Biomedical subjects
Publications and source records attributed to K Hayakawa.
It has been thought that neurohypophysial involvement manifesting as central diabetes insipidus in lymphocytic hypophysitis is rare. The radiological and clinicopathological features of two cases represent a variant of lymphocytic adenohypophysitis and/or lymphocytic infundibulo-neurohypophysitis are discussed.
We report two adult Japanese sisters with L-2-hydroxy-glutaric aciduria (acidemia), both of whom were much older (aged 57, 47 years old) than previously reported patients (from neonate to 44 years old), and who presented with differing severity. Magnetic resonance imaging revealed typical subcortical white matter lesions in both cases and showed brainstem atrophy and thickness of the calvarium in the elder sister. L-2-Hydroxyglutaric acid levels were increased in urine, plasma, and cerebrospinal fluid. These cases suggest that organic acid analysis is necessary even in elderly patients who seem to have neurodegenerative disorders.
The outcome of limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer (NSCLC) was analyzed to discuss the elective irradiation of regional lymph nodes. From 1976 through 1994, 36 patients with peripheral stage I NSCLC were treated with definitive radiation therapy (RT) alone at Gunma University hospital. The total dose ranged from 60 to 81 Gy with a 2 Gy-daily standard fractionation, although only one patient received 48 Gy. Ten patients received elective irradiation of the regional lymph nodes with a total dose of 40 Gy or more. The overall response rate was 97% with 31% complete responses. The overall survival rates at 3 and 5 years were 42 and 23%, and disease-specific survival rates were 56 and 39% at 3 and 5 years, respectively. In 26 patients without the elective regional irradiation, disease-specific survival rates at 3 and 5 years were 53 and 40%, respectively, whereas they were 64 and 39% in 10 patients with the regional nodal irradiation. The cumulative 5-year local progression rate was 28%, and the overall progression rate was 60% at 5 years. Four patients had a local recurrence as the only site of initial tumor progression. Combined local and regional progression was seen in two patients, and one patient had a local recurrence in combination with distant metastasis. Twelve patients had distant failure without evidence of local or regional progression. Only one patient without regional nodal irradiation developed an isolated regional failure. No patient had serious complications related to RT. High-dose limited field RT is justified for medically inoperable patients with peripheral stage I NSCLC. The regional nodal irradiation can be omitted in these pulmonary compromised patients because of the low regional relapse rate. Dose-escalation by a conformal RT with a small target volume can be expected to provide a better local control rate and better survival.
To determine whether the well-accepted hypoxia theory accounts for hyperventilation-induced electroencephalogram (EEG) slowing, the authors monitored changes in cerebral oxygenation and end-tidal concentrations of carbon dioxide in 67 patients with epilepsy (age range = 5-12 years) during the hyperventilation activation test in a routine EEG examination. Relative concentration changes in cerebral oxygenated, deoxygenated, total hemoglobin, and oxidized cytochrome oxidase were measured by near-infrared spectroscopy in the frontal region. In all patients, except one who demonstrated EEG slowing, total and oxygenated hemoglobin decreased, and cytochrome oxidase was not reduced. EEG slowing occurred intermittently in 22 patients and was not synchronous with changes in either the cerebral oxygenation or end-tidal concentration of carbon dioxide. The degree of EEG slowing was diminished or the slow waves disappeared abruptly within 1 second after the cessation of hyperventilation in 22 patients when both the cerebral oxygenation and end-tidal concentration of carbon dioxide were still at low levels. The findings during the recovery periods do not confirm the hypoxia theory. It is thus supposed that more subtle mechanisms are the cause of EEG slowing.
