External dose measurements to investigate the body-size dependence of personal dosemeter responses in areas affected by the Fukushima Daiichi nuclear accident.

To formulate necessary protective measures after a large-scale nuclear accident, it is crucial to understand the levels of radiation to which persons living in radionuclide-contaminated areas are exposed. Individual monitoring using personal dosemeters (PDs) plays a role in this, although PDs were not originally intended to be used by members of the public. The present study investigated PD responses in areas highly affected by the Fukushima Daiichi nuclear accident, as well as the dependence of those measurements on body size. Three types of commercially available electronic PDs, including D-shuttle, which has often been used in Fukushima, were placed on the front surfaces of three age-specific anthropometric phantoms imitating a 5-y-old, a 10-y-old and an adult male, and these phantoms were then exposed to radiation in an open field in the affected area. In the case of D-shuttle, the ratios of PD readings to the ambient dose rate for the 5-y-old phantom and the adult male phantom were 0.79 and 0.72, respectively. The ratios were somewhat higher for the other PDs; any PDs showed higher readings than the effective doses estimated by simulations based on the assumed ground deposition of 134Cs and/or 137Cs over the affected areas.

Does preoperative enhanced CT predict requirement of intestinal resection in the patients with incarcerated myopectineal hernias containing small bowel?

PURPOSE: Bowel wall enhancement on CT imaging is considered one of the useful features for the prediction of the presence of irreversible ischemic change in patients with small bowel obstruction. However, the applicability of CT imaging in patients with incarcerated hernias has not been investigated in detail. The aim of this retrospective study was to evaluate the feasibility of preoperative CT findings for the prediction of the presence of irreversible ischemic change in patients with incarcerated hernias containing small bowel. METHODS: Included in this study were 76 patients who underwent surgery for preoperatively diagnosed incarcerated hernias containing small bowel (27 inguinal hernias, 37 femoral hernias and 12 obturator hernias) at our hospital between January 2011 and June 2020. The preoperative clinicoradiological features were compared between the groups, and predictors for intestinal resection were evaluated. RESULTS: Nineteen patients required intestinal resection (Resection group), and the other 57 patients did not require intestinal resection (Nonresection group). Multivariate analyses revealed that age ≥ 80 years (p = 0.018, odds ratio = 6.604) and the absence of bowel wall enhancement (p = 0.032, odds ratio = 51.200) were independent predictors for intestinal resection. In resected specimens, all patients with an absence of bowel wall enhancement on preoperative enhanced CT had ischemic changes extending beyond the muscularis propria. CONCLUSIONS: Preoperative enhancement CT yields useful information for the prediction of the presence of irreversible ischemic change in patients with incarcerated hernias containing small bowel.

Dose estimation of a soft X-ray exposure incident.

A dose reconstruction was carried out on a case in which a worker was exposed to soft x rays using time motion studies, an ionization chamber for low energy photon measurements, and CdZnTe (CZT) spectrometry. The worker estimated his dose to be over 600 mSv. However, the doses to the skin and testes were evaluated to be 14 and 0.44 mSv, respectively, with an effective dose of 0.099 mSv.

Variation of microvascular blood flow augmentation--supercharge in esophageal and pharyngeal reconstruction.

AIM OF THE STUDY: A gastric tube is commonly used in thoracic esophageal reconstruction. When a gastric tube is not available, pedicled jejunum transfer and colonic interposition are alternative methods. Oral end of the reconstructed esophagus occasionally has poor blood flow and may result in partial necrosis of the oral segment. We performed additional microvascular blood flow augmentation, the "supercharge" technique, to improve a blood flow circulation in the oral segment of the reconstructed esophagus. METHODS: A series of 86 esophageal reconstructions with microvascular blood flow augmentation using the "supercharge" technique were performed. Reconstructive methods included a gastric tube in five patients, a gastric tube combined with a free jejunual graft in one, an elongated gastric tube in eight, a pedicled colonic interposition in 22, and a pedicled jejunum in 50. Recipient vessels were used in neck or chest region. RESULTS: The color and blood flow of the transferred intestine appeared greatly improved after microvascular blood flow augmentation. Thrombosis was noticed in three patients during the surgery, and all thrombosies were salvaged by re-anastomosis. There were only three patients with partial graft necrosis of oral segment, two patients with anastomotic leakage, one anastomotic stricture. CONCLUSIONS: Augmentation of microvascular blood flow by this "supercharge" technique can be expected to reduce the risk of leakage and partial necrosis of the transferred intestine. This technique contributes to the successful reconstruction of esophageal defect.

