Urban resilience: Analyzing the policies of U.S. cities.

Resilience has become an important concept in urban governance, yet, the policies that cities actually adopt and implement to build resilience remain largely unknown. The lack of empirical studies on resilience policies hinders our ability to develop theory, ask new questions, and test hypotheses. The goal of this paper is to quantify and compare policies and programs of the 101 largest cities in the U.S. that tangibly affect resilience. We develop a set of resilience policies and then search government websites for evidence of adoption of those policies. To explore patterns of policy adoption, we conduct factor analysis and correlation. We find that resilience does not coalesce around any particular sets of programs. Instead, resilience is a flexible concept, modified to address local context. Substantive groupings of policies do not explain policy adoption. Different dimensions such as funding and level of needed commitment may better explain empirical patterns of policy adoption. Across cities, greater attention must be dedicated to addressing drivers of social vulnerability and climate change impacts. By examining what cities are doing and whether there are underlying patterns to the policies they pursue, we tackle basic empirical questions of how to make sense of the evolving resilience landscape.

Modulation of PAR(1) signalling by benzimidazole compounds.

BACKGROUND AND PURPOSE: Recently, a small molecule (Q94) was reported to selectively block PAR(1) /Gα(q) interaction and signalling. Here, we describe the pharmacological properties of Q94 and two analogues that share its benzimidazole scaffold (Q109, Q89). Q109 presents a modest variation from Q94 in the substituent group at the 2-position, while Q89 has quite different groups at the 1- and 2-positions. EXPERIMENTAL APPROACH: Using human microvascular endothelial cells, we examined intracellular Ca(2+) mobilization and inositol 1,4,5-trisphosphate accumulation as well as isoprenaline- or forskolin-stimulated cAMP production in response to thrombin. KEY RESULTS: Q89 (10 µM) produced a leftward shift in the thrombin-mediated intracellular Ca(2+) mobilization concentration-response curve while having no effect on the E(max) . Both Q94 (10 µM) and Q109 (10 µM) reduced intracellular Ca(2+) mobilization, leading to a decrease in E(max) and an increase in EC(50) values. Experiments utilizing receptor-specific activating peptides confirmed that Q94 and Q109 were selective for PAR(1) as they did not alter the Ca(2+) response mediated by a PAR(2) activating peptide. Consistent with our Ca(2+) results, micromolar concentrations of either Q94 or Q109 significantly reduced thrombin-induced inositol 1,4,5-trisphosphate production. Neither Q94 nor Q109 diminished the inhibitory effects of thrombin on cAMP production, indicating they inhibit signalling selectively through the G(q) pathway. Our results also suggest the 1,2-disubstituted benzimidazole derivatives act as 'allosteric agonists' of PAR(1) . CONCLUSIONS AND IMPLICATIONS: The Q94 and Q109 benzimidazole derivatives represent a novel scaffold for the development of new PAR(1) inhibitors and provide a starting point to develop dual signalling pathway-selective positive/negative modulators of PAR(1) .

Anti-Ma2 associated paraneoplastic neurological syndrome presenting as encephalitis and progressive muscular atrophy.

A 36 year old man with a history of testicular germ cell tumour presented six months after bilateral orchidectomy with progressive amnesia, irritability, vertical gaze palsy, and generalised seizures. Eight months after initial onset of symptoms, he demonstrated a head drop with muscular atrophy of the upper limbs, shoulder girdle, and posterior neck. He reported no sensory disturbances and his sensory examination was normal. The overall clinical presentation was consistent with motor neurone disease. Cerebrospinal fluid analysis revealed mild pleocytosis and increased protein concentration. Serum and cerebrospinal fluid were positive for the anti-Ma2 antibody by western blot analysis and immunostaining. Abnormal high signal in the grey matter was noted in the cervical spinal cord and brain by T2 weighted magnetic resonance imaging (MRI). The patient was treated with corticosteroids, intravenous immunoglobulin, and antiepileptic medication. The patient improved clinically and symptom progression ceased after initiation of treatment. There was complete resolution of the abnormal brain MRI lesions; however, the cervical spinal cord MRI lesion and muscular atrophy remained unchanged. It is suggested that the anti-Ma2 antibody is involved not only in encephalitis, but may also play a role in the cervical spinal cord lesions resulting in a motor neurone disease-like presentation.