Skull base surgery was performed on 18 patients with anterior skull base injuries. The operative technique consisted of opening the operative field in the anterior skull base via a coronal incision and a frontal craniotomy, debridement of the anterior skull base including the injured dura mater, performing drainage from the anterior skull base to the nasal cavity by ethmoidectomy, and reconstructing the resulting dural and anterior skull base defect using bilateral temporal musculo-pericranial flaps and a bone graft. Seventeen of the 18 patients recovered without any complications, although epidural abscesses in the anterior skull base had been present in four patients at the time of the operation. Only one patient developed an epidural abscess in the anterior skull base after the operation. None of the patients developed any other complications including meningitis, recurrent liquorrhoea or cerebral herniation. Satisfactory aesthetic results were achieved in 16 of the 18 patients. In one patient, uneven deformity of the forehead, which was caused by the partial sequestration of the frontal bone due to postoperative infection, was observed. In another patient, a depressed deformity of the forehead, which was caused by the partial loss of the frontalis muscle following the use of the frontal musculo-pericranial flap instead of a temporal musculo-pericranial flap, was observed. Anterior skull base reconstruction using bilateral temporal musculo-pericranial flaps provides excellent results in terms of patient recovery and aesthetics.
The possible existence of a beta3-adrenergic receptor (beta3-AR) in the human detrusor muscle was investigated by in vitro functional studies and analysis of mRNA expression. Isoprenaline, noradrenaline and adrenaline each produced a concentration-dependent relaxation of the human detrusor. The rank order for their relaxing potencies was isoprenaline (pD2 6.37+/-0.07) > or = noradrenaline (pD2 6.07+/-0.12) > or = adrenaline (pD2 5.88< or =0.11). Neither dobutamine (beta1- and beta2-AR agonist) nor procaterol (beta2-AR agonist) produced any significant relaxation at concentrations up to 10(-5) M. BRL37344A, CL316243 and CGP-12177A (beta3-AR agonists), relaxed the preparations significantly at concentrations higher than 10(-6) M. The pD2 values for BRL37344A, CL316243 and CGP-12177A were 6.42+/-0.25, 5.53+/-0.09 and 5.74+/-0.14, respectively. CGP-20712A (10(-7) - 10(-5) M), a beta1-AR antagonist, did not affect the isoprenaline-induced relaxation. On the other hand, ICI-118,551, a beta2-AR antagonist, produced a rightward parallel shift of the concentration-relaxation curve for isoprenaline only at the highest concentration used (10(-5) > M) and its pKB value was 5.71+/-0.19. Moreover, SR58894A (10(-7) - 10(-5) M), a beta3-AR antagonist, caused a rightward shift of the concentration-relaxation curve for isoprenaline in a concentration-dependent manner. The pA2 value and slope obtained from Schild plots were 6.24+/-0.20 and 0.68+/-0.31. The beta1-, beta2- and beta3-AR mRNAs were all positively expressed in detrusor smooth muscle preparations in a reverse transcription polymerase chain reaction assay. In conclusion, the present results provide the first evidence for the existence of the beta3-AR subtype in the human detrusor. They also suggest that the relaxation induced by adrenergic stimulation of the human detrusor is mediated mainly through beta3-AR activation.
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Postoperative evaluation by three-dimensional (3D) computed tomography (CT) was performed in 15 patients who underwent anterior skull base reconstruction using two musculopericranial flaps and a grafted bone sandwiched between the two flaps. Especially in the case of large bone grafts (4 x 4 cm or more), the graft was positioned with the convex side facing upward into the cranial cavity to avoid creating an intracranial dead space. The extent of the absorption and changes in the contour of the grafted bone were evaluated. Imaging was done at a CT level of 150 using a Proceed 3-D CT scanner (Yokogawa Medical Co., Tokyo, Japan). Donor bone for grafting to the skull base was harvested the cranium in 10 patients and the ilium in 5 others. Patients ranged in age from 7 to 76 years (mean, 47); there were 10 men and 5 women. The grafted bone ranged in size from 1 x 2 cm to 5 x 8 cm (1 x 2 cm to about 4 x 3 cm: 10 patients; 4 x 4 to about 5 x 8 cm: 5 patients).No marked absorption of grafted bone was seen in these 15 patients, and no brain hernia occurred. In patients with large bone grafts (4 x 4 cm to about 5 x 8 cm), a graft that had been positioned with the convex side facing upward into cranial cavity at the time of transplant was subsequently observed to be transformed into a downward convex contour of normal skull base. Fostoperative infection did not occur because of the dead space nor were there any symptom of pressure on the brain because of the upward convexity of the grafted bone.The present reconstructive method is not only a minimum invasive but also a safe and reliable method for anterior skull base surgery.
