bluuebunny/crossref_metadata_2025 huggingface dataset:
SPECIFICITY IN THE EFFECTS ON BRAIN METABOLISM OF TWO DIFFERING NEUROTROPIC VIRUSES
Authors: Nickle Margaret , Kabat Herman
Published: June 2004

1. Brain tissue infected with the virus of Western equine encephalomyelitis shows specific differences in metabolism from brain tissue infected with the virus of poliomyelitis.

2. With added glucose concentration of 121 mg. per cent, oxygen utilization of poliomyelitic brain is significantly below normal and that of encephalitic brain is not.

3. With added glucose concentration of 217 mg. per cent, oxygen utilization of encephalitic brain is significantly below normal and that of poliomyelitic brain is not.

4. With lactate-glucose as the substrate, oxygen utilization of encephalitic brain is significantly below normal and that of poliomyelitic brain is not.

5. With pyruvate-glucose as the substrate, neither encephalitic brain nor poliomyelitic brain differs significantly from normal in oxygen consumption.

6. With succinate-glucose as the substrate, oxygen utilization of poliomyelitic brain is significantly above that of the normal control in the 1st hour.

7. With added glucose concentration of 37.5 mg. per cent, anaerobic metabolism of encephalitic brain is significantly below the normal whereas that of poliomyelitic brain is not.

8. With added glucose concentration of 229.5 mg. per cent, anaerobic metabolism of both encephalitic brain and poliomyelitic brain is significantly below the normal.
FURTHER OBSERVATIONS ON THE RELATION OF THE EYE TO IMMUNITY IN EXPERIMENTAL SYPHILIS
Authors: Chesney Alan M. , Woods Alan C.
Published: June 2004

Two experiments are reported in which rabbits originally inoculated with syphilis and treated late in the course of the disease (174th to 210th day) were reinoculated subsequently in both corneas with the homologous strain of syphilitic virus. In each animal one cornea was inoculated with dead tubercle bacilli prior to reinoculation with the syphilitic virus. This procedure was carried out in order to bring about a non-specific inflammatory reaction with resultant vascularization, the intention being to find out if such vascularization would render the cornea more resistant to inoculation with the homologous strain of syphilitic virus. The results of both experiments were similar and while they were not conclusive, they indicated that there was a tendency for corneas which had been injected with dead tubercle bacilli to be more refractory to a subsequent inoculation with homologous syphilitic virus than the corneas of the same animals that had not been injected with dead tubercle bacilli. This tendency may be interpreted as suggestive evidence for the view that in the syphilitic rabbit there develop circulating antibodies toward the homologous strain of T. pallidum.
STUDIES ON A NON-HEMOLYTIC STREPTOCOCCUS ISOLATED FROM THE RESPIRATORY TRACT OF HUMAN BEINGS
Authors: Mirick George S. , Thomas Lewis , Curnen Edward C. , Horsfall Frank L.
Published: June 2004

The results of studies on the immunological relationship between streptococcus MG and Streptococcus salivarius type I are described. Evidence is presented to show that Streptococcus salivarius type I, like streptococcus MG, possesses a capsular polysaccharide antigen. Similarities in the capsular polysaccharides of these two different species of non-hemolytic streptococci appear to be responsible for their immunological relationship.
THE SPIROCHETICIDAL ACTION OF PENICILLIN IN VITRO AND ITS TEMPERATURE COEFFICIENT
Authors: Eagle Harry , Musselman Arlyne D.
Published: June 2004

1. Penicillin was found to be actively spirocheticidal in vitro against the Reiter, Kazan, Nichols, and Noguchi strains of so called S. pallida, and a strain of mouth spirochetes. The threshold concentration was 0.01 unit per Cc. (1–160,000,000 penicillin). The rate and degree of action increased with the concentration of penicillin up to a level of approximately 0.1 to 0.25 unit per cc., which rendered more than 99 per cent of the organisms non-viable within 12 hours. Higher concentrations did not appreciably accelerate the effect.

2. Within the range 4 x 104–107 organisms per cc., the initial rate at which the spirochetes were killed was not affected by their number. Consistent with that observation, no demonstrable penicillin was bound or inactivated by thick suspensions. The amount of penicillin required to sterilize suspensions of varying density nevertheless varied to a large extent with the initial number of organisms. This was only in part due to the progressive deterioration of the penicillin with prolonged incubation; and the persistence of organisms resistant to the drug, and perhaps an adaptative change after prolonged exposure to penicillin, may be contributing factors.

3. The organisms remained actively motile for a period of 8 to 24 hours after they had been rendered non-viable by the action of penicillin. Even 500 units of penicillin per cc., or approximately 10,000 times an effectively spirocheticidal concentration, did not accelerate that delayed immobilization. It follows that, although penicillin rapidly renders the organisms non-viable, the metabolic system affected is not immediately essential to the life of the cell, and the motility and presumably other vital functions remain unaffected for a significant number of hours.

