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Biomedical subjects

G Lewandowski

Publications and source records attributed to G Lewandowski.

18 recordsLinked to original sources
PubMed2002

Herpes simplex type 1 infects and establishes latency in the brain and trigeminal ganglia during primary infection of the lip in cotton rats and mice.

The majority of the human population has been infected with herpes simplex virus type 1 (HSV-1). During a typical primary episode, HSV-1 spreads from the oral pharynx to the trigeminal ganglia, where a latent HSV-1 infection is established. Cold sores at the mucocutaneous junction of the lip are the typical manifestation of recurrent HSV-1. We investigated whether HSV-1 also infects the brain during the primary infection. We used HSV-1 infected BALB/c mice and inbred cotton rats as models. While both species were susceptible to HSV-1 infection, the time course of lesion formation and healing in the cotton rat more closely reflected that seen in humans. In both species, HSV-1 replicated in the brainstem and cerebellum, as well as the trigeminal ganglia during a primary infection of the lip. The brain infection was produced by a low inoculation dose, and did not cause observable neurologic signs or mortality. Using PCR and RT-PCR techniques, we demonstrated HSV-1 thymidine kinase in the absence of infectivity in the brains of both species 30-40 days after primary infection.

Animals↗
PubMed1998

The use of fluoroscopy to guide needle placement in interstitial gynecological brachytherapy.

PURPOSE: Interstitial brachytherapy is generally performed for gynecological malignancies with extensive parametrial involvement, by inserting the needles through a transperineal template. Often, the implanted needles are not parallel, and the multiple sources can be difficult to identify on localization radiographs, especially if obtained with a portable X-ray unit. We have used fluoroscopy to guide the needles for interstitial brachytherapy to treat various gynecological malignancies. Because the resultant needles are parallel, dosimetry can be performed based on the template hole positions used, rather than identifying individual sources. This report focuses on the technique; the outcome of patients implanted with this technique will be reported separately. METHODS: Seventy-one patients were implanted transperineally with 192iridium using a Syed template under fluoroscopic guidance, from September 1989 to May 1995, for bulky parametrial disease, narrow vagina, extensive vaginal involvement, recurrent disease after previous course of pelvic radiation therapy, or in cases in which the patient had previously undergone hysterectomy. 137Cesium was added in a central tandem in cases with a cervical os. Thirty patients were treated for primary cervical or vaginal carcinoma; 41 patients were treated for recurrent disease from endometrial or cervical cancers. The brachytherapy dose (prescribed to the periphery of the implant) was 40 to 55 Gy when used alone (15 patients) and 22-40 Gy when used as a boost to 34.2 to 59.4 Gy of pelvic external-beam radiotherapy (56 patients). The patients were followed for 6 to 63 months. RESULTS: In all cases, some of the needles had to be repositioned to improve the alignment. Hence, the use of fluoroscopy aided in achieving parallel placement of the needles in all implants as seen on anterior-posterior radiographs. Because the 192iridium sources were ordered beforehand based on the preplan, and the dosimetry was based on idealized geometry of the template hole positions, all patients were loaded on the same day of implant. CONCLUSION: Fluoroscopically guided perineal interstitial brachytherapy is a feasible technique for use in various gynecological malignancies. The use of fluoroscopic guidance helped to achieve parallel needle placement in all of our implants, but it required repositioning of some of the needles in all cases. The parallel positioning allowed the use of preplanned dosimetry, minimizing the delay in loading of the patients. The outcome of the patients treated using this technique is currently undergoing analysis and will be reported separately.

Brachytherapy↗
PubMed1998

Evidence for deficiencies in intracerebral cytokine production, adhesion molecule induction, and T cell recruitment in herpes simplex virus type-2 infected mice.

We examined the intracerebral T cell response in mice infected with neurovirulent HSV-2 strains and an avirulent HSV-1. In HSV-2-infected brains, (i) IL-1beta, TNF-alpha and IFN-gamma mRNA expression was low, (ii) ICAM-1 and VCAM-1 were not induced, (iii) few CD4+ or CD8+ cells were detected. By contrast, in HSV-1-infected brains, (i) cytokine mRNA expression was high, (ii) adhesion molecules were strongly expressed, (iii) many T cells were detected. We suggest that deficient T cell extravasation into HSV-2-infected brain regions is caused by negligible ICAM-1 and VCAM-1 expression, which is due to low expression of critical cytokines.

Animals↗
PubMed1998

Evidence that deficient IFN-gamma production is a biological basis of herpes simplex virus type-2 neurovirulence.