Constant involvement of the Betz cells and pyramidal tract in amyotrophic lateral sclerosis with dementia: a clinicopathological study of eight autopsy cases.

We investigated clinicopathologically pyramidal signs, including hyperreflexia, Babinski sign, and spasticity, and the involvement of the primary motor cortex and pyramidal tract, in eight Japanese autopsy cases of amyotrophic lateral sclerosis (ALS) with dementia. Pyramidal signs were observed in seven (88%) of the eight autopsy cases. Hyperreflexia and Babinski sign were evident in seven (88%) and three (38%) patients, respectively, but spasticity was not observed in any of the eight patients. Loss of Betz cells in the primary motor cortex was evident in the seven cases in which this structure was examined. Astrocytosis in the fifth layer of the primary motor cortex was noticed in three cases. In all eight cases, involvement of the pyramidal tract was obvious in the medulla oblongata, but no involvement of the pyramidal tract was found in the midbrain. Involvement of the pyramidal tract in the spinal cord, particularly of large myelinated fibers, was observed in all six cases in which the spinal cord was examined. In ALS with dementia, pyramidal signs were shown to be present more frequently than previously believed, and the clinicopathological correlation between pyramidal signs and involvement of the pyramidal tract was obvious. Constant involvement of Betz cells and the pyramidal tract in ALS with dementia has not been reported. Our clinicopathological findings may make a contribution to the understanding of the clinicopathological hallmarks of this disorder. Furthermore, we believe that this study will also contribute to the elucidation of the nosological status of ALS with dementia.

[Characteristics of hyperacuity sensitivity in normal and cyclovertical deviated subjects].

PURPOSE: To compare the sensitivity of hyperacuity of cyclovertical deviated patients with that of normal subjects. SUBJECTS AND METHODS: The sensitivity of hyperacuity was measured in 42 normal and 12 cyclovertical deviated patients, using a newly developed computerized device which randomly presents two targets opposed vertically or horizontally on a cathode ray tube(CRT) display. RESULTS: In normal subjects, lower thresholds were obtained when the targets were aligned either vertically or horizontally. These highly sensitive ranges were defined as "the neutral zone of hyperacuity". An anisotropy of the sensitivity of hyperacuity was observed. i.e., better thresholds were obtained when the offset was set away from the neutral zone, whereas worse thresholds were obtained when the offset as close to the neutral zones. In cyclovertical deviated patients, the thresholds of hyperacuity were high around the neutral zones, which may indicate dysfunction of the central nervous system. CONCLUSION: This analytical method may be useful to investigate the pathophysiology of the patients with cyclovertical deviations.

SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein.

Genetic etiologies of at least 20% of autosomal dominant cerebellar ataxias (ADCAs) have yet to be clarified. We identified a novel spinocerebellar ataxia (SCA) form in four Japanese pedigrees which is caused by an abnormal CAG expansion in the TATA-binding protein (TBP) gene, a general transcription initiation factor. Consequently, it has been added to the group of polyglutamine diseases. This abnormal expansion of glutamine tracts in TBP bears 47--55 repeats, whereas the normal repeat number ranges from 29 to 42. Immunocytochemical examination of a postmortem brain which carried 48 CAG repeats detected neuronal intranuclear inclusion bodies that stained with anti-ubiquitin antibody, anti-TBP antibody and with the 1C2 antibody that recognizes specifically expanded pathological polyglutamine tracts. We therefore propose that this new disease be called SCA17 (TBP disease).

Sporadic amyotrophic lateral sclerosis with multiple system degeneration: a report of an autopsy case without respirator administration.

