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Biomedical subjects

D Phillips

Publications and source records attributed to D Phillips.

At least 91 records · Page 5Linked to original sources

Testins are localized to the junctional complexes of rat Sertoli and epididymal cells.

UNLABELLED: Testin I and Testin II were originally identified as Sertoli cell products with similar NH2-terminal amino acid sequences. Secretion of testins is stimulated by testosterone in Sertoli cell-enriched cultures. By contrast the secretion of testins from intact seminiferous tubules appears to be inversely related to germ cell number. In the present study testin antiserum that recognized both Testin I and Testin II ("testin") was used to localize these proteins in tissue secretions by immunofluorescence. Testin was localized at the base of the seminiferous epithelium at Sertoli-Sertoli junctions. Fluorescence also appeared to be located at the sites of interaction between spermatoids and Sertoli cells. A punctate pattern of fluorescence was also present in the cytoplasm of Leydig cells; without electron microscopic studies it was not possible to determine which structures the antibodies bound to in these cells. In the epididymis the reaction product was localized at the apices of the epithelial cells adjacent to the lumen at the sites of known junctional complexes. A variety of positive and negative controls indicated that staining was specific for testins. CONCLUSIONS: This is the first study to associate testins with junctional complexes. Relative to other junctional proteins, testins are unusual because of their small size and because they are secreted proteins.

Animals

Influence of different photoperiods on development of gonad, cloacal gland and circulating thyroid hormones in male Japanese quail Coturnix coturnix japonica.

One day old chicks of Japanese quail were exposed to different photoperiods (LD, 8:16, 13.5:10.5, 16:8 and LL) and observations (testes weight, cloacal gland size, body weight and circulating thyroxine and triiodothyronine) were taken at the age of 3, 5, 7, 9 and 16 weeks. Results indicate that immediate reproductive development occurred in birds exposed to long photoperiods (greater than 12 hr). Growth under LD 8:16, was not apparent till 7th week and by 16 weeks, degree of gonadal development was similar in all the birds, irrespective of photoperiodic treatment. Whereas body weight of the intermediate and long day (LD 13.5:10.5, 16:8 and LL) treated birds increased upto 5th week and remained constant thereafter. But the chicks maintained under short day length (LD 8:16), showed spontaneous increase till the end of the study and birds were much heavier compared to all other groups. Plasma T4 concentration increased with increasing age till 9th week and remained unaltered thereafter. On the other hand T3 level did not change till 7th week followed by a decline. It is suggested that the initiation and degree of gonadal growth in quail depends on the availability of daily photoperiod, until the achievement of full breeding condition. Peak level of T4 observed in 9 week old birds may be involved in the development of photorefractoriness at that age.

Aging

No evidence for social class inequalities in intervention for coronary heart disease in Otago 1987-9.

OBJECTS: to investigate whether social class differences in access to cardiac surgical interventions (angioplasties and coronary artery bypass grafting) could explain social class inequalities in mortality from coronary heart disease. METHODS: rates of therapeutic interventions to treat coronary heart disease were calculated for male patients aged less than 65 years admitted for the first time to Dunedin Hospital with a principal diagnosis of ischaemic heart disease (ICD codes 410-414) during the three year period from 1 January 1987 to 31 December 1989. Patients were categorised into different socioeconomic groups using the Elley-Irving social class scale. RESULTS: no statistically significant trend across social class was observed in the cumulative incidence of cardiac surgical interventions (angioplasties, coronary artery bypass grafts). Similarly there was no statistically significant trend across social class in the incidence rates of cardiac surgical interventions, even after adjustment for age. CONCLUSIONS: social class inequalities in access to cardiac surgical intervention do not appear to explain the observed inequalities in mortality from coronary heart disease.

Angioplasty, Balloon, Coronary

Preparative, analytical and fluorescence spectroscopic studies of sulphonated aluminium phthalocyanine photosensitizers.

Fluorescence spectroscopic studies were carried out on aluminium phthalocyanine with defined numbers (mono, di, tri and tetra) of sulphonate groups. Selective sulphonation was achieved using one of two synthetic methods to prepare a mixture of components which were separated using reverse-phase liquid chromatography. Fluorescence lifetimes were measured in methanol and buffer solution using time-correlated single-photon counting with picosecond laser excitation; the lifetime shows little variation with the number of sulphonate groups. Using steady state excitation, fluorescence quantum yields were determined for the tetrasulphonated component (phi F = 0.51) and, for comparison, unsulphonated aluminium phthalocyanine.

Indoles

Calcium-independent phosphodiesterase inhibitors as putative antidepressants: [3-(bicycloalkyloxy)-4-methoxyphenyl]-2-imidazolidinones.