Although immune response control of herpes simplex virus (HSV) has been well demonstrated, numerous HSV-2 strains are neurovirulent in immunocompetent mice. Using an RNase protection assay and an ELISA, we found that HSV-2-infected mice exhibited a deficient IFN-gamma response, an inability to clear virus, and eventual death. An HSV-based amplicon vector expressing mouse IFN-gamma was constructed and packaged into HSV-1-helper virus (HSV(pIFN-gamma)). In mice treated with HSV(pIFN-gamma), (i) the LD50 of HSV-2(G) increased 5000-fold, (ii) intracerebral IFN-gamma expression increased 10-fold, and (iii) HSV titer rapidly decreased. We suggest that the deficient IFN-gamma response is a basis for HSV-2 neurovirulence in mice.

Animals↗
PubMed1997

Immunohistochemical examination of intracerebral T cell recruitment and adhesion molecule induction in herpes simplex virus-infected mice.

Herpes simplex virus type 1 (HSV-1) infection in the nervous system is tightly controlled by the T-cell-mediated response. This report describes the temporal relationships among HSV-1 infection, intracerebral adhesion molecule induction, and T cell migration in intravitreally inoculated mice. HSV-1 immunoreactivity, initially detected at 3 days, increased in area and intensity in the superior colliculus, oculomotor nucleus, and geniculate through 5 days. By 6 days, HSV-1 was nearly undetectable in the same regions and the mice survive the infection. At the peak of HSV-1 immunoreactivity, ICAM-1 and VCAM-1 were strongly expressed in all infected brain regions. Additionally, in these region a few CD4+ and CD8+ T cells were detected. The heaviest T cell migration and adhesion molecule expression occurred at 6 days, coinciding with the decrease in HSV-1 immunoreactivity. However, in SCID and athymic mice, HSV-1 was not cleared from the brain and the mice died. Together, these data suggest that HSV-1 infection of the brain is followed by adhesion molecule induction in and T cell extravasation into the infected brain regions. Most importantly, an efficient T cell response was required to eradicate infectious HSV-1 from the brain.

Animals↗
PubMed1994

Alteration of intracerebral cytokine production in mice infected with herpes simplex virus types 1 and 2.

Previously we reported that a lethal strain of herpes simplex virus type 2 (HSV-2) infects the brain following ocular inoculation of mice. We now demonstrate that HSV-2 mediates an unusual intracellular sequestering of class II major histocompatibility complex (MHC) antigens. With use of an RNase protection assay, we observed a selective inhibition of IFN-gamma and IL-6 gene transcription in brains of mice infected with HSV-2. It is likely that the inhibition of cytokine gene expression was mediated through a failure to activate CD4+ lymphocytes. These data suggest that the infecting herpesvirus can influence the profile of intracerebrally produced cytokines, which in turn may determine the outcome of the infection.

Animals↗
PubMed1994

Role of mycelium and extracellular protein in the biodegradation of 2,4,6-trichlorophenol by Phanerochaete chrysosporium.

The biodegradation of 2,4,6-trichlorophenol (2,4,6-TCP) by Phanerochaete chrysosporium was studied in batch systems. In experiments with mycelial suspension, the degradation of 2,4,6-TCP was found to occur in the absence of ligninase. Chloride ion was recovered in nearly stoichiometric amounts at the end of the process. The microorganism did not retain its degradation ability for more than 6 days under substrate-deficient conditions. Neither the mycelium nor the extracellular protein alone could degrade 2,4,6-TCP; both were required for complete degradation to occur. In experiments in which 2,4,6-TCP was exposed to the culture supernatant separated from its mycelium, negligible degradation was obtained and no chloride ion was recovered. No degradation was observed even when the supernatant was supplemented with hydrogen peroxide as a possible cosubstrate. In experiments performed with washed mycelium separated from its supernatant, no degradation took place until the mycelium released additional extracellular protein 5 to 6 h into the incubation. Additions of washed mycelium separated from its supernatant to active cultures also produced an increase in the rate of degradation in correspondence with the protein release. The protein release was independent of the presence of 2,4,6-TCP. The addition of cycloheximide to inhibit the synthesis of de novo proteins completely suppressed the release of protein by the mycelium and resulted in no 2,4,6-TCP degradation. Additions of culture supernatants containing a high concentration of extracellular protein to active cultures produced an increase in the rate of 2,4,6-TCP degradation.(ABSTRACT TRUNCATED AT 250 WORDS)

Basidiomycota↗
PubMed1991

Identification of human papillomavirus type 16 in primary and recurrent cervical cancer following radiation therapy.