4. The rate at which the organisms were killed by penicillin increased with temperature in the range 8–40°C. With an original inoculum of 106 spirochetes per cc., the percentage of organisms surviving after 24 hours at 39–40°, 36–37°, 32–33°, 22–23°, and 8°C. was 0.02, 0.2, 1, 10, and 100 respectively; and those results were independent of the concentration of penicillin in the range 0.25 to 250 units per cc. If these observations with a non-pathogenic organism in vitro are applicable to the pathogenic organism in vivo, they suggest that the combined use of fever and penicillin in the treatment of syphilis may be more effective than either alone.
AN ETIOLOGIC CONSIDERATION OF DONOVANIA GRANULOMATIS CULTIVATED FROM GRANULOMA INGUINALE (THREE CASES) IN EMBRYONIC YOLK
Authors: Anderson Katherine , DeMonbreun W. A. , Goodpasture E. W.
Published: June 2004

1. A microorganism identical with that originally described by Anderson has been cultivated in pure strain from two additional cases of granuloma inguinale by means of inoculating the yolk of chick embryos with uncontaminated human tissue containing Donovan bodies.

2. The morphological and cultural characteristics of the three isolated strains are described and discussed.

3. This microorganism has been cultivated in vitro only in media containing embryonic yolk. It failed to grow on any of a variety of artificial media.

4. It has not proved to be pathogenic for common experimental animals.

5. The Donovan body is reproduced in the epithelial cells of the yolk sac and in the yolk. The microorganism evidently reproduces both extracellularly and intracellularly.

6. The microorganism produces in culture antigens that elicit immune reactions in the skin and serum of granuloma inguinale patients.

7. This microorganism is judged to be a bacterium and the etiological agent of granuloma inguinale.

8. It is proposed that these strains of the bacterium be the type of a new genus, Donovania, in recognition of Donovan's original description of the pathognomonic bodies of granuloma inguinale; and that the specific name granulomatis be applied to designate its relationship to the characteristic lesion of the disease.
NUTRITION OF THE HOST AND NATURAL RESISTANCE TO INFECTION
Authors: Schneider Howard A. , Webster Leslie T.
Published: June 2004

1. A diet of whole wheat and whole dried milk has been shown to promote a higher survival rate, among W-Swiss mice subjected to S. enteritidis infection, than that promoted by a "synthetic" diet.

2. The demonstration of this ability of diet to condition natural resistance has been found to depend upon the genetic constitution of the mice employed. The demonstration has been possible in W-Swiss mice, a strain only moderately inbred and retaining a degree of genetic variability. The demonstration has not been possible in three highly inbred strains of mice selected so that they differed predictably from one another in natural resistance.

3. The nutritional factors involved are present in whole wheat and are absent or negligible in dried whole milk. Their nature has not yet been determined.
BACTERIOSTATIC EFFECT OF HUMAN SERA ON GROUP A STREPTOCOCCI
Authors: Rothbard Sidney
Published: June 2004

1. Heparin was more satisfactory for preventing blood from clotting than defibrination, potassium and ammonium oxalate, or sodium citrate in bacteriostasis of group A streptococci in the presence of streptococcal antibodies in convalescent serum.

2. Blood from rabbit, guinea pig, or sheep could not be substituted for human blood in promoting bacteriostasis when human antibody was used. Mixtures of human leukocytes and plasma of each of these animals or of animal leukocytes and human plasma were also not effective with human antibody.

3. Complement, leukocytes, and a thermostable factor which was found in human plasma were essential in the indirect bacteriostatic technique employed for the inhibition of streptococcal growth in the presence of convalescent human serum.

4. The thermostable component was active in human serum, as well as in plasma, in 1:12 dilution, withstood storage at 4° C. for at least 7 weeks, and was destroyed by heating at 70° C. for 30 minutes.
THE METABOLISM OF THE KIDNEY IN EXPERIMENTAL RENAL HYPERTENSION
Authors: Raska Sigwin B.
Published: June 2004

These investigations are part of an attempt to study and interpret the intermediary metabolism of the kidneys in experimental renal hypertension. Hypertension was produced in dogs by the clamping procedure of Goldblatt and associates or by the silk perinephritis method of Page. Enzymatic studies were made by means of Warburg's manometric method. Cytochrome c was in addition determined spectrophotometrically. Tissue slices, homogenized tissue, and tissue extracts were used.

A study of the cytochrome c concentration and the activities of the cytochrome oxidase and succinic dehydrogenase systems of kidneys from normal dogs and dogs with experimental renal hypertension was made. It was found that the cytochrome c concentration and the activities of the cytochrome oxidase and succinic dehydrogenase systems were markedly lower in the kidney slices and in the tissue suspensions from hypertensive dogs.

Tissue suspensions and extracts of kidneys from hypertensive dogs showed an inhibitory effect on the activity of the cytochrome oxidase and succinic dehydrogenase, and the amine oxidase systems. Renin preparations also showed a marked inhibitory effect on the activities of cytochrome oxidase, succinic dehydrogenase, l-amino acid oxidase, and amine oxidase systems.

