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Biomedical subjects

M Furukawa

Publications and source records attributed to M Furukawa.

At least 289 records · Page 16Linked to original sources

Presence of platelet-activating factor-acetylhydrolase in milk.

Human milk contains numerous factors such as immunoglobulins, lactoferrin, lysozyme, macrophages, etc., which serve an immunoprotective role. Platelet-activating factor (PAF) is one of the most proinflammatory agents thus far described. PAF is metabolized to the biologically inactive lysoPAF by the enzyme PAF-acetylhydrolase (PAF-AH). In the present study we have demonstrated that PAF-AH activity is present in human milk. The activity was associated with aqueous phase and was not stimulated by the addition of bile salts or Ca2+. The activity of PAF-AH in human milk was not affected by the addition of propranolol or NaCl. PAF, and 1-acyl-2-acetyl-glycerophosphocholine were the only substrates cleaved by the enzyme. Based on these properties it is concluded that the milk PAF-AH is not the lipoprotein or bile salt-stimulated lipase known to be present in milk. Inhibitor studies revealed that the enzyme in human milk was the plasma type PAF-AH. The activity of PAF-AH was stable at pH 4.0 at 37 degrees C and the activity varied in milk samples obtained from various species. The enzyme was secreted by milk macrophages. The presence of PAF-AH in human milk may explain, in part, the beneficial effects of breast feeding in the prevention of necrotizing enterocolitis by inactivating the potent proinflammatory autacoid, PAF.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Singly-linked catenation and knotting of cisplatin-DNA adduct by DNA topoisomerase I.

We studied the topological interaction between topoisomerase I (topo I) and cisplatin-DNA adduct. The topoisomers of the cisplatinized DNA formed by topo I are different in none-, low- and high-cisplatin concentrations to bind to DNA. Two unique topologically distinct invariants, singly-linked catenane and torefoiled knot DNA generated from cisplatin adduct, by topological reaction but not from none cisplatinized DNA. The results are discussed in relation with a possible recombinational role of cisplatin on the topological reaction with DNA.

Cisplatin↗

Deficiencies in factors IX and VIII: what is now known.

Genetic defects both gross and subtle have recently been identified in about 900 patients with hemophilia A or B. The defects, which include deletions, insertions, and point mutations, reveal much about genetic structure-function relationships in hemophilia. These insights will lead to improved treatment of bleeding disorders and perhaps to their cure.

Base Sequence↗

Changes of plasma des-gamma-carboxy prothrombin levels in patients with hepatocellular carcinoma in response to vitamin K.

The effect of menaquinone-4 (MK-4, vitamin K2) was studied on des-gamma-carboxy prothrombin (DCP or PIVKA-II) levels in three subjects with vitamin K deficiency and five patients with hepatocellular carcinoma (HCC) with positive DCP. The half-life of DCP in HCC patients after intravenous MK-4 administration (50 mg daily for 14 days) was determined to be 60 hours, identical to that found in vitamin K-deficient subjects who received MK-4. When a single dose of MK-4 (10 mg) was given intravenously to three patients with HCC and elevated DCP, the levels decreased with a reduction rate identical to that in vitamin K-deficient subjects for the first 1 to 3 days, followed by an increase reaching the previous level in 7 to 10 days. Changes in plasma coagulant activity were compared between subjects with vitamin K deficiency and those with HCC before and after a single dose of MK-4 (10 mg). The activity increased in DCP-positive patients with HCC as in vitamin K-deficient subjects who received the same single dose of MK-4. The increase was greater in HCC patients with higher DCP levels. These results suggest that the level of plasma DCP in patients with HCC responded to vitamin K with the same sensitivity as that in vitamin K-deficient subjects. When patients with HCC underwent effective tumor therapy (resection or arterial embolization), the reduction rate (slope of DCP decline) was found to be identical to that in vitamin K-deficient subjects given with MK-4. In patients with less effective therapy, the reduction rate was smaller, or there was an increase in DCP. These observations strongly suggest that sequential measurements of the DCP reduction rate after treatment for HCC are useful for assessing therapeutic effects.

