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Biomedical subjects

K Kosaka

Publications and source records attributed to K Kosaka.

At least 217 records · Page 12Linked to original sources
PubMed1992

Islet amyloid polypeptide (IAPP) gene analysis in a Japanese diabetic with marked islet amyloid deposition.

Islet amyloid polypeptide (IAPP) is a major constituent of pancreatic amyloid deposits in many patients with non-insulin-dependent diabetes mellitus (NIDDM). We analyzed the IAPP gene in a Japanese diabetic with marked islet amyloid deposition. Pancreatic specimens were obtained from an 87-year-old NIDDM patient who had had diabetes for 37 years. All islets (100/100) in his pancreas had IAPP-positive amyloid deposition, and 70% of the area of the islet was replaced by amyloid. We amplified the coding regions as well as the upstream region of the IAPP gene by polymerase chain reaction (PCR). The products of PCR were sequenced, and the sequences of the coding regions were identical to the Caucasian ones. However, the nucleotides of two positions of 5'-upstream and one position of intron 2 were different from the Caucasian data: the upstream region of the IAPP gene in the patient had cytosine substituted for thymine at -259, and had two alleles including cytosine and adenine at -229, respectively. The nucleotide of position 539, that is guanine, was deleted. A possible difference in the IAPP promoting region between the Japanese and Caucasian population was suggested.

Aged↗
PubMed1992

Neurotransmitter changes in early- and late-onset Alzheimer-type dementia.

Neurotransmitter-related markers were examined in Alzheimer-type dementia (ATD) and studied whether or not there is biochemical difference between the early- and late-onset sub-groups. Postmortem brains were obtained from neuropathologically diagnosed ATD patients and control subjects with no clinico-neuropathological findings indicative of neuropsychiatric diseases. Neurochemical data in the early- and late-onset groups were compared to the age-matched younger and older control groups, respectively, and expressed as a percentage of the mean value in the respective controls. Choline acetyltransferase activity and concentrations of serotonin and noradrenaline were more severely depleted in the early-onset ATD group than in the late-onset ATD group. These findings indicative of heterogeneity of ATD patients were discussed from the pathogenetic and therapeutic viewpoints.

Aged↗
PubMed1992

An autopsied case of dentatorubropallidoluysian atrophy with atypical pathological features.

This is a report of an autopsied case of dentatorubropallidoluysian atrophy (DRPLA) with atypical neuropathological findings. The patients was a 31-year-old female. Her clinical symptoms were epileptic seizures, cerebellar ataxia, choreoathetosis and dementia. A neuropathological examination revealed the fibrillary gliosis in various areas of the CNS and severe degeneration in the cerebellar cortex and nucleus fasciculi dorsalis in addition to a marked degeneration of the dentatorubropallidoluysian systems. The present case is diagnosed neuropathologically as DRPLA associated with the findings of chronic diphenylhydantoin intoxication and epileptic brain damage.

Atrophy↗
PubMed1992

Large scale production and characterization of lyophilized pyridoxalated hemoglobin-polyoxyethylene (PHP).

Lyophilized PHP as an oxygen carrier is prepared from outdated red cell and dicarboxymethylated polyoxyethylene. In order to apply PHP for a clinical use, a large scale production of high quality PHP has been studied. We have set up a 20 L scale production flow of PHP88. The product was tested to confirm the quality and lot-to-lot consistency. The blood group specific materials were weakly positive in stroma-free hemoglobin (SFH), however, were found negative in the PHP of this scale. The amount of phosphatidylethanolamine (PE) in purified SFH and PHP88 reconstituted solution was 0.19 +/- 0.04 and 0.03 +/- 0.01 ppm, respectively. Contamination of viruses such as HBV and Non A non B hepatitis virus could not be observed in the final product. Elimination and inactivation of HIV was validated through a spike test. The characterizations of the final products in 20 L scale were done through MW, P50, Hill coefficient, viscosity, and molecular weight distribution by SDS-PAGE and batch to batch consistency was also confirmed. The results show that production process is appropriate to eliminate the blood group materials, PE and virus, and produce PHP of high quality. Lyophilized PHP88 can be produced by addition of maltose and can be stored over 1 year.

Biotechnology↗
PubMed1992

[A case of general paresis with marked improvement of cerebral blood flow after antiluetic therapy--case report].