A significant increase was found in the kidney of dogs whose other kidney had been removed or subjected to Goldblatt's or Page's technique in the activities of the cytochrome-cytochrome oxidase system, the succinic dehydrogenase system, and in the concentration of nucleotide-bound phosphorus, of flavin-adenine dinucleotide, and of the nicotinamide-adenine dinucleotides (coenzymes I and II). From the results of these studies it can be concluded that an increase in the concentration and activity of the respiratory enzymes precedes hypertrophy of the kidney. This can be explained by the assumption that an increase in the activity of the respiratory biocatalysts acts as a stimulus for cell growth and multiplication.
HEREDITARY ACHONDROPLASIA IN THE RABBIT
Authors: Pearce Louise , Brown Wade H.
Published: June 2004

Pathological observations on hereditary achondroplasia in the rabbit have been described. At autopsy, the chief features of interest are: reduced size with disproportionately shortened extremities and large head, cutaneous and subcutaneous edema of variable degree and distribution, small shortened bones with a cartilaginous appearance and texture, immature teeth, and cleft palate in one-fourth the cases; blood-stained fluid in the thoracic and abdominal cavities; a comparatively small heart pointing to the right of the midline, a very large firm thymus, a large pale soft spleen, a large swollen liver with red mottling, and a stomach distended with thin greenish mucus but no milk.

The mean relative weights of all organs in terms of the net body weight were larger than those of normal new-born litter mates. The mean actual weights of the kidneys, the brain, and especially the spleen and the thymus were also larger than their respective normal values, those of the heart, liver, and adrenals were slightly smaller, while that of the pituitary was the same.

Histologically, all endochondral cartilages show marked abnormalities of differentiation with pronounced deficiency of ossification. Calcification of membranous bones is likewise deficient. The histological abnormalities of the long bones are very similar to, if not identical with, those characteristic of human fetal chondrodystrophy, the creeper fowl condition, the "bull-dog" calf, and achondroplasia of the dog.

No histological evidence was found in any organ which would suggest a basis for a responsible causal agent of the abnormality. Minor to marked vascular dilatation and congestion and edema is a variable feature but is fairly widely distributed. The changes in the thyroid indicate an active gland. The cellular pattern of the pituitary is characterized by some increase in basophilic cells. The lymphoid elements of the spleen are more or less depleted. The hemopoietic tissue in the spleen and liver is reduced in amount. In blood obtained from the heart, there is a reduction in the numbers of red and white cells and platelets and in the hemoglobin content as well; immature cells and particularly normoblasts are comparatively numerous.
ENDURING IMMUNITY FOLLOWING VACCINATION OF MICE WITH FORMALIN-INACTIVATED VIRUS OF RUSSIAN SPRING-SUMMER (FAR EASTERN, TICK-BORNE) ENCEPHALITIS
Authors: Casals J. , Olitsky Peter K.
Published: June 2004

A single course of two intraperitoneal injections of formalin-inactivated virus of Russian spring-summer encephalitis induced in albino mice a solidly immune state which endured almost throughout life. Active virus is therefore not essential for the production of a high degree of lasting immunity. The immune response to vaccination consists of resistance to peripherally introduced active virus and development of circulating antibody.

A correlation has been found to exist throughout the long period of the immune state between the titer of neutralizing antibody, as determined by the intraperitoneal method described, and the degree of immunity to peripherally introduced active virus. Thus laboratory tests for the immunizing power of a vaccine suggest themselves, to be carried out by an estimation in vaccinated mice of (a) immunity to peripherally inoculated active virus, and (b) serum virus-neutralizing antibody determined by the intraperitoneal method.

The rôles as indicators of immunity in vaccinated mice of complement-fixing antibody in the serum, of the intracerebral challenge dose of virus, and of the intracerebral method for testing neutralizing antibody are discussed.

Finally, if the immune response of man to vaccination with formalin-inactivated virus of Russian spring-summer encephalitis follows the pattern of the response of mice as here described, and if the correlation of neutralizing antibody with immunity to peripherally introduced virus applies to man as to mice, then possibly the degree of immunity in human beings following vaccination can be appraised by a peripheral test for neutralizing antibody in the serum.
STUDIES ON PNEUMONIA VIRUS OF MICE (PVM)
Authors: Horsfall Frank L. , Curnen Edward C.
Published: June 2004

This study on pneumonia virus of mice (PVM) was carried out in order to obtain as accurate data as possible on the degree of variation which may be expected in titrations of the virus or of antibodies against it in vivo. It is believed that the knowledge gained will facilitate further investigations on this latent pneumotropic virus and make possible a more exact assessment of the significance of experimental results obtained with the agent.

The reproducibility of 50 per cent maximum score titration end points with PVM in mice is such that the chances are 19 out of 20 that a difference of 1.084 log units (i.e. a twelvefold difference) in the end points obtained in two separate titrations is significant. The reproducibility of 50 per cent maximum score serum dilution end points in neutralization tests with PVM in mice is such that the chances are 19 out of 20 that a difference of 0.626 log units (i.e. a fourfold difference) in the end points obtained with two sera against similar amounts of virus is significant.

It was found that there is a linear exponential relationship between the serum dilution end point and the quantity of PVM used in a neutralization test. This relationship appears to be identical with immune serum obtained from different animal species, and appears also to be identical to the linear relationship described previously in similar studies with influenza A virus.
Basaloid Squamous Cell Carcinoma of the Larynx: A Report of Four New Cases
Authors: Erisen Levent M. , Coskun Hakan , Ozuysal Sema , Basut Oguz , Onart Selcuk , Hizalan Ibrahim , Tezel Ilker
Published: June 2004

Objectives: This study is designed to report the clinical and pathologic features and outcome of cases of basaloid squamous cell carcinoma (BSCC) of the larynx treated in our clinic.

Study Design: A retrospective review of the medical records of these patients.

