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Biomedical subjects

C Herman

Publications and source records attributed to C Herman.

At least 37 records · Page 2Linked to original sources
PubMed1995

Degradation of sigma 32, the heat shock regulator in Escherichia coli, is governed by HflB.

The heat shock response in Escherichia coli is governed by the concentration of the highly unstable sigma factor sigma 32. The essential protein HflB (FtsH), known to control proteolysis of the phage lambda cII protein, also governs sigma 32 degradation: an HflB-depleted strain accumulated sigma 32 and induced the heat shock response, and the half-life of sigma 32 increased by a factor up to 12 in mutants with reduced HflB function and decreased by a factor of 1.8 in a strain overexpressing HflB. The hflB gene is in the ftsJ-hflB operon, one promoter of which is positively regulated by heat shock and sigma 32. The lambda cIII protein, which stabilizes sigma 32 and lambda cII, appears to inhibit the HflB-governed protease. The E. coli HflB protein controls the stability of two master regulators, lambda cII and sigma 32, responsible for the lysis-lysogeny decision of phage lambda and the heat shock response of the host.

ATP-Dependent Proteases↗
PubMed1995

Regulation of the heat-shock response depends on divalent metal ions in an hflB mutant of Escherichia coli.

HflB, also called FtsH, is an essential Escherichia coli protein involved in the proteolysis of the heat-shock regulator sigma 32 and of the phage regulator lambda cll. The hflB1(Ts) allele (formerly called ftsH1) conferring temperature-sensitive growth at 42 degrees C is suppressed by loss of the ferric-uptake repressor Fur and by anaerobic growth. We show here that suppression requires TonB-dependent Fe(III) transport in the hflB1(Ts) fur mutant during aerobic growth at 42 degrees C and Feo-dependent Fe(II) transport during anaerobic growth at 42 degrees C. Temperature-resistant growth of hflB1(Ts) strains is also observed at 42 degrees C in the presence of a high concentration of Fe(II), Ni(II), Mn(II) or Co(II) salts, but not in the presence of Zn(II), Cd(II), Cu(II), Mg(II), Ca(II) or Cr(III) salts. However, neither Ni(II) nor a fur mutation permits growth in the complete absence of HflB. The heat-shock response, evaluated by an htpG::lacZ fusion, is overinduced in hflB1(Ts) strains at 42 degrees C because of stabilization of sigma 32. Growth in the presence of Ni(II) or in the absence of the Fur repressor abolishes this overinduction in the hflB1(Ts) strain, and, in the hflB1(Ts) fur mutant, sigma 32 is no longer stabilized at 42 degrees C. These results reinforce the recent observation that HflB is a metalloprotease active against sigma 32 in vitro and suggest that it can associate functionally in vivo with Fe(II), Ni(II), Mn(II) and Co(II) ions.

ATP-Dependent Proteases↗
PubMed1995

Leptomeningeal dissemination of malignant glioma simulating cerebral vasculitis. Case report with angiographic and pathological studies.

BACKGROUND: The complex clinical and radiological picture of leptomeningeal spread of tumor is well recognized as a problem of systemic cancer but is less frequent in primary cerebral glioma, particularly as a presenting picture. While brain ischemia and infarction may occur in patients with subarachnoid tumor, the mechanism for these complications remains unclear. Angiographic and pathological demonstrations of direct vascular involvement by disseminated glioma are particularly sparse. We report a patient presenting with multiple infarctlike lesions with postmortem evidence of direct vascular involvement by glioma. CASE DESCRIPTION: A 54-year-old woman presenting with seizures, headache, and changes in mental status was found to have vascular narrowing in cerebral blood vessels and ischemic lesions on neuroimaging studies of the brain, interpreted as cerebral vasculitis. A brain biopsy showed leptomeningeal glioma. Postmortem examination demonstrated a glioblastoma arising around the right sylvian fissure with extensive subarachnoid dissemination of tumor. The leptomeningeal tumor caused vascular narrowing by encasement, direct vascular wall invasion, and thrombosis and was associated with underlying infarctlike foci of parenchymal necrosis. CONCLUSIONS: This case demonstrates an unusual presentation of glioblastoma clinically and radiographically mimicking cerebral vasculitis, and it illustrates a variety of mechanisms for tumor-produced vascular compromise.

Cerebral Angiography↗
PubMed1994

Pseudoepitheliomatous hyperplasia in chronic cutaneous wounds. A flow cytometric study.

