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Biomedical subjects

C Morales

Publications and source records attributed to C Morales.

At least 109 records · Page 6Linked to original sources

Loss of CO2 reactivity of cerebral blood flow is associated with severe brain damage in mechanically ventilated very low birth weight infants.

BACKGROUND: Early detection of pathophysiological factors associated with permanent and severe brain damage in preterm infants requiring intensive care is a major issue in neonatal neurology. The aim of this study was to investigate if an abnormal CO2 reactivity of cerebral blood flow in high risk very low birth weight infants is associated with severe brain injury demonstrated at autopsy or by neurodevelopment examination at 18 months. METHODS: The CO2 reactivity of cerebral blood flow (xenon-133) was measured in 18 mechanically ventilated, severely ill, very low birthweight infants (gestational age 26-32 weeks, birthweight: 630-1360 g) during the first 36 hours of life. Cerebral outcome was assessed on autopsy findings (n = 8) or at the age of 18 months using Bayley developmental scales (n = 10). RESULTS: Eight infants with normal development at 18 months (within mean +/- 2.5 SD of reference group) and two infants with normal cerebral autopsy findings had a median CO2 reactivity of 24.4%/kPa CO2 (interquartile range 14.7-41.2). Two infants with abnormal development (> 2.5 SD below mean) and six infants with hypoxic-ischaemic encephalopathy at autopsy has a median CO2 reactivity of 3.4%/kPa CO2 (interquartile range 8.0-11.7). CONCLUSION: In mechanically ventilated very low birthweight infants low CO2 reactivity of cerebral blood flow (below 10%/kPa CO2) during the first 36 hours of life was associated with poor neurodevelopmental outcome or hypoxic-ischaemic encephalopathy at autopsy. Loss of CO2 reactivity may play a role in the pathogenesis of hypoxic ischaemic encephalopathy. It is a candidate for predicting early severe brain damage in preterm infants requiring intensive care and for controlling the effect of early interventions.

Brain↗

[Menkes' disease: anatomo-clinical presentation of a case].

We describe a case of Menke's disease with severe neurological involvement, convulsive crises and characteristic hair anomalies (scanty, fragile, macroscopically hypopigmented and microscopically kinked) which led to rapid diagnosis. Vascular abnormalities with elongated, twisted arteries, skeletal abnormalities (more wormian cranial bones than usual, lateral spurs of metaphyses) and vesicle diverticuli. Electron microscopy of skeletal muscle showed concentrically laminated bodies, possibly of mitochondrial origin. Respiratory chain enzyme activity was normal. The patient died at the age of two and a half. On necropsy, histological abnormalities characteristics of the illness were seen (loss of neurones in the granular layer of the cerebellum, the neurones of Purkinje had thickening of the dendrites which spread out in the form of a weeping willow, reduplication and fragmentation of the internal elastic layer of muscle arteries). In the cortex of the cerebellum mega-mitochondria with electron-dense bodies, were seen on electron microscopy. This is the first case of Menke's disease described in the Spanish literature which includes pathology and electron microscope studies.

Brain↗

[Diagnosis and treatment of laryngeal radionecrosis].

Three cases of laryngeal radionecrosis are reported. In two cases partial surgery after radiotherapy probably triggered the radionecrosis. All patients were treated successfully with medical therapy. Laryngeal radionecrosis is an uncommon complication of radiotherapy for carcinoma of the head and neck. The interval between conclusion of radiation therapy and development of radionecrosis ranges from 3 to 12 months. Neither computed tomography nor magnetic resonance imaging differentiate between necrotic tissue and recurrent tumor. Humidification, broad spectrum antibiotics, steroids, and hyperbaric oxygen, with or without surgery, are successful in many cases.

Carcinoma, Squamous Cell↗

Effects of gonadotrophins on the proliferative activity of somatic testicular cells in neonatal and prepubertal rats.

