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Biomedical subjects

K Hashimoto

Publications and source records attributed to K Hashimoto.

At least 37 records · Page 2Linked to original sources

Hepatic haemodynamics and microvascular architecture after portal venular embolization in the rat.

To clarify the relationship between hepatic damage and alterations of hepatic microvascular architecture and haemodynamics following portal venule occlusion, the present study was performed in rats which had been injected into the portal vein with 700,000 plastic beads (30-35 microns in diameter). When the occluded segment of the portal venule was short, infarction did not occur because of the prompt development of vascular channels bypassing the obstructed venules. On the other hand, when the occluded segment was long, infarction usually occurred. In this case, formation of collateral vascular channels began as dilatation of the sinusoids in the vicinity of the occluded portal venules and increased in diameter and developed into new portal venules in 5 days. Increased portal vascular resistance after embolization was normalized after 5 days in parallel with the progression of reconstruction of vascular channels. Reduced bile production returned to a normal level 3 days after embolization. Necrotic tissue was resorbed completely and replaced by fibroblasts 5 days after embolization. These findings indicate that the development of infarct following portal venule occlusion depends on the length of the occluded segment, and that hepatic microvasculature has a great capacity for adaptation and rapid reconstruction of vascular channels which leads to speedy recovery from hepatic circulatory disturbances and resulting hepatic damage.

Animals

Enhancement of murine alveolar macrophage functions by orally administered beta-glucan.

The effect of orally administered SSG, a beta-1,3-glucan obtained from the culture filtrate of the fungus Sclerotinia sclerotiorum IFO 9395, on alveolar macrophage (AM) functions of CDF1 mice was examined. SSG administered orally (20, 40, 80 or 160 mg/kg) for 10 consecutive days enhanced the lysosomal enzyme activity of AM. The greatest enhancing effect was observed at 80 mg/kg of SSG. Multiple oral administrations of SSG (10 consecutive days) were needed to induce significant enhancing effects. Phagocytic activity and interleukin-1 (IL-1) production of AM were also augmented by oral administration of SSG, and the kinetics of the activated state differed depending on the kind of activity. However, H2O2 production of AM was not affected by SSG. Orally administered SSG also (40 or 80 mg/kg, 10 consecutive days) increased the number of AM and the greatest increment was observed 14 days after the first administration. On the other hand, the supernatant of Peyer's patch (PP) cells from mice administered SSG (80 mg/kg) orally stimulated the lysosomal enzyme activity of AM in vitro, and enhanced colony stimulating activity (CSA) was detected from this supernatant. These results demonstrate that SSG given by the oral route can activate murine AM both qualitatively and quantitatively, and it would mediated, at least in part, by the activation of PP cells in the intestine.

Adjuvants, Immunologic

Monoclonal anti-melanoma antibodies IKH-1 and IKH-2 which work on formalin-fixed, paraffin embedded tissues: characterization, clinical trials and comparative studies with HMB-45.

Mouse monoclonal antibodies (MoAbs), IKH-1 and IKH-2, were produced against cloned human melanoma cells, KHm-6, which were cultured with 12-O-tetradecanoylphorbol-13-acetate (TPA) and processed by formalin fixation and alcohol dehydration (FFAD). According to the biochemical analysis, antigenic substances which reacted with IKH-1 were 34.0-60.0 kDa glycoproteins, and those which reacted with IKH-2 were 33.5, 34.5 and 36.0 kDa glycoproteins. Immunoelectron microscopy revealed that reaction products of IKH-1 were seen in some membranous vesicles, premelanosomes and cell membrane of TPA-treated KHm-6 cells, while IKH-2 recognized only premelanosomal structures. Immunohistochemical tests revealed that IKH-1 and IKH-2 have a high sensitivity (94.0% and 85.0%, respectively) to formalin-fixed, paraffin-embedded (FFPE) tissue sections of malignant melanomas. IKH-1 had a high specificity and IKH-2 and 100% specificity to FFPE tissue sections of melanocytic lesions.

Animals

Regional imaging of brain tissue calcium ions using aequorin.

To investigate regional changes in calcium ion concentrations, we developed a new histochemical method using aequorin, a calcium ion-sensitive photoprotein. In this method, reagent film containing aequorin was made and an unfixed slice of frozen brain 16 microns thick was placed on it. Tissue calcium ions permeated the reagent layer and the bioluminescence of aequorin-calcium ions was recorded photographically with high spatial resolution. There was a close linear relationship (r = 0.903) between the optical density of the bioluminescent images and the logarithmic values of the tissue calcium ion concentration. Using this method, we could visualize the regional tissue calcium ion distribution in pathological states in rat brains.