Cutaneous squamous cell carcinomas (SCC) arising in a setting of chronic regeneration and repair tend to be highly aggressive lesions prognostically distinct from SCC arising in solar-damaged skin. Full thickness thermal injury and chronic nonhealing ulcers are predisposing conditions in up to 2% of SCC. A significant association has been suggested to exist between pseudoepitheliomatous hyperplasia (PH) and SCC. Three-hundred-eighty-six surgical cases of skin excised secondary to severe burns (n = 254) or chronic ulcers (n = 132) were reviewed, yielding 43 (11%) with PH. Flow cytometric DNA analysis was performed on paraffin-embedded sections. Thirty cases without PH were studied in addition to the 43 cases with PH. The majority (39/43) of the PH cases showed a single diploid population with a mean S-phase of 13.7%. Four cases (9.3%) showed an aneuploid peak. All cases without PH were diploid with a mean S-phase of 9.0%. In this study, PH was present in 11% of cases reviewed, and showed a 50% mean higher S-phase than comparable cases without PH. Aneuploidy was present in 9.3% of the PH cases studied. SCC may arise from a subgroup of PH in a background of rapidly proliferating keratinocytes.

Carcinoma↗
PubMed1993

Cell growth and lambda phage development controlled by the same essential Escherichia coli gene, ftsH/hflB.

The lambda phage choice between lysis and lysogeny is influenced by certain host functions in Escherichia coli. We found that the frequency of lambda lysogenization is markedly increased in the ftsH1 temperature-sensitive mutant. The ftsH gene, previously shown to code for an essential inner membrane protein with putative ATPase activity, is identical to hflB, a gene involved in the stability of the phage cII activator protein. The lysogenic decision controlled by FtsH/HflB is independent of that controlled by the protease HflA. Overproduction of FtsH/HflB suppresses the high frequency of lysogenization in an hflA null mutant. The FtsH/HflB protein, which stimulates cII degradation, may be a component of an HflA-independent proteolytic pathway, or it may act as a chaperone, maintaining cII in a conformation subject to proteolysis via such a pathway. Suppressor mutations of ftsH1 temperature-sensitive lethality, located in the fur gene (coding for the ferric uptake regulator), did not restore FtsH/HflB activity with respect to lambda lysogenization.

ATP-Dependent Proteases↗
PubMed1992

Prognostic significance of DNA ploidy in male breast carcinoma. A retrospective analysis of 32 cases.

BACKGROUND: DNA aneuploidy has been prognostically significant in female breast carcinoma of low stage, but its value in male breast carcinoma remains undetermined. METHODS: Flow cytometric DNA analyses were performed retrospectively on paraffin-embedded tissue from 32 men with breast carcinoma (mean follow-up time, 5.97 years [standard deviation +/- 4.63]; range, 1 to 18 years). RESULTS: Multivariate discriminant function analysis showed only tumor size less than 2 cm to be independently predictive of better disease-free survival (P less than 0.05). DNA ploidy (aneuploid, 25 patients; diploid, 7 patients) and lymph node status (positive, 22 patients; negative, 10 patients) were not predictive of survival, regardless of tumor size. CONCLUSIONS: The authors concluded that DNA ploidy may not significantly predict survival in male breast carcinoma.

Adult↗
PubMed1992

Flow and image cytometric DNA analysis in Ewing's sarcoma.

Ewing's sarcoma is the second most common bone tumor in childhood, with an overall 5-yr survival of 40%. It is one of the poorly differentiated small spherical cell tumors frequently requiring distinction from rhabdomyosarcoma, neuroblastoma, osteosarcoma, primitive neuroectodermal tumor, and lymphoma. The majority of rhabdomyosarcomas, neuroblastomas, and osteosarcomas are aneuploid, whereas Ewing's sarcomas are usually diploid. To determine whether there is any correlation between DNA content, morphology, site, and survival in Ewing's sarcoma and extraosseous Ewing's sarcoma, 21 tumor samples were studied retrospectively (3 extraosseous Ewing's and 18 Ewing's sarcomas). The DNA analysis was performed on disaggregated paraffin-embedded tissue nuclei by flow (FCM) and image (IC) cytometry and correlated with the histology and clinical history. The DNA ploidy by FCM on 17 of 18 Ewing's sarcoma samples was 12 diploid, 1 aneuploid, and 4 tetraploid. By IC, the DNA ploidy on 16 samples was 13 diploid, 1 aneuploid, and 2 tetraploid. Three samples were nonevaluable (1 by FCM and 2 by IC). The agreement between FCM and IC was 12 of 16 (75%). The extraosseous Ewing's sarcoma tumors were 2 diploid and 1 aneuploid by IC. In this study there was no correlation between the DNA ploidy and either the histology, site, or survival.