This report concerns an autopsy case of amyotrophic lateral sclerosis (ALS) with unusual clinical and neuropathological findings. The patient was a Japanese man without hereditary burden who was 49 years old at the time of death. His clinical manifestation included dysarthria at age 48, followed by dysphagia, atrophy and fasciculation of the tongue, muscle weakness in the four extremities, tremor, rigidity, increased deep tendon reflexes in the upper and lower extremities, and incoordination of the four extremities. He died of respiratory failure 12 months after the disease onset. No respirator administration was performed throughout the clinical course. The neuropathological examination revealed not only degeneration of upper and lower motor neuron systems, including the presence of Bunina bodies and ubiquitin-immunoreactive neuronal inclusions in the lower motor neurons, but also prominent degeneration of the substantia nigra and dentate nucleus with slight neuronal loss in the locus ceruleus and pontine nucleus. To our knowledge, this is the first reported case of sporadic ALS without dementia and respirator support, showing degeneration of the substantia nigra and dentate nucleus. This report may contribute to the resolution of the question concerning the neuropathological heterogeneity of sporadic ALS with respiratory support.

Right ventricular infarction with cardiogenic shock treated with percutaneous cardiopulmonary support: a case report.

A patient with a right ventricular infarction was resuscitated with percutaneous cardiopulmonary support (PCPS), after attempts at reperfusion, high-dose inotropic support and intra-aortic balloon counterpulsation failed to improve the hemodynamic compromise. Emergency PCPS improved the cardiogenic shock and the reduced right ventricular load, allowing the ischemic right ventricle to recover in the setting of unsuccessful reperfusion. This case demonstrates the use of PCPS as a hemodynamic support device for spontaneous recovery of the ischemic right ventricle. PCPS may be a potential therapy for patients with right ventricular infarction.

[A 40-year-old woman with progressive dementia and abnormal behavior].

We report a 40-year-old Japanese woman who died after 12 years history of progressive dementia and abnormal behaviors. She was well until 1985 at her age of 28 years old, when she had an onset of behavioral change in which she drank much, neglected house-keeping works, and her life style became sloppy. At age 30, she became unable to understand written sentences, and paced up- and down in and out of her house. She was admitted to other hospital where marked dementia with disorientation and memory loss were noted. Slight increase in CSF protein and decrease in the peripheral nerve conduction velocity were also noted at that time. In the next year, she started to have convulsions. These symptoms had progressively become worse and was admitted to Tokyo Metropolital Matsuzawa Hospital in June of 1991 when she was 34 years of age. Despite marked dementia, she was able to walk normally, no motor paralysis, cerebellar ataxia, nor dyskinesia were noted. Deep tendon reflexes were diminished. MRI revealed T-2 high signal intensity lesions involving the white matter of the cerebrum predominantly in the frontal region. In about one year, she started to show difficulty in gait, and she became bed-ridden in July of 1994. She was discharged to home for a while, but required admission again. She expired on February 5, 1998. Her younger brother had an essentially similar dementing disease and he expired at the age of 35 years. The parents were of first cousins. The patient was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had adult form of metachromatic leukodystrophy, because of white matter change in the frontal lobe, decrease in nerve conduction velocity, convulsion, marked dementia, and consanguineous marriage with a similarly affected brother. Most of the audience agreed with this conclusion, but the differential diagnosis from globoid cell leukodystrophy was felt difficult from the clinical findings alone. Post-mortem examination revealed marked atrophy in the frontal lobe. Cerebellum appeared to be smaller than normal. In the coronal sections, marked atrophy of the white matter with brown discoloration was noted. The lateral ventricles were dilated. Klüver-Barrera staining revealed marked demyelination with relative preservation of the U-fibers. PAS-positive materials were deposited in some astrocytes as well as neurons. Metachromatic deposits were noted not only in the cerebrum but also cerebllum after staining with acid cresyl violet. Pathologic diagnosis was consistent with adult type of metachromatic leukodystrophy.

[Left subclavian artery approach for insertion of IABP].

A 62-year-old man admitted with a complication of chest pain. Cardiac catheterization showed three vessel disease with ventricular dysfunction (EF 40%). And aortagram showed that he had arteriosclerosis obliterans (ASO). While he was waiting for operation, the frequency of chest pain increased. It was considered necessary for him to have IABP catheter inserted. We chose left subclavian artery as an access for the insertion of IABP catheter. The catheter was easily introduced into the descending aorta under the fluoroscopy. Emergency CABG was performed the day after insertion of IABP catheter. IABP removed the next morning of operation. Operation and postoperation course was uneventful. In this case, the insertion and the removal were possible under local anesthesia. Left subclavian approach was useful for emergency case with ASO.

