric sequences on chromosomes 7, 10, 11, 17, 18, X and Y was detected within interphase nuclei in formalin-fixed and paraffin-embedded sections of the routinely processed bladder cancers from 20 patients. The percentage of hyperdiploid cells (three or more spots) was estimated using light microscopy. RESULTS: The percentage of hyperdiploid cells for chromosomes 7, 11 and 17 was highly correlated with increasing tumour grade (P < 0.01, Spearman rank correlation) or increasing pathological stage (P < 0.01). The percentage of hyperdiploid cells for chromosome Y was not correlated with either grade or stage (P > 0.05). As high tumour grade and stage are both indicative of more aggressive tumour behaviour and a worse prognosis, these findings suggest that the percentage of hyperdiploid cells, especially for chromosomes 7, 11 and 17, may be highly predictive of bladder tumour aggressiveness. CONCLUSION: These preliminary results suggest that measurement of numerical chromosome aberrations using in situ hybridization in bladder cancer may offer a new objective and quantitative assay of the biological potential of individual tumours.

Aged↗
PubMed1995

Effects of clonidine and yohimbine on parasympathetic reflex salivation and vasodilatation in cat SMG.

The present experiments were designed to examine the site of action of the alpha 2-adrenoceptor agonist, clonidine, and the alpha 2-antagonist, yohimbine, on the salivary secretion response to parasympathetic and sympathetic stimulation in the cat submandibular gland (SMG). The parasympathetic reflex salivary secretion was significantly affected by both clonidine and yohimbine (clonidine reduced and yohimbine increased the amount of saliva secreted) while the reflex vasodilator response was not affected by either agent. No degree of methacholine-induced salivation was affected by prior treatment with either clonidine or yohimbine. The salivation elicited by facial nerve root stimulation was markedly reduced by clonidine but potentiated by yohimbine. Prior treatment with scopolamine completely abolished the salivary secretion induced by either methacholine or facial nerve root stimulation. Clonidine and yohimbine had no effect on SMG salivation elicited by sympathetic stimulation. These results indicate that the alpha 2-agonist and antagonist act specifically on parasympathetic salivary fibers but have no effect on parasympathetic vasodilator fibers. They thus suggest that postganglionic parasympathetic innervation is differentiated into salivary and vasodilator fibers.

Animals↗
PubMed1995

Sensitization of nociceptive C-fibers in zinc-deficient rats.

A marked decrease in zinc concentration was observed in plasma (P < 0.001), hindpaw skin (P < 0.01), and dorsal skin (P < 0.01) in zinc-deficient rats (rats fed a zinc-deficient diet for 3 wk), compared with the control rats fed the same zinc-deficient diet supplemented with ZnCO3 (50 mg/kg diet). The threshold intensity needed to elicit vasodilatation in the hindpaw skin of the zinc-deficient rats on electrical stimulation of the saphenous nerve in a peripheral direction was markedly lower (P < 0.01) than that in the control rats. No difference was observed between control (n = 5) and zinc-deficient rats (n = 5) in the magnitude of the plasma extravasation evoked by either histamine or substance P. There was no difference between control and zinc-deficient rats in terms of the dose-response curve for release of histamine by substance P. Prostaglandin E2 (PGE2) concentration in the hindpaw skin of the zinc-deficient rats was nearly fourfold higher (P < 0.01) than that of the control rats, whereas no difference in the leukotriene B4 level in the hindpaw skin was observed between control and zinc-deficient rats. From the present study, it seems likely that an increased level of PGE2 in the vicinity of the nociceptive C-fiber terminals in the hindpaw skin of zinc-deficient rats may sensitize the terminals of the nociceptive C-fibers of the saphenous afferent nerve in the hindpaw and thus facilitate the production of antidromic vasodilatation.

Afferent Pathways↗
PubMed1995

The small GTP-binding protein, rho p21, is involved in bone resorption by regulating cytoskeletal organization in osteoclasts.

