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Biomedical subjects

G Herman

Publications and source records attributed to G Herman.

At least 19 recordsLinked to original sources

Effects of short- and long-term wheel deprivation on running.

The effects of wheel deprivation on running were explored. Eight male rats, well habituated to wheels, were each deprived of wheels for periods of 0, 1, 3, and 10 h during the night (Experiment 1) and 0, 1, 3, and 10 days (Experiment 2). In Experiment 1, as wheel deprivation lengthened, wheel running in the first 24 h of access increased. After 10 days of wheel deprivation subsequent daily running decreased (by 70%), and feeding was suppressed for several days. This temporary decline may be due to detraining and the rats physical inability to run more. Experiment 3 with 12 rats found that the running increase after 3-h wheel deprivation was proportional to the amount of running normally occurring during the deprivation period. Over the short-term, running appears to be regulated like other appetitive behaviors.

Animals↗

Complete removal of nonpalpable breast malignancies with a stereotactic percutaneous vacuum-assisted biopsy instrument.

BACKGROUND: Several devices have been developed for sampling nonpalpable mammographic breast lesions. Complete removal of malignancies with a stereotactic percutaneous directional vacuum-assisted biopsy instrument has been reported. STUDY DESIGN: We reviewed our experience with the percutaneous vacuum-assisted biopsy instrument to identify instances of complete excision of cancers: no residual carcinoma found at surgical excision for malignancies diagnosed by the percutaneous vacuum-assisted biopsy instrument. The radiologic and pathologic characteristics of malignancies completely removed by the percutaneous vacuum-assisted biopsy instrument were compared with those of malignancies with residual carcinoma found at surgical excision. RESULTS: Fifty-two malignancies were diagnosed by the percutaneous vacuum-assisted biopsy instrument: 16 infiltrating ductal carcinomas, 5 infiltrating lobular carcinomas, and 31 ductal carcinomas in situ. No residual carcinoma was found at surgical excision in 9 (17%) of the 52 malignancies. Patients with complete removal of the malignant lesion were younger than patients with incomplete removal (52 versus 58 years; p = 0.069). Completely removed malignancies were smaller on mammography (4 versus 17 mm; p = 0.213), and more specimens were removed (19 versus 15; p = 0.074). All nine completely removed malignancies presented with calcifications without a mass (p = 0.112), and all nine were ductal carcinoma in situ (p = 0.019). CONCLUSIONS: Complete removal of nonpalpable breast malignancies is possible with the stereotactic percutaneous directional vacuum-assisted biopsy device. Complete removal is more likely with removal of a large number of specimens from small areas of mammographic calcifications due to ductal carcinoma in situ.

Biopsy↗

[Heparin-induced thrombocytopenia with unfractionated heparin. A prospective study of inpatient treatment of internal medicine patients].

AIM: To investigate the influence of unfractionated heparin on heparin-induced thrombocytopenia (HIT) type II. PATIENTS AND METHOD: In 162 patients with internal diseases treated therapeutically of prophylactically with unfractionated heparin (heparin sodium, heparin calcium), we carried out a prospective study to determine the incidence of HIT type I and II. 55.6% of the patients were female (n = 90) with an average age of 76.5 years (range: 25 to 96 years) and 44.4% male (n = 72) with an average age of 67.5 years (range: 17 to 93 years). A platelet count was taken regularly before the start of heparin treatment, on the first day of treatment and then every second day from day 5 to 20. Whenever HIT II was suspected, an HIPA test was performed. RESULT: Type I HIT occurred in 10%, type II in 3% of the cases. Two of the 5 patients with type II developed severe thrombotic complications. CONCLUSION: In view of the high incidence of HIT, regular platelet counts should always be carried out in patients receiving heparin treatment.

Adult↗

The mouse X-linked developmental mutant, tattered, lies between DXMit55 and Xkh and is associated with hyperkeratinization.

The X-linked mouse mutant phenotype, tattered (Td), is associated with prenatal lethality of males and has been mapped previously to the proximal region of the mouse X chromosome. We report here a refined position for Td and demonstrate that it lies in the approximately 0.9-cM interval between DXMit55 and Xkh. This enables us to predict that the human homologue lies either between CLCN5 and the evolutionary breakpoint that lies between GATA1 and PFC or distal to XK and proximal to the evolutionary breakpoint that lies between XK and DMD. Histological analysis of dorsal skin taken from 5-day-old heterozygous animals revealed that the mutation was associated with patches of hyperkeratinzation in the epidermis and in the hair follicles, accompanied by a mild inflammatory infiltrate in the underlying dermis.