Ultrastructural characterization of the tau-immunoreactive tubules in the oligodendroglial perikarya and their inner loop processes in progressive supranuclear palsy.

Coiled bodies and interfascicular threads are conspicuous white matter abnormalities of brains of patients with progressive supranuclear palsy (PSP). Both structures are argyrophilic and immunoreactive for the microtubule-binding protein tau. This report concerns the ultrastructural localization of interfascicular threads and their relationship to coiled bodies in five PSP patients. We showed for the first time that abnormal tubules with a 13- to 15-nm diameter and fuzzy outer contours were the common structures of coiled bodies in the oligodendroglial perikarya and of interfascicular threads. Moreover, the tubules were immunolabeled by anti-tau antibodies. The abnormal tau-positive tubules of interfascicular threads were located in the inner loop of the myelin sheath. Our study further indicated that the thread-like structures in the white matter comprised, at least in part, oligodendroglial processes, and that they were also present in gray matter. We consider that the formation of coiled bodies in the perikarya and of interfascicular threads represents a common cytoskeletal abnormality of the oligodendroglia of PSP patients. Moreover, even though the white matter alterations of PSP resemble those of corticobasal degeneration, there are certain ultrastructural differences in the abnormal oligodendroglial tubules of the two diseases.

[A 54-year-old man with progressive proximal muscle atrophy and gynecomastia].

We report a 54-year-old man with progressive proximal muscle atrophy and gynecomastia. The patient had an insidious onset of weakness in his lower extremities at age 14, in that he noted a difficulty in standing up from a chair. Soon after he noted some difficulty in climbing up stairs. At age 35, he noted weakness in his arms; his weakness slowly progressed in that he became unable to walk or stand alone before 40 years of age. He also noted gynecomastia at that age. He was admitted to our hospital for the work up on September 16, 1993, when he was 54-year-old. On admission, he was alert and oriented; his BP was 150/70 mmHg; he had bilateral gynecomastia, however, no other skeletal deformities were found. On neurologic examination, he was mentally sound without dementia, and his higher cerebral functions were normal. Cranial nerves also appeared intact without facial atrophy, dysarthria, or dysphagia; no atrophy was noted in the tongue. He had marked muscle atrophy in both upper and lower extremities more marked in the proximal portions; muscle strength was approximately in the range of 2/5 to 3/5 in the proximal parts, and 4/5 in the distal parts in both upper and lower extremities. No fasciculation was noted; muscle tone was flaccid; no ataxia was present. Deep reflexes were either lost or markedly diminished. No Babinski sign was noted. Sensation was intact. Laboratory examination revealed normal blood counts; serum CK was slightly increased to 131 IU/l; ECG showed complete right bundle branch block; EMG revealed no active units in the right biceps brachii, deltoid, quadriceps femoris, and triceps surae muscles; in other muscles tested, motor unit potentials of low amplitude and short duration were seen; in the right tibialis anterior muscle, however, motor unit potentials with an amplitude up to 6 m V were also seen. Nerve conduction velocities were normal. A diagnostic procedure was performed. He was discussed in the neurological CPC, and the chief discussant arrived at the conclusion that this patient had Becker type of progressive muscular dystrophy. In her differential diagnosis, the possibility of Kennedy-Alter-Sung syndrome was discussed because this patient had gynecomastia. However, the discussant excluded that possibility because of absence of both bulbar symptoms and typical neurogenic changes in his EMG. The diagnostic procedure was a muscle biopsy on the left tibialis anterior muscle. Histologic observation on HE stained specimens revealed marked inequality in the muscle fiber diameters, increase in endomysial nuclei, proliferation of connective tissue, and fiber splitting.(ABSTRACT TRUNCATED AT 400 WORDS)

[An autopsy case of hereditary cerebellar atrophy (Holmes-type) with mental symptoms and rhythmic skeletal myoclonus].

