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Biomedical subjects

H Koike

Publications and source records attributed to H Koike.

At least 19 recordsLinked to original sources

Prevention of onset of Parkinson's disease by in vivo gene transfer of human hepatocyte growth factor in rodent model: a model of gene therapy for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SNi). As neurotrophic factors support the survival and enhance the function of dopaminergic neurons, gene therapy using neurotrophic factors has become the center of interest. Thus, we focused on hepatocyte growth factor (HGF) as a neurotrophic and angiogenic growth factor. At 7 days before injection of 6-hydroxydopamine into the SNi, stereotaxic transfection of human HGF or lacZ plasmid was performed into the unilateral striatum of rats. Expression of human HGF in the injected sites could be detected in rats transfected with HGF plasmid DNA, using immunohistochemical staining. Consistently, human immunoreactive HGF protein could be detected at least up to 12 days after transfection. Interestingly, PD rats transfected with lacZ demonstrated amphetamine-induced rotational asymmetry. However, transfection of HGF plasmid DNA resulted in significant inhibition of abnormal rotation up to 24 weeks in a dose-dependent manner. Over 90% of dopaminergic neurons were lost in PD rats transfected with lacZ, whereas over 70% survived in rats transfected with HGF, as assessed by immunohistochemical staining. Overall, the present study demonstrated that overexpression of HGF prevented neuronal death in a PD rat model, providing a potential novel therapy for PD.

Animals↗

Overexpression of stathmin in oral squamous-cell carcinoma: correlation with tumour progression and poor prognosis.

Stathmin is an intracellular phosphoprotein that is overexpressed in a number of human malignancies. Our previous study using proteomic profiling showed that significant upregulation of stathmin occurs in oral squamous-cell carcinoma (OSCC)-derived cell lines. In the current study, to determine the potential involvement of stathmin in OSCC, we evaluated the state of stathmin protein and mRNA expression in OSCC-derived cell lines and human primary OSCCs. A significant increase in stathmin expression was observed in all OSCC-derived cell lines examined compared to human normal oral keratinocytes. In immunohistochemistry, 65% of the OSCCs were positive for stathmin, and no immunoreaction was observed in corresponding normal tissues. Real-time quantitative reverse transcriptase-polymerase chain reaction data were consistent with the protein expression status. Moreover, stathmin expression status was correlated with the TNM stage grading. Furthermore, we found a statistical correlation between the protein expression status and disease-free survival (P=0.029). These results suggest that expression of stathmin could contribute to cancer progression/prognosis, and that stathmin may have potential as a biomarker and a therapeutic target for OSCC.

Aged↗

No evidence to indicate topographic dependency on bone formation around cp titanium implants under masticatory loading.

In vitro studies have proved the topographic dependency upon osteogenesis on titanium plate by investigating the cell-adhesion, -shape, -proliferation, -differentiation, ALP activity and osteocalcin production of osteogenic stem cells, MG36, MC3T3-E1 and wild strains of bone formative cells from animal and human. However, this in vivo study on bone growth around cp titanium dental implants under masticatory loading did not demonstrate significant difference among the different surface roughness in the range of Ra 0.4-1.9 microm, Rz 2.8-11.2 microm, Rmax 3.6-28.1 microm and Sm 2.9-41.0 microm, which was estimated by measuring the bone contacts, bone occupancies and bone bonding strengths at the implant/bone marrow interface. It is revealed that the topographic dependency on the osteogenetic activity is apt to be covered with wide variation in bone healing potential under the clinical condition with functional biting load.

Animals↗

Relationship between tooth contacts in the retruded contact position and mandibular positioning during retrusion.

We conducted a series of studies with the purpose to investigate the locations of tooth contacts in the retruded contact position (RCP) and to discuss their significance in the stomatognathic system. In the present study, the relationship between the locations of RCP contacts and mandibular positioning during retrusion was examined. Thirty dentists and clinical residents were selected as subjects. One specialist in prosthetic dentistry examined each subject for the location of the RCP contacts. The mandibular positioning during retrusion was measured using a mandibular movement analysis system with six degrees of freedom. Originally programmed software was developed. Five reference points were selected: the central lower incisor (point I), the first molars on both sides (points RM and LM) and the condyles on both sides (points RC and LC). Tooth contact was observed most frequently at the second molar, followed by the first premolar. Points I, RM and LM all moved in an inferior-posterior direction, whereas points RC and LC moved in various directions ranging from superior-posterior to inferior-posterior. When the subjects were divided into two groups according to the most anterior tooth of occlusion in the RCP, the condylar positioning tended to be more superior in the group with molar contact than that with premolar contact. These results suggest that the locations of RCP contacts could be an important factor in jaw guidance during retrusion.

