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Biomedical subjects

M Moran

Publications and source records attributed to M Moran.

At least 109 records · Page 6Linked to original sources

Multiple rheumatoid nodules of the renal cortex.

We report the findings of a large localized collection of rheumatoid nodules in the renal cortex of a male patient with long-standing seropositive rheumatoid arthritis. Rheumatoid nodules are a rare occurrence in the urinary tract, with only two previous reports of renal involvement, to our knowledge. A possible relationship, on the basis of immunologically mediated mechanisms, to accompanying chronic pyelonephritis is proposed.

Arthritis, Rheumatoid↗

NMR pulse relaxation studies on the normal aging and cataractous lens.

Proton NMR pulse relaxation experiments have been performed in this and other laboratories mainly on animal lenses and some human lenses. In order to evaluate T1 and T2 analyses as a potentially useful (non-invasive) parameter in delineating lenticular changes in normal aging human rabbit lenses, and in human cataracts, we performed a series of pulse relaxation studies on human eye bank lenses 10 to 93 yr of age, on fresh intact human cataracts and on normal rabbit lenses. Additional spectroscopic studies (fluorescence and 31P-NMR) were also performed on the lenses in order to correlate these parameters with the data relating to 'water phases' in the lens. These experiments demonstrate a potential additional parameter for evaluating 'molecular' changes in the aging and cataractous lens.

Adolescent↗

The common src homology region 2 domain of cytoplasmic signaling proteins is a positive effector of v-fps tyrosine kinase function.

A conserved noncatalytic domain SH2 (for src homology region 2) is located immediately N terminal to the kinase domains of all cytoplasmic protein-tyrosine kinases. We found that the wild-type v-fps SH2 domain stimulated the enzymatic activity of the adjacent kinase domain 10-fold and functioned as a powerful positive effector of catalytic and transforming activities within the v-fps oncoprotein (P130gag-fps). Partial proteolysis of P130gag-fps and supporting genetic data indicated that the v-fps SH2 domain exerts its effect on catalytic activity through an intramolecular interaction with the kinase domain. Amino acid alterations in the SH2 domain that impaired kinase function interfered with association of the SH2 domain with the kinase domain. Deletion of a conserved octapeptide motif converted the v-fps SH2 domain from an activator to an inhibitor of tyrosine kinase activity. This latent inhibitory activity of v-fps SH2 has functional implications for phospholipase C-gamma and p21ras GTPase-activating protein, both of which have two distinct SH2 domains suggestive of complex regulation. In addition to regulating the specific activity of the kinase domain, the SH2 domain of P130gag-fps was also found to be required for the tyrosine phosphorylation of specific cellular proteins, notably polypeptides of 124 and 62 kilodaltons. The SH2 domain therefore appears to play a dual role in regulation of kinase activity and recognition of cellular substrates.

Amino Acid Sequence↗

Photographic and spectroscopic correlations of human cataracts.

Intracapsular cataracts obtained within 3 h after surgical extraction were photographed with the CCRG technique and immediately subjected to fluorescence spectroscopy followed by 31P- and 13C-nuclear magnetic resonance (NMR) spectroscopy. Fluorescence spectroscopy demonstrates an excellent correlation between nontryptophan fluorescence intensities and lens color. An interesting correlation was also observed between the degree of light scatter as determined by the 290-nm excitation peak for intrinsic lens tryptophan fluorescence and the CCRG (photographic) appearance of these cataractous lenses. Based on 100 cataracts analyzed, there is a strong correlation between this kind of light scattering measurement and the type and degree of lens opacification. A similar correlation is evident with the 31P-NMR organophosphate profiles in the lenses in which the sugar phosphate levels are elevated only in diabetic patients with cataracts ('diabetic cataracts'). Aside from fluorescence and 31P-NMR spectroscopy, selected lenses were also incubated with 5.5 nM 13C-glucose as soon as they were obtained, and the foregoing spectroscopy was performed, followed by 13C-NMR analyses to detect and monitor for sorbitol accumulation in young versus old normal lenses and in diabetic cataracts. These studies clearly demonstrate a direct correlation between nontryptophan-fluorescent chromophore levels, light scattering (determined by tryptophan excitation peaks), lens age and cataract type. In addition, the organophosphate profiles clearly delineate the diabetic cataracts, and the 13C-NMR spectra correlate well with the age-related decrease in aldose reductase activity.

Aged↗

Two years of cyclophosphamide and 5-fluorouracil as adjuvant chemotherapy for stage II and III breast carcinoma.

