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Biomedical subjects

K Hamaguchi

Publications and source records attributed to K Hamaguchi.

At least 91 records · Page 5Linked to original sources

[The effectiveness of discharge planning (DSP) in home care--comparison of conditions of cancer patient shifted to home treatment before and after DSP introduction].

We developed a discharge planning (DSP) procedure as a method to assess the family and cancer patient situation when making the shift to home care, and we herewith report its significance. DSP is intended to sustain the patient's quality of life (QOL) and improve it; for a smooth transition to treatment at home, the family and patient situation must be assessed from various perspectives. The prospective illness conditions, needed medical treatment and care should be appropriately planned, with due recognition of the roles to be played and the requisite pooling of professional information in order to handle emergencies and the like when such arise. In the present study, in order to clarify issues dealing with DSP effectiveness, we compared 34 patients on home care, 17 before DSP and 17 thereafter. The results indicated that following the introduction of DSP, the home care increased for patients with gastroenterological problems such as pain, general debilitation, poor appetite, constipation, diarrhea and the like and those impulsiveness, vomiting and mental symptoms overlapping. With the proper assessment at the time of the transition to home care, this care could be continued. Moreover, with patient satisfaction, there was the need for assessment over the course in order to evaluate treatment and care. In the days to come, there is the need to improve this approach with a scoring system in the evaluation.

Activities of Daily Living↗

Effect of modifying histidine residues on the action of Bacillus amyloliquefaciens and barley-malt alpha-amylases.

Modification of porcine pancreatic alpha-amylase (PPA) and Taka-amylase A(TAA) with diethyl pyrocarbonate (DEP) causes activation of the release of p-nitrophenol from p-nitrophenol alpha-maltoside (G2PNP), and a decrease in amylase activity (hydrolysis of alpha-1,4 glucosidic bonds in starch). Among the possible sites of modification, attention focuses on three histidine residues present around the active site of alpha-amylases of many different origins. In PPA these are His 101, His 201, and His 299, with His 101 and His 299 being very close to the site of catalysis and thus perhaps directly or indirectly involved in the catalysis. On the other hand, His 201 is located on the aglycon side of the catalytic site, and we have suggested that it is involved in the increase of PNP release after chemical modification. Investigations of site-directed mutagenesis of the histidine residues of human pancreatic alpha-amylase support this identification. Although the degree of sequence similarity among alpha-amylases of different origins is low, there are several conserved short regions. Most belong to the structural components of the active site in PPA and TAA. Furthermore, there is a close similarity in the three-dimensional structures of PPA and TAA. The conserved residues around the active site in all alpha-amylases suggest some universal structural similarities in these active sites. Therefore, we examined the effects of the chemical modification of histidine residues in Bacillus amyloliquefaciens alpha-amylase(BLA) with DEP and made a comparison with modification of barley alpha-amylase isoenzyme II(BAII), using identical substrate systems. These two alpha-amylases have more substrate binding subsites than PPA and TAA, and have similar action patterns with malto-oligosaccharides.

Bacillus↗

IDDM susceptibility associated with polymorphisms in the insulin gene region. A study of blacks, Caucasians and orientals.

Previous studies have suggested an association between polymorphisms in the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Most of the studies so far have been performed in Caucasoid populations. We have investigated 418 random IDDM patients and 422 healthy control subjects from three different ethnic groups; Tanzanian blacks, Norwegian Caucasians and Japanese orientals. Our data suggest that polymorphisms in the insulin gene region confer susceptibility to IDDM in Caucasians, and that a similar tendency though not statistically significant is observed among Tanzanian blacks, while no significant contribution is seen among Japanese orientals. We further demonstrate that the disease-associated genotype INS +/+ confers susceptibility independently of HLA class II alleles associated with IDDM. Compared to the contribution of particular HLA-DQ alleles in IDDM susceptibility, the additional risk conferred by the insulin gene region polymorphism is, however, small. Genotyping of the insulin gene region will therefore most probably not be a useful tool in the prediction of IDDM.