Animals↗

Clustering of mutations in the biotin-binding region of holocarboxylase synthetase in biotin-responsive multiple carboxylase deficiency.

Holocarboxylase synthetase (HCS) catalyses the biotinylation of the four biotin-dependent carboxylases found in humans. A deficiency in HCS results in biotin-responsive multiple carboxylase deficiency (MCD). We have identified six different point mutations in the HCS gene in nine patients with MCD. Two of the mutations are frequent among the MCD patients analyzed. Four of the mutations cluster in the putative biotin-binding domain as deduced from the corresponding Escherichia coli enzyme and consistent with an explanation for biotin-responsiveness based on altered affinity for biotin. The two others may define an additional domain involved in biotin-binding or biotin-mediated stabilization of the protein.

Amino Acid Sequence↗

X-linked myotubular myopathy: clinical observations in ten additional cases.

X-linked myotubular myopathy (XLMTM) is a recessively inherited disorder, lethal to males in the first months of life. Since the first report in 1969, at least 90 cases have been described in the literature. Diagnosis is confirmed by muscle biopsy. Linkage studies have localized the disorder to the Xq28 region, close to the loci for X-linked hydrocephalus and MASA syndrome. We report on 10 additional cases of XLMTM from six different families. In addition to classic clinical features of XLMTM, our patients showed interesting associated findings which included birth length > 90th centile and large head circumference with or without hydrocephalus in 70%, narrow, elongated face in 80%, and slender, long digits in 60% of cases. There was concordance in the occurrence and severity of hydrocephalus in most sib pairs. These features in a "floppy" male infant serve as clues for early clinical diagnosis of XLMTM, which can then be confirmed by muscle biopsy. Development of polyhydramnios was observed in the third trimester of an at-risk dizygotic twin gestation monitored by serial sonography with confirmation of XLMTM at birth.

Birth Weight↗

A comparative transcriptional map of a region of 250 kb on the human and mouse X chromosome between the G6PD and the FLN1 genes.

The transcriptional organization of the region of the mouse X chromosome between the G6pd and the Fln1 genes was studied in detail, and it was compared with the syntenic region of the human chromosome. A cosmid contig of 250 kb was constructed by screening mouse cosmid libraries with probes for human genes and with whole cosmids. Overlapping cosmids were aligned by comparing EcoRI and rare-cutter restriction enzyme digestions. The gene order and the orientation of transcription were determined by hybridization with fragments from the 5' and 3' moieties of each cDNA. Our work demonstrates that all of the new genes identified in human are present in the mouse. The size of the region, 250 kb, is also very similar, as are gene order and gene organization: the transcriptional organization in "domains" described in human is found to be identical in the mouse. The major difference detected is the much lower content in rare-cutter restriction sites, which is related to the lower G+C and CpG content of mouse DNA. The very high conservation that we have described suggests that a potent selective pressure has contributed to such conservation of gene organization.

Animals↗

Magnetic resonance imaging in schizophrenia: relationship with clinical measures.

Relationships were examined between clinical features of schizophrenia and cerebrospinal fluid (CSF) volume in brain obtained by magnetic resonance imaging (MRI) in a sample of 59 patients. The volumes of the cerebral hemispheres and CSF were measured with a computer program designed to separate reliably neural tissue from CSF. The CSF to cranial volume ratios were related to history, symptom profile and outcome functioning. Earlier age of onset was associated with higher sulcal CSF ratio, r = -0.40. The anatomic measures were unrelated to symptom severity. However, patient subtypes differed in the laterality of measures. Higher left hemispheric ratios were seen in patients with severe negative symptoms, and left predominance of ventricular relative to sulcal ratios was associated with the presence of hallucinations and delusions. The results suggest that while higher CSF is related to earlier age of onset, the clinical symptoms are more related to its lateralization. This is consistent with the hypothesis that schizophrenia is a lateralized brain disease.

Adolescent↗

X linked myotubular myopathy (MTM1) maps between DXS304 and DXS305, closely linked to the DXS455 VNTR and a new, highly informative microsatellite marker (DXS1684).