The proliferative activity of the different testicular somatic cell lineages was studied in neonatal and prepubertal rats after treatment with recombinant FSH (recFSH) and human chorionic gonadotrophin (hCG). Male rats were treated on days 5-9 or 15-19 with 1 or 3 IU/rat.day, respectively, of recFSH, 10 IU/rat.day of hCG or vehicle and sacrificed the day following the last injection. Proliferation was studied by the immunohistochemical demonstration of DNA-incorporated 5-bromodeoxyuridine (BrdU) in both paraffin- and Epon-embedded tissues. No differences existed for the labeling indices in paraffin- or Epon-embedded tissues, but the identification of some cell types were easier in these latter one. At 10 days of age, no significant differences were found for the proliferative activity of the different cell types, except for the labeling index of foetal Leydig cells that was increased in hCG-treated animals. At 20 days of age, treatment with recFSH increased the testicular weight and tubule diameter, as well as the size of adult type Leydig cells and the labeling index of macrophages. Treatment with hCG increased the testicular weight and the number and size of adult-type Leydig cells, as well as the labeling indices of mesenchymal, adult-type Leydig cells and macrophages. These results indicate that the effects of gonadotrophin treatment on the different somatic testicular cell types are dependent on both the type of cells and their developmental stage.

Analysis of Variance↗

Central nervous system vasculopathy in neonatal lupus erythematosus.

Central nervous system involvement in neonatal lupus erythematosus (NLE) has not been previously reported. We report four patients with NLE, all with complete congenital heart block and three with cerebral ultrasound and color Doppler flow imaging (CDFI) studies demonstrating evidence of associated vasculopathy in the gangliothalamic vasculature. CDFI confirmed blood flow through the affected vessels, indicating that blood flow was not compromised at this early stage. Short-term follow-up revealed no signs of progression of the vasculopathy, focal ischemia, gangliothalamic atrophy, or neurological impairment. Nevertheless, the implications of this finding with respect to the natural history of NLE remain to be defined, particularly in cases in which the disease develops into systemic lupus erythematosus later in life. Besides specific diagnostic studies for NLE, cerebral ultrasound, and CDFI studies are mandatory in all cases of complete congenital heart block, regardless of whether mothers are diagnosed as having connective-tissue disease or not. Neonates with signs of vasculopathy in the gangliothalamic region should be examined for NLE.

Autoantibodies↗

Anaphylaxis to erythromycin.

BACKGROUND: Erythromycin and its salts belong to the larger class of macrolides. Erythromycin is well tolerated. The most common side effects are gastrointestinal distress, nausea, and vomiting, which are dose related. Allergic and pseudoallergic reactions due to macrolide antibiotics are uncommon. Anaphylaxis and acute respiratory distress appear in the literature as case reports. METHODS: We report a 24-year-old man who presented 12 years ago a systemic allergic reaction to penicillin, confirmed by skin tests and detection of specific IgE (RAST). Since then he had tolerated erythromycin on several occasions. Nine months ago, his general practitioner prescribed erythromycin orally as treatment for a respiratory infection. Thirty minutes after taking the first dose, 500 mg, he developed an anaphylactic reaction. The episode subsided with treatment with high dose corticosteroids, antihistamines, and epinephrine. Skin prick tests and intradermal tests were performed with erythromycin at different concentrations. We also measured total IgE and specific IgE to erythromycin by CAP and Phadezym RAST (Pharmacia, Uppsala, Sweden), respectively. We also performed a Prausnitz-Küstner test (PK test), and oral challenge test. RESULTS: Skin testing to erythromycin was not helpful because of cutaneous hyperreactiviness. No significant levels of specific IgE to erythromycin were detected. The oral challenge and the Prausnitz-Küstner test were positive. CONCLUSIONS: The positive history and oral challenge test suggested an anaphylactic reaction to erythromycin. The positive Prausnitz-Küstner test demonstrated the presence of specific IgE to erythromycin.

Adult↗

Labiatae allergy: systemic reactions due to ingestion of oregano and thyme.