Adult↗

Intravenous immunoglobulin treatment in painful sensory neuropathy without sensory ataxia associated with Sjögren's syndrome.

Patients having neuropathy associated with Sjögren's syndrome may present with pain and superficial sensory involvement in the absence of sensory ataxia. Treatment for this form of associated neuropathy has not been established. The case of a patient with painful sensory neuropathy associated with Sjögren's syndrome, whose symptoms, particularly pain, responded well to intravenous immunoglobulin both at onset and in a relapse, is reported. Other patients with painful sensory neuropathy associated with Sjögren's syndrome may also be candidates for intravenous Ig treatment.

Aged↗

Clinicopathologic features of nonsystemic vasculitic neuropathy and microscopic polyangiitis-associated neuropathy: a comparative study.

OBJECTIVE: To compare clinicopathologic findings in nonsystemic vasculitic neuropathy (NSVN) and microscopic polyangiitis-associated neuropathy (MPAN). METHODS: Patients clinicopathologically confirmed to have NSVN (n=23) or MPAN (n=40) were compared with respect to clinical, electrophysiologic, and histopathologic features. RESULTS: Clinical features of neuropathy such as initial symptoms, progression, and distribution of sensory and motor deficits were similar in both groups, while functional compromise was greater in MPAN than NSVN. Abnormalities of laboratory data including those reflecting severity and extent of inflammation such as C-reactive protein were more conspicuous in MPAN than NSVN. Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) were positive in two-thirds of patients with MPAN but negative in all NSVN. Electrophysiologic and histopathologic findings indicated axonal neuropathy in both groups, whereas the reduction of compound muscle action potentials in the tibial nerve and sensory nerve action potentials in the median nerve was significantly more profound in MPAN than NSVN. As for the epineurial perivascular infiltration, frequencies of cell-specific markers for T lymphocytes, macrophages, and B lymphocytes among cells infiltrating the vasculitic lesions were essentially similar between groups. CONCLUSIONS: Clinicopathologic profiles and vascular pathology were similar between NSVN and MPAN but the age at onset, severity, and presence of p-ANCA were clearly different. Further study is needed to clarify the pathogenesis of NSVN and its place in the vasculitic spectrum of diseases.

Action Potentials↗

Neuronal intranuclear hyaline inclusion disease showing motor-sensory and autonomic neuropathy.

BACKGROUND: Neuronal intranuclear hyaline inclusion disease (NIHID), a rare neurodegenerative disease in which eosinophilic intranuclear inclusions develop mainly in neurons, has not yet been described to present as hereditary motor-sensory and autonomic neuropathy. METHODS: Patients in two NIHID families showing peripheral neuropathy were evaluated clinically, electrophysiologically, and histopathologically. RESULTS: In both families, patients had severe muscle atrophy and weakness in limbs, limb girdle, and face; sensory impairment in the distal limbs; dysphagia, episodic intestinal pseudoobstruction with vomiting attacks; and urinary and fecal incontinence. No patients developed symptoms suggesting CNS involvement. Electrophysiologic study showed the reduced motor and sensory nerve conduction velocities and amplitudes, and also extensive denervation potentials. In sural nerve specimens, numbers of myelinated and unmyelinated fibers were decreased. In two autopsy cases, eosinophilic intranuclear inclusions were widespread, particularly in sympathetic and myenteric ganglion neurons, dorsal root ganglion neurons, and spinal motor neurons. These neurons also were decreased in number. CONCLUSION: Patients with neuronal intranuclear hyaline inclusion disease (NIHID) can manifest symptoms limited to those of peripheral neuropathy. NIHID therefore is part of the differential diagnosis of hereditary motor-sensory neuropathy associated with autonomic symptoms. Intranuclear hyaline inclusions in Schwann cells and in the myenteric plexus may permit antemortem diagnosis of NIHID.

Aged↗

Clinical and electrophysiologic correlates of IVIg responsiveness in CIDP.