Methods: Four cases of BSCC of the larynx were treated in our department. Histopathologic slides were reevaluated to confirm the diagnosis. Immunohistochemical studies were performed, and file records were reviewed. Follow‐up was available for all patients and ranged between 11 and 72 (mean 37) months.

Results: All patients were male (mean 57), with supraglottic or transglottic larynx tumors. Two patients presented with stage‐II disease and the other 2 with stage‐IV disease. Initial diagnosis was invasive squamous cell carcinoma in 3 patients and BSCC in one patient. Two patients who had stage‐II disease underwent partial laryngectomy and bilateral neck dissections; total laryngectomy and bilateral neck dissections were performed in stage‐IV patients. Three patients received adjuvant postoperative radiotherapy, and 2 of them also received additional chemotherapy. Patients with stage‐IV disease were found to have 4 and 27 metastatic lymph nodes on histopathologic examination and died because of distant metastases at 11 and 14 months, respectively. Patients with stage‐II disease did not have cervical metastasis on histopathologic examination and were alive and free of disease at 52 and 72 months respectively.

Conclusion: In contrast with the literature reporting the tendency of more aggressive clinical behavior of the BSCC, we can say that BSCC has a behavior similar to conventional squamous cell carcinoma based on our 4 cases.
Role for Postoperative Radiation Therapy in Adenoid Cystic Carcinoma of the Head and Neck
Authors: Silverman Damon A. , Carlson Thomas P. , Khuntia Deepak , Bergstrom Richard T. , Saxton Jerrold , Esclamado Ramon M.
Published: June 2004

Objective: Clarify the role for postoperative radiation for adenoid cystic carcinoma (ACC) of the head and neck as it relates to tumor site, T‐stage, and surgical margin status.

Study Design: Retrospective cohort study at an academic tertiary care hospital.

Methods: A review of 129 patients with biopsy‐proven ACC was performed. Previous treatment failures and nonoperative candidates were excluded, with 75 patients considered eligible for further study. Patients were grouped according to treatment modality and Kaplan‐Meier estimates of overall survival, locoregional control, and distant control were compared using log‐rank tests. Patients were also stratified according to tumor site, T‐stage, and surgical margin status, and pair‐wise comparisons of treatment outcome within each group were performed using Wald tests from Cox proportional hazards models.

Results: Twenty‐five patients were treated with surgery alone, and 50 were treated with surgery and postoperative radiation. There was no significant difference in outcome between treatment groups when correlated with tumor site (P = .89). However, postoperative radiation was associated with improved overall survival for advanced T‐stage (T4) tumors (P = .019) and greater locoregional control for patients with microscopically positive margins (P = .018). There was no demonstrated benefit of postoperative radiation for patients with microscopically negative margins (P = .93).

Conclusions: The findings of this study suggest that advanced T‐stage and positive microscopic margins are important factors in determining the necessity for postoperative radiation therapy for ACC of the head and neck and that radiation therapy may not be necessary for patients with early T‐stage tumors and negative surgical margins.
Role of Free Radicals and Antioxidants in Nasal Polyps
Authors: Dagli Muharrem , Eryilmaz Adil , Besler Tanju , Akmansu Halit , Acar Aydin , Korkmaz Hakan
Published: June 2004

Objectives/Hypothesis: The aim of this study is to determine the role of free radicals and antioxidants in nasal polyps.

Study Design: Prospective, randomized, controlled study.

Methods: Thirty‐one patients with nasal polyposis and a control group consisting of 19 patients with septal deviation and lower turbinate hypertrophy were included in the study. Levels of the antioxidants retinol, β‐carotene, α‐tocopherol, and ascorbic acid were measured from the sera of the patients with nasal polyposis and the control group. Plasma levels of superoxide dismutase activity (SOD), glutathione peroxidase (GSHPX) activity, and reduced glutathione (GSH) were also obtained. As a peroxidation product, the levels of the malondialdehyde‐thiobarbituric acid (MDA) combination were measured from the plasma of patient and control groups. Measurements of MDA, GSH, and α‐tocopherol levels were also taken from the polyp tissue and turbinate mucosa of the control group.

Results: The blood levels of antioxidants and MDA as an oxidant were significantly different in the patient group compared with the control group (P < .01). The tissue levels of antioxidants and MDA were significantly different in the patients with polyposis compared with the control group (P < .01). The blood and tissue anti‐oxidant levels were found to be decreased, and MDA levels as an oxidant increased significantly in the patient group with polyposis when compared with the control group, and there was a negative correlation between oxidative stress and antioxidants.

Conclusion: This study demonstrates that oxidative stress and tissue and blood antioxidants in the patients with polyposis were significantly different compared with the control group. The blood and tissue antioxidant levels decreased, and MDA levels, as an oxidant, increased significantly in the patient group with polyposis when compared with the control group. The current study demonstrates that there is strong evidence related to oxidative stress in the pathogenesis of nasal polyposis, and antioxidants can have a preventive role in free–radical‐mediated tissue damage in nasal polyposis.
Questioning the Relationship between Cochlear Otosclerosis and Sensorineural Hearing Loss: A Quantitative Evaluation of Cochlear Structures in Cases of Otosclerosis and Review of the Literature
Authors: Nelson Erik G. , Hinojosa Raul
Published: June 2004

Background: The literature provides conflicting information regarding the prevalence and cause of sensorineural hearing loss (HL) in individuals with otosclerosis.