Adolescent↗
PubMed1991

Corneal ulcer and adverse reaction rates in premarket contact lens studies.

We analyzed clinical data on 22,739 contact lens wearers who were studied and whose lenses were approved under 48 manufacturer-sponsored studies for the Food and Drug Administration between 1980 and 1988. The incidence of corneal ulcers was low in the cosmetic (nontherapeutic) daily-wear soft and rigid gas-permeable lens wearers (1/1,923 and 1/1,471 patient-years, respectively). Corneal ulcers and severe adverse reactions occurred two to four times more frequently in extended-wear cosmetic soft and rigid gas-permeable lens wearers than in cosmetic daily-wear lens wearers. Aphakic extended-wear soft lens users were nine times more likely to develop a corneal ulcer when compared to the soft daily-wear cosmetic group. Corneal abrasions and keratitis accounted for 81 of 159 severe adverse reactions, whereas corneal ulcers accounted for 28 of 159 adverse reactions. The data indicate that overnight extended wear of contact lenses is associated with a greater risk of serious, sight-threatening complications than daily wear.

Aphakia↗
PubMed1990

Flow and image cytometric DNA analysis in rhabdomyosarcoma.

Rhabdomyosarcoma is the most common malignant soft-tissue tumor in childhood, with an overall 3-year disease-free survival of 73%. DNA content is known to correlate with prognosis and therapy response in many cancers. To determine the role of DNA content in rhabdomyosarcoma, 23 tumor samples were studied retrospectively: 18 primary tumors and 5 post-chemotherapy recurrences or specimens obtained at second-look surgeries. The DNA analysis was performed on disaggregated paraffin-embedded tissue nuclei by flow and image cytometry and correlated with the histology and clinical history. Of the primary tumors 4 were diploid, 4 polyploid, and 10 aneuploid (9 with a single aneuploid G0G1 peak and 1 multiploid) by flow cytometry. The concordance rate between flow and image cytometry was 19 of 23 (83%); one case did not have flow cytometry available. Most embryonal rhabdomyosarcomas were aneuploid (10 of 12; 83%), and they had a high incidence of recurrence in Stages III and IV (4 of 12; 33%). Although aneuploidy in pediatric cancers may predict a therapeutic response and good prognosis, this was not supported by our findings in rhabdomyosarcoma. The tumor DNA content correlated with the clinical stage but not with the patient's clinical course or tumor histopathological type. DNA content did not appear to be as important a prognostic tool as tumor stage.

Adolescent↗
PubMed1990

St. Anthony's fire: successful reversal of ergotamine-induced peripheral vasospasm by hydrostatic dilatation.

A 60-year-old trauma victim developed severe ischemia of all four extremities following administration of heparin-dihydroergotamine as prophylaxis against deep venous thrombosis. Despite cessation of heparin-dihydroergotamine and infusion of intraarterial papaverine into the right femoral artery, both lower extremities progressed to frank gangrene and amputation (above-knee on the left and below-knee on the right). However, both ischemic upper extremities were salvaged following intraoperative hydrostatic dilatation with balloon catheters. Ergotism is an avoidable and potentially treatable cause of peripheral gangrene in the critically-ill patient.

Catheterization↗
PubMed1990

Incidental white matter hyperintensities on magnetic resonance imaging in HIV-1 infection. Multicenter AIDS Cohort Study.

Magnetic resonance (MR) scans were performed as part of a prospective neuropsychological study within the Multicenter AIDS Cohort Study. Fifty HIV-1-seronegative men, 85 HIV-1-seropositive men without constitutional symptoms, and 14 with symptomatic HIV disease underwent MR imaging using a uniform protocol. Scans were rated by neuroradiologists blinded to all clinical details except age. The majority of MR scans were normal in all of the clinical groups and no covert mass lesions or diffuse white matter abnormalities were identified. Focal hyperintensities in the white matter were observed in 24% of the HIV-1 seronegatives, 26% of HIV-1 asymptomatic seropositives (CDC II/III), and 17% of those with ARC/AIDS. No significant associations were noted between the white matter hyperintensities and HIV-1 serostatus, neurological abnormalities, CD4 count, alcohol or drug use, hypertension, or smoking. In one individual classified with early HIV-1 dementia, MR demonstrated several hyperintensities in the deep parietal white matter, but at autopsy no microscopic abnormalities corresponding to the MR findings were identified. Our studies imply that focal white matter hyperintensities identified on MR are not specific for HIV-1 infection and are probably incidental and of no clinical significance.