Adenosine Triphosphate

Papular mucinosis (scleromyxoedema) complicating diffuse systemic sclerosis: clinical features and electron microscope observations.

Papular mucinosis (scleromyxoedema) is an uncommon disorder characterized by generalized papular eruption and cutaneous induration, which may be associated with a variety of extracutaneous manifestations. Although scleroderma and papular mucinosis share many features, they are clinically and histologically distinct entities. We report here a patient with diffuse scleroderma who developed superimposed papular mucinosis. Degranulating mast cells were a prominent ultrastructural finding in the involved skin. The occurrence of scleroderma and papular mucinosis, two uncommon cutaneous indurative diseases, in the same patient has not been described previously.

Biopsy

Central interaction between endothelin and brain natriuretic peptide on vasopressin secretion.

OBJECTIVE: To examine the interaction between i.c.v. administration of endothelin and brain natriuretic peptide (BNP) on vasopressin (AVP) secretion in unanesthetized, freely moving rats. METHODS: I.c.v. cannulation and femoral artery catheterization were performed 7-8 days and 2 days before the experiment, respectively. Endothelin and BNP were injected into the third ventricle through the guide cannula. One millilitre of blood was collected for AVP measurement 30 min before and 10 min after i.c.v. injection. RESULTS: Central administration of endothelin (20 or 40 pmol/2 microliters) dose-dependently evoked the elevation of plasma AVP levels. Preinjection of BNP (0.2 or 1 nmol/3 microliters, i.c.v.) dose-dependently attenuated central endothelin (40 pmol/2 microliters)-induced plasma AVP secretion. CONCLUSIONS: We have already reported that BNP attenuated central endothelin-induced pressor response and plasma catecholamine secretion. Taken together, the results indicate that BNP attenuated central endothelin-induced pressor response, at least partially, by suppressing sympathetic nervous system activation and plasma AVP secretion.

Animals

Regulation of pulmonary resistance during cardiopulmonary preservation.

To characterize the neural and vasoactive mediators of pulmonary vasoconstriction and determine whether the beneficial effect of isoproterenol could be mimicked by other agents that increase cyclic adenosine monophosphate, heart and lung organ blocks were harvested from calves and studied in a normothermic autoperfusion circuit. In the experimental protocol, measurements were obtained (A) after sternotomy but before autoperfusion (in vivo); (B) during stimulation of in vivo control with tert-butyl hydroperoxide (t-BuOOH), a lipid peroxide; (C) after cannulation and institution of in situ autoperfusion (innervated preparation); (D) following denervation and explanation (ex vivo); (E) during stimulation of ex vivo preparation with t-BuOOH; and (F,G) after administration of isoproterenol, aminophylline and prostaglandin E1 to the ex vivo preparation with (time G) and without (time F) stimulation using t-BuOOH. Plots of transpulmonary pressure gradient versus cardiac output were generated for each animal, and an index of pulmonary vascular resistance was obtained from the slope of the linear relationship. Blood samples were collected for measurement of thromboxane-B2, 6-keto-prostaglandin-F1 alpha, and complement activation products C3a and C5a. Pulmonary vasoconstriction occurred during in situ autoperfusion prior to denervation and increased further following denervation and ex vivo autoperfusion; vasoconstriction correlated with increased levels of circulating vasoactive mediators. The pulmonary vasoconstrictor response was greater in the denervated vascular bed compared with the innervated state. All agents reduced postexplant pulmonary vasoconstriction. We conclude that agents that increase cyclic AMP modulate the pulmonary vasoconstrictor response and thus may enhance lung preservation in the autoperfusion model as well as with other current preservation methods.

Alprostadil

Cytokeratin polypeptide profile of Merkel cells in human fetal and adult skin: difference of expression of cytokeratins in epidermal and dermal Merkel cells.