BACKGROUND: There are no cases described in the medical literature of systemic allergic reactions due to oregano (Origanum vulgare) or thyme (Thymus vulgaris). These herbs belong to the Lamiaceae (Labiatae) family which comprises other plants such as hyssop (Hyssopus officinalis), basil (Ocimum basilicum), marjoram (Origanum majorana), mint (Mentha piperita), sage (Salvia officinalis) and lavender (Lavandula officinalis). OBJECTIVE: We describe three systemic allergic reactions caused by oregano and thyme in the same patient. METHODS: Skin tests with inhalant allergens and plants of the Labiatae family were done. We used the prick by prick technique with dried commercial plants and prick tests with extracts prepared with the Frugoni method in our patient and in ten control patients. Total serum IgE was determined by Phadezym IgE PRIST (Pharmacia). Specific IgE was measured by two methods: CAP system (Pharmacia) and Phadezym RAST (Pharmacia Diagnostics, Uppsala, Sweden) with activated discs of the allergenic extracts that were prepared in our laboratory. RESULTS: Skin tests with inhalants were positive to grasses. Skin tests with plants of the Labiatae family were positive in all cases when the skin prick technique was used; tests were negative with basil and lavender, and positive with all the others when we used the prick by prick technique. We did not detect any positive skin tests nor specific IgE to plants of the Labiatae family in control patients. Total serum IgE was 406 U/mL. Specific IgE was detected to all herbs tested; higher levels were obtained with the CAP system. CONCLUSIONS: Plants belonging to the Labiatae family seem to show cross-sensitivity on the basis of clinical history and in vitro and in vivo test results.

Food Hypersensitivity↗

Proliferative activity in the different ovarian compartments in cycling rats estimated by the 5-bromodeoxyuridine technique.

The ovary is one of the most active proliferating tissues, and several methods for assessing cellular proliferation have been used to study follicular kinetics during the estrous cycle in the rat. In this study, we have estimated the proliferative activity of the different ovarian tissue compartments by using the 5-bromodeoxyuridine (BrdU) technique. Adult cyclic rats were studied 1 h after pulse-labeling with BrdU. Follicles were divided by size as small (mean diameter < 275 micrograms) or large (mean diameter > or = 275 micrograms). Small follicles were recorded into five classes: 1) primordial follicles (formed by flattened pre-granulosa cells), 2) unilaminar primary follicles (which ranged from having at least one enlarged pre-granulosa cell up to having a complete layer of cuboidal granulosa cells), 3) multilaminar class a (having 1-2 layers of granulosa cells and measuring up to 75 micrograms in diameter), 4) multilaminar class b (76-150 micrograms), and 5) multilaminar class c (151-274 micrograms). Large follicles were recorded into classes 1-5 according to previous classifications [Osman P. J Reprod Fertil 1985; 73:261-270]. Primordial follicles and about 70% of unilaminar primary follicles were unlabeled, whereas all of the remaining classes of small and large follicles were labeled. The labeling index (percentage of BrdU-positive cells) increased in parallel with follicle size but showed a progressive decrease in large preovulatory follicles and a centripetal pattern of cell proliferation. Atretic follicles showed a significantly lower number of labeled cells than healthy follicles of the same size. The number of proliferating cells was not related to follicle size but was inversely correlated with the degree of atresia. Cyclic CL showed intense proliferative activity that was well correlated with functional activity. The number of labeled cells was maximal in metestrus, decreased in the succeeding days, and was very low in proestrus. Proliferating cells seemed to correspond to vascular cells lining blood vessels. These results indicate that the BrdU technique is a useful, accurate, and sensitive method for assessing cellular proliferation in the rat ovary.

Animals↗

A novel rat homolog of the Saccharomyces cerevisiae ubiquitin-conjugating enzymes UBC4 and UBC5 with distinct biochemical features is induced during spermatogenesis.

The Saccharomyces cerevisiae ubiquitin-conjugating enzymes (E2s) UBC4 and UBC5 are essential for degradation of short-lived and abnormal proteins. We previously identified rat cDNAs encoding two E2s with strong sequence similarity to UBC4 and UBC5. These E2 isoforms are widely expressed in rat tissues, consistent with a fundamental cellular function for these E2s. We now report a new isoform, 8A, which despite having >91% amino acid identity with the other isoforms, shows several novel features. Expression of the 8A isoform appears restricted to the testis, is absent in early life, but is induced during puberty. Hypophysectomy reduced expression of the 8A isoform. In situ hybridization studies indicated that 8A mRNA is expressed mainly in round spermatids. Immunoblot analyses showed that 8A protein is found not only in subfractions of germ cells enriched in round spermatids but also in subfractions containing residual bodies extruded from more mature elongated spermatids, indicating that the protein possesses a longer half-life than the mRNA. Unlike all previously identified mammalian and plant homologs of S. cerevisiae UBC4, which possess a basic pI, the 8A isoform is unique in possessing an acidic pI. The small differences in sequence between the 8A isoform and other rat isoforms conferred differences in biochemical function. The 8A isoform was less effective than an isoform with a basic pI or ineffective in conjugating ubiquitin to certain fractions of testis proteins. Thus, although multiple isoforms of a specific E2 may exist to ensure performance of a critical cellular function, our data demonstrate, for the first time, that multiple genes also permit highly specialized regulation of expression of specific isoforms and that subtle differences in E2 primary structure can dictate conjugation of ubiquitin to different subsets of cellular proteins.