Adult↗

PCPA reduces both monoaminergic afferents and nonmonoaminergic synapses in the cerebral cortex.

In order to examine the possible trophic, nontransmitter role of monoaminergic fibers in the adult CNS, synaptic structures were examined in different laminae of the somatosensory cortex of the rat following a p-chlorophenylalanine (PCPA)-induced decrease of monoamine. Synaptic densities were reduced in a dose-dependent fashion by 30-50% in the target area of monoamine fibers following four injections of PCPA made over a 1-week period. Although serotonin- and tyrosine hydroxylase-immunopositive profiles were frequently observed in all laminae of the cerebral cortex, only a few such profiles had the morphology of synapses. Therefore, virtually all of the reduction in synaptic structures following PCPA treatment involved nonmonoaminergic fibers.

Animals↗

Descending necrotizing mediastinitis secondary to a retropharyngeal abscess.

A rare case of descending necrotizing mediastinitis (DNM) secondary to a nontraumatic retropharyngeal abscess is reported. Even in the era of antibiotics, the mortality of DNM is still around 40%. In spite of drainage of a localized neck abscess, and the administration of systemic antibiotics, the retropharyngeal abscess extended to the pericardial and pleural cavities. Several drainage procedures and thoracotomies were performed to treat the bilateral empyemas and purulent pericarditis. The patient was discharged on hospital day 52. Computed tomography was used to follow the progression of disease, and assess the efficacy of treatment. DNM is a very aggressive form of mediastinitis. The importance of proper mediastinal drainage, as well as the systemic administration of antibiotics, must be emphasized.

Candidiasis↗

IgA nephropathy associated with portal hypertension in liver cirrhosis due to non-alcoholic and non-A, non-B, non-C hepatitis.

A 69-year-old female was admitted to our hospital because of leg edema, proteinuria (2.1 g/day), and gross hematuria. She had non-alcoholic liver cirrhosis of unknown etiology. Esophageal varices also were found. Examination of the renal biopsy specimen revealed mesangial proliferative glomerulonephritis with IgA deposits. Propranolol was administered orally to reduce portal hypertension, resulting in a progressive decrease in urinary microalbumin excretion. This case suggests that portal hypertension is involved in the pathogenesis of IgA nephropathy in liver cirrhosis.

Aged↗

[A case of pontine hemorrhage presenting with abnormal vertical ocular movements].

A 52-year-old woman was admitted to hospital because of sudden loss of consciousness. Neurological examination on admission revealed a comatose consciousness level, horizontal and upward palsies of both eyes and quadriparesis. The diagnosis of pontine hemorrhage was confirmed based on a brain CT scan, which showed a high density area involving the bilateral pontine tegmentum and right midbrain tegmentum at the inferior collicular level. The left eye moved downward below its primary position, and the movements usually comprised rapid downward and slow upward excursions and, on occasion, slow downward and rapid upward excursions, and were arrhythmical with irregular amplitudes. Oculocephalic maneuver did not modify the ocular movements. No horizontal movements were seen with ice-cold water irrigation into the ear canal on either side. Sixty days after hemorrhage onset, her right eye began to assume the same abnormal vertical movements as the left one, and 90 days after their onset, the ocular movements became oscillations. The abnormal vertical ocular movements in our patient were characterized by irregularities of phase, rhythm and amplitude. Accordingly, they were easily differentiated from ocular bobbing and ocular dipping. As these abnormal ocular movements resembled those of a float pulled by a fish, we propose they be termed ocular floating. The paramedian pontine reticular formation (PPRF) is believed to excite the burst neurons of the rosral interstitial nucleus of medial longitudinal fasciculus (riMLF) responsible for upward gaze and inhibit those for downward gaze. This role was suggested by the clinical observation that a pontine tegmental lesion causes upward gaze palsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral Hemorrhage↗

Immunohistochemical study of human advanced glycosylation end-products (AGE) in chronic renal failure.

