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Biomedical subjects

M Mizushima

Publications and source records attributed to M Mizushima.

At least 19 recordsLinked to original sources

The region from phenylalanine-17 to phenylalanine-28 of a yeast mitochondrial ATPase inhibitor is essential for its ATPase inhibitory activity.

Mitochondrial ATP synthase (F(1)F(o)-ATPase) is regulated by an intrinsic ATPase inhibitor protein. In the present study, we investigated the structure-function relationship of the yeast ATPase inhibitor by amino acid replacement. A total of 22 mutants were isolated and characterized. Five mutants (F17S, R20G, R22G, E25A, and F28S) were entirely inactive, indicating that the residues, Phe17, Arg20, Arg22, Glu25, and Phe28, are essential for the ATPase inhibitory activity of the protein. The activity of 7 mutants (A23G, R30G, R32G, Q36G, L37G, L40S, and L44G) decreased, indicating that the residues, Ala23, Arg30, Arg32, Gln36, Leu37, Leu40, and Leu44, are also involved in the activity. Three mutants, V29G, K34Q, and K41Q, retained normal activity at pH 6.5, but were less active at pH 7.2, indicating that the residues, Val29, Lys34, and Lys41, are required for the protein's action at higher pH. The effects of 6 mutants (D26A, E35V, H39N, H39R, K46Q, and K49Q) were slight or undetectable, and the residues Asp26, Glu35, His39, Lys46, and Lys49 thus appear to be dispensable. The mutant E21A retained normal ATPase inhibitory activity but lacked pH-sensitivity. Competition experiments suggested that the 5 inactivated mutants (F17S, R20G, R22G, E25A, and F28S) could still bind to the inhibitory site on F(1)F(o)-ATPase. These results show that the region from the position 17 to 28 of the yeast inhibitor is the most important for its activity and is required for the inhibition of F(1), rather than binding to the enzyme.

Amino Acid Motifs↗

Interstitial pneumonia in Hermansky-Pudlak syndrome: significance of florid foamy swelling/degeneration (giant lamellar body degeneration) of type-2 pneumocytes.

Although usual interstitial pneumonia (UIP)-like IP has been known as the most serious complication of Hermansky-Pudlak syndrome (HPS), its pathologic features and pathogenesis are poorly understood. We investigated biopsied and autopsied lung tissues from five patients who died of UIP-like IP associated with HPS (HPSIP). The salient histopathologic features of HPSIP observed were: (1) alveolar septa displaying florid proliferation of type-2 pneumocytes (2PCs) with characteristic foamy swelling/degeneration; (2) patchy fibrosis with lymphocytic and histiocytic infiltration centered around respiratory bronchioles, occasionally showing constrictive bronchiolitis; and (3) honeycomb change without predilection for the lower lobes or subpleural area. Those peculiar 2PCs were histochemically characterized by the over accumulation of phospholipid, immunohistochemically by a weak positivity for surfactant protein, and ultrastructurally by the presence of numerous giant lamellar bodies that compressed the nucleus with occasional cytoplasmic disruption, together suggesting a form of cellular degeneration with an over accumulation of surfactant (giant lamellar body degeneration). The present study strongly indicates that there is a basic defect in the formation/secretion process of surfactant by the 2PCs in HPS, which may well be the triggering factor for the HPSIP development. Other factors, such as macrophage dysfunction, may be working synergistically for further acceleration of the inflammatory process.

Adult↗

[A case of asymptomatic meningioma at left frontal convexity: evaluation using of WAIS-R at preoperation and postoperation].

The authors reported a case of 39-year-old man with incidentally found meningioma whose postoperative WAIS-R scores were improved significantly. He got a minor head injury run in a car collision and showed no neurological findings on admission. Computed tomography revealed no traumatic abnormalities but left frontal convexity meningioma. Total removal of the tumor was performed 3 weeks after the admission. Preoperative verbal IQ, performance IQ, lower full IQ were 105, 95, 100 respectively, and improved to 113, 112, 114 postoperatively. An asymptomatic patient with incidentally found meningioma could have higher brain function disturbances, which could be improved after its resection, therefore we should operate on such a patient more positively.

Adult↗

Leydig cell hyperplasia and the maintenance of bone volume: bone histomorphometry and testicular histopathology in 29 male leprosy autopsy cases.

This study was conducted to determine if osteoporosis in male leprosy patients is caused by testicular atrophy. Bone volume (BV/TV), trabecular number (TbN), trabecular thickness (TbTh), and trabecular separation (TbSp) were measured in two areas in decalcified paraffin sections of lumbar bones from 29 male leprosy and 6 male nonleprosy autopsy cases. We found significant differences in the average BV/TV measurements among the 7 patients with nodular Leydig cell hyperplasia (BV/TV 12.24%) and the 22 patients without hyperplasia (BV/TV 7.35%) and 6 patients without leprosy (BV/TV 12.98%). Bone volume was maintained in patients with nodular Leydig cell hyperplasia, and we determined no clinical factor other than the Leydig cell hyperplasia that reflected the bone volume. The osteoporosis of male leprosy patients was attributed to secondary gonadal dysfunction due to testicular atrophy, and Leydig cell hyperplasia appears to preserve bone volume.