Aged↗

Effects of hyperthermia on intracellular calcium concentration and responses of cancerous mammary cells in culture.

Effects of hyperthermia on the intracellular calcium concentration (Cai) of an established mouse breast cancer cell line, MMT060562, were studied using fura-2 fluorescence microscopy and the whole-cell clamp technique. A sudden change of temperature from 37 to 45 degrees C induced a transient increase in the fluorescence ratio permeability of the cell membrane and inward current. Deletion of extracellular calcium abolished the fluorescence ratio response to the rise in temperature. Cai of some cells increased after hyperthermia treatment at 44-48 degrees C for 20 min, but the average increase of Cai was negligible. After hyperthermia treatment, spontaneous oscillation of Cai, chemical responses to ATP and bradykinin and the mechanically-induced spreading response diminished. However, the mechanically induced increase of Cai within the stimulated cell remained even after hyperthermia treatment. Suppression of the ATP-induced Cai response recovered to about half the original level within 12 h. Blockage of protein synthesis with cycloheximide (100 microM) had no effect on the recovery. The D-myo-inositol 1,4,5-triphosphate (IP3)-dependent increase of Cai remained intact even after hyperthermia treatment. It is concluded that hyperthermia treatment increases both the permeability of the cell membrane and Cai, but decreases the sensitivity of cells to ATP and bradykinin, presumably due to modification of the signal transduction mechanism.

Adenosine Triphosphate↗

Academic success of integrated hearing-impaired pupils who had enrolled in the early written-oral language program.

Data on academic success were analyzed for 37 hearing-impaired pupils who had been trained by the Written-Oral Language Method before school age. Seventy-one percent of pupils whose average hearing level was less than 89 dB and 77% of pupils whose hearing was 90 to 120 dB succeeded academically. Degree of hearing impairment, speech intelligibility, and gender were not important to their success. Linguistic competence evaluated just before enrollment in a normal educational setting at 6 years of age was the only factor significant to their academic success. However, we propose that the investigation of other factors, IQ and age at the start of preschool training program, must be analyzed in more detail in the future.

Child Language↗

Intratemporal facial nerve neurinoma without facial paralysis.

A 38-year-old man was referred by his general practitioner to our department on 28 October 1991, with a 2-week history of vertigo. A left aural polyp was identified. The audiogram showed a moderate conductive loss on the left side. Computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the presence of the expanding lesion in the descending portion of the facial nerve. However, there was no seventh nerve paresis. At operation, the neurinoma (Schwannoma) filled the middle ear cleft and extended from the genu to the stylomastoid foramen. The floor of the middle ear had been eroded, exposing the jugular bulb. Facial nerve paresis is the usual presenting feature of a facial neurinoma. The case is presented for the reason that the absence of facial palsy as a presenting feature is rather rare, especially in the cases with large tumor and extensive bone erosion.

Adult↗

Angiosarcoma of the nasal cavity.

Angiosarcoma of the nasal cavity is extremely rare. We present a case of angiosarcoma of the nasal cavity in an eight-year-old boy. He was treated with medial maxillectomy via lateral rhinotomy. The histological diagnosis was confirmed by immunohistological stain with Factor VIII-like antigen. Magnetic resonance imaging (MRI) was useful in determining the extent of the tumour.

Child↗

Immunophenotypes of the palatal tonsil lymphocytes in Cowden's disease.

Cowden's disease is characterized by multiple hamartomas and neoplasias of ectodermal, mesodermal and endodermal origin. A case of a 22-year-old man suffering from nocturnal dyspnoea is reported. The patient had a large number of hyperkeratotic, lichenoid papules, scattered over the right side of the trunk, back and palm. In his oral cavity, papules were present on the gingiva and hard palate. The patient was operated on for tonsillar hypertrophy and for excluding the possibility of malignant lymphoma. An examination of immunophenotypes of the palatal tonsil lymphocytes revealed B-cell proliferation and poly-clonal immunoglobulin.