Although the incidence of neurosyphilis has declined dramatically after the World War II because of the development of antibiotics, it is recently increasing a little bit. There has been few reports on the neuroimaging of general paresis. We studied a fresh case of general paresis by X-ray CT (XCT), MRI and PET scans, and report the changes of neuroimages before and after the therapy. A 38-year-old man was admitted with disorientation, thought disorder and personality change. He also had insomnia and megalomania. There were neither obvious neurological signs nor particular changes of the XCT scan abnormalities on admission. His clinical symptoms were gradually worsened within three months, when the XCT and MRI scans showed moderate brain atrophy especially in the frontal and temporal lobes with mild dilatation of the lateral ventricles. In the PET study, the cerebral blood flow was decreased in the entire brain, especially in the frontal lobes, although the thalamus and the basal ganglia had normal levels. By immunological procedures and the cerebrospinal fluid (CSF) studies, the diagnosis of general paresis was made. He was treated with penicillin G and other antibiotics. In one year after his first therapy, many symptoms vanished. Although the cerebral atrophy was a little advanced, the cerebral blood flow was dramatically increased. As far as we know, this is the first PET study of general paresis before and after penicillin treatments.

Adult↗
PubMed1991

Diabetic retinopathy in non-insulin-dependent diabetes mellitus patients: the role of gliclazide.

Diabetic retinopathy is the most common cause of human blindness between the ages of 30 and 67 in the industrialized world. Retinopathy has a multifactorial etiology. Standard treatment has aimed at correcting only disturbed glucose metabolism, but this may lead only to the partial amelioration of certain hemobiologic factors. In addition to its metabolic action, gliclazide has been shown to have specific hemobiologic properties; studies with gliclazide in animals and humans have shown significant improvements of platelet abnormalities, stimulation of prostaglandin I2 synthesis, and enhancement of fibrinolytic activity. In humans, open-label studies have shown that gliclazide treatment leads to stabilization of background retinopathy in non-insulin-dependent diabetics and, more recently, these beneficial effects have been confirmed in controlled studies lasting up to 37 months in which other sulfonylureas were used. The Japanese Diabetic Retinopathy Program studied the progression of retinopathy over a 5-year period, comparing gliclazide with other sulfonylureas and with placebo. This study showed that, with equivalent metabolic control, there was a trend toward a lower rate of deterioration and a significantly lower incidence of preproliferative retinopathy in the group receiving gliclazide compared with those receiving other sulfonylureas. Overall, the specific hemobiologic actions of gliclazide appear to offset or retard the progression of diabetic retinopathy and may have the advantage of lowering the incidence of preproliferative retinopathy.

Diabetes Mellitus, Type 2↗
PubMed1991

Tyrosine hydroxylase-like immunoreactive neurons in the olfactory bulb of the snake, Elaphe quadrivirgata, with special reference to the colocalization of tyrosine hydroxylase- and GABA-like immunoreactivities.

The distribution and structural features of tyrosine hydroxylase-like immunoreactive (TH-LI) neurons were studied in the olfactory bulb of a snake, Elaphe quadrivirgata, by using pre- and post-embedding immunocytochemistry at the light microscopic level. In contrast to rodent olfactory bulbs previously reported, many TH-LI neurons were seen not only in the main olfactory bulb (MOB) but also in the accessory olfactory bulb (AOB). With regard to the TH-like immunoreactivity, there appeared no appreciable differences between MOB and AOB. As in mammalian MOB, the majority of TH-LI neurons were clustered in the periglomerular region and appeared to send their dendritic branches into glomeruli, which as a whole make an intense TH-LI band in the glomerular layer (GML). In the external plexiform/mitral cell layer (EPL/ML) of MOB and AOB as well as in the outer sublamina of the internal plexiform layer (OSL) of AOB, an appreciable number of TH-LI neurons were scattered, extending dendritic processes which appeared to make a loose meshwork. TH-LI neurons in EPL/ML (including OSL) appeared to consist of at least two morphologically different types. The first had a small perikaryon and one or two smooth dendrites which usually extended to GML and were frequently confirmed to enter into glomeruli. The second had a larger perikaryon and 2-3 dendrites which branched into several varicose processes extending in EPL/ML/OSL but appeared not to enter into glomeruli. The TH-like immunoreactivity was rarely seen in the internal plexiform layer and internal granule cell layer. The colocalization of GABA-like and TH-like immunoreactivities was further studied. Almost all TH-LI neurons in both EPL/ML/OSL and GML contained GABA-like immunoreactivity irrespectively of the type of TH-LI cells.