The origin of Merkel cells is uncertain, although current evidence by immunohistochemical keratin marker studies favors an epidermal derivation. We studied the expression of keratin species in Merkel cells of human fetus and adult using 19 anti-keratin antibodies. Epidermal and dermal Merkel cells contained not only simple epithelium-type but also some stratified epithelium-type keratins. Interestingly, expression of some keratins was different between epidermal and dermal Merkel cells, for example, AN3 (50, 58 kD) and CKB1 (50 kD) recognized epidermal Merkel cells, but not dermal Merkel cells. These results suggest that surrounding keratinocytes influence the expression of cytokeratins in Merkel cells or that dermal Merkel cells undergo a modification from keratin-producing epidermal Merkel cells to a more neural cell type by the association with nerve endings in the upper dermis. On the other hand, certain cytokeratin polypeptides recognizable with Ks19.1 (40 kD), CK5 (45 kD), and CAM5.2 (52.5 kD) were expressed in both epidermal and dermal Merkel cells. The expression of simple epithelium-type keratins in Merkel cells remained even after the epidermal basal cells gradually lost their expression.

Adult

The growth regulation of keratinocytes.

Taken together, all these results suggest that TGF-alpha and amphiregulin are the major growth factors for positive growth control, although we don't know which plays the central role. For negative growth control, TGF-beta is the major factor. However, it remains to be solved which isoform of TGF-beta is naturally involved in keratinocyte growth regulation.

Amphiregulin

The role of growth factor in wound healing.

A pig wound healing model was developed to study the morphological processes involved in incisional and excisional wound healing, the immunohistochemical localization of TGF-alpha in wound healing, and the latter's relevance. In incisional wounds, a few layers of epidermis were regenerated after only 32 hours. In contrast, several layers of epidermis were regenerated on day 7 in excisional wounds. In general, the incisional wound model is useful for evaluating tensile strength, while the excisional wound model is suitable for evaluating epidermal regeneration. Immunohistochemical study showed that keratinocytes migrating from wound edges expressed TGF-alpha very faintly, while TGF-alpha was present prominently in the upper several layers of the epidermis adjacent to the wound, which resembled normal epidermis and showed no changes during the wound healing process.

Animals

Tinea versicolor: histologic and ultrastructural investigation of pigmentary changes.

A comparative histopathologic study is made between the hypopigmented and hyperpigmented skin lesions of pityriasis versicolor and normal skin areas utilizing histochemical stains and electron microscopy. There were no differences found between the population of Dopa-positive melanocytes within the hypopigmented and hyperpigmented lesions and the normal skin areas. The total epidermal pigmentation was diminished in hypopigmented lesions. The keratin layer was found to be significantly thicker in hyperpigmented lesions and contained more organisms. In hypopigmented lesions, melanocytes contained fewer and smaller melanosomes and exhibited signs of degenerative cellular changes.

Cell Count

A case of adult T-cell leukemia/lymphoma, histologically presenting CD30-positive large cell lymphoma.

A 48-year-old Japanese woman with adult T-cell leukemia/lymphoma (ATLL), histologically presenting CD30-positive large cell lymphoma is reported. The patient, who was from an ATLL endemic area in Japan, had cutaneous nodules in the head, trunk, and extremities, and cervical lymph node swelling; these had been found three months before her admission to our hospital. A biopsy specimen of a skin lesion showed diffuse large cell lymphoma; the lymphoma cells were positively stained with CD30 (Ki-1/Ber H-2), CD4 (helper-T), and CD25 (interleukin-2 receptor) antibodies. Anti HTLV-1 antibody (ATLA) was detected in the serum, and molecular cytogenetic studies of lymphoma cells showed both positive T-cell receptor rearrangement and HTLV-1 specific DNA sequences.

Antigens, CD

Spinal arachnoid cyst in a newborn infant.

A male infant was born with asphyxia following a prolonged breech delivery at 39 weeks of gestation. He had a chylohemothorax from birth. Soon after birth he exhibited flaccid paraplegia with an absence of deep tendon reflexes in the lower extremities. At 17 days of age, magnetic resonance imaging (MRI) disclosed a hypodense area in the thoracic cord between C7 and Th4 in T1-weighted images, and spinal sonography revealed an echo-free space compressing the spinal cord in the same region observed with MRI. A spinal cyst was removed surgically at 24 days of age. The cyst was confirmed by pathology to be a true arachnoid cyst between C7 and Th4. The cause of this cyst may have been a spinal cord injury during the perinatal period.

Arachnoid Cysts

Juvenile colloid milium: clinical, histological and ultrastructural features.

We report the clinical, histological and ultrastructural features of juvenile colloid milium affecting a brother and sister. In this rare condition, translucent papules develop on sun-exposed areas of skin, with onset in childhood. Histologically and ultrastructurally, the papules consist of amyloid-like material derived from epidermal keratonocytes. A review of the literature suggests a possible genetic abnormality that leads to sun-induced degeneration of keratinocytes.

