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Biomedical subjects

K Kosaka

Publications and source records attributed to K Kosaka.

At least 19 recordsLinked to original sources
PubMed1992

High levels of nervous system-specific proteins in cerebrospinal fluid in patients with early stage Creutzfeldt-Jakob disease.

Concentrations of several proteins that are characteristic of the nervous system were time-sequentially analyzed by radio- and enzyme-immunoassay in the cerebrospinal fluid (CSF) of patients with Creutzfeldt-Jakob disease (CJD). We found abnormally high levels of several proteins, such as neuron-specific enolase (NSE), S-100b protein, brain-type isozyme of creatine kinase (CK-BB) and alpha subunit of GTP binding protein G0 (G0 alpha) in the early stage of the disease. Generally, these protein levels were far higher in CJD patients than in normal controls and other neurological patients in the early stage before the typical clinical manifestations were evident. These levels increased to maxima when the disease activity was most prominent and returned to normal or mildly elevated levels in the terminal stage. The results imply that these protein levels can serve as biochemical markers for the presence of an active destructive process in CJD brain and provide us with a useful indicator for early diagnosis of CJD.

Brain↗
PubMed1992

Postnatal X-ray irradiation effects on glomerular layer of rat olfactory bulb: quantitative and immunocytochemical analysis.

In the rat olfactory bulb, the majority of interneurons in the glomerular layer (GL) are supposed to be generated during first postnatal week. Low and repeated doses of X-rays (200 rad x 4 and 200 rad x 6) were used during this period to impair the development of interneurons. The resulting effects of olfactory bulb neurons were examined stereologically and immunocytochemically in animals of 4 and 12 weeks of age. Quantitative analysis showed that, 1) the volume of the GL decreased to 55% (1200 rad) - 70% (800 rad) of control, 2) numerical cell densities in GL decreased to 40% (1200 rad) - 60% (800 rad) of control, thus resulting in 3) a decrease of the total cell number in GL to 20% (1200 rad) - 40% (800 rad) of control in irradiated olfactory bulbs of animals 4 weeks old. In comparison, mitral cells, which are generated prenatally, were much less affected (total cell number: 70-80% of control), indicating a selective loss of cells generated during the first postnatal week in GL. Effects on somata and processes immunoreactive for GABA, tyrosine hydroxylase (TH), calbindin D-28K and parvalbumin (PV) were examined in irradiated bulbs of both 4 and 12 week-old rats. All of these immunoreactive elements showed a drastic decrease in all layers. Semiquantitative analysis showed that in the GL, calbindin D-28K immunoreactive (calbindin D-28K(+)) neurons decreased more extensively than TH immunoreactive (TH(+)) and GABA-like immunoreactive (GABA(+)) neurons; that is, TH(+) and GABA(+) neurons decreased to 20% (1200 rad) - 40% (800 rad) of control, whereas calbindin D-28K(+) neurons decreased to 10% (1200 rad) - 30% (800 rad) of control in the GL of irradiated bulbs. These findings indicated that larger proportions of calbindin D-28K(+) neurons might be generated during the first postnatal week than those of GABA(+) and TH(+) neurons. Furthermore, in irradiated bulbs the proportion of GABA(-)TH(+) cells in TH(+) cells increased to about twice of control, and the estimated total numbers of GABA(-)TH(+) cells in irradiated rats were 95% (800 rad) and 40% (1200 rad) of control. These observations suggest that the majority of GABA(-)TH(+) neurons were less affected by X-ray irradiation during the first postnatal week and thus that they might be generated in the prenatal period. Since during the first 2 postnatal weeks, neurons showing GABA(-)TH(+) were not seen in GL (Kosaka et al. 1987a), the majority of GABA(-)TH(+) neurons in adult olfactory bulb were assumed to change their phenotype at some postnatal developmental period.

Animals↗
PubMed1992

Selective loss of nigral neurons in Alzheimer's disease: a morphometric study.