In patients with diabetic renal failure plasma advanced glycosylation end-products (AGE) levels are reported to be elevated and dialyzer of continuous ambulatory peritoneal dialysis (CAPD) is usually used with a high glucose concentration. Here, an immunohistochemical study on human AGE accumulation in vascular beds and peritonea of patients with chronic renal failure (CRF) or those on CAPD was undertaken. Further, the influence of aging was studied using AGE-specific monoclonal antibody. 1. AGE accumulation was observed in radial arterial walls (from vascular intima to smooth muscle layer) of diabetic patients with CRF. Even in some non-diabetic patients with CRF (n = 3/6), especially in those with a long history of CRF and dialysis treatment, similar positive staining was seen in vascular walls. No AGE staining was observed in any renal tissue of age-matched control subjects including tissue from patients with acute renal failure. 2. Although AGE accumulation was not seen in the peritonea of CRF patients with no prior CAPD therapy, it was seen in the mesothelial layers and in adjacent coarse connective tissues of peritonea from patients on CAPD (n = 6), even from as early as only 3 months of CAPD therapy. 3. AGE accumulation was observed in the vascular bed of the non-diabetic aged kidney with normal function, but not in that of the young kidney. Thus, AGE accumulation in the vascular bed may depend on the degree and term of renal impairment and on aging in addition to diabetes. AGE accumulation in the peritonea became positive following CAPD treatment, indicating that it might affect the efficiency of CAPD.

Adult↗

[A Japanese pedigree with oculopharyngeal muscular dystrophy].

We investigated a Japanese pedigree with oculopharyngeal muscular dystrophy (OPMD) which included the probands of two sisters and a brother. Case 1 (Fig. 1): A woman born in 1940 at Fuji City, Shizuoka prefecture (Pacific coast side, which located about 80 miles west from Tokyo) was insidiously suffering from dysphagia and eye lid ptosis since her age of 40. She was admitted to Shizuoka Red Cross Hospital when 48 years old, because of difficulty of going upstairs. Neurological examination revealed severe eye lid ptosis without eye movement disorders, dysphagia, and moderate weakness on neck and proximal muscles of extremities without definite atrophy and fasciculation. In the laboratory data, serum creatine kinase level was slightly elevated to 215 U/l. Electromyographic findings showed myogenic pattern on the extremities but no evidence of the existence of myasthenia gravis and neurogenic involvement. Intranuclear tubular filaments were found in 3% of muscle fibers from her left biceps muscle. Case 2: The elder sister of the case 1 was suffering from eye lid ptosis without eye movement disorder and severe dysphagia since the age of 44. Case 3: The younger brother of the case 1 was suffering from dysphagia and proximal muscle weakness since the age of 40. We found eye lid ptosis, dysphagia and/or proximal muscle weakness in 24 cases (men: 12 cases, women: 12 cases) out of 50 examined members of this pedigree after their ages of 40 (Fig.3; family tree). It was concluded that this pedigree had cases of oculopharyngeal muscular dystrophy with autosomal dominant inheritance which was quite rare in Japanese.

Female↗

[Idiopathic pure sudomotor failure].

We describe three cases of acquired generalized anhidrosis without other autonomic and somatic nervous dysfunctions (idiopathic pure sudomotor failure; IPSF) and a review of the literature was made in regard to the clinical features of this disease. Patient 1. A 17-year-old man was found to be severely anhidrotic and intolerant to heart loading, which produced an immediate sharp pain over the entire body surface in April, 1989. Sudden and spontaneous remission occurred in July, 1990, but relapsed six months later. He was admitted to our hospital seeking for therapy in April, 1991. There were no abnormal findings on physical and neurological examinations except for anhidrosis. Patient 2. A 14-year-old boy was admitted to our hospital in March 1991 with complaints of intolerance to heart loading and sharp pain, which had begun ten months before admission. Physical and neurological examinations revealed no abnormal findings except for anhidrosis. Patient 3. A 21-year-old woman suddenly experienced a burning sensation in the whole body in 19th, February, 1991, which was followed by severe pain. She was admitted to our hospital in the next day. Apart from sensory impairment of glove and stocking type, neurological examination revealed no abnormal findings. Reflex sweating to pilocarpine was absent in all three cases, suggesting abnormality in the postganglionic sudomotor nerves or cholinergic receptors. Skin biopsy was performed in one patient (patient 1), and revealed no abnormalities of the sweat glands and ducts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Cross-resistance to diverse drugs is associated with primary cisplatin resistance in ovarian cancer cell lines.