Objective: The purpose of this study was to further evaluate the association between involvement of the cochlear endosteal layer with otosclerosis and sensorineural HL.

Study Design: Retrospective case review.

Methods: Temporal bones and audiograms from five individuals with otosclerosis were evaluated. The cochlear elements were quantified. The location and extent of the cochlear element loss was correlated with the location and extent of endosteal involvement with otosclerosis.

Results: A reduction in the population of cochlear elements was observed in most individuals; however, the reduction was not proportional to the extent of endosteal involvement with otosclerosis. The cochlear elements remained normal adjacent to some areas of endosteal involvement with otosclerosis. One individual with extensive cochlear otosclerosis had normal hearing and predominantly normal cochlear elements.

Conclusion: This study demonstrates a variable amount of degeneration of the cochlear elements in individuals with otosclerotic involvement of the endosteum. The reduction in the population of cochlear elements was not related to the extent and location of endosteal involvement with otosclerosis. These findings suggest that factors that limit the effect of otosclerotic endosteal involvement on the cochlear elements or processes that effect the cochlear elements directly and are independent of bone involvement may be present.
Restoring Vocal Fold Movement after Transection and Immediate Suturing of the Recurrent Laryngeal Nerve with Local Application of Basic Fibroblast Growth Factor: An Experimental Study in the Rat
Authors: Motoyoshi Kazumi , Hyodo Masamitsu , Yamagata Takahiko , Gyo Kiyofumi
Published: June 2004

Objective: To evaluate the effects of basic fibro‐blast growth factor (bFGF) on the recovery of vocal fold movement and the attenuation of laryngeal muscle atrophy after transection of the recurrent laryngeal nerve (RLN).

Study Design: Quantitative assessment of vocal fold movement using the video cassette recorder (VCR) image‐analysis method and histologic examination of the laryngeal muscle.

Methods: Fifty‐eight Wistar rats underwent RLN transection and one of the following three procedures: 1) transection of the RLN alone (transection group, n = 18), 2) suture of the nerve stumps followed by local administration of phosphate‐buffered saline (PBS) solution using an osmotic pump (PBS group, n =20), or 3) suture of the nerve stumps followed by local administration of bFGF (FGF group, n = 20). Vocal fold movements were recorded with VCR by way of a rigid endoscope, and the VCR images were analyzed on a computer. Histologic changes in the thyroarytenoid (TA) muscle were evaluated by measuring the cross‐sectional area of the muscle and average size of muscle fibers.

Results: In the transection group, vocal fold movement did not recover, and atrophy of the TA muscle gradually progressed after sectioning the nerve. In contrast, vocal fold movement as assessed by VCR image‐analysis recovered in some cases in the immediate suturing groups, more markedly in the FGF group (34.1 ± 29.1%) than in the PBS group (5.5 ± 7.9%) (P < .05). Histologically, atrophy of the laryngeal muscle was significantly attenuated by the local administration of bFGF.

Conclusion: bFGF facilitates regeneration of the transected RLN and attenuation of intrinsic laryngeal muscle atrophy, thereby restoring laryngeal function.
Effect of Mastoid Oscillation on the Outcome of the Canalith Repositioning Procedure
Authors: Motamed M. , Osinubi O. , Cook J. A.
Published: June 2004

Objective: The canalith repositioning procedure (CRP), as described by Epley, is a well‐established method of treatment for benign paroxysmal positional vertigo (BPPV). Debate exists as to whether simultaneous application of a mastoid oscillator confers any added benefit. The aim of this study was to examine this question.

Study Design: Prospective randomized study.

Method: Eighty‐four subjects with unilateral posterior canal BPPV were randomized into two groups. The oscillator group was treated by CRP with mastoid oscillation and the nonoscillator group was treated by CRP alone. Positive outcome was regarded as complete resolution of symptoms and a negative Dix‐Hallpike's test after a 4 to 6 week follow‐up period.

Results: Five patients were lost to follow‐up. Twenty‐eight (72%) patients from the oscillator group and 26 (65%) patients from the nonoscillator group had a positive outcome. This difference was not significant (χ2 = 0.17, P = .68)

Conclusion: For the treatment of posterior canal BPPV, concurrent mastoid oscillation with CRP does not significantly alter the short‐term outcome.
Mutation Detection of GJB2 Using IsoCode and Real‐Time Quantitative Polymerase Chain Reaction With SYBR Green I Dye for Newborn Hearing Screening
Authors: Kudo Takayuki , Oshima Takeshi , Kure Shigeo , Matsubara Yoichi , Ikeda Katsuhisa
Published: June 2004

Objectives/Hypothesis: Recent developments in molecular genetics have opened a new era in genetic analysis accompanied by new concepts concerning genetic disorders. Although 30 genes responsible for nonsyndromic deafness have been discovered as of March 27, 2003, the connexin 26 gene (GJB2) is commonly found in cases of deafness of unknown origins. The GJB2 contains a predicted open reading frame of 785 base pairs, which makes it relatively easy to detect mutations. Accordingly, mutation analysis of GJB2 should be suitable for the screening of congenital deafness.

Study Design: Prospective study.

Methods: IsoCode Stix is a useful device to isolate DNA from small samples of blood, which can be delivered from remote areas. To apply the detection of common mutations of GJB2 to hearing screening, DNA was extracted from several droplets of blood applied to the IsoCode device, and an allele‐specific amplification method with real‐time quantitative polymerase chain reaction was performed using GeneAmp 7700 with SYBR Green I dye.