[The last period of surgical site infection after pulmonary resection for lung cancer with hemodialysis; report of a case].

An 80-year-old man had been on maintenance hemodialysis for nondiabetic chronic renal failure from June 1996. He underwent investigation of an abnormal chest X-ray and was referred to our hospital with a diagnosis of squamous cell carcinoma in the upper lobe of the right lung. On February 20, 2003, right upper lobectomy was performed. The postoperative course was uneventful and he was discharged on postoperative day 13. Two weeks later he was readmitted with a wound infection. Although he received antibiotics, drainage, and wound lavage, his fever persisted and chest X-ray showed inflammatory changes in the right lower lung field. He was placed on mechanical ventilation for dyspnea. After this, his respiratory function became stable and he could be weaned from the ventilator within 2 weeks. The subsequent course was uneventful and he was discharged 1 month after re-admission. This patient needed ventilation due to weakness caused by wound infection. Such infection is uncommon but can be fatal for a compromised host, so we administered antibiotics for 3 days until the wound closed.

Quantitative evaluation of 218Po behaviour in air in an artificial environment.

Experiments were carried out in a small enclosed booth for the purpose of understanding and modelling (218)Po behaviour. The experiment was conducted under two kinds of conditions without and with injection of incense smoke. A working model of (218)Po behaviour was applied to analyse the measured data. Under the condition without incense smoke, temporal changes in aerosol-attached and unattached (218)Po concentrations were successfully reproduced by the model. The deposition rate of unattached fraction and the rate of attachment were determined by the working model. Under the condition with incense smoke, temporal changes in (218)Po concentration were poorly simulated by the model. This can be attributed to the significantly increased aerosol concentration in small size ranges which is not properly considered in the attachment rate calculation in the model.

Neuronal degeneration in the brain of the brindled mouse--a light microscope study.

The brindled mouse (Mobr) is a neurological mutant mouse with a deficiency in copper transport. This mutant has many clinical as well as biochemical features in common with Kinky hair syndrome (KHS) in humans (Tab. 1). Male hemizygotes (Mobr/Y) are characterized by the absence of fur pigment and curly whiskers. They become inactive, losing weight at around the 10th-12th post-natal day. They usually die in an emaciated state around the 15th-16th postnatal day. The brain weight is usually about three fourths of that of littermate controls. Microscopically, widespread neuronal degeneration was noted in the cerebral cortex and thalamic nuclei of male hemizygotes after the 12th post-natal day. The degeneration continued to increase until death. Scattered degenerated cells were also noted in the cerebellum. No such degenerative changes were observed in the brain of female heterozygotes (Mobr/+) or in normal or starved littermates. These degenerative changes of neurons in the brindled hemizygote mouse will be compared with the neuropathological changes observed in KHS and in experimental animals with copper deficiency, and the possible pathogenesis of these changes will be discussed.

The effect of copper supplementation on the brindled mouse: a clinico-pathological study.