Amino Acid Sequence↗

Changes of catalase activity after ischemia-reperfusion in rat retina.

Catalase activity was evaluated in Long Evans rat retina after ischemia and reperfusion. Ischemia was induced by ligation of the optic nerve and vessels. Rats were sacrificed after 15 and 120 min of reperfusion, respectively. Catalase activity was assessed by Claiborne's method and was expressed as U/mg of protein. In the first group, retinas of each animal were pooled. In the second group, ischemia was induced in the right eye with the left eye serving as control. In the first group, enzyme activity was 7.39 +/- 0.26 (n = 11), 7.67 +/- 0.27 (n = 9) and 9.15 +/- 0.45 (n = 7) for the sham-operated, 15- and 120-min reperfusion groups, respectively. There was a significant difference between the control and 120-min reperfusion groups (p < 0.001). In the second group, there was a significant (p < 0.01) increase in catalase activity in the ischemic eye compared to the non-ischemic eye after 15 (n = 7) and 120 min (n = 9) of reperfusion. These findings may suggest a rapid activation of catalase activity during the ischemia-reperfusion sequence.

Animals↗

In vivo manipulation (depletion versus activation) of testicular macrophages: central and local effects.

Testicular macrophages are a relevant cell type for the regulation of Leydig cell steroidogenesis. The availability of liposome technology allows in vivo manipulation of macrophages in order to analyze their role in the regulation of the hypothalamic-pituitary-testicular axis. In this study, adult (70 days of age) and prepubertal (22 days of age) rats were injected intratesticularly with liposomes containing either dichloromethylene diphosphonate (C12MDP) to deplete testicular macrophages or muramyl tripeptide (MTP-PE) to activate them. Control rats were injected with the corresponding volumes of 0.9% NaCl. Animals were killed 10 days after treatment. Adult rats injected bilaterally or unilaterally with C12MDP liposomes showed increased serum LH and testosterone concentrations, as well as increased testosterone concentrations in the testicular interstitial fluid. In unilaterally injected rats, testosterone concentrations in the interstitial fluid were higher in the macrophage-containing testes than in the contralateral, macrophage-depleted testes. Adult rats treated bilaterally with MTP-PE liposomes showed increased numbers of testicular macrophages, whereas the number of Leydig cells was unchanged. Serum LH concentrations were decreased, but no changes were found in testosterone concentrations. Prepubertal rats treated bilaterally with C12MDP liposomes showed decreased numbers of Leydig cells. However, serum LH and testosterone concentrations were increased. Otherwise, prepubertal rats treated bilaterally with MTP-PE liposomes showed increased numbers of macrophages and Leydig cells, as well as increased serum testosterone concentrations. These data suggest that testicular macrophage-derived factors act at two different levels in the pituitary-testicular axis: first, at a central level by inhibiting LH secretion, and secondly, at a local level by stimulating Leydig cell steroidogenesis.

Acetylmuramyl-Alanyl-Isoglutamine↗

Occupational allergy due to spider mites: Tetranychus urticae (Koch) and Panonychus citri (Koch).