Formalin-fixed, paraffin-embedded tissue blocks from 13 women with cervical carcinoma that recurred following radiation therapy were evaluated for the presence of human papillomavirus (HPV) by in situ hybridization using ribonucleic acid 35S-labeled probes for HPV types 6, 11, 16, and 18. Ten of thirteen patients also had pretreatment biopsies from their primary tumors available for analysis. HPV 16 was detected in both primary and recurrent lesions in 4 women. In 1 case, HPV was detected in the primary tumor and not in the recurrence. HPV 16 was also present in three recurrent cancers from which primary lesions were not available for probing. Radiation therapy did not alter the hybridization signal strength or pattern, suggesting that the HPV genome copy number was not significantly affected. The persistence of HPV 16 in recurrent cervical carcinoma is consistent with the theory that HPV plays a role in maintaining the malignant state.

Adult↗
PubMed1991

A comparison of breast-feeding data from the National Surveys of Family Growth and the Ross Laboratories Mothers Surveys.

This study compares rates of breast feeding reported in the National Surveys of Family Growth with those from the Ross Laboratories Mothers Surveys. Both surveys have documented rates of breast feeding over the last 30 or more years. Despite differences in survey methodology, both surveys document similar long-term trends in breast feeding. The similarities of rates in breast feeding also are evident across several maternal sociodemographic characteristics. We conclude that both surveys produce reliable and useful estimates of breast feeding.

Adult↗
PubMed1990

The use of in situ hybridization to show human papillomavirus deoxyribonucleic acid in metastatic cancer cells within lymph nodes.

Southern blot hybridization has been used to identify human papillomavirus types in both primary tumors and lymph node metastases. However, this technique requires fresh-frozen tissue and is incapable of localizing deoxyribonucleic acid sequences to specific cell types in the tumor sample. In contrast, in situ hybridization precisely locates viral sequences within tumor cells while preserving cellular architecture. Further, in situ hybridization requires only small samples of formalin-fixed, paraffin-embedded tissues. Five lymph nodes (from four patients) containing metastatic cervical squamous tumor cells (identified with hematoxylin and eosinophil staining) were analyzed with in situ hybridization techniques with human papillomavirus type 16 deoxyribonucleic acid probes labeled with sulfur 35. The primary cervical cancer from all four patients had been shown to contain human papillomavirus type 16 sequences by Southern blot. Three specimens from two patients clearly showed the presence of human papillomavirus type 16 sequences within the nuclei of metastatic tumor cells, whereas two specimens were nondiagnostic most likely as a result of the small volume of cancer relative to the size of the lymph node. This information indicates that it is the tumor cells themselves that contain viral deoxyribonucleic acid and provides additional evidence linking human papillomavirus with cervical carcinogenesis.

Autoradiography↗
PubMed1990

Hysterectomy with extended surgical staging and radiotherapy versus hysterectomy alone and radiotherapy in stage I endometrial cancer: a comparison of complication rates.

Extended surgical staging (ESS) has been added to total hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) in patients with clinical Stage I endometrial cancer in order to better define patterns of metastatic spread and the response to treatment. Adjuvant radiotherapy has a demonstrated efficacy in decreasing central recurrence in Stage I disease. The combined use of radical surgery and pelvic radiotherapy for cervical cancer patients results in an increased incidence of complications. This study compares major complication rates in Stage I endometrial cancer patients who underwent either TAHBSO with ESS or TAHBSO alone followed by adjuvant external beam radiotherapy (RT). Records of 52 patients with clinical stage I endometrial cancer were reviewed. Thirty-two patients underwent TAHBSO plus ESS and 20 patients had TAHBSO alone. All patients received postoperative, whole pelvis external radiotherapy. Four patients suffered complications potentially related to treatment which required rehospitalization, and all 4 were in the group which had undergone ESS. A comparison of complication rates between the ESS + RT group (4/37 or 10.8%) and TAHBSO + RT group (0/20) suggested a trend toward significance (P less than 0.10). Treatment protocols using extended surgical staging prior to adjuvant radiotherapy in Stage I endometrial cancer should examine complications potentially related to this combination, to further define treatment risks and benefits.

Adult↗
PubMed1990

Vulvar condylomas and squamous vestibular micropapilloma. Differences in appearance and response to treatment.