Brindled mottled is a neurological mutant mouse. Hemizygous males have many clinical and biochemical features in common with kinky hair syndrome (KHS) in humans, and usually die around postnatal day 15, after severe emaciation. Neuronal mitochondrial abnormalities and neuronal degeneration in the cerebrum and cerebellum were constant neuropathological findings in this mutant. A single intraperitoneal injection of cupric chloride, 10 micrograms/g body weight, resulted in an improvement of clinical symptoms and prevention of neuronal degeneration. The degree of improvement was dependent on the date of injection, and day 7 to 10 postnatal appeared to the most effective date. The male hemizygotes which received cupric chloride injections at day 7 or 10 overcame the lethality, and no neuronal degeneration was detected in these mice, although neuronal mitochondrial changes were still persistent. However, following two injections at days 7 and 10, no abnormalities were detected in the cerebral cortical neurons. Even at the ultrastructural level, abnormal mitochondria were very scarce. In the cerebellum, however, mitochondrial changes in the Purkinje cells, particularly in the rostral portion, and generation of white matter were noted in these mice, which were clinically perfectly healthy, judging from the growth rate and behavior. However, cerebellar changes were far less in those which received additional injections later on. These observations indicate that, at least in brindled mutant mice, supplementation of copper is quite beneficial for clinical improvement and the prevention of neuropathological lesions, but the date of administration appears to have crucial importance.

Recombinant variants of tissue-type plasminogen activator containing amino acid substitutions in the fibronectin finger-like domain and the kringle 1 domain.

Tissue-type plasminogen activator (t-PA) is a fibrin-specific agent which is used to treat acute myocardial infarction. Pharmacokinetically, t-PA is characterized by a rapid clearance from the circulation. In a previous study, we constructed variant forms of t-PA with genetic modifications at the fibronectin finger-like domain (finger domain) or at the kringle 1 domain (K1 domain). The finger modified variant, t-PA N37S.S38V.G39V.R40E. A41F.Q42S had about a 6.0-fold higher plasma half-life in vivo than wild-type t-PA. Two variants with modifications in the K1 domain, t-PA G161R.K162R.S165W and t-PA N115P, showed an improved kinetic parameters and a 2.2-fold higher plasma half-life in vivo than wild-type t-PA, respectively. To create a recombinant variant of t-PA with a higher enzymatic activity and a further prolonged half-life in vivo, the genes containing each modifications were joined and expressed in animal cells. The two variants, t-PA N37S.S38V.G39V.R40E.A41F.Q42S.G16 1R.K162R.S165W and t-PA N37S.S38V.G39V.R40E.A41F.Q42S.N11 5P, were purified from conditioned media and their biochemical, pharmacokinetic and thrombolytic profiles were investigated. Although the variant t-PA N37S.S38V.G39V.R40E.A41F.Q42S.G16 1R.K162R.S165W demonstrated an impaired enzymatic activity compared to the wild-type t-PA, the half-life of the variant, t-PA N37S.S38V.G39V.R40E.A41F.Q42S. N115P, following intravenous bolus injection in rabbits was considerably longer than that of finger-domain modified variants.(ABSTRACT TRUNCATED AT 250 WORDS)

Recombinant variants of tissue-type plasminogen activator containing amino acid substitutions in the finger domain.

Tissue-type plasminogen activator (t-PA) is a fibrin-specific agent which has been used to treat acute myocardial infarction. In an attempt to clarify the determinants for its rapid clearance in vivo and high affinity for fibrin clots, we produced five variants containing amino acid substitutions in the finger domain, at amino acid residues 7-9, 10-14, 15-19, 28-33, and 37-42. All the variants had a prolonged half-life and a decreased affinity for fibrin of various degrees. The 37-42 variant demonstrated about a 6-fold longer half-life with a lower affinity for fibrin. Human plasma clot lysis assay estimated the fibrinolytic activity of the 37-42 variant to be 1.4-fold less effective than that of the wild-type rt-PA. In a rabbit jugular vein clot lysis model, doses of 1.0 and 0.15 mg/kg were required for about 70% lysis in the wild-type and 37-42 variant, respectively. Fibrinogen was degraded only when the wild-type rt-PA was administered at a dose of 1.0 mg/kg. These findings suggest that the 37-42 variant can be employed at a lower dosage and that it is a more fibrin-specific thrombolytic agent than the wild-type rt-PA.