Adult↗

Horseshoe anomaly of the pancreas.

A 72-year-old man with recurrent pancreatitis and a horseshoe-shaped anomaly of the pancreas is described. The diagnosis was made by endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography scan; laparotomy was confirmatory. The abnormal duct branched to the lower left from an enlarged Santorini's duct; a thin Wirsung's duct was joined at its distal portion to the junction of the abnormal duct. The anomaly was associated with a cystic dilatation of the common bile duct with stone and cholecystolithiasis. This anomaly is considered to be a variation of the dominant dorsal duct syndrome.

Aged↗

Secondary T-cell lymphoma presenting as a giant ulcer.

Secondary cutaneous T-cell lymphoma may present with various types of skin lesions, but rarely produces ulceration in contrast to primary cutaneous T-cell lymphoma. We report a case of malignant lymphoma of the tonsil that recurred as a giant cutaneous ulcer on the back of a 45-year-old man. Biopsy of the ulcer revealed a malignant lymphoma of diffuse, mixed-cell type. Surface marker analysis of the tumour cells showed suppressor/cytotoxic T-cell characteristics. The skin lesions were treated by electron beam therapy.

Humans↗

Epstein-Barr virus BZLF1 transactivator is a negative regulator of Jun.

The Epstein-Barr virus BZLF1 protein that can induce the lytic cycle in latently infected cells is a transcription factor partially homologous to Fos and binds not only the canonical TPA (tetradecanoyl phorbol acetate)-responsive element (TRE) site but also sequences deviating from the TRE consensus sequence. Thus, expression of cellular genes regulated by AP-1, including the autoregulated AP-1 family, should be affected by BZLF1. However, induction of only Fos by BZLF1 was observed in a gel mobility shift assay using an oligonucleotide probe containing the TRE sequence and the antibody against Fos protein. The c-jun promoter, which contains a binding site for Jun and BZLF1, was stimulated by Jun but not by BZLF1. Furthermore, BZLF1 inhibited stimulation of the c-jun promoter by Jun. Jun together with Fos effectively activated the collagenase promoter that contains a single TRE site. However, not only was BZLF1 unable to stimulate the collagenase promoter, but it also inhibited activation by Jun and Fos. On the other hand, BZLF1 stimulated constructs containing multimeric binding sites. These results and those of previous studies of Epstein-Barr virus promoters regulated by BZLF1 indicate that BZLF1 requires adjacent multiple DNA-binding sites for cooperative interaction to function as a transactivator and to repress the activation by Jun of promoters containing a single TRE site. This suggests that BZLF1 evolved to confer distinct regulatory patterns upon viral target genes and cellular AP-1-responsive genes.

Base Sequence↗

Evidence of platelet-activating factor in nasal polyps.

Platelet-activating factor (PAF) was measured in human nasal polyps obtained from patients with chronic sinusitis. PAF was quantitated by platelet-aggregating activity and was found to be 7.8 +/- 1.8 pg/micrograms phosphorus of polyp phospholipid (mean +/- SE; n = 23). In the polyps, phosphatidylcholine constituted 30% of the total phospholipids, of which 8.5% was the ether-linked type. Incubations of replicates of the fresh polyps in Tyrode's solution in the presence of calcium ionophore A23187 and antihuman immunoglobulin E resulted in 295 and 65% increases in the amount of PAF, respectively. Thus, nasal polyps in humans with chronic sinusitis possess PAF and have the potential to produce PAF upon stimulation. The participation of PAF in nasal polyp formation is discussed.

Adolescent↗

[The effects of early manual instruction on the oral language development of two deaf children].

