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K Sahashi

Publications and source records attributed to K Sahashi.

At least 55 records · Page 3Linked to original sources
PubMed1994

[Levels of soluble CD4 and soluble CD8 in patients with sarcoidosis].

Levels of soluble CD4 (sCD4) and soluble CD8 (sCD8) in serum and bronchoalveolar lavage fluid (BALF) were determined in 36 patients with sarcoidosis and 20 healthy controls by an ELISA method. In addition, the possible sources of sCD4 and sCD8 were examined in detail. The sCD4 levels in serum did not differ significantly between sarcoidosis patients and controls. The sCD8 levels in the sera of sarcoidosis patients with a high serum angiotensin-converting enzyme (ACE) level were significantly higher than those of patients with a normal serum ACE level (413 +/- 148 U/ml vs. 297 +/- 76 U/ml, p < 0.01). The high ACE group also had significantly increased serum sCD8 levels as compared to controls (323 +/- 111 U/ml, p < 0.05). In the sarcoidosis patients, the mean serum sCD8 level was 308 +/- 46 U/ml in stage 0, 339 +/- 107 U/ml in stage I, 557 +/- 141 U/ml in stage II, and 474 +/- 211 U/ml in stage III. The stage II group had a significantly higher sCD8 level than either the stage 0 or I groups (p < 0.05). In the sarcoidosis patients, the sCD8 level correlated significantly with the level of either ACE or soluble Interleukin-2 receptor in serum (p < 0.05). The sCD4 level in BALF was significantly higher in sarcoidosis patients than in controls (4.10 +/- 1.90 U/ml vs. 2.39 +/- 0.12 U/ml, p < 0.01), while the sCD8 level in BALF tended to be higher in sarcoidosis patients than in controls (4.31 +/- 4.39 U/ml vs. 2.02 +/- 1.52 U/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Progressive external ophthalmoplegia and myositis.

We reported a senile male patient with progressive external ophthalmoplegia (PEO) and myositis. The ophthalmoplegia was severe, but other neuromuscular features were nearly normal. Muscle enzymes in serum were moderately elevated. Autoimmune, endocrinological or malignant diseases were not observed during the previous 4 years. Pathology of non-weak limb muscles biopsied twice was consistent with active inflammatory myopathy. The ragged-red or cytochrome c oxidase-negative fibers, which are a hallmark of mitochondrial myopathy with PEO, were not increased in comparison with age-matched control muscles. Analysis of mitochondrial DNA in muscle by the Southern blot method did not reveal any deletions. It was concluded that the inflammatory myopathy, myositis clinically localized at the ocular muscles, is an important and distinct disorder in PEO.

Aged↗
PubMed1992

Increased mitochondrial DNA deletions in the skeletal muscle of myotonic dystrophy.

Mitochondrial abnormality in the skeletal muscles of 13 patients with myotonic dystrophy was analyzed by both histochemical and molecular biologic methods. Nine of 13 patients had ragged-red fibers (50 +/- 116 per 10,000 muscle fibers, mean +/- SD), and 10 patients had cytochrome c oxidase-negative fibers (41 +/- 90 per 10,000 muscle fibers). Southern blot analysis detected no mitochondrial DNA deletions, while PCR revealed multiple mitochondrial DNA deletions in all the specimens. Direct sequencing of one of the deleted mitochondrial DNAs disclosed that the junctional sequence of a 3,460-bp deletion involved a 6-bp directly repeated sequence (5'-TAGAAG-3') flanked by C-rich regions located on the CO3 gene and the ND5 gene. Quantitative analysis of PCR amplified deleted mitochondrial DNAs revealed that the amount of deleted mitochondrial DNAs had positive correlation both with the frequencies of ragged-red fibers and cytochrome c oxidase-negative fibers. Although deleted mitochondrial DNAs were observed even in controls above age 30, the mean amount of deleted mitochondrial DNAs in patients with myotonic dystrophy was significantly higher than in controls. Moreover, the increase of deleted mitochondrial DNAs with aging was more marked in myotonic dystrophy than in controls. These results suggest that increased mitochondrial DNA deletions and consequent impairment of mitochondrial function contribute to the pathophysiology of myotonic dystrophy.