Animals↗
PubMed1991

Parvalbumin-immunoreactive neurons in the cortex in Pick's disease.

Parvalbumin (a calcium-binding protein)-immunoreactive (PV-Ir) neurons in the cerebral cortex were examined in 20 postmortem brains obtained from elderly controls and patients with Pick's disease (PD). The type of PV-Ir neurons and their distribution in control and PD brains were similar. The number of PV-Ir neurons in PD brains did not differ significantly from that in the control brains either. These findings suggested that PV-Ir neurons in the cortex are not affected in PD brains. A significant loss of PV-Ir neurons has already been reported in brains obtained from patients with Alzheimer-type dementia (ATD), and the present results suggest the possibility that the damage of PV-Ir neurons might be comparatively selective for ATD brains.

Aged↗
PubMed1991

Striatopallidonigral degeneration in Pick's disease: a clinicopathological study of 41 cases.

The frequency and degree of stiatopallidonigral (SPN) degeneration were examined in 41 autopsy cases of Pick's disease. Based on the degree of SPN degeneration, these cases were arranged into four groups: 1) group I (severely degenerate; 19.5%), 2) group II (moderately degenerate; 22.0%), 3) group III (mildly degenerate; 36.5%), and 4) group IV (non-degenerate; 22.0%). 17 of the 41 cases had a definite (moderate to severe) SPN degeneration. The striatum, especially the caudate nucleus, was most frequently and most severely affected, while the internal segment of the globus pallidus was least frequently and least severely affected. In general, the oral portions of the SPN nuclei were more severely involved. In addition, in the putamen and globus pallidus the dorsomedial portions adjacent to the internal capsule were apt to be affected more markedly than the other portions. In the substantia nigra the degeneration tended to be more predominant in the pars reticulata than in the pars compacta, although both were usually involved. In addition, the medial to central portions of the substantia nigra were more vulnerable. In comparing the severely and moderately degenerate groups (groups I and II) with the mildly and non degenerate groups (groups III and IV), the former had more female cases, longer duration of illness, and more third-stage cases. In addition, the former contained more cases with lower brain weight and (predominant) frontal atrophy type, and more atypical cases without Pick bodies, or with symmetrical pyramidal tract degeneration or with combined traumatic lesions. It is notable that in all cases with definite SPN degeneration no extrapyramidal involuntary movements had been detected.

Adult↗
PubMed1991

Mutagenic activities of tryptophan metabolites before and after nitrite treatment.

The mutagenic activities of 16 kinds of tryptophan metabolites, before and after nitrite treatment, were examined in the Ames test. None of the compounds showed mutagenic activity before nitrite treatment. After nitrite treatment under acidic conditions, 11 compounds showed mutagenic activity towards Salmonella typhimurium TA100 strain in the absence of a metabolic activation system. Tryptophan induced 1000 revertant colonies/mumol, while 5-hydroxyindole, 5-hydroxytryptamine and 3-hydroxykynurenine, all containing a hydroxy group in the molecule, induced 11,000, 5200 and 2700 revertant colonies/mumol, respectively. These results indicate that the introduction by nitrite treatment of a hydroxy group into the indole or benzene ring of tryptophan-related compounds increases their mutagenic activity.

Biotransformation↗
PubMed1991

A pilot clinical trial of a new oral hypoglycemic agent, CS-045, in patients with non-insulin dependent diabetes mellitus.

CS-045, (+/-)-5-[4-(6-hydroxy-2,5,7,8-tetramkethylchroman-2- ylmethoxy)benzyl]-2,4-thiazolidinedione, lowers plasma glucose in several animal models of non-insulin dependent diabetes mellitus (NIDDM) presumably by increasing insulin sensitivity. Little adverse effect was found in a phase 1 study on healthy male subjects. In order to test its efficacy in lowering plasma glucose in NIDDM in man, a pilot multi-center clinical trial of CS-045 was carried out in 146 patients with NIDDM whose glycemic control was inadequate (FPG greater than 140 mg/dl) on diet and/or other oral hypoglycemic agents. CS-045 was given orally in a daily dose of 200 mg or 400 mg for 12 weeks in addition to the previous treatment. The mean fasting plasma glucose (FPG) and fructosamine began to decrease within 2 weeks and the mean HbA1c within 8 weeks. After 12 weeks, the FPG fell from 192 +/- 41 to 155 +/- 45 mg/dl (P less than 0.01), fructosamine from 3.7 +/- 0.6 to 3.3 +/- 0.6 (P less than 0.01), and HbA1c from 8.9 +/- 1.5 to 8.1 +/- 1.5% (P less than 0.01). The drug was effective in 39% of patients in that FPG fell by more than 20% of the initial value. This rate of efficacy was the same when CS-045 was given alone or together with other oral hypoglycemic agents. The drug was more effective in a dosage of 400 mg than with 200 mg (the rate of efficacy 46% vs 25%) and more effective in obese patients than in lean patients (46% vs 25%).(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMed1991

[Study on argyrophilic inclusions of multisystem atrophy (Oppenheimer)].