Results: DNA extracted from IsoCode was purified within 45 minutes, which was sufficient to detect the full sequence of GJB2. Four types of common GJB2 mutations were reliably detected within 2.5 hours.

Conclusion: IsoCode and real‐time quantitative polymerase chain reaction will be promising tools for newborn screening of deafness genes in the future in DNA‐based deafness screening, allowing early diagnosis of deafness and prompt training for language development.
De novo proteins from designed combinatorial libraries
Authors: Hecht Michael H. , Das Aditi , Go Abigail , Bradley Luke H. , Wei Yinan
Published: June 2004

Combinatorial libraries of de novo amino acid sequences can provide a rich source of diversity for the discovery of novel proteins with interesting and important activities. Randomly generated sequences, however, rarely fold into well‐ordered proteinlike structures. To enhance the quality of a library, features of rational design must be used to focus sequence diversity into those regions of sequence space that are most likely to yield folded structures. This review describes how focused libraries can be constructed by designing the binary pattern of polar and nonpolar amino acids to favor proteins that contain abundant secondary structure, while simultaneously burying hydrophobic side chains and exposing hydrophilic side chains to solvent. The “binary code” for protein design was used to construct several libraries of de novo proteins, including both α‐helical and β‐sheet structures. The recently determined solution structure of a binary patterned four‐helix bundle is well ordered, thereby demonstrating that sequences that have neither been selected by evolution (in vivo or in vitro) nor designed by computer can form nativelike proteins. Examples are presented demonstrating how binary patterned libraries have successfully produced well‐ordered structures, cofactor binding, catalytic activity, self‐assembled monolayers, amyloid‐like nanofibrils, and protein‐based biomaterials.
Analysis of the “thermodynamic information content” of a Homo sapiens structural database reveals hierarchical thermodynamic organization
Authors: Larson Scott A. , Hilser Vincent J.
Published: June 2004

Classification of the amounts and types of lower order structural elements in proteins is a prerequisite to effective comparisons between protein folds. In an effort to provide an additional vehicle for fold comparison, we present an alternative classification scheme whereby protein folds are represented in statistical thermodynamic terms in such a way as to illuminate the energetic building blocks within protein structures. The thermodynamic relationship is examined between amino acid sequences and the conformational ensembles for a database of 159 Homo sapiens protein structures ranging from 50 to 250 amino acids. Using hierarchical clustering, it is shown through fold‐recognition experiments that (1) eight thermodynamic environmental descriptors sufficiently accounts for the energetic variation within the native state ensembles of the H. sapiens structural database, (2) an amino acid library of only six residue types is sufficient to encode >90% of the thermodynamic information required for fold specificity in the entire database, and (3) structural resolution of the statistically derived environments reveals sequential cooperative segments throughout the protein, which are independent of secondary structure. As the first level of thermodynamic organization in proteins, these segments represent the thermodynamic counterpart to secondary structure.
The Dynamics of Self‐employment and Ethnic Business Ownership among Taiwanese in Australia
Authors: Chiang Lan‐hung Nora
Published: June 2004

Taiwan‐born business and skilled migrants who settle in Australia have high unemployment rates despite being well educated and fairly affluent. This phenomenon, commonly found in Australia among new Asian immigrants, has seldom been researched. Using qualitative methodologies, including ethnographic interviews and participant observation, this paper examines economic integration of recent Taiwanese business and skilled migrants in three Australian cities: Sydney, Brisbane, and Melbourne. The results indicate that Taiwanese immigrants find it difficult to secure employment, start profitable businesses, and adapt to the host society. The integration challenges include: lack of fluency in English, different social and cultural milieu, lack of familiarity with Australian business culture and labour relations, complex rules and regulations governing the establishment of business enterprises, small size of the market, high taxes, and lack of willingness to take up work not commensurate with their education and economic background. Policy recommendations to foster early integration of skilled migrants from Taiwan are included.
Do Urban Agglomeration Effects and Household Amenities have a Skill Bias?*
Authors: Adamson Dwight W. , Clark David E. , Partridge Mark D.
Published: June 2004

There are several hypotheses why urban scale affects wages. Most focus on agglomeration economies that increase labor demand, especially for high‐skilled workers (e.g., dynamic externalities stress knowledge transfers, and imply the urban wage gap favors skilled workers). Others stress urban amenities that increase labor supply and decrease wages. Amenities should have a stronger influence on affluent households if they are normal goods. By examining whether urban‐scale affects net returns to education, it can be determined whether skilled workers are influenced more by urban productivity or amenities. Empirical results suggest net returns to education decline with urban scale, implying a key role for urban amenities in affecting skilled workers.
No phytochelatin (PC2 and PC3) detected in Salix viminalis
Authors: Landberg Tommy , Greger Maria
Published: June 2004