PURPOSE: To investigate cell killing by means of low dose-rate irradiation (LDRI) combined with concurrent mild hyperthermia and to determine the effect of low-dose caffeine on this combination treatment. MATERIALS AND METHODS: Human lung adenocarcinoma cells, LK87, were treated with LDRI (50 cGy/h) in combination with mild hyperthermia at 41 degrees C and low-dose caffeine (1 mM). Cell survival was estimated by clonogenic assay. Flow-cytometry was performed with PI staining using FACScan. Heat-shock protein (HSP72/73) was measured by the Western blotting method. All treatments were simultaneously performed for up to 48 h (24 Gy). RESULTS: LDRI cytotoxicities were enhanced by hyperthermia at 41 degrees C. D0 calculated from the dose-response curve for LDRI combined with 41 degrees C was 3.46 Gy whereas it was 6.55 Gy for LDRI alone. The survival curve for LDRI +41 degrees C demonstrated no chronic thermotolerance up to 48 h. For LDRI + simultaneous low-dose caffeine, cell killing was also enhanced, where D0 was 3.38 Gy at 37 degrees C. Radiosensitization caused by caffeine was enhanced by combination with simultaneous mild hyperthermia at 41 degrees C, where D0=1.78 Gy. Cell cycle analysis demonstrated remarkable G2 and mild G1 arrest for LDRI alone, but only G1 arrest was observed for LDRI combined with 41 degrees C and for LDRI combined with caffeine. Strong and early G1 arrest was observed in the treatment with LDRI + caffeine at 41 degrees C. The amount of HSP72/73 in the combination of LDRI with caffeine at 41 degrees C was less than that at 41 degrees C alone. CONCLUSION: LDRI cytotoxicity was enhanced by non-lethal hyperthermia. Low dose caffeine produced further cell killing in the combination of LDRI with mild hyperthermia.
BACKGROUND: Risk factors for severe radiation pneumonitis, which often spreads beyond treatment portals and may even be bilateral, have not been fully investigated. The purpose of this study was to identify important factors associated with severe radiation pneumonitis. METHODS: 111 cases of primary lung cancer, treated with radiotherapy or chemoradiotherapy, were retrospectively analyzed. RESULTS: Severe radiation pneumonitis occurred in 17 cases (15.3%). The ratio of interstitial change in lungs before radiotherapy and radiotherapy to the contralateral mediastinum with > 40 Gy in the radiation pneumonitis group (RP group) was significantly higher than in patients without radiation pneumonitis (control group) (47.1% vs 5.3%; P < 0.001 and 58.8% vs 27.7%; P = 0.037, respectively). Using logistic regression analysis, interstitial changes before radiotherapy and radiotherapy to the contralateral mediastinum of > 40 Gy were significant risk factors associated with severe radiation pneumonitis. CONCLUSIONS: These data suggest that pre-existing interstitial changes detected by chest radiography or computed tomography and radiotherapy to the contralateral mediastinum (> 40 Gy) may predict the development of severe radiation pneumonitis.