We report on the clinicopathological findings in autosomal recessive hereditary cortical cerebellar atrophy of the Holmes type (H-CCA). Although based on the patient's family tree we cannot rule out the possibility of sex-linked recessive hereditary disease, both clinically and pathologically we differentiated this case from sex-linked recessive hereditary cortical cerebellar atrophy, in which lesions are widely distributed and associated with a variety of symptoms, since the major clinical feature was cerebellar ataxia, and the major lesions were limited to the olivocerebellar system. The patient's initial symptom was a motor disturbance in the upper extremities at the age of 16. This was followed by chronic progression of his symptoms, with cerebellar ataxia becoming the major symptom. The patient died unexpectedly at 40 years of age as a result of choking caused by misswallowing. The total period of observation was 24 years. The clinical features in this case were juvenile onset at age 16 with motor disorders of the upper extremities, followed by cerebellar ataxia, mental symptoms, mainly consisting of personality changes, and associated rhythmic skeletal myoclonus (RSM). Even though the patient died in the middle stage of the disease, pathologically there were extensive lesions in the olivocerebellar system, i.e., extensive degeneration not only of Purkinje cells but of granular cells and the molecular layer, and the distribution of the lesions was characteristic, with more extensive degeneration in the neocerebellum than in the paleocerebellum.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes with recurrent abdominal symptoms and coenzyme Q10 administration.

A male with mitochondrial myopathy, encephalopathy, lactic acidemia, and strokelike episodes is reported. He had also recurrent episodes of ileus. Muscle biopsy revealed ragged-red fibres. The cytochemistry of cytochrome c oxidase (CCO) showed scattered nonstained fibres, while all muscle fibres were heavily stained by immunocytochemistry using CCO antibody. These findings suggest that partical CCO deficiency may be present in the skeletal muscles of the patient. NADH cytochrome c reductase in the patient's muscle mitochondria was low compared with normal controls (about 26%), although succinate cytochrome c reductase was normal. Coenzyme Q10 administration (90 mg/day) did not improve CSF lactate levels, but did decrease plasma lactate levels. His muscle weakness slightly improved.

Effects of paraquat on mitochondria of rat skeletal muscle.

The effect of the herbicide paraquat (N,N'-dimethyl 4,4'-bipyridium), known to damage the lipid cellular membrane by peroxidation with superoxide radicals and a singlet oxygen, was investigated on skeletal muscle mitochondria. Minced rat gastrocnemius muscles were incubated in 8 mM paraquat solution. Mitochondrial fractions prepared from the incubated muscles were examined with respect to respiratory function and the enzyme activity of cytochrome c oxidase and succinate-cytochrome c reductase in the electron transport chain. The ADP/O ratio, RCR, and state 3 rates (= oxygen consumption in state 3) decreased gradually. State 4 rates (= oxygen consumption in state 4) increased in the initial stages and decreased after longer incubations. Enzyme activities gradually increased. These results suggested that paraquat damaged the mitochondrial membrane and disrupted oxidative phosphorylation in the early stage of incubation. Also, the electron transport chain was accelerated in the earlier stage and broken following a longer incubation. The inhibitory modality of paraquat on mitochondrial respiration was shown to be different from that of other known inhibitors.

Isolation and characterization of I5B2, a new phosphorus containing inhibitor of angiotensin I converting enzyme produced by Actinomadura sp.

A new inhibitor of angiotensin I converting enzyme, I5B2, was isolated from the culture broth of Actinomadura sp. No. 937ZE-1. This compound contains N-methylvaline, tyrosine and 1-amino-2-(4-hydroxyphenyl)ethylphosphonic acid. The microorganism also produced another inhibitor, I5B1, which is identical with K-4 isolated from Actinomadura sp. as an antihypertensive agent.

Isolation and characterization of ancovenin, a new inhibitor of angiotensin I converting enzyme, produced by actinomycetes.

Ancovenin, an inhibitor of angiotensin I converting enzyme isolated from the culture broth of a Streptomyces species, is a dialysable peptide composed of sixteen amino acid residues containing unusual amino acids such as threo-beta-methyllanthionine, meso-lanthionine, and dehydroalanine.