The presence of CD5LOW+NK cells in normal controls and patients with pulmonary tuberculosis.

CD5 antigen is present on all normal alpha beta T cells and some B cells. Human NK cells do not usually express CD5 antigen, but we found a subset of CD5LOW+ (low density of CD5) NK cells in some patients with pulmonary tuberculosis. Unlike CD5-NK cells, most CD5LOW+NK cells had HLA-DR. We observed few CD5LOW+NK cells in the normal controls and some in the large granular lymphocyte (LGL) population purified by Percoll density centrifugation. Sorted CD5LOW+NK populations were LGL. The CD5LOW+NK cells had high lytic activity on K562 cells in a 4-h 51chromium release assay. Our results indicate that there is a previously unidentified subset of NK cells.

Inhibition of endothelium-dependent hyperpolarization by endothelial prostanoids in guinea-pig coronary artery.

1. In smooth muscle of the circumflex coronary artery of guinea-pig, acetylcholine (ACh, 10(-6) M) produced an endothelium-dependent hyperpolarization consisting of two components. An initial component that occurs in the presence of ACh and a slow component that developed after ACh had been withdrawn. Each component of the hyperpolarization was accompanied by an increase in membrane conductance. 2. Indomethacin (5 x 10(-6) M) or diclofenac (10(-6) M), both inhibitors of cyclooxygenase, abolished only the slow hyperpolarization. The initial hyperpolarization was not inhibited by diclofenac nor by nitroarginine, an inhibitor of nitric oxide synthase. 3. Both components of the ACh-induced hyperpolarization were abolished in the presence of atropine (10(-6) M) or high-K solution ([K+]0 = 29.4 mM). 4. The interval between ACh-stimulation required to generate an initial hyperpolarization of reproducible amplitude was 20 min or greater, but it was reduced to less than 5 min after inhibiting cyclooxygenase activity. Conditioning stimulation of the artery with substance P (10(-7) M) also caused a long duration (about 20 min) inhibition of the ACh-response. 5. The amplitude of the hyperpolarization generated by Y-26763, a K+-channel opener, was reproducible within 10 min after withdrawal of ACh. 6. Exogenously applied prostacyclin (PGI2) hyperpolarized the membrane and reduced membrane resistance in concentrations over 2.8 x 10(-9)M. 7. At concentrations below threshold for hyperpolarization and when no alteration of membrane resistance occurred, PGI2 inhibited the initial component of the ACh-induced hyperpolarization. 8. It is concluded that endothelial prostanoids, possibly PGI2, have an inhibitory action on the release of endothelium-derived hyperpolarizing factor.

A patient with diabetes mellitus and severe arterial embolism.

An 89-year-old man with diabetes mellitus was admitted to the hospital because of a low-grade fever and a disturbance in consciousness. He had been diagnosed as having diabetes mellitus at the age of 22 years and had been taking oral hypoglycemic drugs for 16 years at least. A few days before admission, a loss of appetite was noticed by his family; he developed a stupor on the day of admission. On physical examination, his lower extremities were pale and his skin temperature was low. Laboratory tests showed an increase in his white blood cell count and his blood culture was positive for Staphylococcus aureus. An MRI showed that the abdominal aorta was totally occluded beneath the renal arteries, and no significant collateral circulation was observed. He was given antibiotics and anticoagulants, but his general condition continued to worsen. Laboratory tests showed renal failure and liver dysfunction, indicating multi-organ failure. On the 24th day of admission, he died of respiratory and heart failure. An autopsy showed the aorta to be totally occluded beneath the renal arteries by an embolism; atherosclerotic changes were rather mild. Acute plaque change on the surface of the aorta may have induced the sudden development of emboli in the aorta.

In vitro proliferative and differentiated responses of lymphoma cells to PHA and IL-4 in a patient with intermediate lymphocytic lymphoma.