The locus for X linked recessive myotubular myopathy (MTM1) has previously been mapped to Xq28 by linkage analysis. We report two new families that show recombination between MTM1 and either DXS304 or DXS52. These families and a third previously described recombinant family were analysed with two highly polymorphic markers in the DXS304-DXS52 interval, the DXS455 VNTR and a newly characterised microsatellite, DXS1684 (82% heterozygosity). These markers did not recombine with MTM1 in the three families. Together with the recent mapping of an interstitial X chromosome deletion in a female patient with moderate signs of myotubular myopathy, our data suggest the following order of loci in Xq28: cen-DXS304-(DXS455, MTM1)-DXS1684-DXS305-DXS52-tel. This considerably refined localisation of the MTM1 locus should facilitate positional cloning of the gene. The availability of highly polymorphic and very closely linked markers will markedly improve carrier and prenatal diagnosis of MTM1.

Base Sequence↗

[Benign testicular and paratesticular tumors].

Five cases of benign testicular and paratesticular tumors are reported which have been treated by conservative methods. A literature review is presented about the most frequent benign testicular and paratesticular neoplasms. The preoperative diagnosis and the choice of treatment are discussed.

Adenomatoid Tumor↗

Biogenesis of synaptic vesicles.

The basic endosomal recycling pathway can be modified to generate transcytotic vesicles, storage vesicles and synaptic vesicles. Sorting into synaptic vesicles requires specialized sorting information not present in the transcytotic and storage vesicle proteins. Using mutagenesis we have distinguished the signals for rapid endocytosis and SV targeting in synaptobrevin. Finally, we have evidence that synaptic vesicles can be generated from an endosomal compartment in vitro.

Animals↗

Gender differences in age effect on brain atrophy measured by magnetic resonance imaging.

A prospective sample of 69 healthy adults, age range 18-80 years, was studied with magnetic resonance imaging scans (T2 weighted, 5 mm thick) of the entire cranium. Volumes were obtained by a segmentation algorithm that uses proton density and T2 pixel values to correct field inhomogeneities ("shading"). Average (+/- SD) brain volume, excluding cerebellum, was 1090.91 ml (+/- 114.30; range, 822.19-1363.66), and cerebrospinal fluid (CSF) volume was 127.91 ml (+/- 57.62; range, 34.00-297.02). Brain volume was higher (by 5 ml) in the right hemisphere (P less than 0.0001). Men (n = 34) had 91 ml higher brain and 20 ml higher CSF volume than women (n = 35). Age was negatively correlated with brain volume [r(67) = -0.32, P less than 0.01] and positively correlated with CSF volume (r = 0.74, P less than 0.0001). The slope of the regression line with age for CSF was steeper for men than women (P = 0.03). This difference in slopes was significant for sulcal (P less than 0.0001), but not ventricular, CSF. The greatest amount of atrophy in elderly men was in the left hemisphere, whereas in women age effects were symmetric. The findings may point to neuroanatomic substrates of hemispheric specialization and gender differences in age-related changes in brain function. They suggest that women are less vulnerable to age-related changes in mental abilities, whereas men are particularly susceptible to aging effects on left hemispheric functions.

Adult↗

Magnetic resonance imaging in schizophrenia. I. Volumetric analysis of brain and cerebrospinal fluid.

The study reports magnetic resonance imaging data for 42 patients with schizophrenia and 43 normal controls. Volumetric measures were obtained with a validated computerized algorithm for segmentation of cranial volume into brain tissue and central and peripheral cerebrospinal fluid (CSF), with high inter-operator reliability. Patients did not differ significantly in whole-brain volume, but had higher whole-brain CSF volume and higher ratios of ventricular and sulcal CSF to cranial volume. Covarying age and education did not affect the differences. However, there was considerable overlap both in CSF volumes and in volume-cranium ratios, and most patients were within the normal range. This suggests that anatomic changes reflected in CSF can provide a limited substrate for schizophrenia and may apply only to subpopulations. Although there was no gender x diagnosis interaction, the results for sulcal CSF were significant only for men, whereas for women, the ventricular ratios were marginally higher in patients.

Adolescent↗

Sexually transmitted papilloma viral infection in the male. VII. Is cancer of penis sexually transmitted?

Four cases are reported of squamous cell carcinoma of the genital tract in males. The close association of HPV 16/18 with in situ squamous carcinoma affecting the penis is demonstrated. The first documented case of a primary penile squamous cell carcinoma with metastatic deposits yielding positive HPV 16/18 isolates as shown by in situ DNA hybridization again demonstrates a close association of this virus to malignancy in humans. The clinical implications of these findings strongly suggest that squamous cell carcinoma of the penis is a sexually transmitted disease. A thorough examination of both sexual partners is necessary when Bowenoid papulosis or penile carcinoma is present, since the female partner is at high risk for cervical neoplasia.

Adult↗

Alpha-adrenoceptor subtypes in dog saphenous vein that mediate contraction and inositol phosphate production.