Adolescent↗
PubMed1992

Strong correlation between the number of CAG repeats in androgen receptor genes and the clinical onset of features of spinal and bulbar muscular atrophy.

X-linked spinal and bulbar muscular atrophy (SBMA), a motor neuron disease associated with androgen insensitivity, is caused by androgen receptor gene mutations with an increased number of tandem CAG repeats in exon 1. We investigated the increased number of CAG repeats in androgen receptor genes of 19 SBMA patients and found that this correlated strongly with the age at onset of muscle weakness. Thus, SBMA is the first genetic disease in which a strong correlation between the degree of genetic abnormality (number of CAG tandem repeats) and clinical phenotypic expression is demonstrable. The results further indicate that androgen gene mutation is directly involved in the degeneration of motor neurons.

Adult↗
PubMed1992

[A mother and her son with autosomal dominant bulbar spinal muscular atrophy].

We reported a 49-year-old mother and her 28-year-old son with autosomal dominantly inherited bulbar spinal muscular atrophy (AD-BSMA). They showed progressive bulbar paresis, muscle wasting and weakness dominant in the proximal groups of limb muscles, and finger tremor. Onset of illness was in adult life. In laboratory examinations, elevated creatine kinase in serum and neurogenic changes either in EMG or muscle biopsy were noted. The son had neither gynecomastia nor abnormal sexual hormone levels which were observed in the sex-linked recessive bulbar spinal muscular atrophy (SR-BSMA). Elongation due to the CAG repeats at the androgen receptor gene of the X chromosome in SR-BSMA was not detected. In conclusion, it is clear that AD-BSMA is different from SR-BSMA on the basis of clinical and genetical aspects.

Adult↗
PubMed1992

[Quantitative skeletal muscle pathology of aging regarding ragged-red fibers and cytochrome c oxidase-negative fibers].

A statistical analysis of mitochondrial abnormality of aging in human skeletal muscle fibers was performed. Sixty one muscle samples were obtained from patients with acute medical illness autopsied strictly within 2 hours after death, or with orthopedic or surgical diseases biopsied with informed consents. The patients aged from 16 to 89, averaging 58 +/- 21 years in males and 21 to 92, averaging 55 +/- 20 years in females. Sections were stained by modified Gomori's trichrome, succinate dehydrogenase and cytochrome c oxidase-negative [CCO(-)] fibers approximately in 10,000 fibers in each muscle were evaluated. Both RRF and CCO (-) fibers were not observed below the fourth decade, but sequentially increased with age, especially after the seventh decade. The incidence of CCO (-) fibers was higher than that of RRF. RRF did not necessarily correspond to CCO (-) fibers. The present quantitative pathological result is a useful tool to evaluate the mitochondrial function in fresh human skeletal muscles by the age.

Adolescent↗
PubMed1991

Direct DNA sequencing from colony: analysis of multiple deletions of mitochondrial genome.

We have developed a rapid and efficient nucleotide sequencing technique, named the colony direct sequencing method, which combines both the conventional cloning method for picking up a single gene and the polymerase chain reaction (PCR) method for amplifying the gene directly from a colony. In the present study, the colony direct PCR product was used both for identification of the DNA insert and for nucleotide sequencing by an automated DNA analysis system. A nucleotide sequence of 300 to 400 bp could be determined within 13 h after picking the bacterial colonies on LB medium plates. We applied this method to sequencing of junctional regions of multiple deleted mtDNAs in two siblings with inherited recurrent myoglobinuria. Mitochondrial DNA fragments with deletions were amplified by PCR and then cloned into plasmids. Among 48 white colonies propagated on LB medium plates, nine different clones were identified by PCR directly from colonies. Determination of six different junctional sequences disclosed involvement of directly repeated sequences of 2 to 12 bp in length on each side of the deletions. We believe that the colony direct sequencing method will be a powerful tool in molecular genetics for identification of a single gene among polymorphic DNAs.