Myosin light chain kinase (MLCK) phosphorylates the light chain of smooth muscle myosin enabling its interaction with actin. This interaction initiates smooth muscle contraction. MLCK has another role that is not attributable to its phosphorylating activity, i.e., it inhibits the ATP-dependent movement of actin filaments on a glass surface coated with phosphorylated myosin. To analyze the inhibitory effect of MLCK, the catalytic domain of MLCK was obtained with or without the regulatory sequence adjacent to the C-terminal of the domain, and the inhibitory effect of the domain was examined by the movement of actin filaments. All the domains work so as to inhibit actin filament movement whether or not the regulatory sequence is included. When the domain includes the regulatory sequence, calmodulin in the presence of calcium abolishes the inhibition. Since the phosphorylation reaction is not involved in regulating the movement by MLCK, and a catalytic fragment that shows no kinase activity also inhibits movement, the kinase activity is not related to inhibition. Higher concentrations of MLCK inhibit the binding of actin filaments to myosin-coated surfaces as well as their movement. We discuss the dual roles of the domain, the phosphorylation of myosin that allows myosin to cross-bridge with actin and a novel function that breaks cross-bridging.
OBJECTIVE: To determine the efficacy of stereotactic radiotherapy (SRT) in the treatment of recurrent nasopharyngeal carcinoma. STUDY DESIGN: A retrospective review of the outcome of SRT for patients with recurrent nasopharyngeal carcinomas following definitive conventional radiation therapy. METHODS: Five patients were treated with daily static multiportal irradiation. Two Gy was administered with eight isocentric portals in a single plane 5 days a week, and the plane was changed for every 20 to 30 Gy. Of these patients, three had poorly differentiated squamous cell carcinoma. Tumor sizes ranged from 1 to 15 cm3, with a median size 3.2 cm3. Median follow-up time from SRT was 34 months (range, 4-61 mo). RESULTS: Four of five recurrent tumors responded well and achieved complete regression. Three patients have survived without evidence of local recurrence with a median follow-up time of 34 months. Marginal recurrence was observed at the posterosuperior wall in a patient with adenoid cystic carcinoma at 30 months after SRT. One patient who received SRT after the two complete courses of radiation therapy died 6 months after SRT as a result of rupture of a branch of the left carotid artery, but autopsy revealed no local residual tumor. CONCLUSIONS: Stereotactic radiotherapy with isocentric multiportals in one plane, which is changed at every 20 to 30 Gy, can provide local control with acceptable toxicity in patients with recurrent nasopharyngeal carcinoma, but increased clinical experience and longer follow-up will be necessary to evaluate the overall role of this technique in nasopharyngeal carcinoma.
A monomeric isocitrate dehydrogenase has been crystallized for the first time. This enzyme catalyzes the conversion of isocitrate to oxalosuccinate and subsequently to alpha-ketoglutarate and CO(2); the coenzyme NADP(+) is reduced to NADPH during the reaction. Polyethylene glycol 2000 monomethyl ether was used to crystallize the enzyme in space group C2 with unit-cell parameters a = 137.1, b = 54.6, c = 126.4 A, beta = 108.2 degrees. The very small crystal (0. 05 x 0.20 x 0.05 mm) diffracted to 3.5 A d spacing using synchrotron radiation.
BACKGROUND: It was recently reported that A to G transition mutations at positions 2143 and 2144 in the 23S rRNA gene are associated with clarithromycin resistance in Helicobacter pylori. AIMS: To study the incidence and mechanism of development of clarithromycin resistance by analysing these mutations. SUBJECTS: Eighty two H pylori positive patients who had an endoscopic examination and no history of treatment with macrolide antibiotics. METHODS: Clarithromycin resistance was screened for by polymerase chain reaction-restriction fragment length polymorphism of the 23S rRNA gene coupled with antibiotic susceptibility testing. In clinical isolates with mutations or resistance, mutations in individual colonies were analysed by direct sequencing. RESULTS: Of the 79 amplicons (DNA fragments amplified by polymerase chain reaction), Alw26I and MboII digestion disclosed the mutation in four (5%) and one (1%) respectively. However, the Alw26I cleavage was incomplete in two of the four amplicons, as was the MboII cleavage. Individual colony analysis of the isolates with incomplete cleavage patterns showed the presence of both wild type and mutated strains in the 23S rRNA genes. CONCLUSIONS: Both clarithromycin sensitive and resistant strains colonised in some patients with no history of exposure to macrolides. The results suggest that resistant strains may not be formed but selected by clarithromycin administration.