Aged↗

Neovascularization of the outermost area of herniated lumbar intervertebral discs.

In 64 surgically treated herniated lumbar intervertebral discs, we performed histopathological studies of neovascularization in the outermost layer of the herniated mass in various types of hernia. We obtained specimens separately from the capsule tissue covering the herniated mass and the inner tip tissue of the herniated mass for comparison. Histologically, in most cases, the capsule tissue was the outermost layer of the annulus fibrosus or posterior longitudinal ligament, and the inner tip tissue was the nucleus pulposus. In the capsule tissue, newly formed small blood vessels were present in 73.4% of the total cases examined, regardless of the hernia type. However, the frequency and degree of such vessels in the tip tissue were significantly higher in hernias that perforated the posterior longitudinal ligament than in those that did not. When the intervertebral disc herniates, new blood vessels proliferate in the capsule of the hernial tissue. At the stage when the hernial capsule tissue is still present, these vessels were observed to have difficulty reaching the inner tip portion. These findings suggest that when the nucleus pulposus portion of the herniated mass perforates the posterior longitudinal ligament, it may be subject to a stronger neovascularization reaction.

Adolescent↗

Lymphoplasmacyte-rich meningioma: a case report with histological and immunohistochemical studies.

This report concerns a 64-year-old woman with a lymphoplasmacyte-rich meningioma. Radiographically and macroscopically, the tumor had the appearance of an ordinary meningioma. Components of the meningothelial cells were positively immunostained for epithelial membrane antigen. The results of immunohistochemical assays with the antibodies to surface markers of lymphocytes L26 and UCHL-1 indicated that the lymphoplasmacellular proliferation was not neoplastic but probably represented an immune reaction of the host.

Female↗

Intracranial germinoma with Down's syndrome: a case report and review of the literature.

BACKGROUND: Down's syndrome's association with malignancies such as leukemia is well known, but its association with brain tumor appears to be rare. We reviewed such rare cases of Down's syndrome and intracranial germ-cell tumor. CASE REPORT: A 10-year-old boy with Down's syndrome and intracranial germinoma located in the left basal ganglia is reported. The patient presented with right hemiparesis and was treated with a combination of surgery, chemotherapy with cisplatin and etoposide, and irradiation. CONCLUSIONS: We speculate that the percentage of germ-cell tumors is high among Down syndrome patients with brain tumors and that the most common site is the basal ganglia.

Basal Ganglia↗

Prospective study of nesidioblastosis in newborns and infants: hypoglycemic seizures, epileptogenesis and the significance of the C-peptide suppression test in pancreatectomy.

The long-term follow-up of chronic hyperinsulinemic seizures, epileptogenesis and other neurological complications in five patients who were treated with conservative therapy followed by pancreatectomy during the neonatal period and infancy, who were confirmed to have diffuse nesidioblastosis are described. The reaction pattern of the C-peptide (CPR) suppression test and its relation to the final extent of pancreatectomy was examined in four patients. The chronological change in electro-encephalography (EEG) and its epileptogenesis was also examined in each patient during hyperinsulinemic hypoglycemia, and during normoglycemia in a long-term post-pancreatectomy follow-up. All patients demonstrated several types of hypoglycemic seizures, ranging from apnea, erratic seizures, evolving to generalized/unilateral tonic-clonic or tonic seizures, myoclonic seizures and EEG abnormalities. Four of five patients still suffered from epilepsy at the age of 4-22 years. The reaction pattern of the CPR suppression test showed dichotomy, with a hyper-reactive pattern in two patients who required total pancreatectomy to control hypoglycemia, and a suppression pattern in two other patients treated with 90-95% pancreatectomy. Neonatal onset and subsequent myoclonic seizures were ominous signs of epileptogenesis to various types of intractable epilepsy and other neurological sequelae. A prompt diagnosis and pancreatectomy of a sufficient extent at the first operation are essential. The CPR suppression test may be useful for a prompt diagnosis and selection of the extent of pancreatectomy.

Blood Chemical Analysis↗

Osteoporosis due to testicular atrophy in male leprosy patients.