The synthesis and biological properties of a novel series of selective calcium-independent phosphodiesterase inhibitors are described. These compounds also inhibit the specific binding of [3H]rolipram to rat brain membranes and exhibit efficacy in preclinical models of antidepressant activity in mice, such as reducing immobility in the forced-swim test and reversing reserpine-induced hypothermia. Imidazolidinones 4 and 16 were found to be the most potent compounds studied.

Animals

The detection of phthalocyanine fluorescence in normal rat bladder wall using sensitive digital imaging microscopy.

The ability to detect photosensitisers in tissue at a microscopical level is important when studying photodynamic therapy (PDT) in both normal and malignant tissue. We have studied the fluorescence distribution of aluminium sulphonated phthalocyanine (A1SPc) in the normal rat bladder using a cooled CCD (charge coupled device) imaging system with computerised image processing. This system makes it possible to carry out a quantitative assessment of photosensitiser fluorescence in the various layers of the bladder wall. The highest fluorescence intensities were obtained within 1 h of intravenous administration but there was little selectivity of uptake between layers. A1SPc was eliminated from the deeper muscle layers more quickly than from the superficial layers of the bladder wall so that by 24 h a 4:1 ratio of fluorescence intensity was apparent which persisted at least until 72 h, although the absolute amount of photosensitiser declined. Following irradiation by red light (675 nm), photobleaching of the sensitiser in the deeper layers further increased this ratio. Direct absorption of A1SPc by the bladder wall following intravesical administration proved unreliable.

Administration, Intravesical

Distribution and photodynamic effect of disulphonated aluminium phthalocyanine in the pancreas and adjacent tissues in the Syrian golden hamster.

Necrosis of small volumes of tumour tissue with photodynamic therapy (PDT) can be achieved relatively easily. For this to be clinically relevant, it is essential to know what the same treatment parameters do to adjacent normal tissues into which the tumour has spread. For pancreatic cancers, local spread to vital structures is common. We have studied chemical extraction, microscopic fluorescence kinetics and photodynamic effects of disulphonated aluminum phthalocyanine (AlS2Pc) in normal pancreas and adjacent tissues in hamsters. Chemical extraction exhibited a peak duodenal concentration of AlS2Pc 48 h after sensitisation, with levels much higher than in stomach and pancreas. With microscopic fluorescence photometry highest levels were seen in duodenal submucosa and bile duct walls 48 h after photosensitisation. Pancreatic ducts, duodenal mucosa and gastric mucosa and submucosa exhibited intermediate fluorescence with relatively weak fluorescence in pancreatic acinar tissue and the muscle layer of the stomach. As expected, on the basis of fluorescence intensity and chemical extraction studies, the duodenal and bile duct wall were the most vulnerable tissues to photodynamic therapy. When the dose of 5 mumol kg-1 of sensitiser was used, duodenal perforations, gastric ulcers and transudation of bile from the bile duct occurred. However, the lesions in the stomach and bile duct healed without perforation or obstruction, so only the duodenum was at risk of serious, irreversible damage. Using a lower dose of photosensitiser markedly reduced damage.

Animals

The objective assessment of nasal patency.

Nasal patency was measured by five techniques in 24 subjects and the results compared. In addition three pulmonary parameters were measured as well as height and weight. Nasal resistance to airflow measured by active anterior rhinomanometry was found to be highly correlated with peak nasal inspiratory flow rate. Other correlations were also noted. Peak nasal inspiratory flow was itself highly correlated with pulmonary peak expiratory flow rate as well as with several other parameters. The possible reasons for these correlations are discussed in terms of fluid mechanics.

Adult

Comparison of distribution and photodynamic effects of di- and tetra-sulphonated aluminium phthalocyanines in normal rat colon.

We have previously reported photodynamic therapy of normal rat colon using aluminium sulphonated phthalocyanine (AISPc). In that study, the AISPc used was a mixture of phthalocyanines of different degrees of sulphonation. Phthalocyanines of defined degrees of sulphonation have recently become available and we compared the distribution of the di- and tetra-sulphonates (AIS2Pc and AIS4Pc) in rat colon and colon wall structures employing both chemical extraction and fluorescence photometry using a charge coupled device imaging system. Also, the photodynamic effects produced by these components in rat colon were compared at various times after photosensitization. After intravenous photosensitizer administration using equimolar doses, the concentration of AIS2Pc in colon fell off more rapidly with time than AIS4Pc. Differences were noted in the microscopic distribution of these compounds, with the di-sulphonate exhibiting peak fluorescence in colon wall structures by 1 h after photosensitization, while mucosal fluorescence with the tetra-sulphonate peaked at 5 h. Fluorescence was also lost from the colon wall much more slowly with the tetra-sulphonate, which tended to be retained in the submucosa. Maximum photosensitizing capability was seen at 1 h with AIS2Pc and no lesions could be produced with photodynamic therapy at 1 week, with up to 5.65 mumol/kg. With AIS4Pc (5.65 mumol/kg), while no lesions could be produced with light treatment at 1 h, photodynamic therapy at 1 week produced lesions only slightly smaller than those produced with treatment at 48 h (the time of maximum effect), and significant photosensitization was present at 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum

Autosomal dominant inheritance of autoantibodies to thyroid peroxidase and thyroglobulin--studies in families not selected for autoimmune thyroid disease.