Phytochelatins (PCs) have been detected in a large range of plant species, but their role in heavy‐metal tolerance is unclear. Various clones of Salix viminalis are differently tolerant to heavy metals, and the aim of this work was to investigate whether PCs were differently expressed in tolerant compared with sensitive clones. In a long‐term study, five clones with high or low metal tolerance were cultivated 21 days without or with Cd (1 or 10 µM), Cu (0.3 or 7 µM), Ni (15 µM), Pb (7 µM) or Zn (10 or 100 µM). Controls were further used in a short‐term study where Cd (1 µM) was added and samples were collected 0, 15 and 30 min, 1, 3 and 24 h after start of treatment. PCs were analysed on high performance liquid chromatography (HPLC) using two different methods: post‐column derivatization using Ellmans reagent and pre‐derivatization with monobromobimane. Thlaspi caerulescens treated with Cd was used as internal PC standard. No PCs could be detected in Salix with either of the two methods in any of the treatments: different clones, metals, concentrations, plant parts or treatment time. The 16 thiol peaks shown were the same in both control and treated plants. Both HPLC methods showed PC peaks when Thlaspi was used but these peaks could not be associated with any of the 16 peaks. The amino acid composition of the 16 peaks was not the expected composition of that of PCs. Thus, Salix viminalis have no detectable levels of PCs, which in turn are not involved in heavy metal tolerance in Salix.
Phylogenetic relationships of fish leeches (Hirudinea, Piscicolidae) based on mitochondrial DNA sequences and morphological data
Authors: Y. Utevsky Serge , Trontelj Peter
Published: June 2004

Utevsky, S. Y. & Trontelj, P. (2004). Phylogenetic relationships of fish leeches (Hirudinea, Piscicolidae) based on mitochondrial DNA sequences and morphological data. — Zoologica Scripta, 33, 375–385.

Phylogenetic relationships of fish leeches (Piscicolidae) were deduced from combined mitochondrial DNA sequences of 12S rDNA and COI genes using Bayesian inference and Maximum Likelihood, as well as from a combined molecular‐morphological data matrix using Maximum Parsimony. Monophyly of the family was confirmed. The traditional subdivision into three subfamilies, the Platybdellinae, Pontobdellinae, and Piscicolinae, received weak support, but was not challenged by alternative groupings. In contrast to prior classifications, a basal split emerged between the Pontobdellinae on the one hand, and the Platybdellinae and Piscicolinae on the other. The complex coelomic system of pontobdellines is viewed as plesiomorphic, and independent reductions of the coelom in other fish leech groups are hypothesized. According to the inferred phylogeny, seawater was the primary habitat of fish leeches. Eurasian freshwaters were colonized by a species‐rich freshwater clade (genera Piscicola, Baicalobdella, Cystobranchus and Caspiobdella) and, probably independently, by the Asian genus Limnotrachelobdella.
Plate 493. Lechenaultia biloba Goodeniaceae
Authors: Morrison David , George Alex
Published: June 2004

Summary.  Lechenaultia biloba Lindl. (Goodeniaceae), blue leschenaultia, one of Western Australia's well‐known blue flowers, has been grown in Britain since the 1840s.
Food does not affect the pharmacokinetics of solifenacin, a new muscarinic receptor antagonist: results of a randomized crossover trial
Authors: Uchida Taisuke , Krauwinkel Walter J. , Mulder Hans , Smulders Ronald A.
Published: June 2004

Aim  To determine the effect of food ingestion on the pharmacokinetic profile of solifenacin succinate (YM905; Vesicare®), a new bladder selective muscarinic receptor antagonist for the treatment of overactive bladder, a chronic disease usually caused by involuntary detrusor muscle contractions during bladder filling.

Methods  A randomized, two‐period, crossover study in two groups of 12 healthy men (aged 18–45 years, body weight 60–100 kg, body mass index ≤30). A single 10‐mg dose of solifenacin was administered to the first group in the fasting state during period 1 and in the fed state during period 2, and to the second group in the fed state during period 1 and in the fasting state during period 2 (10 mg is two times the suggested starting dose). There was a 14‐day washout between treatment periods. Parameters obtained included Cmax, AUClast, and AUC0–inf, as well as t1/2, tmax, and tlag.

Results  One subject withdrew during the first period for personal reasons. No statistically or clinically significant pharmacokinetic differences occurred between subjects in the fed and fasting states. All geometric mean ratios were close to 1 (Cmax, 1.033; AUClast, 1.068; AUC0–inf, 1.040). The 90% confidence intervals (CIs) fell in the predefined no‐food‐effect boundaries of 0.8–1.25 (Cmax, 0.953–1.120; AUClast, 0.990–1.153; AUC0–inf, 0.976–1.109). The mean difference in t1/2 was − 3.8 h (90% CI 7.6– 0.0). There were no significant differences between the fed and fasting states with regard to tmax and tlag (P > 0.05).

Conclusions  The pharmacokinetics of oral solifenacin was not affected by food ingestion, suggesting that this drug may be administered with or without food. The results observed in this investigation are consistent with those of previous studies of solifenacin.
Clinical pharmacology of clemastine in healthy dogs
Authors: HANSSON H. , BERGVALL K. , BONDESSON U. , HEDELAND M. , TÖRNEKE K.
Published: June 2004