Rho protein (rho p21), a p21ras-related small guanine nucleotide binding protein, regulates cytoskeletal organization in a number of different types of cells. Evidence has indicated that Clostridium botulinum-derived ADP-ribosyltransferase (C3 exoenzyme) specifically ADP-ribosylates rho p21 at Asn41 and renders it functionally inactive. In this study, we examined the involvement of rho p21 in osteoclastic bone resorption using the C3 exoenzyme. When osteoclast-like multinucleated cells obtained from cocultures of mouse osteoblastic cells and bone marrow cells were placed on dentine slices, they formed ringed structures of podosomes containing F-actin (corresponding to the clear zone) within 8 hours. Many resorption pits were formed on dentine slices after culture for 24 hours. The C3 exoenzyme at 0.15-10 micrograms/ml added to the culture medium disrupted the ringed structure of podosomes in osteoclast-like cells in a dose-dependent manner. Correspondingly, pit formation by osteoclast-like cells on dentine slices was dose-dependently inhibited also by adding the C3 exoenzyme. Microinjection of the C3 exoenzyme into osteoclast-like cells placed on culture dishes completely disrupted the ringed podosome structure within 20 minutes. The amount of the rho p21 which was ADP-ribosylated by the C3 exoenzyme in vitro was much greater in purified osteoclast-like cells than in osteoblastic cells. Prior exposure of the purified osteoclast-like cell preparation to the C3 exoenzyme in vivo markedly decreased the amount of unribosylated rho p21. This indicated that the C3 exoenzyme incorporated into osteoclast-like cells effectively ADP-ribosylates rho p21 in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1995

Antimicrobial activity of lasalocid against Selenomonas ruminantium--effect of changes in pH induced by changing glucose concentration.

A significant decrease in pH occurred in the culture medium when cells of Selenomonas ruminantium HD-4 were incubated in the presence of relatively high concentrations of glucose (0.4 and 1.0%). Forty microM lasalocid reduced cell growth to 35.5 and 35.7% of control growth, respectively, for 0.05 and 0.4% glucose, while growth was completely inhibited by 40 microM lasalocid in the presence of 1.0% glucose. In the presence of 80 microM lasalocid, cells were unable to grow within 24 hr at any glucose concentration. In the case of treatment with 10 microM lasalocid, growth was inhibited when pH decreased below 6.0 in the presence of 0.4 and 1.0% glucose. With 0.05% glucose, pH never reduced to below 6.4 within 24 hr and there was no significant effect of lasalocid on either growth or pH. When cultures were treated with 10 microM lasalocid at the mid-exponential phase, growth was moderately inhibited and abnormal cells which had outer membrane detached from the inner membrane layer resulting in cell lysis were found in thin sections. These results indicate that the presence of large amounts of glucose decreases pH in culture medium and that the decrease in pH to below about 6.0 causes the increased effect of lasalocid on the growth of S. ruminantium. These results suggest that the antimicrobial activity of lasalocid is potentiated by a decrease in extracellular pH.

Anti-Bacterial Agents↗
PubMed1995

[Nephron sparing surgery of patients with renal cell carcinoma in a solitary kidney or bilateral renal cell carcinoma].

PURPOSE: The objective of this study is to evaluate the efficacy of nephron sparing surgery for renal cell carcinoma in patients with a solitary kidney or bilateral tumors. PATIENTS AND METHODS: From 1982 to 1994, a total of 12 patients with a solitary kidney or bilateral tumors underwent nephron sparing surgery. The survival and complications were examined. RESULTS: The patients were 11 males and 1 female. Three patients were in stage 1, 6 in stage 2, 2 in stage 3, and 1 in stage 4, and the mean tumor size was 3.4 cm (0.8-6.5). The complications were post-operative bleeding in one patient and slight transient renal dysfunction which didn't require hemodialysis in 3 patients. The local recurrence was observed in 1 patient (8.3%), metastasis in 3 (25%), no evidence of disease in 8 (66.7%), alive with cancer in 1 (8.3%), death due to cancer in 2 (16.7%), death due to other disease in 1 (8.3%), and the 5 year survival of all patients was 62.5%, that was almost the same as the result of 141 renal cell carcinoma patients treated with nephrectomy in our hospital. The disease free survival rate of the patients in stage 1 and 2 seems to be higher than in stage 3 and 4 with no significant difference (p = 0.0956). CONCLUSION: These results suggest that nephron sparing surgery for renal cell carcinoma in patients with a solitary kidney or bilateral tumors is a useful therapy.

Aged↗
PubMed1995

[A comparative study of DNA measurement of bladder cancer from image cytometry and chromosome aberration in in situ hybridization].