We have previously obtained, by exposure to near continuous increasing concentrations of cisplatin, a panel of human ovarian cancer cell lines that exhibit a wide range of primary resistance to the drug (9- to > 400-fold). These cells had strikingly increased (4- to 50-fold) levels of glutathione (GSH) as compared with the drug-sensitive cells of origin (A. K. Godwin et al., Proc. Natl. Acad. Sci. USA, 89: 3070-3074, 1992). Utilizing this panel of resistant cell lines, we evaluated cross-resistance to classical alkylating agents, natural product drugs, and irradiation. We observed that cross-resistance to carboplatin paralleled that of cisplatin, culminating in approximately 250-fold resistance. Similarly, melphalan cross-resistance continued to increase to > 400-fold and again paralleled the primary cisplatin resistance. Cell lines with low to very high levels of resistance to cisplatin are 8- to 850-fold resistant to the epipodophyllotoxin derivative etoposide. Cross-resistance is also observed for other natural product drugs, including Adriamycin (approximately 80-fold), mitoxantrone (approximately 440-fold), and taxol (approximately 40-fold). Cross-resistance to irradiation is, however, modest (< 2-fold). The cells with the greatest primary resistance to cisplatin most commonly had the highest cross-resistance to the other drugs examined. The cross-resistance to the natural product category drugs was found not to be mediated by the products of either the multidrug resistance 1 (MDR1) or multidrug resistance-associated protein (MRP) genes based on lack of coordinate increased expression or amplification of these genes as assessed by Northern and Southern blot analyses. Furthermore, verapamil failed to markedly increase drug sensitivity. Although there was no indication that these natural product drug efflux pumps were operative, we observed decreased doxorubicin accumulation in these cell lines cross-resistant to natural products. In addition, alternations in DNA topoisomerase II mRNA levels, which have been observed in a variety of human tumor cell lines selected in vitro for resistance to etoposide or teniposide, were not detected. Only intracellular levels of GSH correlated with cross-resistance to these diverse anticancer agents and partial loss of resistance was associated with a marked decrease in glutathione levels. In the absence of alternative mechanisms, we speculate that the very broad clinically relevant cross-resistance seen in this model system may, at least in part, be the direct result of GSH-mediated drug inactivation or may be due to a combination of GSH conjugation to drug and conjugate efflux mediated by the putative ATP-dependent glutathione S-conjugate export pump.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Transformation of rat ovarian epithelial and Rat-1 fibroblast cell lines by RAST24 does not influence cisplatin sensitivity.

Recent reports suggest that expression of an activated c-Ha-ras oncogene is associated with cisplatin resistance in NIH-3T3 fibroblasts. To investigate the generality of these observations, cisplatin cytotoxicity was determined in a series of clonal Rat-1 fibroblast and rat ovarian surface epithelial (ROSE) cell lines carrying a zinc-inducible metallothionein-RAST24 fusion gene, MTRAST24. Cisplatin sensitivity in RAS-transformed fibroblast sublines did not differ from parental controls. Induction of mutant RAST24 expression by zinc sulfate did not affect the cisplatin sensitivity of individual cell lines. Expression of mutant p21Ha-RAS varied more than 40-fold in these fibroblast sublines. Similarly, there was no difference in cisplatin sensitivity between parental ROSE controls, neomycin phosphotransferase transfected controls, or MTRAST24 transfectants. Finally, the cisplatin sensitivity of RAS-transformed ROSE cells was similar to that of spontaneously transformed ROSE cells. Overall, these observations suggest that there is little relationship between mutant ras expression and cisplatin sensitivity in rat epithelial and fibroblast cell lines.

Animals↗

Synaptic loss following removal of serotoninergic fibers in newly hatched and adult chickens.