The speech and language training for deaf children at our clinic is performed using a multisensory method, which consists of reception and expression training for sign language and fingerspelling as well as auditory training, lip reading, and written language training (the Kanazawa Method). We have already reported that acquisition of written language is not dependent on oral language, and that written language is easier to learn than oral language for deaf children. In the present investigation, we analyzed the acquisition of comprehensible and expressive vocabulary in sign language and fingerspelling. The subjects were two children congenitally deaf at levels higher than 105dB. Recorded language samples by the age of 48 months were analyzed. Acquisition of sign language was found to be significantly easier than acquisition of oral language. The development of expressive noun words, function words, and Wh-question words in sign language at the early period was almost equivalent to that of hearing peers, and then the sign language appeared transfer to the oral language. These results suggest that early presentation of sign language with written and oral language is effective in the acquisition of communicative attitudes, function words and interrogative sentences which are most difficult for the hearing-impaired. It was shown that early presentation of sign language with written and oral language serves to promote acquisition of oral language.

Child↗

[Study of behavioral and histological change in mice following olfactory bulbectomy].

Behavioral and histological changes in mice following bilateral olfactory bulbectomy were studied. Mice were trained to discriminate between a 0.01% Cycloheximide solution and distilled water. After olfactory bulbs were removed, discrimination was lost, and had not returned 300 days after bulbectomy. The histological changes observed by light microscope were as follow. Degeneration of olfactory epithelium was observed immediately after the bulbectomy, followed by decrement of the epithelial thickness and the number of olfactory cells. An increase in both epithelial thickness and the number of olfactory cells was observed 14 days after the bulbectomy, and epithelial thickness 300 days after the bulbectomy was similar to that of the sham-operation group. At 300 days after the bulbectomy, axons of olfactory cells migrated through the lamina cribrosa, but didn't contact the forebrain. In this study, the olfactory bulb was considered to have played a role in functional recovery of olfactory behavior, and that olfactory cells were continuously renewed under conditions of target organ, i.e. olfactory bulb, loss.

Animals↗

[Clinical observations on parosmia].

We reviewed the clinical records of 15 patients with parosmia examined in our department from April 1987 to September 1990. Seven (29.2%) of 24 patients with olfactory disturbance caused by traumatic injury complained of parosmia. Eight (23.2%) of 34 patients with olfactory disturbance caused by influenza also showed parosmia. The incidence of parosmia between two groups was not statistically significant (p greater than 0.05). Parosmia was observed in none of 42 patients with olfactory disturbance caused by nasal-paranasal diseases. All patients (n:15) always perceived odors as unpleasent. Twelve of them had spontaneous parosmia, and three patients recognized the unpleasant smell when an odor came. In comparison with the auditory system, we speculated that spontaneous parosmia resembles tinnitus. The cause of tinnitus is recognized as a disturbance of the auditory nerve (the first order neuron). Tinnitus is rare in patients with conductive hearing loss, and cases of olfactory disturbance of the "respiratory dysosmia" did not complain of parosmia. Post-traumatic olfactory disturbance is caused by transection of the fila olfactoria, which is part of an olfactory neuron, while post-inflammatory olfactory disturbance is caused by damage to olfactory receptor cells. Furthermore, the fact that the incidence of parosmia between the two groups was not statistically significant suggests the same etiological mechanism in receptor cells. We consider that parosmia is caused by damage to olfactory sensory neurons.

Adolescent↗

Biology of factor IX.

Hemophilia B, one of two common hereditary bleeding disorders, is caused by a deficiency of factor IX in the circulation. Molecular mechanisms of hemophilia B are highly heterogeneous including gene deletions, insertions, complex rearrangements, and a large number of point mutations. Currently, hemophilia B is treated by plasma protein replacement therapy. This therapy is effective but exposes patients to possible side effects and complications such as infection of blood-borne pathogens including hepatitis viruses and HIV-1. Intensive efforts to develop alternative, safer therapies for hemophilia B, including somatic gene therapy, are now under way.

Amino Acid Sequence↗