Adenosine Triphosphatases↗
PubMed1991

Mitochondrial DNA deletions in inherited recurrent myoglobinuria.

We describe two brothers with inherited recurrent exertional myoglobinuria and alcohol intolerance associated with distinct morphological abnormalities of muscle mitochondria and multiple deletions of muscle mitochondrial DNA. Patient 1 (26 years old) and Patient 2 (21 years old) had recurrent episodes of myoglobinuria provoked by strenuous exercise or alcohol intake, from the age of 18 years. Although their serum lactate and pyruvate levels were normal at rest, they were significantly elevated by aerobic exercise. Histochemistry of their biopsied limb muscles showed ragged-red fibers and cytochrome c oxidase-negative fibers as well as degenerating and regenerating fibers. Electron microscopy showed pronounced accumulation of abnormal mitochondria containing paracrystalline inclusions and moderate increases of glycogen particles. The enzyme activities of the electron-transfer complexes in the isolated muscle mitochondria of Patient 2 were within normal ranges. Southern blot analysis revealed multiple deletions of mitochondrial DNA, some of which were common between the patients. Polymerase chain reaction of their muscle mitochondrial DNA detected multiple abnormal fragments indicating mitochondrial DNA deletions. We propose that a defect of the mitochondrial energy-transducing system due to multiple mitochondrial DNA deletions is a novel genetic cause of inherited recurrent myoglobinuria.

Adult↗
PubMed1991

[HTLV-I associated myelopathy (HAM) and sarcoid myopathy].

A 65-year-old house-wife developed dirty erythematous rash on her face in April, 1989. Almost simultaneously, she complained of muscle soreness and weakness on both lower extremities. Pathological findings of the skin biopsy at that time was consistent with those of sarcoidosis with moderate inflammatory cell infiltration. In December, 1989, when she was admitted to our hospital, her lower extremities were paretic with marked spasticity, and mild bladder dysfunction was noted. HTLV-I antibody titers in serum and cerebrospinal fluid were significantly elevated. Biopsied limb skeletal muscle revealed the findings of the sarcoid myopathy with small inflammatory cell infiltration in endomysium. HLA haplotypes showed A24, B7, BW61, CW7, CW8, DR1 and DR4 which show relatively common types of those in HAM. Corticosteroid treatments including the methylprednisolone pulse therapy healed the skin lesion, but did not improve her neurological signs. Paraplegia and urinary disturbance were progressive. It is concluded that the inflammatory sarcoid myopathy with HAM in this patient may be caused by a common abnormal immunological background.

Aged↗
PubMed1991

[Recent advances of paraneoplastic neuromuscular syndromes].

Paraneoplastic neuromuscular syndromes reveal heterogeneous clinical features and often associate with particular tumor types. Patients presenting with one of the more distinctive syndromes, such as subacute cerebellar degeneration and Lambert-Eaton myasthenic syndrome, should undergo a careful search for detecting an occult malignancy. At present, an autoimmune pathogenesis has been clearly demonstrated only for the Lambert-Eaton syndrome. Specific autoantibodies in other syndromes may be diagnostic in identifying an underlying malignancy as a tumor marker. The precise role of antibodies in producing tissue damage and clinical manifestation is still controversial.

Cerebellar Diseases↗
PubMed1991

[Myoglobinuria caused by multiple deletions of mitochondrial DNA].