Neurotransmitters such as serotonin (5HT) may have nontransmitter, trophic-like functions in the developing and adult nervous system. In order to examine this possibility in the avian spinal cord, we have quantified synapse numbers on spinal neurons following treatment with drugs that result in the destruction of 5HT positive axons. Either p-chlorophenylalanine or reserpine was injected into newly hatched or adult chickens. Following treatment for 7 days the density of nonserotoninergic synapses was considerably decreased in the targets of 5HT fibers. By contrast, neither change was observed in the dendritic structures of spinal motoneurons or in the distribution of substance P and enkephalin positive fibers. These data suggest that 5HT may play an important role in the normal increase and maintenance of synapses in developing and adult animals. A lesion of 5HT neurons may not only alter neurochemistry but also alter the general synaptic structures of the brain. While 5HT containing fibers were depleted in a dose-dependent fashion we cannot rule out the possibility that other neurotransmitter systems were depleted at higher dose of PCPA and reserpine.

Animals↗

Indispensable role of tissue-type plasminogen activator in growth factor-dependent tube formation of human microvascular endothelial cells in vitro.

Epidermal growth factor (EGF) stimulates the migration and proliferation of, and tissue-type plasminogen activator (tPA) synthesis in, human omental microvascular endothelial (HOME) cells in culture, as well as inducing the formation by these cells. In the present study, we examined the effects of various growth factors, i.e., transforming growth factor-alpha (TGF-alpha), insulin-like growth factor 1 (IGF-1), and hepatocyte growth factor (HGF) on HOME cells, and compared their effects with that of EGF. IGF-1 stimulated the proliferation and migration of these cells at a level comparable to EGF. EGF and TGF-alpha induced expression of tPA in HOME cells, while IGF-1 and HGF did not. EGF and TGF-alpha induced tube formation by HOME cells in type I collagen gel, while IGF-1 and HGF did not. The stimulatory effect of EGF on tube formation in the gel was blocked by anti-tPA antibody and by a serine protease inhibitor, aprotinin. When exogenous tPA and IGF-1 or HGF were added simultaneously to the culture, a marked induction of tube formation in the gel was observed. Exogenously added tPA alone, however, had no such inducible effect on tube formation. These results indicated an indispensable role of tPA in growth factor-dependent tube formation by HOME cells. Two subsets of growth factors appeared to modulate angiogenesis: One with fully active angiogenic activity which could induce PA (this included EGF and TGF-alpha), and the other, which could not induce PA and was not angiogenic, but could promote angiogenesis in the presence of PA. This subset included IGF-1 and HGF.

Cell Division↗

Morphologic variations of dense deposit disease: light and electron microscopic, immunohistochemical and clinical findings in 10 patients.

Twenty-one renal biopsy specimens obtained from 10 patients with dense deposit disease (DDD) were investigated using light microscopy, electron microscopy and immunohistochemistry. The patients included four females and six males aged 6 to 35 years (mean 16.1 years). A morphological diagnosis of DDD was made following the ultrastructural detection of continuous intramembranous dense deposits (CIMDD) in some capillary loops of at least one of the series of the repeated biopsies from each patient. With light microscopy, six patients showed membranoproliferative glomerulonephritis (MPGN). The other four patients showed diffuse proliferative glomerulonephritis (DPGN) with acute lesions showing intraglomerular neutrophilic infiltration, hump formation and endothelial swelling in three and minor glomerular abnormalities in one. Follow-up biopsies were obtained in six patients. Two patients progressed from DPGN to MPGN within 7 months, whereas three patients with MPGN showed morphologic improvement that featured increased capillary patency and regional disappearance of dense deposits along with the reduction of proteinuria. Dense deposit disease did not always feature typical amorphous and osmiophilic CIMDD spreading across the whole width of the lamina densa. This classical ultrastructural manifestation was mainly found in the patients with histologic non-MPGN and a linear peripheral pattern of complement component (C3) deposition. The MPGN patients with a granular peripheral pattern of C3 deposition also had CIMDD, but also additionally featured less dense subepithelial deposits superimposed on the CIMDD to produce an appearance simulating membranous transformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