Recently the tendency to produce autoantibodies to thyroid peroxidase (TPO Ab) and thyroglobulin (Tg Ab) was shown to be inherited as an autosomal dominant characteristic in women but not in men. Because of potential bias in this study which was carried out in families with autoimmune thyroid disease (AITD), the inheritance of thyroid autoantibodies has been evaluated in 49 families unselected for autoimmune thyroid disease. Among these families (24 with facioscapulohumeral disease, 10 with Friedreich's ataxia, and 15 with schizophrenia) the prevalences of TPO Ab and Tg Ab were 27.8% and 26.7%, respectively, in women and 9.2% and 11.7%, respectively, in men. In 40 families where one or more individual had TPO Ab and/or Tg Ab, segregation analysis showed that the tendency to make antibodies was consistent with a Mendelian dominant trait in women but not in men. In young women, however, the prevalence of both TPO Ab and Tg Ab increased with age, rising from 14% and 10%, respectively, at age 15-24 to 35% and 40% at age 35-44. As this is inconsistent with a simple dominant hypothesis, a further segregation analysis by age was carried out in the families unselected for thyroid disease together with 16 pedigrees with AITD previously studied and two additional large AITD families. The results of the combined analysis provided strong support for the hypothesis of dominant inheritance but also showed significant reduction in gene expression among women aged 15-24 yr.

Adolescent

Polyneuropathy syndromes associated with serum antibodies to sulfatide and myelin-associated glycoprotein.

We studied a series of 64 patients with sensory +/- motor peripheral neuropathies by comparing clinical and physiologic features to serum antibody reactivity against compounds containing sulfated carbohydrate moieties. We determined antibody reactivity by an enzyme-linked immunosorbent assay (ELISA) using purified glycolipids and glycoproteins as antigens, and we used high-performance thin-layer chromatography and Western blotting to test the specificity of results. Twelve patients with high titers of IgM antibodies directed against the myelin-associated glycoprotein (MAG) had sensory-motor polyneuropathies with physiologic evidence of demyelination. IgM antibody reactivity to MAG was associated with an IgM serum M protein in five patients. Eight other patients, most with sensory greater than motor polyneuropathies, had high titers of antibody reactivity to sulfatide but not of IgM to MAG. Two had an associated IgM paraprotein. None of the patients with selective serum antisulfatide activity had predominantly demyelinating features on physiologic testing. We conclude that (1) high ELISA titers of antibodies to MAG may be more common than previously suspected in patients with chronic demyelinating sensory-motor neuropathies, and (2) the presence of high titers of antisulfatide antibodies in serum may provide clues to the pathogenesis of otherwise idiopathic, axonal, predominantly sensory neuropathies.

Adult

New family of high-resolution ion exchangers for protein and nucleic acid purifications from laboratory to process scales.

A new family of polymer-based ion exchangers was tested for the purification of acidic and basic proteins on both the analytical and preparative scales. Protein-Pak HR series packings are available as strong cation (SP) and weak anion (DEAE) exchangers, allowing the development of a purification method regardless of the isoelectric point of protein. Three particle sizes, 8, 15 and 40 microns, are offered in scalable Advanced Purification (AP) glass columns or as bulk packings. The lower back pressures of the 15- and 40-microns packings compared to that of the 8-microns material allow rapid throughput of large volumes without exceeding the pressure limitations of the resin or the column. The capacity of the AP1 (100 mm x 10 mm) glass columns, containing these ion-exchange packings, is comparable to other ion-exchange columns. The resolution of mouse serum, plasmids, and a standard protein mixture was demonstrated and compared with the results obtained with other resin-based ion exchangers of similar particle size. Proteins were purified without significant loss of biological activity or mass.

Alkanesulfonates

Altered operant behavior of adult rats after perinatal exposure to a 60-Hz electromagnetic field.

Rats were sham exposed or exposed perinatally to a 60-Hz electromagnetic field, 22 days in utero and the first 8 days post partum. Each of the 30 once-daily exposures was 20 h in duration. The electric component of the field was vertical 30 kV/m rms, and the magnetic field component was 100 microTG rms. Later, as adults, male rats were trained to emit an operant response when reinforced with food on a multiple, random-interval schedule. Exposed rats (N = 21) gradually came to respond at significantly lower rates than did sham-exposed controls (N = 20). This finding was confirmed and extended in a second, independently performed experiment. After a sequence including operant conditioning followed by experimental extinction of responding and then by a suspension of conditioning and finally by more than a month of reconditioning, slower rates of responding were found to persist in the adult animals. The evidence of altered behavior several months after combined, fetal-neonatal exposure to an electromagnetic field presents an interesting contrast with other findings: Field-exposed rats did not differ from sham-exposed rats in terms of body mass, physical appearance, grossly observed activity level, or incidence of disease.