Loss of neurons from the substantia nigra (SN), which is sometimes observed in Alzheimer's disease (AD), was quantitatively analyzed in 10 cases of presenile AD and 19 age-matched controls. On sections from the upper and lower portions of the SN, the pigmented zone (zona compacta) and the non-pigmented zone (zona reticulata) were delineated, and these zones were partitioned into quarters: medial, mid-medial, mid-lateral and lateral. This approach clarified topographical preference of neuronal depletion in the SN of AD; namely (1) pigmented neurons were more severely affected than non-pigmented neurons, (2) neuronal depletion was more marked in the lower SN (-38%, P less than 0.001), where the pigmented neurons in the medial quarter were most severely affected (-51%, P less than 0.001), (3) in the upper SN (neuronal loss: -21%, P less than 0.01), the pigmented neurons in the mid-medial quarter were most severely affected (-43%, P less than 0.01). These findings suggest that some groups of nigral neurons are primarily involved in presenile AD. Gallyas staining after bleaching of melanin pigments uncovered a large number of neurofibrillary tangles (NFTs) mainly in the pigmented zone, especially in the medial quarter. A large number of NFTs, scarse senile plaques, and substantial depletion of neurons form an unique combination of Alzheimer pathology in the SN not well recognized so far.

Aged↗
PubMed1992

Central nervous system changes in mitochondrial encephalomyopathy: light and electron microscopic study.

An autopsy case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is reported. It presented with generalized muscle atrophy, stroke-like episodes, schizophrenia-like mental disorder and progressive dementia. Serum lactate and pyruvate levels were high. In the biopsied muscles, ragged-red fibers were observed by light microscopy and aggregation of abnormal mitochondria with paracrystaline formation by electron microscopy. The most characteristic neuropathological findings were infarct-like lesions widespread in the cerebral cortex. In addition, this case showed some unusual pathological features: (1) diffuse moderate fibrillary gliosis in the whole cerebral and cerebellar white matter, which might have been due to metabolic disturbances; (2) several focal lesions with demyelination and numerous spheroids in the pontocerebellar fibers; and (3) marked degeneration of the posterior columns and spinocerebellar tracts. Electron microscopic examination revealed that abnormal mitochondria were markedly aggregated in smooth muscle cells and endothelium of the cerebral and cerebellar blood vessels. These fine structural findings suggest a "mitochondrial angiopathy".

Acidosis, Lactic↗
PubMed1992

Ultrastructural and immunohistochemical study of degenerate neurite-bearing ghost tangles.

Some ghost tangles in the brains of Alzheimer patients were accompanied by many small argyrophilic structures which were electron microscopically confirmed to be degenerate neurites. In these ghost tangles, roughly dispersed 15 nm straight and occasional twisted tubules were penetrated by proliferated astrocytic processes. Immunohistochemically, these ghost tangles lost immunoreactivities to anti-NFT, -tau and -ubiquitin antibodies, but were thioflavine-S fluorescent, though antigenicity to beta-protein was not proved. This similarity in composition of degenerate neurite-bearing ghost tangles to senile plaques might be induced by the amyloid nature of tubules, which probably provokes the reaction of neuropils.

Aged↗
PubMed1992

Peculiar axonal debris with subsequent astrocytic response (foamy spheroid body). A topographic, light microscopic, immunohistochemical and electron microscopic study.

Foamy spheroid bodies (FSBs) are described, as newly identified pathological structures occurring in human brain. FSBs favoured the substantia nigra pars reticulata (SNPR) and/or globus pallidus (GP) in degenerative conditions especially postencephalitic parkinsonism, progressive supranuclear palsy, pallido-nigro-luysial atrophy and multiple system atrophy. No FSBs were observed anywhere in the presence of substantia nigra pars compacta (SNPC) degeneration, such as occurs in idiopathic Parkinson's disease, or luysio-pallidal system degeneration, such as found in dentato-rubro-pallido-luysial atrophy or Joseph's disease. FSBs were also occasionally identified in the substantia nigra (SN) and/or GP of aged persons. In addition to SN and GP lesions, FSBs were seen in diffuse axonal lesions of long fibre tracts (the corpus callosum, the superior cerebellar peduncle) after non-missile head injuries, and in peri-infarct lesions. Under the light microscope, FSBs appear as slightly eosinophilic, foamy and nearly round objects with vague outlines, measuring approximately 10-50 microns in diameter. Some FSBs contain coarse, eosinophilic clusters at their periphery. FSB stained black when stained by the Gallyas silver method. Some FSBs were immunohistochemically positive for synaptophysin and 68 kDa neurofilament. Glial fibrillary acidic protein-positive fibres were observed alongside and/or inside some FSBs. Electron microscopically, FSBs were found to consist of collections of neuritic debris containing a variety of dense bodies and a small number of both mitochondria and neurofilaments. Some such collections were surrounded by astrocytic processes. These findings strongly suggest that FSBs are collections of small axonal debris destined for removal by astrocytes in due course. A variety of factors (degeneration of the SNPR and/or the GP, injury, infarction, ageing) seemed to be responsible for the histogenesis of FSBs.

Adult↗
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↗