The results after 6 years of a prospective clinical trial of adjuvant chemotherapy with a regimen of two drugs--cyclophosphamide and 5-fluorouracil (CF)-- for 2 years in 97 women with stage II or III breast cancer are reported. Eligible patients were free from distant metastases. All patients began adjuvant therapy within 4 weeks of surgery; therapy consisted of radical, modified, or extended radical mastectomy. No postoperative radiotherapy was given. The results are compared with a historical control group from previous consecutive patients treated by surgery alone. Patients were stratified by age (younger than 50 or older than or equal to 50) and nodal status (one to three positive axillary nodes vs. four or more positive nodes). The estimated 6-year survival was 60% for CF patients vs. 31% for control patients (P = 0.001). The estimated 6-year disease-free survival was 53.6 and 30.3% for CF and control, respectively (P = 0.007). There was a trend toward longer disease-free survival (DFS) and survival (S) in patients treated with CF, but this was not significant in all the subgroups. Disease-free survival was statistically significant in the subgroup of women greater than or equal to 50 years old with one to three positive nodes (P = 0.038); survival in the patients less than or equal to 49 years old with four or more positive nodes (P = 0.0036); and in patients greater than or equal to 50 years old with one to three lymph nodes involvement (P = 0.038).

Adult↗

Prostaglandins and the release of insulin. A review and a proposal.

The effect of prostaglandins or the inhibition of their synthesis on the release of insulin is controversial. Dispute exists because there are apparently disparate experimental results. When the following factors are considered, however, much of the disparity is eliminated: 1) the experimental setting--in vitro or in vivo; 2) the experimental model--animal or human; 3) the experimental additive--the type of nonsteroidal antiinflammatory drug or specific prostaglandin; 4) the relationship of insulin levels to insulin secretion, degradation, and the observed hypoglycemic response. On the basis of such considerations the following conclusions are advanced. 1) From animal studies in vitro it appears that prostaglandins can directly augment insulin release. 2) Results from animal experiments in vivo, however, suggest that systemic prostaglandin administration diminishes insulin release. 3) No human studies have been performed in vitro which examine the insulin secretory response of pancreatic tissue to prostaglandins. 4) Prostaglandins reduce stimulated insulin levels in normal human subjects and in those with diabetes mellitus. Whether insulin secretion is reduced, or clearance is increased, is unknown. 5) Finally, the critical experiment remains to be done, that is the simultaneous examination of insulin, C-peptide, and glucose kinetics during an infusion of a prostaglandin.

Animals↗

Sorbitol generation and its inhibition by Sorbinil in the aging normal human and rabbit lens and human diabetic cataracts.

Fresh intact human cataracts (derived from patients with mature-onset diabetes mellitus and from nondiabetic patients), normal human lenses between 2 and 71 years old and lenses derived from 1.5- to 5-kg rabbits were incubated in Earle's media containing enriched 13C-glucose (5 and 15 mM). 31P NMR organophosphate profiles were obtained at the start and end of each incubation. Sorbinil was added to one of each pair of selected lenses, both incubated with 13C-glucose. All the lenses were frozen after 4h of incubation and were subsequently assayed by 13C NMR spectroscopy. The results demonstrate significant sorbitol generation only in young lenses which can be inhibited by Sorbinil. None of the older normal and cataractous human lenses or the mature-onset diabetic cataracts were capable of generating measurable sorbitol levels although they all showed active glucose metabolism and their organophosphate profiles demonstrated normal high-energy phosphate levels. Increased sugar phosphate levels were usually found in the mature-onset diabetic cataracts. Although our NMR spectroscopy is only sensitive to 10(-3) M levels, such concentrations of sorbitol are required to exert their osmotic effects. These data indicate that high sorbitol levels can only be generated in young human and rabbit lenses and correlate well with the age-related changes in aldose reductase activity in these lenses.

Adolescent↗

Acrylamide and iodide fluorescence quenching studies on whole human lenses and their protein extracts.

Tryptophan fluorescence was monitored in whole lenses (and in soluble crystallin fractions derived from these lenses) before and after incubating them in media containing acrylamide or iodide. The effects of exposing one lens to low level broadband UV radiation were compared with the contralateral lens incubated in the dark. In addition we employed 13C labeled acrylamide in order to monitor (by NMR spectroscopy) which crystallins were most effected. These studies demonstrate an acrylamide fluorescence quenching effect in whole lenses and extracted lens proteins, which is directly age related, as is the extent of its incorporation and binding to specific lens proteins. Iodide had no effect on TRP fluorescence in whole lenses and a slight effect on the extracted crystallins. These data demonstrate differences in the microenvironment of TRP residues in the various lens crystallins and their relative susceptibility to low level UV radiation exposure at doses approaching the ambient in vivo levels in a "real life" situation. This approach helps to delineate the microenvironment of TRP residues in native proteins and the effects of UV exposure on proteins with buried versus exposed TRP residues.