BACKGROUND: Allergy to both house dust and storage mites is well established, but information about other species of mites is scant. OBJECTIVE: One hundred and fifty patients directly exposed to an occupational environment were studied to assess whether spider mites (Tetranychidae) caused their allergic symptoms. We also studied a group of 50 patients from an urban environment, who were not occupationally exposed to spider mites, with a strong sensitization to Dermatophagoides pteronyssinus (RAST class 4). METHODS: Case history (including questions about work-related symptoms), skin tests, RAST and conjunctival provocation tests were performed in both groups using Tetranychus urticae and Panonychus citri extracts as allergens. Cross-reactivity between spider mites and D. Pteronyssinus was determined by RAST inhibition. RESULTS: Fifty-four of 150 rural workers were positive to Tetranychidae and in all cases there was an associated sensitization to D. pteronyssinus. All individuals belonging to the urban group were positive to spider mites. RAST inhibition demonstrated a significant cross-reactivity between Tetranychidae and D. pteronyssinus. Five of fifty-four rural workers sensitized to spider mites developed symptoms only when they handled plants or fruits infested with spider mites and they became asymptomatic when exposure ceased. CONCLUSION: In the rural population studied, 36% of workers were found to be sensitized to spider mites and 10% had symptoms associated with occupational exposure. Since specific IgE antibodies to spider mites could not be detected in the absence of the specific IgE antibodies to D. pteronyssinus, and as all the affected workers were RAST positive to D. pteronyssinus, prior sensitization to house dust mites may be a risk factor for occupational allergy to spider mites.

Adult↗

In male mouse germ cells, copper-zinc superoxide dismutase utilizes alternative promoters that produce multiple transcripts with different translation potential.

Copper-zinc superoxide dismutase (SOD-1) is an enzyme that is widely expressed in eukaryotic cells and performs a vital role in protecting cells against free radical damage. In mouse testis, three different sizes of SOD-1 mRNAs of about 0.73, 0.80, and 0.93 kilobases (kb) are detected. The 0.73-kb mRNA is found in early stages of male germ cells and in all somatic tissues. The mRNAs of 0.80 and 0.93 kb are exclusively detected in post-meiotic germ cells. RNase H digestions and Northern blot analyses reveal that the three SOD-1 mRNAs are derived from two transcripts, a ubiquitously expressed transcript and a post-meiotic transcript, which differ by 114-120 nucleotides. RNase protection assays demonstrate that the additional nucleotides present in the post-meiotic mRNA are solely in the 5'-untranslated region. Using a probe derived from the 5'-untranslated region of the 0.93-kb SOD-1 mRNA, we have established that it originates from an alternative upstream promoter contiguous with the somatic SOD-1 promoter. Polysomal gradient analysis of the three mouse testis SOD-1 mRNAs reveals that the 0.93-kb SOD-1 mRNA is primarily non-polysomal, while the 0.80- and 0.73-kb SOD-1 mRNAs are mostly polysome associated. A faster migrating form of the 0.93-kb SOD-1 mRNA is present on polysomes as a result of partial deadenylation. In a cell-free translation system, the 0.73-kb SOD-1 mRNA translates about 2-fold more efficiently than the 0.93-kb SOD-1 mRNA. These data demonstrate that male germ cells transcribe two size classes of SOD-1 mRNAs with different translation potential by utilizing two different promoters, post-meiotic SOD-1 mRNAs undergo adenylation changes, and one of the post-meiotic SOD-1 mRNAs is transcribed during mid-spermiogenesis and translated days later in a partially deadenylated form.

Adenosine Monophosphate↗

Response to Leydig cell apoptosis in the absence of testicular macrophages.

Removal of apoptotic cells from the tissues appears to be a major function of resident tissue macrophages. In order to investigate further the role of testicular macrophages after massive Leydig cell death, adult rats were injected intra-testicularly with liposome-entrapped dichloromethylene diphosphonate (Cl2MDP-lp, right testis) to deplete testicular macrophages, and with NaCl (left testis) as control. Ten days later, the animals were injected intraperitoneally with ethylene dimethane sulphonate (EDS) to induce Leydig cell apoptosis. In macrophage-containing testes there was a 2-fold increase in the number of macrophages on days 1-3 after EDS treatment and Leydig cells were completely eliminated from the interstitium by the second day after treatment. The main differences in the response to Leydig cell death in macrophage-depleted testes were: (1) an early rise in the concentration of small mononuclear, lymphocyte-like cells, (2) a greater influx of circulating monocytes, (3) the existence of variable inflammatory infiltrates on days 3-4, and (4) the disappearance of infiltrating monocytes by day 10. These results suggest that resident macrophages prevent the inflammatory reaction elicited by massive Leydig cell death.