To identify clinical and electrophysiologic features related to IV immunoglobulin (IVIg) responsiveness in chronic inflammatory demyelinating polyneuropathy (CIDP), the authors conducted a multicenter study on 312 patients with CIDP (199 responders and 113 nonresponders). Muscle atrophy and decreased compound muscle action potential were pronounced in nonresponders of IVIg. Male gender, longer disease duration, and slow progression of symptoms were also associated with IVIg unresponsiveness. Features suggesting axonal dysfunction in peripheral nerves indicated IVIg unresponsiveness in CIDP.

Adult↗

Insulin-like growth factor binding protein-6 inhibits prostate cancer cell proliferation: implication for anticancer effect of diethylstilbestrol in hormone refractory prostate cancer.

Diethylstilbestrol (DES) is a synthetic oestrogen, and its anticancer effects are exerted in androgen-dependent prostate cancer. The administration of DES decreases serum testosterone to castration levels. However, in androgen-independent prostate cancer patients, who are already orchiectomised, the administration of DES improves symptoms and decreases prostate-specific antigen (PSA). The mechanisms responsible for these direct inhibitory effects have been explained as biological actions not mediated by oestrogen receptors. We assessed the gene expression profiles of prostate cancer cells treated with DES, and investigated direct inhibitory effects of DES. DES inhibited the proliferation of LNCaP and PC-3 cells. cDNA microarray analysis showed that expression of many genes was downregulated by DES. However, insulin-like growth factor binding protein 6 (IGFBP-6) gene expression levels were upregulated in PC-3 cells. IGFBP-6 gene expression and protein levels significantly increased after DES treatment. Recombinant IGFBP-6 inhibited cell proliferation, and the inhibitory effect of DES was neutralised by anti-IGFBP-6 antibody. From the immunohistochemical analysis of IGFBP-6 using biopsy samples from androgen-independent prostate cancer, we found IGFBP-6 expression in androgen independent prostate cancer, and that DES treatment increased the IGFBP-6 staining intensity of the cancer cells in one sample. These findings suggested that DES induces IGFBP-6, which inhibits cell proliferation in an androgen-independent prostate cancer cell line, PC-3. IGFBP-6 therefore might be involved in the direct effects of DES in androgen-independent prostate cancer.

Antineoplastic Agents, Hormonal↗

Age associated axonal features in HNPP with 17p11.2 deletion in Japan.

OBJECTIVE: To clarify age related changes in the clinicopathological features of hereditary neuropathy with liability to pressure palsy (HNPP) in Japanese patients with deletion of 17p11.2, particularly concerning axonal abnormalities. METHODS: Forty eight proband patients from 48 HNPP families were assessed as to clinical, electrophysiological, and histopathological features, including age associated changes beyond those in controls. RESULTS: Motor conduction studies showed age associated deterioration of compound muscle action potentials in nerves vulnerable to repetitive compression (median, ulnar, and peroneal nerves), but not in others such as the tibial nerve. Sensory conduction studies revealed more profound reduction of action potentials than motor studies with little age related change. Large myelinated fibre loss was seen in the sural nerve irrespective of age at examination. CONCLUSIONS: Irreversible axonal damage may occur at entrapment sites in motor nerves in HNPP patients, progressing with aging. Sensory nerves may show more profound axonal abnormality, but without age association. The electrophysiological features of HNPP are presumed to be a mixture of abnormalities occurring from early in life and acquired features caused by repetitive insults at entrapment sites. Unlike Charcot-Marie-Tooth disease type 1A, age associated axonal damage may not occur unless the nerves are subjected to compression.

Action Potentials↗

[Off-pump coronary artery bypass for old myocardial infarction associated with jejunotomy for obstructive ileus due to gall bladder stone; report of a case].

In non-cardiac operative cases with inflammatory digestive organ disease, bacterial translocation (BT) often results from non-enteral nutrition postoperatively. If coronary artery bypass grafting (CABG) is performed in the case having old myocardial infarction (OMI) and inflammatory digestive organ disease at first before non-cardiac operation, he seems vulnerable to have severe complications such as multiple organ failure due to systemic inflammatory response syndrome (SIRS) and preexisting BT postoperatively. We performed a off-pump CABG (OPCAB) for OMI associated with jejunotomy for obstructive ileus due to gall bladder stone. No complication was found in the postoperative course. We conclude that combined operation, non-cardiac surgery after OPCAB is worth considering in those cases. And we think OPCAB is better than conventional CABG in such cases, because cardiopulmonary bypass is known to ponder comparable damages to immune system, coagulation system and others.

Aged↗

Pathology of early- vs late-onset TTR Met30 familial amyloid polyneuropathy.