We carried out in vitro B cell colony assays, with phytohemagglutinin-P (PHA-P) and IL-4, on B cells from one intermediate lymphocytic lymphoma (ILL) patient and four chronic lymphocytic leukemia (CLL) patients. Peripheral blood B cells from the ILL patient responded to PHA and IL-4, they proliferated, and differentiated into cells with plasmacytoid cell morphology. They lost the CD19 surface antigen after 10 day co-culture with PHA and IL-4. The bone marrow of this ILL patient contained atypical plasma cells with multiple nuclei. Peripheral blood B cells from the four CLL patients responded to PHA, but IL-4 did not increase PHA-induced B cell colony formation in these cells. The CLL cells did not differentiate into plasma cells, and they were clearly different from the ILL cells in morphology, as shown by scanning electron microscope examination. Since this study was performed on cells from only one ILL patient, further examination of cells from many patients might be necessary to confirm the difference between ILL and B cell-type CLL.

Canine globoid cell leukodystrophy. Part 1. Further ultrastructural study of the typical lesion.

The ultrastructural changes of typical lesions in canine globoid cell leukodystrophy (GLD) have been studied. The globoid cells were located in the cerebral parenchyma as well as in the perivascular Virchow--Robin space. Features suggestive of a passage of the globoid cells from the cerebral parenchyma to the Virchow--Robin space were also observed through the interruptions in the basal lamina. The globoid cells had numerous thin pseudopods and contained various cytoplasmic inclusions which have been described previously. Detailed studies of these inclusions suggest that they represented aggregates of filamentous or linear sub-unit structures. Typical oligodendroglial cells were found on only a few occasions. Both globoid cells and oligodendroglia contained myelin debris, dense bodies and honey-comb like inclusions composed of numerous small myelin figures. In a few instances, crystalline polygonal inclusions identical to those found in the globoid cells, were found in the cytoplasm of the cells which were, with reasonable certainty, identifiable as oligodendroglia. In less affected areas where myelin was still present, degenerating oligodendroglia, with or without recognizable inclusions, were frequently encountered. Astrocytes and endothelial cells contained concentric lamellar inclusions and dense bodies but did not contain the tubular inclusions as seen in globoid cells. The possible significance of the ultrastructural features in regard to the pathogenesis of the GLD have been discussed.

Development of ophthalmoplegia in amyotrophic lateral sclerosis during long-term use of respirators.

Patients with amyotrophic lateral sclerosis (ALS), who survive longer on a life-support system, exceeding the natural course of this disease, show new features of ALS. We report here a clinico-pathologic study of a 51-year-old patient with sporadic ALS who developed progressive external ophthalmoplegia 3 years after he remained on a respirator and died 5 years later, 13 years after the onset of his illness. The external ophthalmoplegia was initially accompanied by preserved doll's eye phenomenon, which later became absent. Autopsy revealed not only degeneration of the upper and lower motor neuron systems typical of ALS, but also degeneration of the Clarke's dorsal nuclei, spinocerebellar tracts, substantia nigra and inferior olives in addition to intracytoplasmic neuronal inclusion bodies in various areas. The oculomotor and abducens nuclei were variably involved, accompanied by neurogenic atrophy of the extraocular muscles. Our case report is consistent with the idea that ALS comprises a heterogeneous group of disorders, and also indicates that long-term use of respirators may make some patients with this illness prone to developing atypical clinical and neuropathologic features which are not observed during the natural course of ALS.

Development of step-specific PET tracers for studying fatty acid beta-oxidation: biodistribution of [1-(11)C] octanoate analogs in rats and a cat.

To evaluate the potential of [1-(11)C]-3-(R,S)-methyloctanoate (BMOA), [1-(11)C]-2-octynoate, and [1-(11)C]-2-decynoate as PET tracers for studying particular steps in fatty acid beta-oxidation, we examined the pharmacokinetics of these compounds in rats and a cat. In rats given these compounds, high levels of radioactivity accumulated in the heart, liver, and kidneys, suggesting their potential as tracers for studying beta-oxidation in these tissues. These organs were clearly visible with PET in a cat given BMOA, indicating the utility of BMOA for imaging these organs.