A study was conducted to examine the relationship of testicular atrophy to bone metabolism in male leprosy patients. The study consisted of 31 leprosy patients (mean age: 62.0 years) and 31 healthy control men (mean age: 60.0 years). Measurements were made of their serum levels of free testosterone (FT), estradiol (E2), luteinizing hormone (LH) and 25-hydroxyvitamin D (25 OHD). Bone mineral density (BMD) was measured at radial sites and the lumbar vertebral bodies (L2-L4) by dual-energy X-ray absorptiometry using a Hologic QDR-2000 densitometer. FT and E2 levels were significantly lower and LH levels higher in leprosy patients than in controls. This represents a primary hypogonadal pattern. A value of 7.20 pg/ml of FT ( = Mean - 1 SD of control) was used as a cut off value, and the subjects were subdivided into a hypogonadal group (HG) and a non hypogonadal group (non-HG). When the subjects were compared for differences in age, age at onset of disease, duration of disease, body mass index and BMD, only the duration of disease and BMD were significantly different between the two groups. Furthermore, BMD of the forearm significantly correlated with FT levels (r = 0.689, P < 0.0001). Low BMD may be due to orchitis and testicular atrophy.

Aged↗

Hantavirus infection among Rattus norvegicus in Japan.

Seroepizootiological study of hantavirus infection among 393 urban rats (Rattus norvegicus) captured in six regions in Japan during the period from 1990 to 1994 was carried out by the indirect fluorescent antibody (IFA) test and Western blot (WB). Fifteen out of 393 (3.8%) rat sera were antibody-positive by IFA, i.e., Tokyo Port (12.8%, 6/47), Shimizu Port (5.7%, 2/35), Otaru Port (1.5%, 1/65) and Nagoya City (3.6%, 6/167). In two other regions, i.e., Kasai Seaside Park and Haneda Airport, rat sera were antibody-negative. One serum with a lower IFA titer, 1:64, from Otaru Port was confirmed to be antibody-positive by WB, while two sera from Shimizu Port (IFA titer, 1:32 and 1:64) were not. In Nagoya City, one out of four sera (IFA titer, 1:32) and one of two sera (IFA titer, 1:64) were also confirmed to be antibody-positive by WB. Continuous hantavirus infection among rats in Tokyo Port, Shimizu Port and Nagoya City and the existence of hantavirus among rats in Otaru Port were demonstrated.

Animals↗

Idiopathic peripheral neuropathy in a horse with knuckling.

We report the pathological findings of the skeletal muscle and peripheral nerves from a male 14-months-old thoroughbred horse showing idiopathic knuckling. The affected animal, when in staining position, presented knuckling at the fetlock joint of both forelegs, and dragged both fore- and hindlegs when attempting forward movement. The skeletal muscles demonstrated neurogenic atrophy characterized by the scattering of single angular fibers, groups consisting of five to ten angular fibers, and multiple fascicles of atrophic and hypertrophic fibers. The severity of changes tended to be a distal gradient. While there was no evidence of fiber loss on light microscopy, a diffuse scattering of myelin ovoid, Wallerian-like degeneration and onion-bulb formations were observed in almost all peripheral nerves collected. The characteristic features in electron microscope were swollen axons, which contained accumulations of organelles, especially degenerative mitochondria and neurofilamanets. Onion-bulb formations were frequently found and were associated with Schwann cell processes and occasional collagen pockets. Other prominent feature were Büngner bands which contained myelin debris and regenerating axons or sprouts. These findings suggested that the nature of this disease was a disturbance in axonal transport and were indicative of a distal axonopathy.

Animals↗

[The efficacy and safety of priming principle with pipecuronium].

The authors evaluated the cumulative dose response of pipecuronium under isoflurane anesthesia, and the efficacy as well as safety of priming principle in 52 patients who underwent elective surgery. The ED95 of pipecuronium was 34.24 +/- 5.34 micrograms.kg-1 in 10 patients and 70 micrograms.kg-1 (not equal to ED95 x 2) was used as total dose (T). The 42 patients were divided to receive either no prime or, 5%, 10%, 15% or 20% of T as a prime followed 5 minutes later by the remaining (intubating) dose. The muscle weakness in awake patients was determined after the priming doses by examining several clinical symptoms and by evaluating the effect of intubating doses on neuromuscular blockade. The priming using 10% of T provided rapid intubating conditions. However, the priming dose caused a significant incidence of symptoms of muscle weakness. Therefore, the priming principle should be used with caution.

Adult↗

A girl with Hermansky-Pudlak syndrome.

A young girl with ocular albinism and the Hermansky-Pudlak syndrome is described. Ocular albinism generally occurs in males. In this condition, the pigmentation of the skin and hair is nearly normal, and the melanin pigment abnormality is limited to the eyeballs. The chief complaints are visual disturbance, nystagmus, and photophobia. A 3-year-old girl was recently brought to our hospital with nystagmus, which she had exhibited since the age of 1 year. Funduscopy resulted in a diagnosis of ocular albinism. Further investigations, specifically, microscopy of her platelets, led us to conclude that she had Hermansky-Pudlak syndrome.

Albinism, Oculocutaneous↗