Animals

Selective necrosis in dimethylhydrazine-induced rat colon tumors using phthalocyanine photodynamic therapy.

Photodynamic therapy is a relatively new method for the local destruction of tumors based on the administration of a photosensitizing agent that is retained in tumors and then activated to produce cytotoxic agents following irradiation with light. The selective retention of photosensitizers by dimethylhydrazine-induced colonic tumors over adjacent normal tissue is small (2:1, tumor to normal), making the possibility of producing selective tumor necrosis with total sparing of normal tissue difficult. Colonic cancers and adjacent normal colon were treated with the same light doses from an argon-pumped dye laser 48 h after intravenous injection of 0.5 or 5 mg/kg of the photosensitizer, aluminum-sulfonated phthalocyanine. There was little difference between the amount of necrosis in the tumor and the adjacent normal colon if the injected dose of photosensitizer was 5 mg/kg. However, at the lower dose of 0.5 mg/g, up to 2 mm of necrosis could be produced in the tumor without damaging the normal colon. In vivo fluorescence measurements showed that the photosensitizer was photodegraded during irradiation. This was confirmed by in vitro fluorescence scans of the normal colon after irradiation; the fluorescence from the photosensitizer was lowest at the point of irradiation. It is postulated that at low dosage, selective necrosis can occur because the photosensitizer is photodegraded in the normal colon before a threshold photodynamic dose is reached, whereas in tumor containing twice as much photosensitizer, a photodynamic threshold dose can be achieved and necrosis produced.

1,2-Dimethylhydrazine

Resource management in New Zealand hospitals: the RUS (resource utilization system) system--an illustration of its applications.

This study demonstrates a potential application in the planning and policy area of a resource management system (known as the Resource Utilisation System (RUS)) first introduced into New Zealand in 1987 and now becoming the definitive resource management tool in the New Zealand public hospital sector. A retrospective cohort of 193 individuals (mean age 60.2 years, 73% males) admitted to Dunedin Public hospital with their first acute myocardial infarction in 1978 was followed through for 10 years in order to describe their inpatient resource utilisation as well as their morbidity and mortality experience. The cumulative mortality for the group over 10 years was 57%. The potential years of life lost (PYLL) amounted to 1340 years, or 6.9 years per person. The overall inpatient resource utilisation amounted to $2,317,300 for the whole group, or $12,006 per person (1988 NZ dollars) over the 10 years follow-up.

Cohort Studies

"Isolated" elevation of alkaline phosphatase: significance in hospitalized patients.

The significance of alkaline phosphatase (AP) elevation with otherwise normal transaminase and bilirubin values remains unclear. We evaluated the clinical outcome of hospitalized patients with an "isolated" AP elevation. Eighty-seven inpatients with isolated AP elevation were identified during February 1984 and followed for 1 year. Forty-five of 87 patients had normalization of AP during the follow-up period, usually within 1-3 months. The most common diagnoses in this group were congestive heart failure in nine, benign bone disease in six, and treatable malignancy in three patients. Twelve patients had no apparent explanation for the transient rise of AP. Persistent AP elevations were noted in 42 patients--14 of whom had terminal malignancies. Clinically obvious life-threatening diagnoses were made in 24 of the patients with persistent AP elevation. The etiology of AP elevation remained enigmatic in seven patients: two died, four are stable during 1 1/2-3 years of follow-up, and one patient was found to have metastatic carcinoma 17 months later. If the initial AP was greater than 1 1/2 times normal, there was a higher likelihood of persistent elevation (68% vs. 41%, p less than 0.05). Isolated elevations of AP in inpatients may be associated with a variety of medical illnesses and often normalize within months. If the AP elevation is persistent, there is usually a clinically obvious diagnosis. A reasonable approach to such patients is a careful history, physical exam, and routine lab studies to detect obvious diagnoses, followed by repeat enzyme determination at 1-3 months.

Alkaline Phosphatase

Granuloma gluteale infantum: case report and review of the literature.

Granuloma gluteale infantum, a benign granulomatous eruption involving the gluteal region, histologically shows a nonspecific dermal inflammatory infiltrate composed of neutrophils, lymphocytes, histiocytes, plasma cells, and eosinophils. It is important to recognize this condition, as it may clinically simulate a neoplastic process. It arises as a complication of primary irritant diaper dermatitis, however, and typically resolves without treatment.

Biopsy