The relationship between interphase cytogenetics and the DNA index measuring SCM of bladder cancer was investigated in 17 patients with bladder tumor. By in situ hybridization, the copy number of chromosomes 1, 7, 10, 11, 17, 18, X and Y was detected. The percentage of hyperdiploid cells for chromosomes 7 and 17 was highly correlated with the increasing DNA index. Since a high DNA index is both indicative of more aggressive tumor behavior and a worse prognosis, these findings suggest that the percentage of hyperdiploid cells, especially for chromosome 7 and 17, may be highly predictive of bladder tumor aggressiveness.

Carcinoma, Transitional Cell↗
PubMed1995

[Postoperative care of neobladder using a detubularized intestinal segment].

Neobladder using a detubularized intestinal segment was constructed in 74 cystectomized patients between October 1986 and July 1994. There were 65 males (87.8%) and 9 females (12.2%) with an average age of 63 years (range 36 to 77 years). The mean follow-up period was 35 months (range 7 to 85). Problems of postoperative care assessed were continence, renal function, metabolic consequences, neoplasms and other complications. Moreover, the impact of these problems on the quality of life was evaluated by a self-administered questionnaire. Continence in the daytime was achieved in 70/74 (94.6%) patients. Nocturnal incontinence was noted in 15/74 (20.3%) patients. Serum BUN and creatinine levels were maintained within normal limits. Metabolic acidosis (base excess < -5.0 occurred in 7/74 (9.5%) patients, 4 patients of whom needed alkalizing agents. Colon adenomas in neobladder were found and resected in 3 patients. The other postoperative complications were stone formation in neobladder in 4 (5.4%), urethral stricture in 7 (9.5%) and ureteral stenosis in 3 (4.1%) patients respectively, which were satisfactorily corrected by endourological procedures. As to quality of life assessment, the majority was satisfied, whereas 11% of the patients reported emotional distress and limitations in the usual physical activities by nocturnal incontinence. Our finding suggest that nocturnal incontinence is the most important problem and we need longer follow-up to evaluate the problems of metabolic consequences and neoplasms of the urinary tract.

Adult↗
PubMed1995

Life time expectancy of hemophilia patients infected with HIV-1 with the risk of hepatocellular carcinoma after HCV infection.

1. INTRODUCTION. The latest statistics how that Japanese hemophilia patients infected with HIV-through clotting factor concentrates may survive more than 10 years after HIV-infection without showing an onset of AIDS [1]. Unfortunately, however, results of the recent surveillance have revealed that about half of hemophilia patients had also been infected with the hepatitis C virus (HCV) [2]. Therefore, some hemophilia patients might suffer from hepatocellular carcinoma triggered by HCV after some latent periods. In the present study, we computed the life time expectancy of hemophilia patients with two risks of HIV-and HCV infections. 2. METHOD. We used the Weibull hazard function h(t) for the hazard rate from AIDS after infection with HIV-1. In order to describe the hazard rate arising from hepatocellular carcinoma after HCV infection, we utilized the theoretical function c(t) with two parameters that were obtained previously by ourselves from a case-controlled study on hepatocellular carcinoma patients infected with HCV through blood transfusion [3]. Substituting necessary parameters estimated for Japanese hemophilia patients into h(t), the life time expectancy t was computed by the following integration; tau=integral of exp(-integral of h(t')+c(t¿) dt') dt, where t' means the time after HIV-infection, and t¿ is a variable composed of tU and times of HIV-and HCV infections. 3. RESULTS AND DISCUSSION. Without hepatocellular carcinoma, the life time expectancy tau of the patients infected with HIV-1 at the age of 20 was computed as 15.0 years. On the other hand, for the same patients with the risk of hepatocellular carcinoma through HCV infection at the age of 10, 15, 20 and 25 years old, values of tau were computed at 12.2, 13.3, 14.1 and 14.4 years, respectively. Especially noticeable was the reduction of tau in cases of HCV infection was prior to HIV-infection. In the present computation, the two risks from HIV-1 and HCV infections were assumed to be additive because no explicit interaction between them has been reported yet. Various long term effects have been found with the development of HIV/HCV therapies; that should also take into account the survival estimation and therapy planning for HIV-1 infected patients in the coming years.

Acquired Immunodeficiency Syndrome↗
PubMed1994

The ability of H-2Dd molecule to affect natural resistance to hemopoietic allografts is an intrinsic property shared by Ddm1 but not Ld.