Suppression of HL-60 cell proliferation by deferoxamine: changes in c-myc expression.

Deferoxamine, an iron chelating agent, inhibits growth of HL-60 cells in a dose-dependent fashion. This inhibition of proliferation was completely blocked by simultaneous addition of equal molar FeCl3, and FeCl3 added after 24 hours of deferoxamine treatment was also effective. After 48 hrs, however, the delayed addition failed to reverse growth inhibition by deferoxamine. We showed that deferoxamine-treated HL-60 cells become arrested in S phase rather than at G1/0 phase. Changes in c-myc expression were examined in these deferoxamine-treated cells. A rapid decline of c-myc RNA expression was followed by increased expression (1.6-fold over untreated controls). Similar results were obtained when the expression of c-myc protein was evaluated. These changes in c-myc expression may be involved in the growth inhibition of HL-60 cells by deferoxamine. These results are contrasted with the effects of the differentiation inducer, 1 alpha,25(OH)2D3.

The increase of CD5LOW+NK cells in patients with multiple myeloma and plasmacytoma.

CD5 antigen is present on all normal alpha beta T cells and some B cells. Human NK cells do not usually express CD5 antigen, but we found a novel subset of CD5LOW (low density of CD5) positive (CD5LOW+) natural killer cells (NK cells) in patients with multiple myeloma (MM) and plasmacytoma. To detect CD5LOW+NK cells, we examined the lymphocytes of 23 patients with MM and plasmacytoma by flow cytometry. Five out of 23 patients had CD5LOW+NK populations. These patients had many more NK cells than the other patients in the peripheral blood and bone marrow. The CD5LOW+NK cells had CD2, low density of CD8, CD16 and CD56, but no CD3, CD19, or CD20. Most of the CD5LOW+NK cells had HLA-DR, unlike the CD5-NK cells. Sorted CD5LOW+CD16+ populations were large granular lymphocytes (LGL). The CD5LOW+NK cells had some lytic activity on K562 cells in a 4-hour 51Cr release assay. Our results indicate that there is a novel subset of NK cells in some patients with MM and plasmacytoma and that CD5LOW+NK cells may be associated with NK cell activation.

Characterization of human tissue-type plasminogen activator variants with amino acid mutations in the kringle 1 domain.

Recombinant variants of tissue-type plasminogen activator (t-PA) were constructed by site-directed mutagenesis and expressed in Chinese hamster ovary cells. Five variants were designed to improve the function of t-PA by mutagenesis in the kringle 1 (K1) domain. The amino acids were replaced with the corresponding residues present in the kringle 2 (K2) domain of native t-PA. The t-PA mutants expressed were as follows: variant E94V.D95G with point mutations in Glu94----Val and Asp95----Gly; variant N115P.S119M, Asn115----Pro and Ser119----Met; variant P125A.R129Q.R13OS, Pro125----Ala, Arg129----Gln and Arg130----Ser; variant G161R.K162R.-S165W, Gly161----Arg, Lys162----Arg and Ser165----Trp; and variant N115P, Asn115----Pro, respectively. The half-life following intravenous bolus injection in rabbits was prolonged in all variants except P125A.R130S. This was particularly true for N115P.S119M. The kinetic parameters for plasminogen activation were improved in t-PA G161R.K162R.S165W which showed a 0.6-fold decrease in Km, and a 1.8-fold increase in Vmax, thus promoting a 2.7-fold increase in kcat/Km compared to native t-PA. For a similar degree of thrombolysis in the rabbit jugular vein thrombosis model, the thrombolytic activity of G161R.K162R.S165W, at the dose tested, was four-fold greater than that of native t-PA. Thus, the substitution of the amino acids in the K1 domain with those corresponding in the K2 domain significantly enhanced the enzymatic activity of t-PA and improved the plasma survival.