Abstract  The pharmacokinetic properties of clemastine were investigated in six healthy dogs and compared with the effect of the drug recorded as inhibition of wheal formation induced by intradermal injections of histamine. Clemastine clearance was high (median: 2.1 L h−1 kg−1) and the volume of distribution large (13.4 L kg−1). The half‐life after intravenous administration was 3.8 h and the plasma protein binding level in vitro was 98%. After oral administration, the bioavailability was only 3%. Given intravenously, clemastine (0.1 mg kg−1) inhibited wheal formation completely for 7 h, whereas the effect after oral administration (0.5 mg kg−1) was minor. The data show that most dosage regimens suggested in the literature for the oral administration of clemastine to dogs are likely to give too low a systemic exposure of the drug to allow effective therapy.
A randomized, controlled study to evaluate the steroid sparing effect of essential fatty acid supplementation in the treatment of canine atopic dermatitis
Authors: SÆVIK BENTE K. , BERGVALL KERSTIN , HOLM BIRGIT R. , SAIJONMAA‐KOULUMIES LEENA E. , HEDHAMMAR ÅKE , LARSEN STIG , KRISTENSEN FLEMMING
Published: June 2004

Abstract A randomized, double blind, placebo‐controlled multicentre clinical trial of 12 weeks’ duration was undertaken in 60 dogs with atopic dermatitis to evaluate the steroid sparing effect of essential fatty acid supplementation. The dogs were randomly assigned to receive either a combination of borage seed oil and fish oil or a placebo, in addition to prednisolone tablets. All dogs received a standardized basal diet. Owners of the dogs recorded pruritus daily using a 10 cm visual analog scale and the dosage of prednisolone was established based on the pruritus score, according to written instructions. The dosage of prednisolone and the use of any concurrent treatment (shampoo and/or ear‐cleanser) were recorded by the owner on a daily basis. The investigators graded the skin lesions at days 0, 42 and 84. The use of prednisolone during the test period was lower in the active group, but the difference was not statistically significant (P = 0.32). The test period was sequentially divided into 43–84, 50–84, 57–84, 64–84, 71–84 and 78–84 days. On day 64, the difference between the active group and the placebo group reached statistical significance (P = 0.04) with an increasing difference towards the end of the study. A statistically significant reduction in the pruritus scores and the total clinical scores from day 0 to day 84 was apparent in both groups (P < 0.0001). At the end of the study, both the pruritus score and the total clinical score were lower in the active group. Our findings indicate a steroid sparing effect of essential fatty acid supplementation in canine atopic dermatitis and, furthermore, that there is a time lag before the effect is attained.
Frequent and occasional species and the shape of relative‐abundance distributions
Authors: Ulrich Werner , Ollik Marcin
Published: June 2004

Recently, three different models have been proposed to explain the distribution of abundances in natural communities: the self‐similarity model; the zero‐sum ecological drift model; and the occasional–frequent species model of Magurran and Henderson. Here we study patterns of relative abundance in a large community of forest Hymenoptera and show that it is indeed possible to divide the community into a group of frequent species and a group of occasional species. In accordance with the third model, frequent species followed a lognormal distribution. Relative abundances of the occasional species could be described by the self‐similarity model, but did not follow a log‐series as proposed by the occasional–frequent model. The zero‐sum ecological drift model makes no explicit predictions about frequent and occasional species but the abundance distributions of the hymenopteran species did not show the excess of rare species predicted by this model. Separate fits of this model to the frequent and to the occasional species were worse than the respective fits of the lognormal and the self‐similarity model.
The ‘species problem’ and testing macroevolutionary hypotheses
Authors: Isaac Nick J. B. , Purvis Andy
Published: June 2004

Species lists change for a variety of reasons, including new information and preferences for different species concepts. Uncertainty over species numbers is potentially damaging to tests of proposed correlates of species richness, particularly if taxonomic changes are biased toward some clades over others. We investigate the effects of this error and bias by testing the same suite of macroevolutionary hypotheses in seven different arrangements of primate taxonomy. This is the first time that the effects of the ‘species problem’ have been systematically investigated in this way. Primates are an excellent model system for examining the effects of taxonomic uncertainty: species numbers have doubled in the past two decades, with the fastest growth in the Neotropics. We found that different variables were significantly associated with species richness in each taxonomic arrangement. However, there were no significant differences among taxonomies in the regression slopes for any predictor variable. We found no tendency for significant correlations to occur in taxonomies with more species, suggesting that the results cannot be explained by a lack of power in the smaller taxonomies. The findings are discussed with reference to the wider implications for testing macroevolutionary hypotheses.
Isolation and characterization of a wound inducible phenylalanine ammonia‐lyase gene (LsPAL1) from Romaine lettuce leaves
Authors: Campos Reinaldo , Nonogaki Hiroyuki , Suslow Trevor , Saltveit Mikal E.
Published: June 2004

Phenylalanine ammonia‐lyase (PAL) catalyses the first step controlling the rate of phenylpropanoid metabolism. Wounding is a ubiquitous stress in nature and in the harvesting and preparation of fruits and vegetables that induces an increase in PAL activity, an accumulation of phenolic compounds and subsequent tissue browning. A wound‐inducible PAL gene (LsPAL1) was isolated from Romaine lettuce by RT‐PCR. The putative protein encoded byLsPAL1is similar to predictive polypeptides sequences for other PALs. The kinetics of PAL mRNA accumulation is similar to those of induced PAL enzyme activity, with enzyme activity following mRNA accumulation by 12 h. Wound‐induced PAL transcripts accumulated in cells close to the wound sites. Tissue printing showed that PAL mRNA was associated with tissue next to the epidermis and vascular bundles. A heterologous PAL protein was expressed inE. coliand was found to show significant PAL activity.