PURPOSE: To investigate the clinical efficacy of radiation therapy for cancer in patients aged 90 years or older. MATERIALS AND METHODS: Cancer cases in 32 patients (11 men, 21 women) aged 90 years or older who underwent radiation therapy in 1970-1997 were retrospectively analyzed. The mean patient age was 92.2 years, with a range of 90-98 years. Head and neck cancer (n = 14 [44%]) and skin cancer (n = 6 [19%]) were the most common. RESULTS: Eleven (79%) of the 14 patients with head and neck cancer were treated with curative intent. Radiation response without any severe complication was observed in nine (90%) of the 10 patients with head and neck cancer treated with curative intent who finished treatment. The median survival time was 8 months (range, 3-55 months) in the 10 patients with head and neck cancer who completed treatment with curative intent. Complete response was achieved in all of the patients with skin cancer without any major sequelae. Complete response was also observed in all three of the patients with non-Hodgkin lymphoma, but two patients treated with adjuvant chemotherapy died of drug-induced pneumonitis. Palliation was achieved in all nine of the patients treated with palliative intent. CONCLUSION: Age of 90 years or older is not a limiting factor for radiation therapy.
A 53 year-old Japanese man was referred to our hospital for persistent priapism, which had been induced by 200 mg (usual dose 25-50 mg) of sildenafil citrate (Viagra) three days earlier. He had a history of erectile dysfunction and had undergone penile injection therapy elsewhere; however, he had not used injection therapy this time. He obtained sildenafil personally without a doctor's prescription. He had not taken any other drugs that affect the metabolism of sildenafil, nor did he have any medical complications that might induce priapism. Since needle aspiration and irrigation were ineffective as first line therapy, surgical treatment was indicated to relieve the condition; a incision of tunica albuginea of both corpora cavernosa was made, and vigorous irrigation of saline washed out the blood clots. This is the first case report of priapism induced by sildenafil. Although this drug can be obtained through private commerce, it should be used under professional guidance as its abuse may lead to severe morbidity.
BACKGROUND: To avoid homologus blood transfusion, we performed the operation for intra-pelvic malignancy with predeposited autologus blood using recombinant human erythropoietin (rH-EPO). MATERIALS AND METHODS: The seven cases of radical prostatectomy and the 15 cases of total cystectomy were analyzed retrospectively. All cases were given ferrons sulfate/200 mg of iron orally every day to the day before the operation and treated with 24,000 unit of rH-EPO subcutaneously every week. The target volumes of preoperative autologus blood collection were 800 to 1,000 ml and 800 to 1,200 ml for radical prostatectomy and total cystectomy, respectively. For each case, 400 ml blood was collected once a week. RESULTS: In cases of radical prostatectomy, the preserved blood volume was 885.7 +/- 157.4 ml and 6 out of 7 operations were successfully performed without additional homologus blood transfusion (85.7%). In total cystectomy, the preserved blood volume was 1,033.3 +/- 167.6 ml and 14 out of 15 operations were successfully performed without additional homologus blood transfusion (93.3%). The bleeding volume during operation showed no significant difference compared to control group where used homologus blood transfusion. Postoperative courses were uneventful and there encountered no severe side effects and complications in all our procedures. CONCLUSIONS: Our study indicates that in cases of radical prostatectomy and total cystectomy, the operation with predeposited autologus blood using rH-EPO is possible to be performed in safe. The effect on long term prognosis of malignancy is not clear, however, this technique is helpful able to avoid hazardous issues related to homologus blood transfusion during the operation.
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