BACKGROUND: Late-onset type I familial amyloid polyneuropathy (FAP TTR Met30) cases unrelated to endemic foci in Japan show clinical features setting them apart from early-onset cases in endemic foci. OBJECTIVE: To compare pathologic features between the early- and late-onset types. METHODS: Pathologic findings in FAP TTR Met30 with onset before age 50 in relation to endemic foci (11 cases) were compared with those in 11 later-onset cases unrelated to endemic foci. RESULTS: Sural nerve biopsy specimens showed predominantly small-fiber loss in early-onset cases; variable fiber size distribution, axonal sprouting, and relatively preserved unmyelinated fibers characterized late-onset cases. Autopsy cases representing both groups showed amyloid deposition throughout the length of nerves and in sympathetic and sensory ganglia, but amounts were greater in early-onset cases. Amyloid deposition and neuronal cell loss were greater in sympathetic than dorsal root ganglia in early-onset cases; the opposite was true in late-onset cases. Size assessment of remaining neurons in these ganglia suggested predominant loss of small neurons in early-onset cases but loss of neurons of all sizes in late-onset cases. Transthyretin-positive, Congo red-negative amorphous material was more conspicuous in nerves from late- than early-onset cases. In extraneural sites, amyloid was more conspicuous in thyroid and kidney from early-onset cases and in heart and hypophysis from late-onset cases. In early-onset cases, cardiac amyloid deposition was prominent in the atrium and subendocardium but was conspicuous throughout the myocardium in late-onset cases. CONCLUSION: The pathology of early- and late-onset FAP TTR Met30 correlated well with differences in clinical findings.

Adult↗

Transfection of NFkappaB-decoy oligodeoxynucleotides using efficient ultrasound-mediated gene transfer into donor kidneys prolonged survival of rat renal allografts.

Nuclear factor kappaB (NFkappaB) plays a pivotal role in the coordinated transactivation of a series of genes of cytokines and adhesion molecules that are highly involved in the onset of acute rejection in organ transplantation. We previously developed decoy cis-elements oligo deoxyribonucleic acid against NFkappaB (NFkappaB-decoy) that effectively inhibited the activation of major inflammatory mediators in vitro and in vivo. Accordingly, we hypothesized that transfection of NFkappaB-decoy into the donor kidney would prevent acute rejection and prolong graft survival, and thus provide effective therapy for renal acute rejection. To transfect NFkappaB-decoy, we employed a novel approach using ultrasound exposure with an echocardiographic contrast agent, Optison, and clearly demonstrated successful transfection of NFkappaB-decoy into renal tissue. The therapeutic effect of NFkappaB-decoy on renal allografts was then evaluated in a rat renal allograft model (Wistar-Lewis). In the control group, graft function significantly deteriorated with marked destruction of renal tissue, accompanied by increased production of major inflammatory mediators, and all animals died of renal failure by 9 days. In contrast, graft function (serum creatinine on day 2, NFkappaB-treated: 0.97+/-0.16 versus control: 1.84+/-0.23 mg/dl, P<0.01) and histological structure were well preserved with significantly decreased expression of NFkappaB-regulated cytokines and adhesion molecules, including IL-1, iNOS, MCP-1, TNF-alpha, and ICAM-1, in allografts transfected with NFkappaB-decoy. As a result, animal survival was significantly prolonged in this group as compared to controls (14.2+/-5.2 versus 7.1+/-1.2 days, P<0.01). Thus, we established a novel ultrasound-Optison-mediated gene transfection approach and demonstrated the significant prolongation of graft survival by the successful transfection of NFkappaB-decoy into the donor kidney in a rat renal allograft model.

Albumins↗

The clinical features of takotsubo cardiomyopathy.

BACKGROUND: Cardiologists have recently recognized a reversible form of heart failure of unknown origin characterized by a takotsubo-shaped hypokinesis of the left ventricle on left ventriculography. AIM: To clarify the clinical features of this cardiomyopathy. DESIGN: Observational study. METHODS: Seven patients with reversible ventricular dysfunction were followed for 4.5 years. Clinical course, routine examinations, and cardiac catheterizations in each patient were documented. RESULTS: The cardiomyopathy developed in six elderly female and one male patients (mean age 75.3 years), all of whom had been exposed to stress. Cardiac enzymes did not significantly increase, but serum norepinephrine increased remarkably (1.19 ng/ml). Coronary angiography revealed normal coronary arteries. However, left ventriculography showed akinesis in the apical segments, together with hyperkinesis in the basal segments (a takotsubo shape). The abnormal kinesis normalized within 17.4 hospital days without any treatment in five patients, and with haemodynamic support for 3 days in the other two. Endocardial biopsies did not suggest any specific pathology. The cardiac events did not recur over a 1-4 year follow-up. DISCUSSION: Coronary vasospasm, myocarditis and other substantial diseases previously described were ruled out as the cause of takotsubo cardiomyopathy in our subjects. Prognosis was good without any form of treatment, provided that the patients survived the severe heart failure state. Catecholaminergic or adrenoceptor-hyperactive cardiomyopathy may be the cause of this cardiomyopathy.