We report two brothers with inherited recurrent myoglobinuria associated with distinct morphological abnormalities of muscle mitochondria and multiple deletions of muscle mitochondrial DNA. Patient 1 (26 years old) and Patient 2 (21 years old) had recurrent episodes of myoglobinuria provoked by strenuous exercise or alcohol intake. Histochemistry of their biopsied limb muscles showed ragged-red fibers and cytochrome c oxidase-negative fibers as well as degenerating and regenerating fibers. Electron microscopy showed a pronounced accumulation of abnormal mitochondria containing paracrystalline inclusions and moderate increases of glycogen particles. Southern blot analysis revealed multiple deletions of mitochondrial DNA, some of which were common to both patients. By the primer shift polymerase chain reaction method, we detected multiple abnormal fragments indicating mitochondrial DNA deletions. Nucleotide sequencing of the deleted regions disclosed directly repeated sequences of 1 to 12 bp on each side of the deletions. Since the end points of mitochondrial DNA deletions were within 20 bp of the major non-coding region, probable mutations in this region contribute to the pathogenesis of multiple mitochondrial DNA deletions found in these patients. We propose that a defect of the mitochondrial energy-transducing system due to multiple mitochondrial DNA deletions is a novel genetic cause of inherited recurrent myoglobinuria.

Base Sequence↗
PubMed1990

Cytoplasmic body and mitochondrial DNA deletion.

A patient with chronic progressive external ophthalmoplegia (CPEO) who had abundant cytoplasmic bodies in muscle fibers and a deletion of mitochondrial DNA is reported. The patient was a 26-year-old male suffering from ophthalmoplegia from age 21. He had a marfanoid skeletal abnormality and perceptive hearing loss, but had neither retinopathy, ataxia, nor dementia. In the mitochondria isolated from the biopsied skeletal muscle, NADH-ubiquinone oxidoreductase activity was slightly decreased, succinate-cytochrome c reductase activity was slightly increased, and cytochrome c oxidase activity remained normal. Southern blot analysis of the muscle DNA identified heteroplasmy composed of a normal-sized mitochondrial DNA and a mutant mitochondrial DNA with a 4.2-kilobase deletion. The PCR plus S1 analysis showed that the deletion extended from nucleotide position 7860 +/- 60 to 12,090 +/- 70. The histological studies of the biopsied muscle revealed ragged-red fibers and cytochrome c oxidase-negative fibers in 15.7% and 18.6% of the muscle fibers, respectively. Other conspicuous histological change was abundant cytoplasmic bodies surrounded by clusters of abnormal mitochondria. The cytoplasmic bodies were found preferentially in type 1 fibers, and exclusively in cytochrome c oxidase-negative fibers and in ragged-red fibers. Focal existence of cytoplasmic bodies in muscle fibers with abnormal mitochondria suggests that segregated distribution of the abnormal mitochondria with deleted mitochondrial DNA is involved in the pathogenesis of cytoplasmic bodies.

Adult↗
PubMed1990

Type I familial amyloid polyneuropathy. A pathological study of the peripheral nervous system.

The neuropathological changes were examined in 2 cases of type I familial amyloid polyneuropathy (FAP), confirmed by a genetic study with human transthyretin (prealbumin) cDNA. These cases were from different foci of type I FAP in Japan, but showed a similar pathology in the peripheral nerves. Loss of dorsal root and sympathetic ganglion neurons, predominantly those of small size, was prominent, whereas ventral horn cells were well preserved. Distally accentuated axonal loss with marked axonal sprouting was the principal feature. Fibre sprouts were ubiquitous throughout the nerves and affected the fibre size distribution. Segmental demyelination and remyelination were prominent in the proximal portions of nerves, but axonal degeneration was more conspicuous in the distal portions. The centrally-directed branches of the primary sensory neurons did not show distally-accentuated axonal loss in the dorsal columns. Amyloid deposits were present universally in the endoneurial spaces of the peripheral nerves, but more prominently in the dorsal root ganglia, sympathetic ganglia and more proximal portions of the nerves, and the distribution correlated well with the occurrence of the pathology of peripheral nerves. Neurofilamentous accumulation was frequent in the proximal axons and neuronal cell bodies of the sensory and sympathetic neurons. Schwann cells and satellite cells to which amyloid deposits were attached frequently showed disappearance of basement membrane and proliferation of distorted processes. The findings in the present cases suggest that the Schwann and satellite cells may be directly affected by the amyloid deposits, but the pathogenetic mechanism of marked axonal and neuronal involvement still remains to be elucidated.