UNLABELLED: Non-hereditary olivo-ponto-cerebellar atrophy (OPCA) and striato-nigral degeneration (SND) have been looked upon as a single disease entity called multisystem atrophy (MSA) by Oppenheimer. This study revealed that both intracytoplasmic argyrophilic inclusions (AI) in pontine neurons and glial (argyrophilic) cytoplasmic inclusions (GCIs) widely distributed in the CNS are characteristics of MSA. MATERIALS: a) 12 cases with MSA, b) 16 cases with autosomal dominant (AD) form of spinocerebellar degeneration (SCD): AD form of OPCA 5 cases, Joseph disease 4 cases, AD-dentatorubropallidoluysian atrophy (Naitoh & Oyanagi's form) 6 cases, AD-spastic ataxia (Brown) 1 case, c) 4 cases with autosomal recessive (AR) form of SCD: AR form of OPCA 1 case, myoclonic epilepsy with ragged-red fibers (MERRF) 1 case, complicated form of spastic paraplegia 2 cases, d) 6 cases with non-hereditary SCD including intoxications: late cortical cerebellar atrophy 1 case, alcoholic cerebellar degeneration 2 cases, phenytoin-induced cerebellar degeneration 1 case, neuroleptic malignant syndrome 1 case, and e) 27 cases with other neuropsychiatric diseases: Alzheimer disease 20 cases, progressive supranuclear palsy 5 cases, schizophrenia 2 cases. METHOD: We examined 10 mu-thick paraffin sections stained with HE, Klüver-Barrera, Bodian, Holzer, Gallyas, and Bielschowski methods. RESULTS: AI in pontine neurons were found only in two cases of MSA. Interestingly no AI could be detected even in cases with AD form of OPCA showing mild degeneration in the pontocerebellar system. On the other hand, GCIs were found in all cases with MSA irrespective of the degree of degeneration in the olivo-ponto-cerebellar or striato-nigral system. However, there was no GCIs in cases with other form of SCD and other neuropsychiatric diseases. Gallyas stain was the best method for detecting GCIs. GCIs were widely distributed in the CNS except for superficial layers of the cerebral cortex, the cerebellar cortex, and the dorsal column of the spinal cord. There were also many GCIs in the putamen, pontine base, and cerebellar white matter, even though these sites were well preserved.

Alzheimer Disease↗
PubMed1991

[A new type of complicated form of hereditary spastic paraplegia showing mental deterioration, quadriplegia with muscular atrophy, sensory disturbance, extrapyramidal disorders, and epilepsy].

UNLABELLED: This study proposes a new type of complicated form of hereditary spastic paraplegia (HSP) and some problems on a clinico-pathological classification of HSP. The present study includes three male and two female patients from two families (A and B). In the family A, four siblings (two males and two females) were affected. Spastic paraplegia developed as an initial symptom. In the family B, a man was affected with spastic paraplegia which had started at the age of eleven. His two half-sisters are normal. All parents in two pedigrees are healthy. The parents in the family B are first cousins. CLINICAL FEATURES: Their physical development was normal, but all of them showed mild mental retardation. Gait disturbance due to spastic paraplegia and mental deterioration developed at the age of high teens. At the age of high 20's, they became unable to walk, because of progressive spastic paraplegia and other complicated neurological impairments including pyramidal disorders in the upper limbs, generalized neurogenic muscular atrophy, sensory disturbance and bradykinesia. Some cases showed rigidity and/or spasticity. At the age of high 30's, they became bed-ridden, because of quadriplegia with generalized muscular atrophy. Three cases in the family A suffered from convulsions which started at the high 30's. Mild athetoid movement in the face and neck was observed in three cases in the family A. All patients became apathetic and indifferent at least by the age of 40. Laboratory findings and data: CT scan yielded brain atrophy and dilatation of the lateral ventricles, atrophy of the corpus callosum and hyperostosis of the cranium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