Aged↗

Chronic inflammatory demyelinating polyneuropathy presenting with features of GBS.

The authors report five patients with inflammatory demyelinating polyneuropathy with a Guillain-Barré syndrome (GBS)-like onset and initial clinical features, but with persistent symptoms similar to chronic inflammatory demyelinating polyneuropathy (CIDP). Patients in the chronic phase improved with corticosteroid or IV immunoglobulin therapy. Patients with apparent GBS who show persistent symptoms may benefit from corticosteroids or other treatment that is beneficial in the management of CIDP.

Adolescent↗

Painful alcoholic polyneuropathy with predominant small-fiber loss and normal thiamine status.

BACKGROUND: Although polyneuropathy related to chronic alcoholism has been reported frequently, its clinical features and pathogenesis remain to be clarified. OBJECTIVE: To determine the clinicopathologic features and pathogenesis of alcoholic polyneuropathy associated with pain in patients with normal thiamine status, particularly in comparison to beriberi neuropathy. PATIENTS AND METHODS: Clinical, electrophysiologic, and histopathologic findings were assessed in 18 patients with painful alcoholic polyneuropathy and normal thiamine status. RESULTS: Symmetric sensory-dominant polyneuropathy predominantly involving the lower limbs was the major clinical pattern. Painful sensations with or without burning quality represented the initial and major symptom. Progression of symptoms usually was gradual, continuing over months or years. Electrophysiologic and pathologic findings mainly indicated an axonal neuropathy. Densities of small myelinated fibers and unmyelinated fibers were more severely reduced than the density of large myelinated fibers, except in patients with a long history of neuropathic symptoms and marked axonal sprouting. CONCLUSIONS: The clinicopathologic features of painful symptoms and small axon loss are distinct from those of beriberi neuropathy. Sensory-dominant involvement with prominent neuropathic pain is characteristic of alcoholic neuropathy when thiamine deficiency is not involved, supporting the view of direct neurotoxic effect by alcohol or its metabolites.

Adult↗

New pharmacologic aspects of CS-866, the newest angiotensin II receptor antagonist.

CS-866 is a new angiotensin II receptor blocker that has demonstrated effectiveness for lowering blood pressure in animal models of hypertension. Given the proposed involvement of the renin-angiotensin system in diabetic nephropathy and atherosclerosis, we have tested CS-866 in animal models of these conditions. The renal protective properties of CS-866 were examined in the Zucker diabetic fatty (ZDF) rat, a model of type 2 diabetes that develops progressive hyperglycemia, glomerulosclerosis, and proteinuria. Treatment of ZDF rats with CS-866 in the diet for 19 weeks resulted in a dose-dependent reduction in urinary protein excretion compared with vehicle-treated control rats, which was independent of changes in blood pressure and glycemic state. The antiatherosclerotic properties of CS-866 were tested in 2 animal models. In the first study, cynomolgus monkeys were fed a high-cholesterol diet for 6 months while receiving CS-866 or vehicle. At the end of this period, CS-866-treated animals had 64% less plaque area in the aorta than controls. CS-866 was also tested in the Watanabe heritable hyperlipidemic (WHHL) rabbit model of atherosclerosis. WHHL rabbits were treated for 32 weeks with CS-866 (1 mg/kg), pravastatin (50 mg/kg), a combination of the 2 drugs, or vehicle. CS-866 had no effect on plasma cholesterol levels and reduced blood pressures minimally. Pravastatin alone reduced serum cholesterol but had no effect on blood pressure or lesion area. In contrast, treatment with CS-866 resulted in a 40% reduction in lesion area compared with vehicle-treated control when given alone and a 50% reduction in combination with pravastatin. On the basis of results from animal models, CS-866 may be a useful treatment for diabetic nephropathy and atherosclerosis.

Angiotensin Receptor Antagonists↗