Adult↗
PubMed1990

[Echo guided percutaneous needle biopsy for diagnosis of thoracic lesions].

Echo guided percutaneous needle biopsy was performed in 32 cases with thoracic lesions. A definitive diagnosis was made histopathologically in 11 (100%) of 11 malignancies, 4 (67%) of 6 benign tumors and 7 (47%) of 15 inflammatory lesions. Furthermore, using cytological specimens, definitive diagnosis was successfully made in 10 (91%) of 11 malignancies and 1 (17%) of 6 benign tumors. Such highly accurate diagnostic rates were due to 1) the accurate puncture of the lesions under real time sonographic guidance, 2) repeated biopsy in case in which sample was inadequate for cytological diagnosis, and 3) aggressive application of needle biopsy for histopathological diagnosis. Following this procedure, three patients suffered from a minor pneumothorax. To prevent pneumothorax, great care is necessary, especially in high risk cases, such as with a pneumatic pattern and thin lesion. One patient suffered from minor hemoptysis but recovered without any medication. No complications were noticed in cases of extrapulmonary lesions. We conclude that echo guided percutaneous needle biopsy is not only a complementary method for biopsy of mediastinal, peripheral pulmonary and chest wall lesions, but due to its simplicity and convenience, it should be a routine method for biopsy of thoracic lesions.

Adult↗
PubMed1990

[Computed tomographic analyses on skeletal muscles in bulbar spinal muscular atrophy].

We analysed the patterns of skeletal muscular involvement in 18 patients with bulbar-spinal muscular atrophy (BSMA) of the Kennedy-Alter-Sung type by using the computed tomographic scanner. Fatty infiltrations were prominent in various skeletal muscles of extremities and trunk, and its degree was severe in the following numerical orders; the gluteal muscles, flexors of the thighs, flexors of the lower extremities, extensors and the adductors of the thighs, the paraspinal muscles, and extensors of the lower extremities. There was statistically significant correlation between fatty infiltrations in flexors of the lower extremities and duration of illness. And were noted findings that the skeletal muscle lesion progressed with the preserved fasciae and sectional areas, fatty infiltrations in the lower extremities were more conspicuous in flexors than in extensors, and compensatory hypertrophic muscles in the thigh were apparent in 50% of cases. In conclusions, the computed tomographic analyses on skeletal muscle of BSMA may be useful to detect distributions, progression of the muscle lesion, in addition to a profile of the myopathic alterations of the disease.

Adult↗
PubMed1990

[Myasthenia gravis associated with tonic pupil].

A 41 year-old female patient with acquired autoimmune myasthenia gravis (MG, IIa type) and tonic pupil (Adie's pupil) of the right side was reported. Adie's pupil was pointed out at the same time of the clinical diagnosis of MG in September, 1988. She had the solitary thymoma identified by pneumo-mediastinograph and mediastinal CT scan. Results of the positive anti-nicotinic AChR antibody titer, the positive edrophonium test and the electrophysiological examination gave unambiguous evidences of acquired autoimmune MG with thymoma. Instillations to the eyes of cocaine, pilocarpine and epinephrine, and the pupillary response to the intravenous injection of edrophonium revealed the postganglionic abnormality mainly in the parasympathetic system. There were no other overt symptoms due to dysautonomia. She refused thymectomy. Her myasthenic and pupillary signs became gradually improving without any immunosuppressive medications. It is concluded that two diseases of the patient may be probably caused by multiple organ- or tissue-specific autoantibodies, in addition to pathogenetic significance of Adie's pupil.

Adie Syndrome↗