A study of 37 women with typical condylomas and so-called squamous micropapilloma was undertaken to determine their response to systemic interferon and/or podophyllin treatment. Thirty lesions were classified as condylomas and 9 as squamous micropapillomas; two women had both lesions. Twenty-six (87%) of 30 condylomas responded, whereas only 1 (11%) of the 9 cases of micropapillomatosis showed a partial response (P less than .001) to podophyllin and/or interferon. Twenty-six biopsies from condylomas in which sufficient DNA was available for analysis contained human papillomavirus (HPV) DNA sequences that hybridized to an HPV 6 + 16 probe mix under nonstringent conditions. In contrast, HPV DNA sequences could not be detected in any of the nine cases of micropapillomatosis. Immunoperoxidase studies performed on these lesions failed to demonstrate viral capsid antigen. Thus, despite certain similarities in the clinical presentation and microscopic features of condylomas and squamous micropapillomas, it is not clear at present whether micropapillomas are HPV-related lesions.

Condylomata Acuminata↗
PubMed1989

Postoperative adjuvant external-beam radiotherapy in surgical stage I endometrial carcinoma.

A combined surgical and radiotherapeutic approach is widely in Stage I endometrial adenocarcinoma. The technique and timing of the radiotherapy varies from center to center. Postoperative external-beam (EB) radiotherapy has the advantage of patient selection based upon surgical findings, comprehensive treatment of the pelvic nodal and vaginal cuff areas, and elimination of the need for an intracavitary procedure. Although frequently utilized, this technique is surprisingly poorly described in the medical literature. From 1979 to 1986, 46 surgical Stage I patients received adjuvant postoperative EB therapy at Georgetown University Hospital (GUH) (Washington, DC). Indications for treatment were Grade greater than or equal to 2 and/or depth of myometrial invasion of greater than 33%. The 5-year actuarial survival was 90% with a disease-free survival of 82%. The failure rate within the irradiated field was 6.5% with a distant failure rate of 8.7%. The rate of significant long-term complications was acceptable at 6.5%. The authors conclude that postoperative EB radiotherapy is an effective adjuvant therapy with results comparable to other available radiotherapeutic techniques.

Adenocarcinoma↗
PubMed1989

Carcinoma of the vulva. Significance of surgical margin involvement in assessing prognosis.

Repeat pathologic analysis was completed in order to independently assign surgical margin status in a group of 61 patients from the Ohio State University gynecologic oncology tumor registry. Patients were entered into the study group after having undergone simple or radical vulvectomy for squamous carcinoma of the vulva. A statement regarding margin status was made following a detailed pathologic review, and parameters--including stage, grade and lymph node involvement--were assigned without regard to outcome. There was no statistically significant difference in the survival or recurrence rate with involved margins. Mean lesion size was significantly larger with involved margins (P less than .05). The survival and recurrence data support a primary surgical attempt at complete excision regardless of the microscopic margin status.

Carcinoma, Squamous Cell↗
PubMed1986

Anticonvulsant activity of piperidinol and (dialkylamino)alkanol esters.

Aromatic and heterocyclic esters of 1-methyl-4-piperidinol and 1,4-dimethyl-4-piperidinol and aromatic esters of (dialkylamino)alkanols were prepared and evaluated for antiepileptic activity by the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole seizure threshold (scMet) assays and for minimal central neurotoxicity by the rotorod ataxia test. The most potent compound, namely the 2-phenylbenzoate (57) of 3-(diethylamino)propanol, was slightly more potent than diphenylhydantoin in the MES assay, while the 2-phenylbenzoate (24) of 1-methyl-4-piperidinol and the 2-phenylbenzoate (56) of (diethylamino)ethanol displayed activity comparable to that of diphenylhydantoin. The 2-phenethylbenzoate ester (6) of 1-methyl-4-piperidinol exhibited one-third the activity of diphenylhydantoin. The 2,4,5-trimethylbenzoate 40 and 2,4,6-trimethylbenzoate 41 of 1-methyl-4-pieridinol were even less potent, but did display activity in the phenobarbital-methsuximide range. Certain compounds interact with sites associated with the GABA receptor-chloride channel complex, but their potencies as anticonvulsant agents do not correlate with interaction at sites on the channel complex. Certain analogues antagonize binding of a batrachotoxin analogue to sodium channel sites, a property indicative of local anesthetic activity. There are structural similarities between 2-phenylbenzoates 57, 56, and 24 and diphenylhydantoin, and the latter anticonvulsant also antagonizes binding of the batrachotoxin analogue.

Amino Alcohols↗