F1 hybrid resistance (HR) to parental bone marrow grafts is mediated by natural killer (NK) cells, and thought to be controlled by the non-class I hemopoietic histocompatibility (Hh) genes linked to the major histocompatibility complex (MHC). However, as in the in vitro NK cytotoxicity against hemopoietic targets, expression of certain class I MHC molecules does affect HR, although mechanisms underlying such an effect are not understood. In this study, we examine the relevance of the "self/non-self" property of class I molecules and the molecular domains responsible for this function. H-2b/Hh-1b lymphoma cells were transfected with class I H-2Dd or Ld gene, and its effect on the Hh-1 phenotype was examined by testing the transfectant's ability to competitively inhibit the in vivo rejection of parental H-2b/Hh-1b bone marrow grafts by irradiated F1 hybrid hosts. Multiple independent clones of transfectants show that the genomic or cDNA of the Dd gene, but not of Ld, renders the Hh-1b-positive cells incapable of inhibiting HR in F1 mice, although both genes belong to the same region of the same haplotype. The same effect could be observed not only in H-2b/d F1 mice for which Dd and Ld are self, but also in H-2b/k F1 mice for which both Dd and Ld are non-self. Thus, this function of the Dd molecule is an intrinsic property, not necessarily related to its self/non-self characteristic relative to the effector cells. Furthermore, given the nature of the assay used in this study, the results favor a "target interference" model as the underlying mechanism of the Dd effect. To locate the relevant domain(s) of the Dd molecule, mutant Ddm1 gene was tested and found to have the same effect as the non-mutant Dd. Ddm1 is a hybrid molecule between Dd and Ld, sharing with Dd only the alpha 1 domain and a portion of the alpha 2 domain. The two N-terminal domains of Ddm1 differ from those of Dd by three amino acid substitutions, two of which affect the molecules' peptide-binding properties.

Animals↗
PubMed1994

Coxsackievirus B3 infection leads to cell death of cardiac myocytes.

In order to address the question whether the virus or immune reactions to the heart induce cardiac damage in the murine model of coxsackievirus B3 induced myocarditis, calcium-resistant cardiac myocytes of a myocarditis susceptible strain of mice were isolated and exposed to myocarditic coxsackievirus B3. The tetrazolium salt MTT was used to visualize the effect of the virus upon cell viability by inverse light microscopy and by an EA test. Coxsackievirus B3 infected isolated adult cardiac myocytes as well as infected cultured cardiac fibroblasts were examined. In vitro the virus killed the myocytes within 16 h of infection whereas the fibroblasts survived the infection. Since coxsackievirus B3 is able to kill cardiac myocytes by itself, immunosuppressive treatment of acute coxsackievirus B3 induced myocarditis may be harmful by eliminating host immune defence mechanisms and, therefore, may lead to an enhanced viral spread and virus induced myocyte necrosis in the heart.

Animals↗
PubMed1994

Comparison of the prophylactic usefulness of epirubicin and doxorubicin in the treatment of superficial bladder cancer by intravesical instillation: a multicenter randomized trial. Kobe University Urological Oncology Group.

A multicentric randomized trial was conducted for the purpose of investigating the prophylactic efficacy of intravesical epirubicin instillation following transurethral resection of superficial bladder cancer in comparison with the efficacy of doxorubicin. The patients were centrally randomized into 2 groups and received 19 intravesical instillations of epirubicin or doxorubicin at 30 mg/30 ml physiological saline twice a week for 4 weeks and then once monthly for 11 months. A total of 150 patients with Ta and T1 superficial bladder cancer were entered in the trial, and 114 were evaluable. The nonrecurrence rates determined for each group at 1 and 2 years by the Kaplan-Meier method were 92.8% and 88.6%, respectively, for the epirubicin group and 86.4% and 81.7%, respectively, for the doxorubicin group. The differences between the two groups were not statistically significant. The main side effects encountered in this study were symptoms of bladder irritation such as micturitional pain, pollakisuria, and hematuria. The respective frequencies of those symptoms were 10%, 15.0%, and 5.0% in the epirubicin group and 14.8%, 14.8%, and 0 in the doxorubicin group. These results suggest that epirubicin is a useful drug, comparable with doxorubicin, for intravesical instillation chemotherapy in the prophylactic treatment of superficial bladder cancer.

Administration, Intravesical↗