Acrylamide↗

Developmental changes in salt acceptability in human infants.

Human infants less than 4 months of age ingested water and moderate concentrations of sodium chloride solution (0.10-0.20 M) in equal amounts. In contrast, infants 4-24 months of age exhibited heightened acceptance of saline solution relative to water. Such a developmental change in salt acceptability is consistent with a hypothesis of postnatal maturation of peripheral and/or central structures underlying this response. Children 31-60 months of age tended to reject saline solution relative to water. This change may in part reflect the effects of experience.

Age Factors↗

Postoperative whole lung irradiation with or without adriamycin in osteogenic sarcoma.

Thirty-six patients with histologically proven osteogenic sarcoma of the extremities, treated between September 1975 and April 1978, are the subject of this report. The primary tumor was treated with radical surgery. Patients received 2000 cGy whole lung irradiation postoperatively in an attempt to control micrometastases to the lung. Twenty-nine of the patients were given Adriamycin (60 mg/m2 IV every 6 weeks for a total dose of 550 mg/m2) in addition to the irradiation. The median, disease-free interval was 118 days for the seven patients treated with lung irradiation only. The median overall survival for these patients is 241 days, with one patient alive with disease. All patients developed lung metastasis. For the 29 patients treated with postoperative lung irradiation and Adriamycin, the median disease-free interval was 372 days, and the median overall survival is 843 days. Nineteen of the patients recurred (65.5%). The differences are statistically significant (p less than or equal to 0.003, median disease-free survival and p less than or equal to 0.03, median survival). This study supports the role of whole lung irradiation plus Adriamycin, in the control of micrometastases in osteogenic sarcoma of the extremities and suggests that additional clinical trials are warranted.

Adolescent↗

Reconstructive surgery for vasculogenic impotence.

A multidisciplinary approach was used to diagnose 12 patients with vasculogenic impotence. Deep dorsal vein ligation was performed in 8 men to treat venous incompetence. Venous arterialization according to the technique of Virag was used in 4 men to treat arterial inflow insufficiency. A 75 per cent success rate was noted for the correction of venous incompetence. With an average followup of 1 year, excellent success was achieved in re-establishing corporeal blood flow with the technique of venous arterialization plus creation of a venocorporeal shunt.

Adult↗

Mean circulatory filling pressure: potential problems with measurement.

Three experimental series using 22 acutely splenectomized mongrel dogs were completed to 1) compare fibrillation (Fib) and acetylcholine (ACh) injection as methods to stop the heart for the mean circulatory filling pressure (Pmcf) maneuver, and 2) test whether Pmcf equals portal venous pressure 7 s after heart stoppage (Pportal7s). Blood volume changes of -10, -20, +10, or +20 ml/kg were imposed and Pmcf and Pportal measurements were obtained. Pportal7s and Pmcf were significantly different with volume depletion but were similar under control conditions. Pmcf with ACh and Pmcf with Fib were significantly different only after a volume change of -20 ml/kg. However, severe pulmonary congestion and atelectasis were detected in animals where Ach was used to stop the heart. In some cases (with injection directly into the pulmonary artery) the damage was severe enough to cause irreversible arterial hypoxia. Thus we conclude that the repeated use of ACh may exert a detrimental influence on pulmonary function, changing the physiological status of the experimental animal. Also, the central venous pressure at 7 s of heart stoppage (Pcv7s) is not a fully accurate estimate of the true mean circulatory filling pressure during the Pmcf maneuver, because Pcv7s did not equal the Pportal7s under all experimental conditions.

Acetylcholine↗

[Nevus on nevus. Apropos of 7 case reports, 3 of them associated with other dysplasias, and 1 with an invasive malignant melanoma].

There is some doubt as to whether naevus pilus is identical with naevus-on-naevus or lentiginous naevus en mottes. The former could be classified together with Becker's naevus among the clinically progressive types of epidermal naevi, whereas the latter could be a truly melanocytic naevus of special expression which, for some authors, might become malignant. Seven cases of naevus-on-naevus with different sizes and locations are reported. In 3 cases the naevus was associated with other pathologies: pigmented sclerotic and kyphoscoliosis, verrucoid epidermal naevus, tuberous angioma and underlying muscular hypertrophy. In every case the diagnosis was confirmed by histological examination. An invasive malignant melanoma on superficial extensive melanoma coexisted with a retiform intradermal naevus pilosus. The hypothesis of complex neuro-ectodermic dysplasia and the histogenesis of malignant melanoma developed upon a naevus-on-naevus are discussed.

Adult↗