1. Studies have been made of the contractile responses to the alpha-adrenoceptor agonists phenylephrine (Phen), cirazoline (Cir) or BHT-920 (BHT) in dog isolated saphenous vein (DSV) rings, using the antagonists yohimbine (Yoh), idazoxan (Idaz), prazosin (Praz), WB-4101 (WB) and nitrendipine or zero Ca2+ medium. 2. Contractile concentration-response curves to Phen or BHT were displaced to the right of controls by Yoh (0.01-3 microM) with mean apparent antagonist dissociation constants (pKBs) of 7.9 and 8.6 respectively. Yoh did not show simple competitive antagonism against either agonist, since the Schild plot slopes were significantly less than unity. Neither the antagonist affinity of Yoh against Phen, nor the slope of the Schild plot was modified in the presence of catecholamine uptake inhibitors, nor in the presence of alpha,beta-methylene ATP, which desensitizes P2-purinoceptors, suggesting that Phen does not release ATP, or noradrenaline to cause contraction in DSV. In the presence of Praz (0.3 microM) the antagonist potency of Yoh (mean pKB 7.4) against Phen was slightly decreased. Yoh had low potency against responses induced by Cir (pKB 6.3). 3. WB (0.001-1.0 microM) was a very potent antagonist of Phen-induced contractions, however, the biphasic Schild plot against Phen could be separated into two affinity sites, a high pKB of 9.3 (equivalent to that obtained using Cir as the agonist; pKB 9.6) and a lower affinity (pKB 8.6). WB showed an even lower antagonist affinity (pKB 7.4) against BHT-induced contractions, suggesting that these effects might be mediated by alpha 2A-adrenoceptors. Praz also appeared to identify two sites using Phen-induced contractions, a high pKB of 8.4 was equivalent to that obtained with Cir (pKB 8.2) and a lower affinity site (pKB 7.7; pA2 7.6; slope 1.1) at which Praz showed competitive antagonism. Higher concentrations of Praz were required to antagonize contractions to BHT (pKB 5.9). 4. Idaz was a weak partial agonist in this tissue with threshold contractile effects at concentrations in excess of 3 microM. Idaz (0.1-1 microM) competitively antagonized the contractile effects of BHT, but showed low antagonist affinity against Phen at these concentrations. 5. Contractions to Phen were slightly antagonized by nitrendipine (1 microM), with a 36% decrease in Emax. Contractions to Phen and Cir were also markedly attenuated in zero calcium medium (with EGTA), but maximum responses of 4.2 +/- 0.1 and 3.6 +/- 0.1 g, could be obtained with these agonists respectively. Only part of the contractile effects to Phen or Cir are therefore due to calcium influx (but L-type channels are not totally implicated), while the contractile effects of BHT were abolished in zero Ca2 + medium. Yoh (0.1 microm) retained its antagonist effects on Phen-induced responses in zero Ca2 + medium. 6. The formation of inositol phosphates (InsPs) in the presence of lithium (10mM) was measured after incubation of intact DSV strips with myo-2-[3H]-inositol. Phen (1-1OO0 microM) and Cir (O.O1-1O microm) induced concentration-dependent increases in total labelled InsP1_3, but BHT showed minimal InsP stimulation. InsPs were recovered after Phen (100,M) stimulation (10min) as labelled InsP1 (71%), InsP2 (25%) and InsP3 (4%). Phen (100 microM)-stimulated InsP1-3 formation was significantly antagonized by Praz (10nM), but was not fully inhibited even after Praz 1 microM. Yoh and Praz (0.1 and 1.0 microM) were equipotent inhibitors of this response, while Idaz (0.3 microM) showed no effects. 7. The receptors in DSV which are stimulated by Phen to cause contraction show characteristics of the alpha lA-adrenoceptor (high pM antagonist affinity for WB-4101 and extracellular calcium sensitivity) and the alpha lB-adrenoceptor (contraction in calcium-free medium, increase in InsP and low nm antagonist affinity of WB). The paradoxical results obtained with Yoh (potent antagonist effects on Phen-stimulated PI and pKB 7.9 on contraction) and Praz (low affinity competitive antagonist of Phen-induced contraction, pKB 7.7 and failure to inhibit completely the PI response at 1 microM), cannot fully exclude an alpha 2B-subtype characterization of these responses. These pharmacological differences suggest that the adrenoceptor involved in the contractile and in particular the second messenger effects of Phen in DSV is not typically an alpha lB-adrenoceptor.

Adrenergic alpha-Agonists↗