Adolescent

Transient bullous dermolysis of the newborn. Retention of anchoring fibril- and basal lamina-like structures in keratinocytes and evidence of collagenolysis.

In a freshly induced blister from transient bullous dermolysis of the newborn, we found in epidermal basal cells structures similar to anchoring fibrils and lamina densa, often in combination. In the upper dermis, collagenolysis and phagocytosis of degenerated collagen fragments were observed. It is concluded that the stellate inclusions previously reported in this disease are prematurely assembled anchoring fibrils and lamina densa. A disturbance of delivery mechanism of precursor materials for anchoring fibrils and lamina densa may cause the deficiency of these structures which are essential for the integrity of dermo-epidermal adhesion. The presence of many normal anchoring fibrils and lamina densa in perilesional skin and their prompt degeneration after rupture of the inclusions previously led us to conclude that lytic enzymes are involved in the formation of blisters in this disease. The new finding of collagen phagocytosis in the lesional dermis seemed to support this contention.

Biopsy

Harlequin fetus with abnormal lamellar granules and giant mitochondria.

A case of harlequin ichthyosis was studied with electron microscopy. From the basal cell to granular cell layers, keratinocytes contained giant mitochondria (860 nm) which exhibited vesicular cristae. Typical lamellar granules were absent; instead, numerous dense cored granules (DCG) and particles containing cored granules (PCG) were produced. Some of these were discharged into the intercellular spaces of granular cells, but the majority failed to be released from the cytoplasm. These retained DCG and PCG coalesced to form large vacuoles and cavities in the stratum corneum. In the hair follicle, keratinized cells failed to loosen and desquamate into the hair canal; instead, they formed concentric keratin rings surrounding hair, a diagnostic feature of this disease. It is suggested that the abnormal lamellar granule underlies the pathogenesis of this disease and that giant mitochondria may be related to an abnormal lipid metabolism of keratinocytes which may affect lipid composition of lamellar granules.

Adult

Beta 2-adrenoceptor-mediated positive dromotropic effects on atrioventricular node of dogs.

The functional significance of beta 2-adrenoceptors in atrioventricular (AV) nodal conduction was investigated by using canine isolated blood-perfused AV node preparations. Dose-dependent shortening of the atrio-His bundle (A-H) interval by dl-procaterol hydrochloride hemihydrate (0.03-1 nmol) injected intra-arterially into the AV node artery was affected little by an infusion of dl-atenolol (10 nmol/min) into the same artery, whereas the dose-response curve for the positive dromotropic effect of procaterol was shifted markedly to the right by approximately 1.5 and 2.5 log units with ICI 118551 [erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylamino-bu tan-2-ol]- hydrochloride (1 and 10 nmol/min). The positive dromotropic effect of dl-T-1583 [alpha-(3,4,5-trimethoxyphenethylaminomethyl)-3,4-dihydroxybenzyl- alcohol] hydrochloride (30-300 pmol), a selective beta 1-adrenoceptor agonist, was shifted to the right by approximately 1.2 log units with dl-atenolol (10 nmol/min) but was affected little by ICI 118551 (10 nmol/min). The dose-response curve for l-isoproterenol hydrochloride (3-100 pmol) was shifted to the right by 0.7 log unit with ICI 118551 (10 nmol/min) and by 1.7 log units with atenolol (10 nmol/min). The dose-response curve for dl-norepinephrine (0.03-1 nmol) was shifted to the right by 1.0 log unit with atenolol only, whereas the curve for l-epinephrine (0.03-1 nmol) was shifted by 0.45 log unit with ICI 118551 (10 nmol/min). These results suggest that both beta 1- and beta 2-adrenoceptors, which coexist on the AV node, play a functional role in AV nodal conduction.

Adrenergic beta-Agonists

Glomerular deposition of alpha 2-macroglobulin in a child with steroid refractory nephrotic syndrome.

A four-year-old male with steroid refractory nephrotic syndrome was found to have diffuse deposition of alpha 2-macroglobulin (alpha 2M) in the glomeruli which showed diffuse mesangial proliferation and partial hyalinization by light microscopy. Camostat mesylate, a commercially available synthetic proteinase inhibitor, led to biochemical and clinical improvement. Twenty-two patients with 7 biopsy-proven renal diseases did not have any deposition of alpha 2M in their kidney tissue. Though the pathogenetic mechanism is unknown, this is probably the first report of the deposition of alpha 2M in renal tissue.

Child, Preschool