AIDS-Related Complex↗
PubMed1988

The public cost of motorcycle trauma.

Despite the effectiveness of motorcycle helmet legislation, many states have repealed these laws during the last decade. Aspects often neglected by policymakers are who pays for the care of these victims and how much of this cost is subsidized by public funds. To determine the extent of this subsidy, we studied the cost of care of 105 motorcyclists hospitalized at a major trauma center during a 12-month period. Total direct costs for these 105 patients, followed up for a mean of 20 months, were more than $2.7 million, with an average of $25,764 per patient. Only 60% of the direct costs were accounted for by the initial hospital care; 23% of costs were for rehabilitation care or readmission for treatment of acute problems. The majority (63.4%) of care was paid for by public funds, with Medicaid accounting for more than half of all charges.

Adult↗
PubMed1988

The medical and social impact of nonaccidental injury.

To determine the medical and economic impact of nonaccidental trauma at a regional trauma and emergency care facility, a prospective patient database was used to follow up all victims of intentional injury admitted during one year. Specific patient data were combined with financial data to determine the medical outcome, expenditure, and hospital reimbursement. We found that 17% of the 2451 trauma patients admitted to our facility were victims of nonaccidental injury. The majority of these patients were severely injured, with an average hospital stay of six days. Hospital charges averaged $13,000 per patient. Three fourths of these individuals required governmental funding for medical care. Six months after completion of the review, only two thirds of all expenditures had been reimbursed. These patients represent a high medical services use group and consume a disproportionately high percentage of medical resources.

Alcohol Drinking↗
PubMed1987

Morphometric analysis of epithelial cells of frog urinary bladder. I. Effect of antidiuretic hormone, calcium ionophore (A23187) and PGE2.

Changes in epithelial cell morphology, especially at the apical plasma membrane, are frequently cited as initial evidence for antidiuretic hormone (ADH)-induced increase in membrane permeability. The effects of ADH and agents that alter and modify calcium and prostaglandin concentrations on the morphology and cytology of the epithelial cells of frog (Rana pipiens) urinary bladder are presented using the techniques of transmission and scanning electron microscopy. It was found that, like ADH, calcium ionophore, A23187, produce intense microvilli formation, microfilament mobilization and an increase in the density of granules and membrane associated vesicles, suggesting a prominent role of calcium in these processes. Moreover, our results suggest that these membrane and cytosolic transformations may be mediated in part through prostaglandin formation, as exogenous PGE2 mimicked these effects, and indomethacin, a prostaglandin synthesis inhibitor, attenuated ionophore's effect on luminal cytomorphology. However, unlike ADH, prostaglandins and ionophore inhibit hormonal-induced increase in transepithelial water flow. These results suggest that other components more distal to the luminal membrane, perhaps the basolateral membrane, may be rate-limiting for transepithelial water flow and possibly are regulated by either changes in calcium concentrations or prostaglandins.

Actin Cytoskeleton↗
PubMed1985

Antibodies to cytokeratin and vimentin in testicular tumour diagnosis.

Thirteen primary and metastatic testicular germ cell tumours, including classical and anaplastic seminomas, and non-seminomatous testicular tumours were examined for their intermediate filament protein (IFP) types. The seminomas were shown to react with a monoclonal and a polyclonal antibody to bovine lens vimentin, while non-seminomatous germ cell tumours were strongly positive for a polyclonal and a monoclonal antibody to cytokeratin. In one case of seminoma with elevated serum levels of beta HCG and alpha FP, cytokeratin positive tumour cells were found. In the case of teratocarcinoma, several components of the tumour could be distinguished using a combination of antisera in double-label immunofluorescence microscopy. The glandular component of this tumour was positive with the polyclonal antikeratin, but also with the monoclonal cytokeratin antibody specific for glandular epithelia (RGE 53). However, the squamous component was negative with this latter antibody. Strikingly, the spindle cell component showed focal positivity for vimentin, with coexpression of cytokeratin and vimentin in some cells. Our data show that antibodies to cytokeratin and vimentin can be helpful in the diagnosis of testicular germ cell tumours, especially in the differentiation between seminomas and non-seminomatous tumours.

Antibodies, Monoclonal↗