Animals↗

Immunological study of Melkersson-Rosenthal syndrome. Lack of response to food additive challenge.

A study was made of six patients with Melkersson-Rosenthal syndrome (MRS) to establish the aetiological role of foodstuffs and/or additives and the possible associated immunological alterations. In all cases Melkersson-Rosenthal syndrome (MRS) was diagnosed both clinically and histologically, excluding other causes of orofacial granulomatosis (OFG). A detailed study of possible triggering factors was performed in all patients. Blood analysis, x-rays and cultures, were always within normal limits, with the exception of the finding of circulating immune complexes (CICs) in three patients with facial palsy associated, and C-reactive protein positivity in two patients who presented persistent labial oedema. All patients were subjected to skin-prick tests with common inhalant allergens and with foods when sensitization to foods were suspected, and patch tests with European Standard Series and pastry components, organic dyes, perfumes and fragrances series. The results were negative in all cases. When asymptomatic, the patients were subjected to a double-blind oral challenge, under placebo control, with additives (monosodium glutamate, tartrazine, sulfites, erythrosine, paraoxybenzoate, sodium benzoate, lactose, aspirin, and annate), which was again negative. In no case did the patients refer the appearance of outbreaks with exposure to foods or contactants, and the course of the disease was unaffected by exclusion diets and the elimination of contactants. To conclude, we observed no sensitization to foods, additives or contactants in our patients. Likewise, there were no antecedents of atopy or hereditary predisposition related to the aetiopathogeny of MRS. The significance of the CIC encountered only in patients with facial paralysis remains to be established, due to the limited number of patients studied.

Adult↗

Role of testicular macrophages in the response of Leydig cells to gonadotrophins in young hypophysectomized rats.

The Leydig cells of young hypophysectomized rats are highly sensitive to the stimulatory effects of exogenous pituitary hormones. The aim of this study was to analyse the role of testicular macrophages in the response of Leydig cells to different hormones. Male rats were hypophysectomized at 28 days of age and 10 days later they were injected intratesticularly with dichloromethylene diphosphonate-containing liposomes (right testis) to deplete testicular macrophages, and with 0.9% NaCl (left testis). One week later, the animals were treated daily with 1 IU rat GH (rGH)/rat, 5 IU recombinant human FSH (recFSH)/rat, 10 IU human chorionic gonadotrophin (hCG)/rat, or vehicle for 7 days. The animals were killed on the day after the last injection. The animals treated with rGH showed increased body weight and increased number and size of testicular macrophages in the left testes, but no significant effects on Leydig cells were found. Treatment with recFSH induced a significant increase in testicular weight and tubular diameter in both testes. In the left testes, the number and size of macrophages were increased; the number of Leydig cells was not changed, although they showed a significantly increased cross-sectional area. This effect was abolished in the right (macrophage-depleted) testes. However, the effect of recFSH on the growth of the seminiferous tubules was not modified by the absence of macrophages. Rats treated with hCG showed increased testicular weight and serum testosterone levels, as well as an increased weight of the ventral prostate. In the left testes, the number and size of both macrophages and Leydig cells were increased. Otherwise, the number of Leydig cells was unchanged in the absence of macrophages, whereas the increase in the size of Leydig cells was partially abolished. These data indicate that testicular macrophages are needed for the response of Leydig cells to gonadotrophin treatment.

Animals↗

Megalocornea-mental retardation syndrome: an additional case.

In 1975, Neuhaüser (Z Kinderheilk 120:1-8) reported on a recessively inherited entity comprising mental retardation, megalocornea, and seizures. The megalocornea-mental retardation (MMR) syndrome (MIM 249310) is a rare entity. There have been 19 previously published cases and the clinical differences observed between reported patients have raised questions regarding the nosology of the syndrome and the issue of heterogeneity versus variability. We report on a new case: a 2 6/12-year-old boy, first child of nonconsanguineous healthy parents with megalocornea (corneal diameter > or = 13 mm), delayed psychomotor development and hypotonia, plus minor facial anomalies.

Cornea↗